Transition-Metal-Catalyzed Oxidative Heck Reactions

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1399

Transition-Metal-Catalyzed Oxidative Heck Reactions TBabak ransiton-Metal-Cat lyzedOxidativeHeckReactions Karimi,* Hesam Behzadnia, Dawood Elhamifar, Pari Fadavi Akhavan, Farhad Kabiri Esfahani, Asghar Zamani Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), P.O. Box 45195-1154, Gava Zang, Zanjan 45137-66731, Iran Fax +98(241)4153225; E-mail: [email protected] Received 5 January 2010; revised 5 February 2010

1 2 2.1 2.1.1 2.1.1.1 2.1.1.2 2.1.2 2.1.2.1 2.1.2.2 2.1.3 2.1.3.1 2.1.3.2 2.1.4 2.2 2.3 3 3.1 3.1.1 3.1.1.1 3.1.1.2 3.1.2 3.1.2.1 3.1.2.2 4

Introduction Oxidative Heck Reactions of Organometallic Compounds With Palladium(II) Catalysts Ligand-Free Reactions Anaerobic Aerobic Ligand-Based Reactions Aerobic Anaerobic Asymmetric Reactions Aerobic Anaerobic With Polymer-Supported Palladium(II) Catalysts With Other Transition-Metal Catalysts With Other Organometallic Compounds Oxidative Heck Reactions of C–H Compounds Catalytic Reactions Intermolecular Reactions Anaerobic Aerobic Intramolecular Reactions Anaerobic Aerobic Conclusions and Outlook

Key words: oxidative Heck coupling, organometallic reagents, oxygen, transition metals, asymmetric catalysis

1

Introduction

Reactions that form carbon–carbon bonds are some of the most important transformations in organic chemistry because the resulting products can be key structural motifs in natural products and well-known building blocks for various oligomers and polymers. Transition-metal-catalyzed approaches for these transformations include Stille, Suzuki and Heck cross-coupling reactions. Despite their widespread application, these methods suffer from the SYNTHESIS 2010, No. 9, pp 1399–1427xx. 201 Advanced online publication: 19.04.2010 DOI: 10.1055/s-0029-1218748; Art ID: E26210SS © Georg Thieme Verlag Stuttgart · New York

disadvantage that they require prefunctionalized sites on each of the coupling partners (such as aryl halides, triflates, stannanes), which results in the formation of significant amounts of by-products and a lack of atom economy. Since the discovery of the first palladium-catalyzed arylation or vinylation of an olefin with an organic halide by Mizoroki1 and Heck,2 this transformation has been widely used for the cross-coupling reaction of a diverse range of olefins and aryl species R1–X, where X = Cl, Br, I, OTf, OTs and N2+ (Scheme 1). Accordingly, during the past decade, several review articles have been published to discuss different feature of this reaction, including the mechanism,3 the development of more effective ligands,4 the application of the Heck reaction for the synthesis of natural products,5 the development of heterogeneous catalysts to address the difficulty of catalyst recovery, and the recycling of expensive palladium species.6 R1 X +

R2

base

R1

R2 + HX⋅base

[Pd]

Scheme 1

Despite the high importance and excellent advances concerning the application of the Heck coupling reaction in organic synthesis, the methodology suffers from the significant inherent problem that the formation of a stoichiometric amount of hazardous halide salts can cause extensive environmental pollution (Scheme 1). For this reason, recent interest has been directed toward the halide-free oxidative coupling reactions via both transmetallation and direct C–H activation7 (Scheme 2). R1 H +

R1 M +

R2

R2

[Pd]

R1

[O] [Pd] [O]

R1

R2

C–H activation

R2

transmetallation

Scheme 2

With ever-increasing environmental concerns, it seems that this area of research can effectively compete with the traditional halide-based coupling reactions especially for large-scale applications. Moreover, because of the low cost and the ready availability of a vast number of arenes (instead of aryl halides in the traditional Heck reaction), the direct C–H activation protocols and those based on molecular oxygen as final oxidant are avenues for the de-

Downloaded by: Dieter Enders. Copyrighted material.

Abstract: Oxidative Heck reactions provide a facile and efficient route to carbon–carbon bond formations. This review is divided into two main sections, the first consisting of oxidative Heck reactions of organometallic compounds such as organoboranes, organosilanols and arylstannanes, and the second covering oxidative Heck reactions via C–H activation, a topic which has become an attractive theme in organic synthesis.

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B. Karimi et al.

Babak Karimi was born in 1969 in Tehran (Iran) and graduated with an M.Sc. (Honors) degree in organic chemistry from Mazandaran University, Babolsar, Iran in 1995. He then moved to Shiraz, where he received his Ph.D. with Prof. Habib Firouzabadi in 1999. In the same year, he obtained the Dr. Arshia Azad Award (Iranian Chemical Society) and Kharazmi Young Researcher Award for the preparation of the best Ph.D. thesis of the year in chemistry in Iran. He

was then appointed as Assistant Professor at the Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran. In 2002, he was promoted to Associate Professor and in 2005, he became a Full Professor in chemistry. In 2004, he received a prestigious Alexander Von Humboldt Fellowship and he was invited to join Prof. Dieter Enders and his research group at the RWTH University of Aachen, Germany, where they worked on a new concept of sup-

ported ionic liquid catalysis. He has published more than 75 scientific papers in prominent and high-quality international journals. His current research interests include the design, preparation and application of new type of supported catalysts based on nanoporous inorganic solids and polymers, as well as the development of novel synthetic methodologies, especially in the areas of carbon–carbon bond-forming reactions, asymmetric catalysis, and protection– deprotection chemistry.

Hesam Behzadnia was born in Shiraz (Iran) in 1980. He completed his undergraduate degree in chemistry from Shiraz University in 2004. Two years later, he

earned his M.Sc. degree from IASBS. He then began his doctoral research, in the Nanochemistry Laboratory at IASBS, on the synthesis and applications of

new family of palladium nanoparticles supported on ordered mesoporous carbon under the supervision of Prof. Babak Karimi.

Dawood Elhamifar was born in Yasouj (Iran) in 1981. He obtained his M.Sc. degree in September 2005 from IASBS. Since 2006, he has been working in the research group of Prof. Babak Karimi at IASBS; his Ph.D. work

is about the synthesis of new periodic mesoporous organosilicas based on ionic liquids and their applications in some organic transformations. His main research interest is the immobilization of ionic liquids into silica

nanostructures and their applications as catalysts and reaction media in some chemical transformations including cross-coupling reactions.

Pari Fadavi Akhavan was born in Bonab (Iran) in 1980. She received her undergraduate education at the University of Tabriz, Iran. She is currently carrying

out her Ph.D. research at IASBS under the guidance of Prof. Babak Karimi, where she is working on the design and synthesis of new N-heterocyclic car-

bene (NHC) palladium selfsupported polymers as nanocatalysts and their applications in cross-coupling reactions.

Farhad Kabiri Esfahani was born in Tehran (Iran) in 1978. He graduated from IASBS in September 2005. His research dealt with catalytic applications of polyoxometalates. He subse-

quently joined Prof. Babak Karimi’s research group in the Nanochemistry Laboratory at IASBS to work toward his Ph.D. He is currently carrying out research on the catalytic applica-

tions of gold nanoparticle systems. His research interests include the preparation of metal nanoparticles and transition-metal-catalyzed reactions.

Asghar Zamani was born in 1979 in Tehran (Iran). He received his B.Sc. in 2002 from Sharif University of Technology

and his M.Sc. in 2005 from IASBS. In 2007, he joined Prof. Babak Karimi’s research group at IASBS as a Ph.D. student. His

current research interest focuses on the development of supported palladium nanoparticle catalysis.

Synthesis 2010, No. 9, 1399–1427

© Thieme Stuttgart · New York


Biographical Sketches

velopment of environmentally acceptable Heck chemistry under more appropriate reaction conditions. However, since the starting arene compounds in many of the C–H activation protocols contain no halogen or similar groups, achieving selectivity is the major challenge in carbon–hydrogen bond activations. The aim of this review is to highlight transition-metal-catalyzed oxidative Heck reactions using either organometallic reagents or non-functional arenes. Due to the critical role of oxidants in these methodologies, we discuss the most important achievements using both chemical and stoichiometric oxidant and molecular oxygen separately.

2

Oxidative Heck Reactions of Organometallic Compounds

The palladium(II)-mediated versions of the Heck reaction using organomercuric acetates,8 organoboronic acids9 and organofluorosilicates10 are the first examples of stoichiometric halogen-free Heck reactions mediated by organometallic compounds; these opened a new window to innovative catalytic oxidative Heck reactions (Scheme 3).

2.1

With Palladium(II) Catalysts

2.1.1

Ligand-Free Reactions

2.1.1.1 Anaerobic The catalytic oxidative Heck-type reaction of arylboronic compounds was first reported by Uemura and Cho in 1994.12 In this study the palladium-catalyzed cross-coupling reactions of aryl- and alkenylboronic acids or tetraphenylborate anion with alkenes were investigated. The reaction of phenylboronic acid (1 mmol) with styrene (1.2 mmol) in the presence of palladium catalyst (0.05 mmol) using different bases and solvents was chosen as a model reaction. The results showed that the use of sodium acetate as base and acetic acid as solvent gave the best yield, whereas the use of other bases, such as sodium ethoxide, lithium acetate, potassium carbonate in methanol, tetrahydrofuran, acetonitrile, dimethylformamide, and benzene solvents afforded moderate yields (26–51%) even at high temperature and for 5–20 hours. Several alkenes and arylboronic acids were employed as substrates under the optimized conditions (Table 1). Table 1

Heck Coupling Reaction in the Presence of Pd(OAc)2 R1

PhHgOAc + Pd(OAc)2 + Ph

Bu

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Transition-Metal-Catalyzed Oxidative Heck Reactions

MeOH

ArB(OH)2 +

Ph

R2

(a)

30 °C, 2 h, 98%

Ph

Pd(OAc)2 NaOAc AcOH, r.t.

Ar

R1 R2

Entry

Ar

R1

R2

Yield (%)

1

Ph

Ph

H

99

2

Ph

Ph

Ph

98

3

Ph

CO2Me

H

73

4

4-MeOC6H5

Ph

H

97

5

4-ClC6H5

Ph

H

39

6

3-O2NC6H5

Ph

H

64

B(OH)2 CO2Me

+ Pd(OAc)2 +

0 °C

Bu (b)

70%

CO2Me

K2 [

Ph

SiF5 ]

+ Pd(OAc)2 +

THF

Ph

r.t., 9 h, 35%

CO2Me

(c)

CO2Me

Scheme 3

In 1968, the first catalytic oxidative Heck reaction was introduced by Heck using arylmercuric chloride and in the presence of various reoxidants, to regenerate palladium(II) from palladium(0).11 He discovered that oxidative coupling of phenylmercuric chloride and methyl acrylate could be catalyzed by Li2PdCl4 in the presence of copper(II) chloride as oxidant at room temperature (Scheme 4). CO2Me

Li2PdCl4, CuCl2 + PhHgCl MeOH, r.t., 2 h 57%

Scheme 4

Ph

CO2Me

Under the same reaction conditions, treatment of phenylboronic acid with 2-substituted propenes gave a mixture of products. The ratio of compounds was dependent on the nature of the alkenes and the molar ratio of substrates.13 Mori and co-workers performed an effective oxidative Heck reaction using a catalytic amount of palladium(II) in the presence of copper(II) acetate as reoxidant in N,Ndimethylformamide.14 The coupling reaction of alkenes bearing electron-withdrawing substitute (Table 2, entries 1 and 2), allyl phenyl ether (Table 2, entry 3), styrene (Table 2, entry 4) and ethyl crotonate (Table 2, entry 5) with phenylboronic acid were successfully performed and the yields of arylated products were moderate to good. The E-configured products were obtained for all alkenes except for acrylonitrile (Table 2, entry 2). Larhed and co-workers investigated the effect of microwave irradiation on the palladium(II)-catalyzed oxidative Heck reaction.15 To determine suitable conditions in terms

Synthesis 2010, No. 9, 1399–1427



REVIEW

1402 Table 2 Acid PhB(OH)2

REVIEW

B. Karimi et al. β-OAc elimination

Oxidative Heck Coupling of Alkenes with Phenylboronic

+

alkene

product

Ar

DMF, 100 °C

Entry

Ar

PdLn

Pd(OAc)2 Cu(OAc)2, LiOAc

Alkene

OAc

β-hydride elimination

Ar

Yield (%)

OAc Pd(II)

1

butyl acrylate

84

2

acrylonitrile

58 (E/Z = 3:1)

3

allyl phenyl ether

79

4

styrene

82

5

ethyl crotonate

62

ArB(OH)2

OAc Pd(II)


Ar LnPd

OAc

OAc

Scheme 5

enhances selectivity via the retention of acetate groups and controls the position of the double bond in Heck products.16–18

Entry

Y

Ar

Temp (°C)

Yield (%) (E/Z)

1

CO2Bu

Ph

125

71

On the basis of these previous studies, Jiao and Su investigated the palladium-catalyzed reaction of allyl acetate with phenylboronic acid in the presence of silver salts and some additives.19 In this reaction, the best results were obtained using palladium(II) acetate (5 mol%), silver acetate (2.0 equiv) as oxidant, copper(II) fluoride (1.0 equiv), and potassium hydrogen difluoride (2.0 equiv) in acetone at 85 °C. Phenyl- and 4-methylphenylboronic acids were active in the reaction with allyl acetate and gave the corresponding products in good to excellent yields with very high regioselectivities (Table 4, entries 1 and 2), whereas sterically hindered arylboronic acid gave a low yield of the corresponding adduct (Table 4, entry 3). Where an arylboronic ester was employed in this transformation, the arylated allyl acetate was obtained in high yield and regioselectivity (Table 4, entry 6), while the use of alkenylboronic ester (Table 4, entry 5) provided the corresponding product in a lower yield.

2

CO2Bu

2-MeOC6H4

125

45 (21:1)

Table 4 Palladium-Catalyzed Oxidative Heck Reaction of Allyl Acetate with Arylboronic Acid Derivatives

3

CO2Bu

2,4,6-Me3C6H2

140

51 (18:1)

organoborane

In this study, the arylated products were obtained with Eselectivity in moderate to good yields. The use of perfluorinated alkenic substrates also gave good yields under the same reaction conditions (Table 3, entries 5 and 6). Table 3 Reaction of Arylboronic Acids with Olefins under Microwave Heating Pd(OAc)2 Cu(OAc)2, LiOAc ArB(OH)2 +

Y

Ar

DMF, 125 °C microwave 15 min

Y

4

CO2Bu

4-(CHO)C6H4

125

58 (25:1)

5

(CF2)5CF3

3,4-(OCH2O)C6H3

125

74 (94:1)

110

a

6 a

(CF2)5CF3

4-BuC6H4

85

Time = 30 min.

In the oxidative Heck process, it is often difficult to control the selectivity of the arylation where an allylic ester is used as substrate (Scheme 5). Moreover, it is well known that the use of silver(I) as oxidant in the palladium(II)–oxidant catalytic system both

R


OAc

CuF2, KHF2 acetone 85 °C, 5 h

Entry

Organoborane

E/Z

Yield (%)

1

PhB(OH)2

20:1

91

2

4-MeC6H4B(OH)2

20:1

92

3

2-MeC6H4B(OH)2

16:1

37

4

4-MeOC6H4B(OH)2

13:1

69

6:1

37

20:1

80

5

O

n-Bu

B O

O

6

MeO

B O

Synthesis 2010, No. 9, 1399–1427

Pd(OAc)2 AgOAc

OAc +


of catalyst, base, reoxidant, temperature and heating time, the reaction system was first examined using phenylboronic acid and butyl acrylate as substrates under microwave irradiation. Under the optimized reaction conditions, phenylboronic acid was oxidatively coupled with butyl acrylate using catalytic amount of palladium(II) acetate (5 mol%), a stoichiometric amount of copper(II) acetate as oxidant, and lithium acetate as base at 125 °C to generate butyl (E)-cinnamate (Table 3, entry 1).

Ar

REVIEW

1403


The chelation between oxygen and palladium atoms in the coupling reaction played an important role in promoting high regioselectivities (Scheme 6).20,21 Intermediate 1 was favored as a result of the steric hindrance between Ph and Hc. This chelation prevented the rotation around the C1– C2 bond and resulted in a syn relationship between Ha and palladium. The subsequent b-Ha elimination of this intermediate led to high E-selectivity.

Table 5

Reaction of Organoboranes with tert-Butyl Acrylate Pd(OAc)2 (10 mol%)

ArB(OR)2 +

CO2t-Bu

Entry

Organoborane

79

MeO B(OH)2

OAc Ph Pd

Yield (%)

B(OH)2

1

CO2t-Bu

Ar

O2, Na2CO3, DMF 50 °C, 3 h

2

O

78 Ac

O

B(OH)2

3 OAc Ph Ha'

Pd O Hb O Hc

H a' Ha Ph

N SO2Ph

Pd O Hb O Hc

O

4

O

β-Ha elimination

1

79

B

MeO

O B

5

85

O

OAc

Ph

Scheme 6

O

S

6

52

B O

2.1.1.2 Aerobic The use of molecular oxygen as an oxidant for palladiumcatalyzed coupling of organoborons with alkenes was first reported by Jung et al.22 The reactivity of butyl acrylate in a coupling reaction with phenylboronic acid was screened using a catalytic amount of palladium acetate in the presence of several bases, including sodium carbonate, sodium acetate, cesium carbonate, and potassium carbonate, in various solvents. It appeared that the use of 10 mol% of palladium(II) acetate and sodium carbonate as base in N,N-dimethylformamide at 50 °C under aerobic conditions gave the best result for the oxidative Heck coupling. Good results with high E-selectivity were obtained in the coupling reaction of phenylboronic acid with both electron-poor and electron-rich alkenes under the described aerobic system (Scheme 7). Pd(OAc)2 (10 mol%) PhB(OH)2 +

X

O2, Na2CO3, DMF 50 °C, 3 h X = CO2t-Bu, Ph, Bn X = OBu

Ph X

In contrast, the reaction of allylbenzene with various aryl boron compounds furnished a mixture of the doublebond-migrated isomers in high yields (Scheme 8). Pd(OAC)2 (10 mol%) O2, Na2CO3 ArB(OR)2

+

Ph

80–86%

Scheme 8

The reaction of alkenes with alkenylboron compounds using molecular oxygen as oxidant in the presence of palladium catalysts was reported by Jung and co-workers in 2004.23 This approach used mild conditions for the synthesis of a wide variety of conjugated dienes (Scheme 9). In this system, the monosubstituted activated alkenes such as tert-butyl acrylate and styrene, as well as non-activated allyl benzyl ether, were used to afford the corresponding E,E-dienes in high yields and stereoselectivities.

86–90%, E only 73%, E/Z = 2:1

Scheme 7

Ph

Ar

DMF or MeCN 50 °C, 3 h

Pd(OAc)2

n-Bu

B

O

NaCO3, O2 + Y

O

n-Bu

Y

DMA, 23 °C 80–92%

Complementary studies on organoboron compounds with electron-donating and electron-withdrawing groups showed similar reactivities in the coupling reactions (Table 5, entries 1–3). It is important to note that the use of arylboronates as precursor resulted in a decrease in the formation of by-products arising from homocoupling of boronic compounds (Table 5, entries 4–6).

Y = CO2t-Bu, Ph, CH2OBn

Scheme 9

It has been shown that the slow addition of organoborons to alkenes improved the yields and decreased the occurrence of homocoupling side reactions. Using such mild reaction conditions, the reaction of cis-hexenyl pinacolboSynthesis 2010, No. 9, 1399–1427



Ha

75

OAc

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B. Karimi et al.

ronic ester with tert-butyl acrylate afforded dienes in good yields and E,Z-selectivity (Scheme 10) showing the retention of the geometry of the alkenylboron compounds during the catalytic process. B

n-Bu

O +

Pd(OAc)2

CO2t-Bu

O

CO2t-Bu

n-Bu

Na2CO3, O2 DMA, 23 °C

86%

Scheme 10

The addition of arylboronic acids to vinyl sulfones and vinylphosphonates to produce the corresponding a,b-unsaturated sulfones and phosphonates, which are common species in natural products, was reported by Kabalka and co-workers.24,25 The formation of the a,b-unsaturated phosphonates and sulfones was carried out using boronic acids in N,N-dimethylformamide at 60 °C in the presence of 10 mol% of palladium acetate and sodium carbonate under oxygen atmosphere. A variety of arylboronic acids containing both electron-donating (Table 6, entries 1 and 2) and electron-withdrawing (Table 6, entries 3–6) groups reacted with diethyl vinylphosphonates and phenyl vinyl sulfone to produce the corresponding products in high yields. It is noteworthy that sterically hindered, di-orthosubstituted boronic acid (Table 6, entries 7 and 8) also afforded the a,b-unsaturated adducts in excellent yields. Table 6 Reaction of Arylboronic Acids with Vinyl Sulfones and Vinylphosphonates Pd(OAc)2 +

Entry

Ar

X

Time (h) Yield (%)

1

4-MeOC6H4

PO(OEt)2

20

85

2

4-MeOC6H4

SO2Ph

15

81

3

4-ClC6H4

PO(OEt)2

18

73

4

4-ClC6H4

SO2Ph

18

79

5

3-O2NC6H4

PO(OEt)2

15

83

6

3-O2NC6H4

SO2Ph

17

76

7

2,6-Me2C6H3

PO(OEt)2

20

86

8

2,6-Me2C6H3

SO2Ph

18

74

9

1-C10H7

PO(OEt)2

15

66

2.1.2

Ligand-Based Reactions

Na2CO3, O2 DMF, 60 °C

Ar

2.1.2.1 Aerobic Since, in the ligand-free Heck-type reactions, palladium(0) species usually aggregate and agglomerate to unreactive palladium clusters and thus retard the coupling reaction, the presence of ligands is necessary in many instances.26 The ligand both stabilizes the catalyst, by preventing the aggregation of palladium(0), and increases the Synthesis 2010, No. 9, 1399–1427

The use of a ligand to stabilize the catalyst in the oxidative aerobic Heck vinylation was first reported by Larhed and co-workers in 2004.27 It was found that the coupling of various arylboronic acids with electron-poor alkenes could be accomplished using palladium(II) acetate catalyst, 2,9-dimethyl-1,10-phenanthroline ligand (dmphen), and N-methylmorpholine base in the presence of molecular oxygen in acetonitrile. A number of alkenes gave the corresponding products with good diastereo- and regioselectivity. The electron-rich arylboronic acids provided high yields without any by-product (Table 7, entries 1 and 2). Furthermore, the meta-substituted electron-poor arylboronic acids afforded the corresponding arylated products in moderate to good yields (Table 7, entries 4 and 5), whereas para-substituted electron-poor arylboronic acids were inactive under the described reaction conditions (Table 7, entry 3). Table 7 Palladuim-Catalyzed Oxidative Heck Reaction Using dmphen as Ligand ArB(OH)2

+

R

Pd(OAc)2, dmphen

Ar

NMM, O2, MeCN 50 °C

R

X

ArB(OH)2

X

regio- and stereoselectivity of the reaction in the case of prochiral olefins. Bidentate nitrogen ligands are the most versatile ligands for these reactions due to their interesting properties,27,28 namely their ability to facilitate the efficient reoxidation of palladium(0) to palladium(II) by molecular oxygen, their low cost, and their high air- and moisture-stability when compared to their phosphine counterparts.


Entry

Ar

R

Yield Pd(OAc)2/ dmphen (mol%) (%)

1

4-MeC6H4

CO2Bu

2:2.4

92a

2

4-MeOC6H4

CO2Bu

1:1.2

70a

3

4-AcC6H4

CO2Bu

1:1.2

0b

4

3,5-(Br)2C6H3

CO2Bu

2:2.4

67b

5

3-AcC6H4

Ph

1:1.2

77c

6

Ph

3-EtOC6H4

2:2.4

83b (a/b = 17:83)

a

Time = 6 h. Time = 12 h. c Time = 24 h. b

In another study, a regioselective a-arylation of enamides (electron-rich olefins) with arylboronic acids was performed using the same system (Table 8).29 In this reaction, electron-rich arylboronic acids gave high yields with excellent regioselectivities (2/3 > 99:1) without any side products (Table 8, entries 1–3). For electron-poor arylboronic acid substrates, low yields were generally obtained with reasonable selectivities, and the corresponding biaryl was detected as a by-product in some cases (Table 8, entries 5 and 6).


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REVIEW Table 8 Aerobic Oxidative Heck Reaction of Arylboronic Acids and Enamides Using Pd(OAc)2, dmphen, and NMM

O2 H Pd

ArB(OH)2

H2 O

L

Pd

Pd

L

n O

N O

Pd(OAc)2, dmphen

Ar

R

2 Ar

+ NMM, O2, MeCN 50 °C, 18 h

R

H R

n

R

O

N

Pd

Pd

L

L

Pd Ar

Ar

L

Ar 7

8

3 Ar

Scheme 11

Entry

Ar

n

2/3

Yield (%)

1

4-MeOC6H4

1

99:1

79

2

4-MeC6H4

1

99:1

96

3

4-BuC6H4

3

96:4

89

4

Ph

3

94:6

80

5

4-ClC6H4

3

92:8

31

6

4-AcC6H4

3

95:5

40

The catalytic pathway was studied with DFT calculations which confirmed the cationic character of the intermediate 4 (Figure 1). These calculations demonstrated that the electron-withdrawing nature of the phenyl ring increased the exothermicity of the p-complex formation. N

6

N Me Pd

palladium(II) species is regenerated through reoxidation of the palladium(0) species by molecular oxygen. An open-air catalytic oxidative Heck reaction of arylboronic acids and olefins using a system comprising palladium(II) acetate, dmphen, and N-methylmorpholine was reported by Larhed and co-workers in 2006.28 The reaction was performed using 2 mol% palladium(II) acetate, 2.4 mol% dmphen and 2 equivalents N-methylmorpholine at room temperature or at 60–80 °C. This method was efficient for the oxidative coupling of arylboronic acids containing an electron-donating methyl group (Table 9, entries 1–5). Moreover, p-acetylphenylboronic acid could be used as the aryl source in the oxidative Heck reaction for the first time (Table 9, entry 6). Table 9 Palladium-Catalyzed Open-Air Oxidative Heck Reaction of Arylboronic Acids with Olefins ArB(OH)2

+

R

Pd(OAc)2, dmphen

4

Larhed and co-workers used electrospray ionization mass spectrometry (ESI-MS) and MS/MS analyses to detect possible cationic palladium complexes as intermediates in a ligand-controlled palladium(II)-catalyzed oxidative Heck type reaction.30 The detection of all potential intermediates as dmphen–palladium(II) complexes implied that the dmphen bidentate ligand was attached to palladium during the entire catalytic cycle (Scheme 11). As shown in Scheme 11, in the first stage arylpalladium(II) complex 6 is generated via a transmetalation process. In the second step, the coordination of palladium(II) to the alkene produces p-complex 7. Then, 7 undergoes a migratory insertion process to form s-complex 8. The Heck product and palladium hydride are then obtained via the b-elimination of intermediate 8. Finally, the active

R

Entry

Ar

R

1

4-MeC6H4

CO2Bu CO2Bu

24 1

93a 94b

2

4-MeC6H4

CO2Bu

96

35b

3

4-MeC6H4

Ph

24

85a (a/b = 15:85)

4

4-MeC6H4

48

71a

24

91c

120

61a

Figure 1

Theoretical studies also proved that electron-rich arylboronic acids have lower insertion barriers, in parallel with weaker p-complexation energies. Moreover, the addition of lithium chloride to the reaction decreased the reaction rate, reinforcing the legitimacy of the cationic pathway.

Ar

NMM, air, MeCN

Ar

Time (h) Yield (%)

O N

5

4-MeC6H4

OBu

6

4-AcC6H4

CO2Bu

a

Temp = r.t. Temp = 80 °C. c Temp = 60 °C. b

In general, bases play a crucial role in the palladium-catalyzed cross-coupling reactions, including in the Suzuki reaction.31 The role of the base in such processes is to facilitate transmetallation of organoboron compounds to organopalladium 10 through organoborate salts 9, resulting in the acceleration of the coupling processes (Scheme 12). However, homocoupling by-products were usually formed in parallel, though in low yields, because of the high reactivity of borate salts 9. Synthesis 2010, No. 9, 1399–1427



N

ArB(OH)2 +

L

Ar

5

R

n

Me

1405


REVIEW

B. Karimi et al.

This result was significant in that it showed that protection of a benzylic hydroxy group is not necessary under these conditions.

Y 1

Ar B(OH)2 PdL2 crosscoupling

transmetallation 1

Ar B(OH)2 9

Ar2

Ar1 Pd L

Y

10

Ar2

Table 11 Base-Free Palladium-Catalyzed Oxidative Heck Reaction of Arylboronic Acids and Olefins

Ar1

ArB(OH)2 + homocoupling PdL2

R1

R1

X

Pd(OAc)2, dmphen R2

Ar1B(OH)2 Y 9 Ar1

Ar1

Scheme 12

In 2006, Jung and co-workers introduced an oxidative palladium(II)-catalyzed cross-coupling reaction of both electron-poor and electron-rich arylboronic acids with olefins in the absence of base, in order to avoid the generation of reactive borate salts (Table 10).26 This reaction was done successfully using palladium acetate, dmphen ligand, and molecular oxygen in N,N-dimethylformamide at room temperature. Several olefins were used, and gave the corresponding coupling products in good to excellent yields (Table 10).

Pd(OAc)2, dmphen +

R O2, DMF, r.t.

Ar

Ar

R1

R2

Protocol, time

Yield (%)

1

4-MeOC6H4

H

CO2Bu

A, 24 h B, 10 min

84 86

2

4-HOCH2C6H4

H

CO2Bu

A, 24 h B, 10 min

83 85

3

Ph

H

CO2Bu

A, 24 h B, 10 min

93 89

4

4-AcC6H4

Me

CO2Bu

A, 72 h B, 10 min A, 192 h B, 20 min

92 90 79 79

5

4-MeC6H4

Me

CO2Bu

H

Ph

A, 24 h B, 20 min A, 48 h B, 10 min

85 91 75 95

R

Entry

Ar

R

Yield (%)

1

Ph

CO2t-Bu

95

2

Ph

CONH2

64a

3

Ph

Ph

93

4

4-MeOC6H4

CO2Bu

61

5

4-Me2NC6H4

CO2Bu

94

6

3-AcC6H4

CO2Bu

72

a

Temp = 50 °C.

Larhed and co-workers reported two base-free catalyst systems for the oxidative Heck reaction between arylboronic acids and olefins.32 One system used palladium(II) acetate (2 mol%) and dmphen (2.4 mol%) with air as reoxidant at room temperature (protocol A), and the other used palladium(II) acetate (1 mol%) and dmphen (1.2 mol%) with p-benzoquinone as reoxidant under microwave heating (protocol B). Regioselective oxidative Heck arylation of various alkenes was successful with both electron-deficient (Table 11, entry 4) and electron-donating (Table 11, entries 1, 2 and 5) arylboronic acids employing these systems. Although palladium(II) systems have also been used for the aerobic oxidation of alcohols,33 here the Heck product was obtained in excellent yield without the formation of any carbonyl by-product where a hydroxy group was present (Table 11, entry 2). Synthesis 2010, No. 9, 1399–1427

R2

Entry

Table 10 Base-Free Aerobic Oxidative Heck Reaction of Arylboronic Acids and Olefins Catalyzed by Pd(OAc)2/dmphen ArB(OH)2

Ar

A: r.t., air B: microwave, 100 °C, p-benzoquinone


To determine the feasibility of these protocols for industrial applications, four oxidative Heck reactions were performed on a 50-mmol scale under microwave heating: two in the presence of p-benzoquinone as the reoxidant, and two with air as the reoxidant. Both systems gave the corresponding coupling products in excellent yields. Jung expanded the application of a tandem palladium-catalyzed oxidative Heck and Suzuki reaction for the preparation of biaryl compounds.34 The oxidative Heck reaction intermediate product 11 was prepared at room temperature, and then allowed to react with phenylboronic acid in a Suzuki coupling in the presence of sodium hydroxide under nitrogen at 50 °C (Table 12). As shown in Table 12, tert-butyl acrylate (Table 12, entries 1 and 2) afforded a mixture of coupling products, whereas the disubstituted olefins ethyl crotonate and bmethylstyrene (Table 12, entries 3 and 4) afforded only tandem oxidative Heck and Suzuki reaction products. 2.1.2.2 Anaerobic In addition to aerobic systems, several anaerobic strategies have been applied for the ligand-based oxidative Heck coupling. A reoxidant-free and base-free oxidative Heck reaction was reported for the selective synthesis of styrenes.35 This palladium-catalyzed oxidative Heck reaction was accomplished by treatment of vinyl acetate with a variety of different arylboronic acids or aryltrifluorobo-


1406

REVIEW One-Pot Tandem Oxidative Heck and Suzuki Reaction B(OH)2

R

2

dppp Pd +

R1 Pd(OAc)2

R1

pathway A

dppp

Pd

dppp

Pd

Ar

H

+ Ar

R2

+ I

dmphen 16 h, r.t. O2

11

I

pathway B dppp Pd +

R

2

R

2

+ R2

12

Ph

Ar

dppp Pd +

Ar

OAc

R1

R1

PhB(OH)2 NaOH 6 h, 50 °C N2

dppp Pd

Ar

OAc Ar

OAc

Scheme 13

13

R1

Entry

R1

R2

Alkene (equiv) Yield (%) of 12 (13)

1

H

CO2t-Bu

2

53 (26)

2

H

CO2t-Bu

1

63 (15)

3

Me

CO2Et

2

81

4

Me

Ph

2

80

Xiao and co-workers reported a new and efficient system for the oxidative Heck coupling of arylboronic acids with olefins without any reoxidant, using acetone as solvent.36 They illustrated that acetone, as a hydrogen acceptor from the X–Pd–H intermediate, plays an important role in this process (Scheme 14). hydrogen acceptor such as acetone

Pd(II)

+

ArB(OH)2 +

R

Pd

Ar

Table 13 Palladium-Catalyzed Oxidative Heck Reaction of Vinyl Acetate with Arylboronic Acid Derivativesa

Pd(0)

H

R

O2, Cu(II), BQ, etc. Ar ArB(OH)2 or

+

OAc

Pd(OAc)2, dppp

Scheme 14

+ Ph

OAc

DMF, mirowave 140 °C, 30 min

ArBF3K

14

71

The reaction was performed in the presence of palladium acetate and dppp ligand at 70 °C in acetone. Both electron-rich and electron-poor arylboronic acids were active in the reaction and gave the corresponding products in good yields and high regioselectivities (Table 14). It is noteworthy that the reaction of electron-deficient olefins such as methyl acrylate with 4-methoxyphenylboronic acid gave the corresponding product in 20% yield, whereas this reaction in the presence of 30 mol% trifluoroacetic acid afforded a good yield (60%) of the same product.

83

Table 14 Oxidative Heck Coupling of Arylboronic Acids with Olefins without any Reoxidant in Acetone

+ ArH

Entry

Aryl source

Yield (%) of 14

1

74 O B(OH)2 B(OH)2

2 BnO Cl

3 S

B(OH)2

B(OH)2 BF3K

4

R1

66

R2

O

(1) Pd(OAc)2, dppp acetone, N2, 70 °C OR3

R2

(2) 3 M HCl, r.t., 1 h R1

BF3K

5

46

Ac a

dppp = 1,3-bis(diphenylphosphino)propane.

rate salts in N,N-dimethylformamide as solvent under microwave irradiation at 140 °C (Table 13). The reaction showed good selectivity for the styrene as major product. Two possible pathways, with two different olefins, were suggested for the formation of styrene under the described reaction conditions (Scheme 13).

Entry

R1

R2

R3

Yield (%)

1

H

H

Bu

89

2

2-MeO

H

Bu

85

3

2-Cl

H

Bu

70

4

H

Me

Et

85

5

4-MeO

Me

Et

84

6

4-Br

Et

Et

80

Synthesis 2010, No. 9, 1399–1427



Table 12

1407


1408

REVIEW

B. Karimi et al.

An efficient intermolecular oxidative Heck reaction catalyzed with a palladium–sulfoxide complex was also reported to produce E-olefins.37 In this investigation 1,2bis(phenylsulfinyl)ethane was used as chelating agent for palladium to control the intermolecular oxidative Heck reaction of a variety of olefins. Reactions were carried out in the presence of benzoquinone (BQ) in a mixture of acetic acid and dioxane at room temperature (Scheme 15). PdLn Y Ar

R

n Pd(OAc)2 ligand

Y n

R


internal

insertion

Ar LnPd

Y n

Excellent enantioselectivity requires a matched coordination of the palladium(II) to both the bidenate ligand and the prochiral olefin, and a partial loss of enantioselectivity occurs because of the competition between cationic and neutral reaction pathways (Scheme 16).47b,48 Therefore, in order to obtain high enantioselectivities in a typical oxidative Heck reaction, the reaction must proceed by way of the cationic pathway (Scheme 16). In fact, the range of enantioselective Heck reactions is essentially limited to aryl and vinyl triflates or iodides, which tend to react via the cationic pathway.16,49 However, since oxidative Heck reactions proceed inherently via a cationic pathway, this reaction can be performed in a highly stereoselective fashion.41

R

terminal Y

Y Ar n

L

R

+

Ar

n

Ar R +

L

X

Y

lower ee

Pd n

(a)

Ar

R

R ligand: PhS(O)CH2CH2S(O)Ph L

L

higher ee

Pd X

Ar

Homoallylic carbonyl and bis-homoallylic carbonyl, alcohol, and thiol functionalites gave the corresponding E-olefin products in good yields and superior selectivity for styrenyl isomers (Table 15). Furthermore, there was palladium–hydrogen isomerization observed under the applied reaction conditions. Table 15 Intermolecular Oxidative Heck Coupling Reaction Using Palladium/Sulfoxide Complex Entry Product

Internal/ Yield terminal (%)

1

(E)-5-phenylpent-4-enoic acid

20:1

80a

2

(E)-ethyl 5-(3,4,5-trimethoxyphenyl)pent-4enoate

8:1

75a

3

butyl[(R,E)-6-phenylhex-5-en-2-yl]sulfane

20:1

56a

4

(E)-ethyl 4-(2-bromophenyl)but-2-enoate

20:1

50b

5

(E)-methyl 4-(2,5-difluorophenyl)but-2-enoate 20:1

51c

R

Scheme 16

2.1.3.1 Aerobic The first catalytic system for the asymmetric organoboron-mediated oxidative Heck reaction was reported by Akiyama et al., who used a combination of palladium(II) acetate, (S,S)-chiraphos, and molecular oxygen with N,Ndimethylformamide as the solvent.41 Several cyclopentene-1-carboxylates were used as alkene substrates in the presence of palladium(II) acetate and (S,S)-chiraphos (15; Figure 2) and gave 31–73% yield and 22–49% ee (Table 16, entries 1–5). Unfortunately, the six-membered carboxylate and the cyano-substituted cyclopentene did not provide satisfactory results (Table 16, entries 6 and 7).

Ph2P

PPh2

a

(S,S)-chiraphos

b

15

Styrenyl/allylic = 20:1. Styrenyl/allylic = 1:18. c Styrenyl/allylic = 1:17.

2.1.3

Figure 2

Asymmetric Reactions

Although good enantioselectivities were obtained in some intramolecular Heck-type reactions, the intermolecular processes studied to date have given poor enantioselectivities, except for those carried out on cyclic olefins such as dihydrofuran and dihydropyrrole.38–44 Prolonged reaction times are usually needed to obtain satisfactory results in most asymmetric Heck-type reactions.45 In the oxidative Heck coupling, however, the reaction times may be shortened if the oxidative addition of the metal center46 is replaced with the transmetallation step.47 Synthesis 2010, No. 9, 1399–1427

(b)


The enantio-determining steps may be the olefin coordination and migratory insertion process. There are two possible conformations of the palladium–(S,S)-chiraphos complex, including the d-conformation with two methyl groups in equatorial orientations and the l-conformation.50 The authors suggested that of the two conformations of the tropos palladium(II)–(S,S)-chiraphos complex, the l-conformation is favored to give the S-configured product (Scheme 17).


Scheme 15

REVIEW

1409


Table 16 Pd(OAc)2/(S,S)-Chiraphos-Catalyzed Enantioselective Aerobic Oxidative Heck Reaction of 4-Trifluoromethylphenylboronic Acids and Cyclopentene-1-carboxylates R

R

CF3

Pd(OAc)2, 15 +

ArB(OH)2

16

+

R

O2, DMF, 50 °C, 4 h

F3 C n

R

n

Yield (%)

ee (%)

1

CO2Me

1

73

46

2

CO2Et

1

72

46

3

CO2i-Pr

1

49

35

4

CO2Ph

1

31

22

5

CO2Bn

1

58

49

6

CO2Me

2

trace

–

7

CN

1

trace

–

Entry

Ar

R

Yield (%) ee (%)

1

Ph

CHO

74

75

2

4-MeOC6H4

CHO

67

73

3

4-Me2NC6H4

CHO

79

75

4

Ph

CO2Me

67

69

5

4-MeOC6H4

CO2Me

76

75

6

6-MeO-2-C10H6

CO2Me

75

62

enantiomeric excesses were obtained (Table 17, entries 4–6). X-ray crystallographic studies illustrated that in the palladium–pyridinyloxazoline complex, the pyridine and oxazoline rings are in the same plane (Figure 4). After the transmetalation step and formation of the aryl–palladium complex, trans-2-methylbut-2-enal coordinates at a 90° angle to the planar pyridinyloxazoline ring.43

ArB(OH)2 olefin P

Pd

Ar

n

Entry

P

R O2, DMF, r.t., 16 h

λ-conformation OO N Pd N

O N Pd N CO2R

P

Pd

CF3

R

R O

P CO2R

17

S-product

F3 C

18

Figure 4

Scheme 17

Jung and co-workers performed an enantioselective intermolecular oxidative Heck reaction of acyclic alkenes with arylboronic acids using a palladium-pyridinyloxazoline diacetate complex 16 (Figure 3) under an oxygen atmosphere (Table 17).51 The reaction of phenylboronic acid and electron-donating boronic acids [4-methoxyphenylboronic acid and 4-(dimethylamino)phenylboronic acid] with trans-2-methylbut-2-enal gave the desired products in good yields and enantioselectivities (Table 17, entries 1–3). With a,b-unsaturated esters, similar yields and

Then alkene can coordinate with the catalyst center in two different conformations, 17 or 18, which differ in the repulsion between the alkene substituents and the tert-butyl group of the oxazoline ring. Accordingly, the coupling products would be obtained through the coordination model 18, which is more favored than model 17. Recently, Jung and co-workers reported the synthesis of chiral tridentate N-heterocyclic carbenes 19 (Figure 5), [NHC–Pd(II)] catalysts that exhibited good activities in the oxidative Heck reaction.52 These chiral catalysts are

N

Pd

Me N

Pd

Pd AcO

O

O

N

OAc

N

R

R

N

N Me

O

t-Bu

O

N

N palladium-pyridinyl oxazoline diacetate 16

Figure 3

O

19a: R = i-Pr 19b: R = Ph

Figure 5

Synthesis 2010, No. 9, 1399–1427



B(OH)2

Table 17 Palladium-Pyridinyloxazoline Diacetate Catalyzed Enantioselective Aerobic Oxidative Heck Reaction of Arylboronic Acids and Olefins

REVIEW

B. Karimi et al.

very stable in nucleophilic solvents such as water and alcohols. The asymmetric oxidative Heck reaction of arylboronic acids with both acyclic and cyclic alkenes was performed using 19 in the presence of oxygen in N,N-dimethylformamide and at room temperature. The related coupling products were obtained in moderate yields and high enantioselectivities (Table 18). Table 18 Chiral Tridentate NHC–Pd(II) Catalyzed Asymmetric Oxidative Heck Reaction O ArB(OH)2

Ar H

catalyst

R

O R

DMF, r.t., 16 h O2 (1 atm)

Entry

Ar

R

Cat.

Yield (%), Config. ee (%)

1

Ph

OMe

19a

49, 91

R

2

2-C10H7

OMe

19a

61, 92

–

3

Ph

H

19a

31, 98

R

4

4-MeOC6H4

H

19b

32, 90

R

used (Table 19, entries 2–5) while ortho-substituted substrates led to very low enantioselectivity (Table 19, entry 6). Moreover, the reaction outcome was not sensitive to the electronic nature of the substituent. Therefore, both electron-poor (Table 19, entries 2 and 3) and electron-rich (Table 19, entries 4 and 5) starting materials gave the corresponding enantioenriched 2-aryl-2,3-dihydrofurans in comparable yields and with 63–78% enantiomeric excess with the (R)-MeOBiphep/copper(II) acetate system. More recently, a palladium-catalyzed oxidative Heck reaction of glycals with arylboronic acids using different oxidants was investigated by Xiong et al.53 The type of oxidant significantly affected the 2-deoxy-C-glycoside products: benzoquinone, copper(II) acetate in the presence of molecular oxygen, and 2,3-dichloro-5,6-dicyano1,4-benzoquinone (DDQ) gave, respectively, the corresponding ketone 20, enol ether 21, and enone 22 products in moderate to good yields (Scheme 18). OTBS O +

R

(HO)2B

TBSO OTBS Pd(OAc)2, MeCN 30–40 °C

2.1.3.2 Anaerobic

OTBS

Gelman and co-workers accomplished an intermolecular enantioselective oxidative Heck reaction between arylboronic acids and 2,3-dihydrofuran using either palladium(II) acetate with (R)-BINAP or (R)-MeOBiphep with copper(II) acetate (Table 19).44

OTBS

Ar

O

DDQ

TBSO

Cu(OAc)2 O2

O

+

20

Ar

Ar

(R)-BINAPa

(R)-MeOBiphepb

Yield (%) ee (%)

Yield (%) ee (%)

Ph

71

57

67

82

2

4-F3CC6H4

32

56

37

78

3

4-FC6H4

47

42

46

75

4

4-MeC6H4

51

43

48

63

5

3-MeC6H4

42

60

47

76

6

2-MeC6H4

35

17

36

1

b

(R)-BINAP = (R)-2,2-bis(diphenylphosphino)-1,1-binaphthyl. (R)-MeOBiphep = (R)-methoxy(biphenylphosphine).

It is noteworthy that the steric properties of the starting materials were very important in the enantiomeric excess achieved: high enantiomeric excess was obtained only when para- or meta-substituted arylboronic acids were Synthesis 2010, No. 9, 1399–1427

21

TBSO

Scheme 18

O

1

a

Ar

OTBS

Pd(OAc)2, (R)-BINAP or (R)-MeOBiphep Cu(OAc)2, THF, r.t. 12 h

Entry

O

OTBS O

ArB(OH)2

Ar

TBSO

22

Table 19 Enantioselective Oxidative Heck Reaction Catalyzed by Pd(OAc)2/(R)-BINAP or (R)-MeOBiphep/Cu(OAc)2 O

O

BQ


The optimized conditions were applied using different types of arylboronic acid derivatives to give their corresponding coupling products (Table 20). As illustrated in Table 20, the different glycoside derivatives could be obtained simply by adjusting the type of oxidant, thereby indicating the significant effect of the Table 20 Preparation of 2-Deoxy-C-glycosides in the Presence of Various Oxidants Entry

Ar

Oxidant

Product

Yield (%)

1

4-MeOC6H4

BQ

20

78

2

4-F3CC6H4

BQ

20

84

3

4-MeOC6H4

Cu(OAc)2, O2

21

78

4

4-F3CC6H4

Cu(OAc)2, O2

21

78

5

4-MeOC6H4

DDQ

22

20

6

4-F3CC6H4

DDQ

22

14


1410

REVIEW

oxidant in the reaction progress. Furthermore, it was shown that DDQ is less effective than the other oxidants. With Polymer-Supported Palladium(II) Catalysts

A polyaniline-supported palladium catalyst system (Pd@PA) was used as a heterogeneous catalyst for the oxidative Heck coupling of a variety of arylboronic acids with activated alkenes in the presence of air under baseand ligand-free conditions.54 The reaction was performed using 5 mol% of catalyst in acetonitrile as solvent at 80 °C, and the corresponding Heck products were obtained with excellent yields and selectivities (Table 21). Table 21 Heck Coupling Reaction of Arylboronic Acids with Butyl Acrylate Using Pd@PA Catalyst Ar ArB(OH)2 +

CO2Bu

23 Ar

Ar

Yield (%)

23/24

1

Ph

94

99:1

2

4-MeC6H4

92

92:8

3

4-MeOC6H4

91

98:2

4

4-FC6H4

88

98:2

5

4-BrC6H4

90

97:3

The authors suggested that the polyaniline polymer was an efficient ligand that facilitated reoxidation of palladium(0) in the presence of molecular oxygen and contributed to the stability and reusability of the catalyst. The supported catalyst system was reused five times without significant loss in activity.

With Other Transition-Metal Catalysts

Other transition metals such as rhodium, ruthenium and iridium have also been applied in the oxidative Heck reaction in recent years. Lautens and co-workers reported a new method for the in situ generation of rhodium complex from [Rh(cod)Cl]2 and bis(p-sulfonatophenyl)phenylphosphane dipotassium salt (TPPDS; Figure 6), which catalyzed the oxidative Heck reaction of arylboronic acids with olefins in aqueous phase (Table 22).55 A number of electron-rich and electron-poor arylboronic acids were used as substrates (Table 22). It is important to

2 TPPDS

Ar B(OH)2

Ar1

Ar2

+

SDS, Na2CO3 H2O, 80 °C

Ar2

Entry

Ar1

Ar2

Yield (%)

1

Ph

Ph

77a

2

4-MeOC6H4

Ph

20a

3

4-MeOC6H4

Ph

85

4

3-IC6H4

Ph

72

5

2-MeC6H4

Ph

86

6

Ph

4-MeOC6H4

76

7

Ph

4-FC6H4

81

CO2Bu

Entry

SO3K

[Rh(cod)Cl]2 TPPDS 1

+

24

PhP

Table 22 [Rh(cod)Cl]2-Catalyzed Oxidative Heck Reaction of Arylboronic Acids and Olefins in Aqueous Media

CO2Bu

Pd@PA MeCN, air 80 °C, 4 h

2.2

note that the use of arylboronic acids containing electrondonating groups increased the observed amount of byproducts that resulted from hydrolytic deboronation. Sodium dodecyl sulfate (SDS) was applied as a phase-transfer salt in order to suppress this unwanted side reaction.

a

Without SDS.

Following this study, the same research group reported another interesting rhodium(I)-catalyzed oxidative Heck reaction, this time employing [Rh(cod)Cl]2 and tert-butylamphos chloride in an aqueous toluene emulsion in the presence of sodium dodecyl sulfate as phase-transfer agent at room temperature (Table 23).56 High yields and selectivities were obtained when the bulky and electronrich tert-butyl-amphos was used instead of TPPDS (Table 23, entry 1). Table 23 [Rh(cod)Cl]2/tert-Butyl-amphos Chloride Catalyzed Oxidative Heck Reaction of Arylboronic Acids and Butyl Acrylate Ar

[Rh(cod)Cl]2 t-Bu-amphos chloride ArB(OH)2 +

CO2Bu 25 +

CO2Bu SDS, H2O/PhMe Na2CO3, r.t., 12 h

Ar

CO2Bu 26

Entry

Ar

Yield (%)

25/26

1

Ph

99

90:10

2

2-MeC6H4

93

86:14

3

2-F3CC6H4

99

30:70

4

2,6-(Me)2C6H4

99

5:95

5

4-MeOC6H4

99

93:7

6

4-AcC6H4

99

86:14

7

3-thienyl

99

96:4

Figure 6

Synthesis 2010, No. 9, 1399–1427



2.1.4

1411


REVIEW

B. Karimi et al.

When 2-trifluoromethyl- and 2,6-dimethylphenylboronic acids were used as arylating substrates, the conjugate addition adducts were the major products although the selectivities were not always ideal (Table 23, entries 3 and 4). The use of a boronic acid containing thiophene as a substituent gave high yield with good selectivity (Table 23, entry 7).

Table 25 RhCl3-Catalyzed Aerobic Oxidative Heck Reaction of Arylboronic Acids and Olefins

Entry

Ar

R1

R2

Yield (%)

The oxidative coupling of different boronic acids with styrene was also studied using catalytic systems containing disulfonated water-soluble ligands and rhodium.57 In an initial experiment, the coupling of phenylboronic acid with styrene using rhodium dimer, tris(m-carboxyphenyl)phosphane trilithium salt and tris(m-sulfonatophenyl) phosphane trisodium salt (m-TPPTC and TPPTS, respectively; Figure 7) in water at 80 °C was investigated (Table 24). A good yield (79%) of stilbene was obtained in the presence of 8 mol% of m-TPPTC, whereas the reaction in the presence of TPPTS as ligand resulted in low yield (Table 24, entry 2). Several boronic acids were used, giving related coupling products in moderate to high yields.

1

Ph

H

CO2Bu

83

2

Ph

H

CO2Me

78

3

Ph

H

CN

69

4

Ph

Me

CO2Me

7

5

4-MeOC6H4

H

CO2Bu

85

6

4-MeO2CC6H4

H

CO2Bu

73

LiO2C

P

NaO3S

R1

RhCl3, Ph3P R2

Ar

H2O/PhMe (1:3) 100 °C, 20h

R2

Martinez et al. reported the first base-free Heck reaction using rhodium complexes as efficient catalysts. In this transformation, potassium aryltrifluoroborates were applied as the arylating agents and acetone was used as the oxidant (Scheme 19).59 [Rh], Ph3P

3

ArBF3K +

Ar

R

R

acetone–dioxane 80 °C

TPPTS

Ar = electron-rich and electron-poor aryl R = CO2Bu, CO2Et, PO(OEt)2, CONHt-Bu, COPr

Figure 7 Table 24 [Rh(cod)Cl]2/m-TPPTC or TPPTS Catalyzed Oxidative Heck Reaction of Arylboronic Acids and Olefins [Rh(cod)Cl]2 ligand Ph

+

ArB(OH)2

P

3

m-TPPTC

R1

ArBH(OH)2 Na2CO3, 80 °C H2O, 12 h

Ar

Ph

Entry

Ar

Ligand

Yield (%)

1

Ph

m-TPPTC

79

2

Ph

TPPTS

31

3

4-BrC6H4

m-TPPTC

96

Scheme 19

The reaction was performed in the presence of 1.5 mol% of catalyst, and 6 mol% of triphenylphosphine at 80 °C in dioxane–acetone (4:1) as the optimized solvent. Both electron-rich and electron-poor substrates were active in this reaction and gave the corresponding products in good yields (Table 26). Table 26 ArBF3K

+

Base-Free Rhodium-Catalyzed Mizoroki–Heck Reaction CO2R

[Rh(CH2CH2)Cl]2 Ph3P acetone–dioxane (1:4) 80 °C

Ar

CO2R

4

4-BrC6H4

TPPTS

24

5

4-MeOC6H4

m-TPPTC

71

Entry

Ar

R

Yield (%)

6

4-MeOC6H4

TPPTS

32

1

4-ClC6H4

t-Bu

71

2

2-C10H7

Et

89

3

3-MeOC6H4

Bu

88

4

4-F3CC6H4

Bu

94

5

4-FC6H4

Et

85

6

2-MeC6H4

Et

92

A mixture of triphenylphosphine and rhodium(III) chloride in toluene/water as solvent was also an effective system in the Heck coupling reaction of arylboronic acids with a,b-unsaturated methyl and butyl esters and an a,bunsaturated nitrile at 100 °C (Table 25).58 While unsubstituted acrylates reacted efficiently to form coupling products in good yields (Table 25, entries 1–3, 5 and 6), the substituted acrylate example gave the corresponding adduct in low yield (Table 25, entry 4). These results showed that the steric nature of the starting materials plays a critical role in this transformation.

Synthesis 2010, No. 9, 1399–1427


The proposed mechanism for this transformation is shown in Scheme 20. Faller and Chase illustrated that the ruthenium complex 27, produced from the reaction of (p-


1412

REVIEW

Table 27 [Ru(p-cymene)Cl2]2 Catalyzed Oxidative Heck Reaction of Haloarylboronic Acids and Butyl Acrylate

OBF3K

ArBF3K

Rh

1413


O

Ar

ArB(OH)2

Rh

+

[Ru(p-cymene)Cl2]2

CO2Bu

Ar

CO2Bu

Cu(OAc)2, quinuclidinone PhMe, r.t. R

O

Rh Ar

R

R

Scheme 20 i-Pr Ru Cl

Cl

Yield (%)

1

4-IC6H4

77

2

3-IC6H4

76

3

4-BrC6H4

63

4

3-BrC6H4

96

5

4-ClC6H4

93

6

3-ClC6H4

77

i-Pr

PhMgBr

Ru Ph3P

Ar

Ph3P

Cl Ph

27

i-Pr

AgSbF6 Ru Ph3P

ethylene

H

2.3

With Other Organometallic Compounds

SbF6

Currently, the Mizoroki–Heck-type reactions of unsaturated compounds that use nucleophilic organometallic reagents such as silanols, organotin and organoantimony compounds are attracting much interest.

Ph 28

Scheme 21

cymene)(PPh3)RuCl2 and phenylmagnesium bromide, reacts with ethylene and silver hexafluoroantimonate(V) to yield styrene hydride complex 28. The Heck product is obtained from a subsequent reductive elimination (Scheme 21).60 Pfeffer and co-workers reported that 2-vinyl-N,Ndimethylbenzylamine was generated via the insertion of ethylene into the cycloruthenated compound ( h6 -C 6 H 6)Ru(C 6H 4 CH 2 NMe 2 )Cl in methanol (Scheme 22).61,62

An example of the palladium-catalyzed coupling reaction of electron-deficient olefins with silanols was developed by Mori and co-workers in 1998.65 The best results were obtained in the reaction of organosilanols with olefins bearing electron-withdrawing groups in the presence of catalytic palladium(II) acetate (10 mol%) with copper(II) acetate (1.5 mmol)/lithium acetate (1.0 mmol) as a final oxidant. Aryl and alkenyl silanols also afforded the coupling products in moderate yields (Table 28). Table 28

Reaction of Organosilanols with Olefins Pd(OAc)2

R1Me2SiOH

i-Pr Ru

Cl

R2

+

ethylene

R1

Cu(OAc)2/LiOAc DMF, 100 °C

R2

Entry

R1

R2

Yield (%)

Scheme 22

1

Ph

COMe

48

These investigations demonstrated that a ruthenium–carbon bond can be formed through a nucleophilic substitution and at the alkene insertion step.63 Also, a major characteristic of ruthenium(II) chemistry is its inertness to organohalides under oxidative conditions. These features and observations may provide a promising opportunity to use ruthenium(II) complexes in the oxidative Heck reaction of haloboronic acids under reaction conditions for which it is generally impossible to effectively use palladium catalysts.63

2

Ph

CHO

37

3

Ph

CN

34

4

Ph

Ph

63

5

4-MeOC6H4

CO2Bu

55

6

2-MeC6H4

CO2Bu

54

7

PhCH=CH

CO2Et

41

8

n-C6H13CH=CH

CO2Et

52

NMe2

MeOH, r.t.

NMe2

Brown and co-workers considered the reaction of butyl acrylate with haloarylboronic acids using ruthenium(II) and copper(II) acetate in toluene at room temperature. Several arylboronic acid substrates substituted with chlorine, bromine, or iodine were successfully applied and gave Heck adducts via selective carbon–boron activation; the products were obtained in good to excellent yields (Table 27).64

The reaction was less effective when other organosilicon derivatives such as PhMe2SiOMe (47%), PhSiMe3 (8%) or PhMe2SiCl (6%) were employed. The palladium-catalyzed Mizoroki–Heck reactions of olefins with silanols were proposed to proceed via the reaction pathway demonstrated in Scheme 23. First, Synthesis 2010, No. 9, 1399–1427



Ar

Entry

REVIEW

B. Karimi et al.

phenylpalladium species 30, produced by transmetallation between organosilicon compound 29 and palladium(II) acetate, adds to the alkene to afford alkylpalladium species 31. A b-hydride elimination from the alkylpalladium species gives the product 32.

Table 30 Palladium-Catalyzed Oxidative Heck Coupling of Cyclic Enamides with Aryl Silanes NHAc

dioxane, 80 °C

PhPdOAc 30

R oxidation R

Ph

Pd(0)

Entry

Ar

Yield (%)

1

Ph

66

2

4-MeOC6H4

51

3

4-MeC6H4

54

4

4-ClC6H4

55

5

4-FC6H4

50

PdOAc 31

R

Ph 32

Scheme 23

Mori and co-workers later found that [Rh(OH)(cod)]2 was also an effective catalyst for the oxidative coupling of silanediols with a,b-unsaturated esters and amides in tetrahydrofuran at 70 °C (Table 29).66 Table 29 [Rh(OH)(cod)]2-Catalyzed Oxidative Heck Reaction of Silanediols and Olefins [Rh(OH)(cod)]2

+

R

Ar

THF, 70 °C, 24 h

reaction of phenytributyltin (1 mmol) with butyl acrylate (1 mmol) proceeded, in the presence of 10 mol% palladium(II) acetate with copper(II) acetate and lithium acetate in N,N-dimethylformamide at 100 °C, to give butyl 3-phenylpropenoate and the homocoupled product in 77% and 16% yields, respectively (Scheme 24). PhSnBu3 +

Pd(OAc)2

CO2Bu

Ph

CO2Bu + Ph–Ph

Cu(OAc)2/LiOAc DMF, 100 °C, 24 h

Scheme 24

R

Entry

Ar

R

Yield (%)

1

Ph

CO2t-Bu

81

2

4-MeC6H4

CO2t-Bu

99

3

4-MeC6H4

CO2t-Bu

78

4

4-MeC6H4

CONMe2

70

5

4-MeC6H4

CONHt-Bu

68

4-MeOC6H4

CONHt-Bu

6

O

(3 equiv)

AcOSiMe2OH

Pd(OAc)2

ArSi(OH)2

Ar

ArSi(OEt)3 O

PhMe2SiOH 29

NHAc Pd(OAc)2 (10 mol%) AgF (3 equiv)

A simple approach to the Heck coupling of aryl stannanes with olefins in the presence of a palladium catalyst, making use of molecular oxygen or copper(II) as oxidant, was reported by Parrish et al.69 The reaction was performed in N,N-dimethylformamide or tetrahydrofuran using sodium acetate as optimum base. Both allylic and nonallylic oleTable 31 Olefins

Reaction of Phenyl(tributyl)tin Reagents with Nonallylic Pd(OAc)2

PhSnBu3

+

R

Ph

NaOAc

76

R

A: CuCl2, THF B: O2, DMF

Quite recently, Zhou et al. reported a new strategy for the direct palladium-catalyzed oxidative Heck coupling of cyclic enamides with aryl silanes via a C–H activation and transmetallation approach.67 The reactions were performed using 10 mol% palladium(II) acetate in the presence of three equivalents of silver fluoride in dioxane at 80 °C. Several organosilanes, including electron-rich and electron-poor substrates, have given the corresponding products in moderate to good yields (Table 30). The authors suggested that the silver fluoride both activates the organosilane substrate and acts as oxidant to reoxidaze palladium(0) to palladium(II). Organotin compounds can also act as organometallic reagents in the oxidative Heck reaction. Mori and coworkers reported the use of organotin compounds in the coupling reaction of various alkenes.68 For example, the

Synthesis 2010, No. 9, 1399–1427


Entry

R

Yield (%) A

B

1

Ac

65

55

2

CN

59

–

3

4-ClC6H4

–

72

4

Bn

65

82

5

TBSO

68

81

60

88

MeO

6

OHC

N


1414

REVIEW


fins gave the corresponding products in good to excellent yields (Table 31).

Pd(OAc)2 Ph2SbCl

In the same study, several aryl stannane derivatives were screened to highlight the effect of the electron density of the starting materials. Both electron-donating and electron-withdrawing substituents afforded good yields under the described reaction conditions. In 1999, Uemura and co-workers reported that organoantimony compounds could also be used in oxidative Heck transformations.70 The authors demonstrated that prop-2en-1-ol can react with diphenylantimony chloride, prepared in situ from triphenylantimony and antimony(III) chloride (2:1),71 in the presence of a catalytic amount of palladium(II) acetate (0.1 equiv) under air to produce 3phenylpropanal (Scheme 25). Pd(OAc)2 (0.1 equiv) OH

+

MeCN 25 °C, air

R

33 Ph2SbCl + O2

PhPd(OAc) HPd(OAc) 36

R

Ph 35

R

Ph

HPd(OAc)

R

Ph

Pd(OAc)

H

34

R

Scheme 26 O Ph

H

Scheme 25

In subsequent studies, it was demonstrated that the presence of at least one equivalent of oxygen is necessary for this catalytic reaction. This was shown by the reaction of prop-2-en-1-ol with diphenylantimony chloride in the presence of 3 mol% of palladium(II) acetate at 25 °C for 24 hours under nitrogen, which generated 3-phenylpropanal in only 1.6% yield. The authors also found that palladium(0) complexes, such as Pd2(dba)3 and Pd(PPh3)4, were inactive in this transformation; therefore, it is unlikely that a palladium(0) species is involved in the catalytic cycle. The proposed mechanism for this reaction is illustrated in Scheme 26. Transmetalation of the diphenylantimony chloride and palladium(II) acetate generates the phenylpalladium species 33. The alkene can bind to the metal, allowing the insertion of alkene into the palladium– carbon bond to afford alkylpalladium species 34. b-Hydride elimination then produces palladium hydride species 36 and the product 35. Finally, 33 can be regenerated by participation of oxygen.

3

PhPd(OAc)

OH Ph

PhSbCl(OAc)

PhSbO2 + HCl

Oxidative Heck Reactions of C–H Compounds

In 1967, Fujiwara and Moritani reported the first example of direct oxidative coupling of arenes with alkenes by way of a C–H activation approach, wherein the double bond of the alkene underwent substitution with aromatic compounds in the presence of a stoichiometric amount of palladium chloride.72,73 This novel reaction opened a new era of palladium(II)-promoted reactions between aromatic compounds and alkenes.7,74–76 Since then, a broad range of

arenes have undergone palladium-assisted stoichiometric oxidative coupling with various olefins. It is also noteworthy that this strategy – oxidative Heck reaction in the presence of a stoichiometric amount of palladium acetate – has been employed in some total syntheses.7,77–83

3.1

Catalytic Reactions

From this point onward we discuss the significant developments of carbon–carbon bond-forming processes that have been achieved with transition-metal catalysts through a direct carbon–hydrogen bond activation of aromatic hydrocarbons. 3.1.1

Intermolecular Reactions

3.1.1.1 Anaerobic In order to overcome the limitations of stoichiometric processes, Tsuji and Nagashima turned their attention to the development of a more direct and efficient protocol for the aromatic substitution of olefins using an anaerobic catalytic approach. In this protocol, tert-butyl perbenzoate was used as the stoichiometric oxidant in the oxidative coupling of benzene and furans with a variety of activated olefins (Table 32).84 In 1987, Hirota et al. prepared 5-alkenylated 1,3-dimethyluracil in 75% yield in the presence of 5 mol% palladium(II) acetate and two equivalents of tert-butyl perbenzoate (Scheme 27).85 O

O MeN O

Pd(OAc)2 (5 mol%) PhCO3t-Bu (2 equiv) +

N Me

MeO2C MeCN, 80 °C 75%

CO2Me

MeN O

N Me

Scheme 27

Synthesis 2010, No. 9, 1399–1427



Ph2SbCl

1415

1416

REVIEW

B. Karimi et al. CN

Table 32 Palladium-Catalyzed Oxidative Heck Coupling with tertButyl Perbenzoate as the Stoichiometric Oxidant

CN

NC [Pd]

Pd(OAc)2 (10 mol%) ligand (10 mol%)

Ph

Ph

H

+ 1 + R

Entry

R

R1

PhCO3t-Bu (1 equiv) 100 °C

R2

2

AcOH, 3 h, 100 °C 1

Ar

Ar

R

R

2

1

Ph

Ph

COMe

65

2

Ph

H

CO2Me

70

3

2-furyl

H

CO2Et

53

4

5-methyl-2-furyl

H

CO2Et

67

H

CO2Me

34

5 OHC

F3 C

Ph

Ph

Pd(OAc)2, BQ CO2Me

t-BuOOH, AcOH–Ac2O 12 h, 90 °C 72%

S O2

NH

N

i-Pr

Scheme 29

as 49% ee, but this report opened a promising area for further investigations of this type of interesting asymmetric oxidative Heck reactions.

Silver benzoate, manganese dioxide, hydrogen peroxide, tert-butyl hydroperoxide and the combination of tert-butyl hydroperoxide and benzoquinone have also been used as the oxidant in the oxidative coupling of arenes with olefins in the presence of catalytic amounts of palladium acetate.86 Among those listed, the combination of benzoquinone with tert-butyl hydroperoxide as the final oxidant resulted in higher efficiency and turnover numbers (TON) up to 280 (Scheme 28). +

O ligand:

O

PhH

CF3

Yield (%)

A highly selective and mild method was reported for the oxidative coupling reaction between anilide derivatives and acrylates in 2002.88 It was found that acetanilide and other aniline derivatives reacted with butyl acrylate through ortho carbon–hydrogen bond activation in the presence of 2 mol% palladium(II) acetate, one equivalent of benzoquinone as the reoxidant, and p-toluenesulfonic acid in toluene and acetic acid at room temperature (Table 34). Table 34 Oxidative Heck Coupling of Substituted Anilide Derivatives with Butyl Acrylate in the Presence of Pd(OAc)2

CO2Me H N

Ph

CO2Bu

+ O

O R

AcOH–toluene (1:2) p-TsOH, 20 °C

R

Scheme 28

H N

Pd(OAc)2 (2 mol%) BQ (1 equiv)

CO2Bu

This catalytic system was especially active for the coupling of heterocycles with activated olefins (Table 33).

Entry

R

Yield (%)

1

4-Me

85

Table 33 Oxidative Heck Coupling of Arenes with Olefins in the Presence of Pd(OAc)2

2

3-Me

91

3

2-Me

38

ArH

+

Pd(OAc)2, BQ PhCO3t-Bu (1 equiv)

R1 R2

t-BuOOH, AcOH–Ac2O 12 h, 90 °C

R1

R2

Ar

Entry Ar

R1

R2

Catalyst (mol%), oxidant (equiv)

Yield (%)

1

Ph

Ph

CO2Et

Pd(OAc)2 (1) BQ (10)

72

2

5-methyl-2-furyl

H

CO2Et

Pd(OAc)2 (0.5) BQ (5)

75

3

2-benzofuranyl

H

CO2Me

Pd(OAc)2 (0.5) BQ (5)

56

4

3-indolyl

H

CO2Me

Pd(OAc)2 (0.5) BQ (5)

52

In 2005, Zaitsev and Daugulis89 reported an alkene arylation process that occurred via a selective C–H activation. A number of N-acylated anilines were found to be good substrates for this palladium(II)-catalyzed coupling reaction in the presence of 5 mol% palladium(II) chloride and one equivalent silver triflate as an additive in N,N-dimethylformamide at 90 °C (Table 35). In the same year, Ricci and co-workers discovered that a C–H activating palladium-catalyzed alkenylation of indole can selectively occur at the 2-position when the nitrogen carries a 2-pyridylmethyl substituent (Scheme 30).90 R N

In 1999, Mikami et al.87 focused on a catalytic asymmetric version of the oxidative Fujiwara–Moritani reaction by using 10 mol% of a chiral sulfonylamido-oxazoline ligand in the presence of 10 mol% palladium(II) acetate (Scheme 29). The resulting enantioselectivity was as low Synthesis 2010, No. 9, 1399–1427


PdCl2 (10 mol%) 2 Cu(OAc)2, MeCN N

+

R

N

N

60 °C, 14 h

R = CO2Me, SO2Ph, CN (E/Z = 2:1]

Scheme 30


ArH

Pd(OCOPh)2 (5 mol%) PhCO3t-Bu (1 equiv)

REVIEW

Transition-Metal-Catalyzed Oxidative Heck Reactions H

Table 35 Oxidative Heck Coupling of Haloolefins with Anilides Using PdCl2 in DMF H NCOR2

O

NCOR2

N

PdCl2 (5 mol%) +

PdLn

OMe

Br

fast

AgOTf, DMF R

R1

1

Entry

R1

R2

N

N

Temp (°C) Time (h) Yield (%)

1

H

t-Bu

90

1

85

2

H

Me

90

2

56

3

4-Me

Me

80

2

80

4

3-MeO

Me

90

1.5

85

H

slow

PdLn-1 N

N

O R= HO alkene, benzoquinone

For this reaction, the authors proposed a tentative mechanism to explain the regiospecific reactivity (Scheme 31). Gaunt and co-workers also exploited a general method for the selective intermolecular alkenylation of free N–H indoles through a solvent-controlled C–H functionalization reaction in the presence of palladium(II) acetate as catalyst.91 The use of dimethyl sulfoxide as a co-solvent with N,N-dimethylformamide in the reaction produced the C3functionalized indole in good yields. Under acidic conditions, the reaction provided the C2-functionalized indole as the major isomer. The authors proposed that in the weakly coordinating solvent system of 1,4-dioxane–acetic acid (3:1), palladation at C3 occurred but the subsequent rearomatization would be slowed, which might allow a migration of the C3–PdX bond to the highly activated 2-position (Table 36). One year later, Gaunt and co-workers introduced an anaerobic and aerobic palladium(II) catalyst system for the oxidative Heck reaction under ambient conditions.92 They showed that this system directed the pyrroles with electron-withdrawing N-protecting groups to only 2-substituted products in good yields. In contrast, reaction with a sterically hindered protecting group like triisopropyl-

Table 36

N

CO2Me

CO2Me N

CO2Me

Pd(OR)Ln-1 H

N

PdLn-1 N

N

Scheme 31

silyl (TIPS) selectively provided only the 3-alkenylated product (Table 37). Thus, it is possible to control the position of C–H bond functionalization via simple sterically and electronically tuned N-pyrrole protecting groups. A palladium(II)-catalyzed 1,2-carboamination reaction of dienes was recently reported, and involves a urea-directed ortho C–H insertion followed by a cyclization sequence that proceeds through formation of intermediate 41 (Scheme 32).93 This result clearly demonstrated that a reactive palladium tosylate species, generated in situ from the palladium(II) acetate precatalyst, can lead to functionalized indolines from readily available N-aryl ureas under mild reaction conditions (Table 38).

Reaction Optimization for the Oxidative Heck Coupling of Indole CO2Bu Pd(OAc)2

HN

solvent, oxidant, 70 °C CO2Bu

+

HN 37

CO2Bu

HN 38

Entry

Catalyst loading (mol%) Oxidant (equiv)

Solvent (v/v)

Conv. (%) [38/37]

1

10

Cu(OAc)2 (1.8)

DMF

54 [>95:5]

2

10

Cu(OAc)2 (1.8)

DMSO

66 [>95:5]

3

10

Cu(OAc)2 (1.8)

DMF–AcOH (3:1)

54 [1:1]

4

20

t-BuOOBza (0.9)

1,4-dioxane–AcOH (3:1)

58 [1:7]

5

10

Cu(OAc)2 (1.8)

DMF–DMSO (10:1)

79 [>95:5]

a

t-BuOOBz = tert-butyl peroxybenzoate. Synthesis 2010, No. 9, 1399–1427



H

1417

REVIEW

B. Karimi et al.

Table 37 Effect of Nitrogen-Protecting Group in Pyrrole C–H Alkenylation R3 R3 N

R2

+

Pd(OAc)2 (10 mol%) t-BuOOBz, 35 °C

Table 39

R2 N

AcOH–dioxane–DMSO

R1

R2

R1

+

R3

egy has been successfully applied for the production of indolines and tetrahydroisoquinolines, which are significant intermediates in synthetic chemistry. Oxidative Heck Coupling of Arylethylamines NHTf

N R1

R1

39

R

40

Pd(OAc)2 (10 mol%) R3

+

2

NHTf R1

R

AgOAc, DCE DMF, 130 °C, 72 h

2

Entry

R1

1

Ac

CO2Bn

65

–

Entry

R1

R2

R3

Yield (%)

2

Boc

CO2Bn

73

–

1

4-TfO

CO2Me

CO2Me

65

3

TIPS

–

72

2

2-Me

H

CO2Me

87

3

H

CO2Me

Ph

51

4

H

CO2Me

4-ClC6H4

56

Olefin

Yield (%) of 39 Yield (%) of 40

O

urea-directed C-H insertion Pd(OAc)2, Ac2O p-TsOH, THF

H

Ln Pd O

NH Me2N

N H

NMe2

O Pd(II)Ln CO2Et BQ

Pd(0)Ln

CO2Et

CO2Et PdLn

NH N Me2N

O

Me2N

R3

Very recently, Cho et al. reported an efficient and selective protocol for the oxidative Heck coupling of pyridine N-oxide with alkenes through a palladium-mediated carbon–hydrogen bond-activation approach.95 The reaction was performed by treating 0.3 mmol of the olefin with the N-oxide (4 equiv), palladium(II) acetate (10 mol%), and silver carbonate (1.5 equiv) as oxidant in 1,4-dioxane at 100 °C. Different alkene derivatives such as ester, amide, ketone and phosphonate (Table 40, entries 1–4) were effectively applied to give the corresponding products in good to excellent yields and selectivities.

O

Table 40 enes

41

Oxidative Heck Coupling of Pyridine N-Oxide with Alk-

Scheme 32

Pd(OAc)2 (10mol%) Ag2CO3 (1.5 equiv) +

Table 38 Oxidative Heck Coupling of N-Aryl Ureas under Mild Reaction Conditions R Pd(OAc)2 (10 mol%), BQ (1 equiv) p-TsOH⋅H2O (0.5 equiv) NH Me2N

O

R N

Ac2O (1 equiv) THF, 50 °C, 4 h

Me2N

Entry

R

Yield (%)

1

CO2Et

82

2

SO2Ph

45

3

CN

70

4

NO2

70

O

R 1,4-dioxane (0.6 mL) 100 °C, 12 h

N

R

O

Entry

R

Yield (%)

1

CO2Bu

91

2

C(O)NMe2

87

3

C(O)Me

62

4

P(O)(OEt)2

70

O

More recently, Yu et al. developed a promising strategy for the alkenylation of arylethylamines via a C–H activation approach.94 The reaction was accomplished using 10 mol% palladium(II) acetate, silver acetate (2.5 equiv), N,N-dimethylformamide (0.1 mL), and dichloroethane (2 mL) at 130 °C. Various arylethylamines and olefins were used as starting materials to give coupling adducts in moderate to high yields (Table 39). Importantly, this stratSynthesis 2010, No. 9, 1399–1427

N


More recently, Rauf et al. showed that the presence of a urea group on the aryl substrates plays a key role in the oxidative Heck coupling of arylureas with butyl acrylate.96 Several arylurea derivatives containing both electrondonating and electron-withdrawing groups on aromatic rings were successfully applied and afforded the corresponding coupling products in moderate yields (Table 41). NMR spectroscopy and X-ray crystallography studies proved the presence of intermediates 42 and 43 in the reaction solution, thereby demonstrating that the urea group played a key role in accelerating the reaction (Scheme 33).


1418

REVIEW Oxidative Heck Coupling of Arylureas with Butyl AcryCO2Bu

H N R

NMe2 O

R2

H N

Pd(OAc)2 (2 mol%)

Table 42 Intermolecular Oxidative Heck Coupling of Imidazo[1,2a]pyridines with Olefins

NMe2

R

H R1

O

N

p-benzoquinone (1 equiv) p-TsOH (1 equiv), acetone

Ph N

R

2

Pd(OAc)2 (0.1 equiv) Cu(OAc)2 (2 equiv)

R1

N

xylene, 120 °C

CO2Bu

Entry

R

Yield (%)

1

2-Me

50

2

3-Cl-4-Me

50

3

3-Cl

52

H N

F

O

F

H N

F

Pd

F

Pd TsO

OTs–

NCMe

MeCN

2

43

42

Scheme 33

Cheng and Gallagher reported a palladium-catalyzed oxidative Heck strategy for the direct and regioselective C–H alkenylation of tetrahydropyrido[1,2-a]pyrimidines.97 This reaction was conducted using palladium(II) acetate (5 mol%) and copper(II) acetate (2 equiv) in N,N-dimethylformamide for 10 hours. The mechanistic studies implied that the reaction showed high regioselectivity for the C7 position over the C9 position (Scheme 34). 9

Bn

N

R1

R2

Yield (%)

1

H

CO2Me

87

2

H

CO2Et

85

3

H

CO2Bn

81

4

Cl

CO2Me

81

Undoubtedly, the most attractive and environmentally friendly version of the oxidative Heck reaction is the coupling reaction of C–H systems in the presence of molecular oxygen as the final oxidant. Fujiwara’s research group turned their attention to the use of a green oxidant in the intermolecular oxidative Heck reaction. Along this line, they discovered that, in the presence of oxygen or air, copper(II) acetate or silver(I) acetate catalytically assisted the palladium acetate in performing its catalytic duties in the course of this reaction (Scheme 35).99

+

R1 O

Pd(OAc)2 (5 mol%) Cu(OAc)2 (2 equiv) DMF

Bn

Pd(OAc)2 (10 mol%) Cu(OAc)2 (10 mol%) O2 (50 atm)

Ph

Ph

AcOH, 80 °C 45%

R1

7

N

Entry

3.1.1.2 Aerobic O

O F

H N

F

Ph N

Scheme 35 N

N

O

R1 = CO2R2, aryl, alkyl

Scheme 34

An efficient and regioselective palladium-catalyzed oxidative methodology was reported for the intermolecular coupling of imidazo[1,2-a]pyridines with olefins.98 This reaction was accomplished in the presence of palladium(II) acetate (10 mol%) as catalyst and copper(II) acetate (2 equiv) as oxidant in xylene at 120 °C. Several imidazo [1,2-a]pyridine derivatives reacted successfully with activated alkenes and gave the corresponding coupling adducts in high yields and excellent regioselectivities (Table 42).

The use of oxygen as oxidant is significant and desirable from the catalytic point of view. Thus, Shue reported the first catalytic coupling of aromatics and olefins by palladium(II) acetate under oxygen as the sole reoxidant, without the use of any co-catalyst (Scheme 36).100

+

Pd(OAc)2, O2 (20 atm) 100 °C

Ph

Ph

Scheme 36

In 1979, Fujiwara and co-workers discovered that heterocycles can also act as suitable precursors for the catalytic oxidative Heck reaction in the presence of molecular oxygen.101 In a palladium-catalyzed reaction, they were able to use a broad range of substrates, including furan and thiophene, converting them into the corresponding products in the presence of two equivalents of copper(II) acetate under atmospheric oxygen or air; however, low yields were observed. Synthesis 2010, No. 9, 1399–1427



Table 41 late

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B. Karimi et al.

An interesting approach to the oxidative Heck reaction involves the selective palladation of arenes, directed by a neighboring functional group. An early example of this approach was reported in 1997 by Miura et al.,102 who found that a palladium–copper-catalyzed reaction in N,Ndimethylformamide at 100 °C in the presence of 4 Å molecular sieves gave the corresponding products in moderate yields (Scheme 37). Pd(OAc)2 (5 mol%) Cu(OAc)2 (5 mol%) 4 Å MS OH

+

CO2Me

CO2Me OH

N2/air (5:1, 1 atm) DMF, 100 °C 56%

Table 43 Oxidative Heck Coupling of Arenes with Alkenes Catalyzed by Pd(OAc)2 Combined with HPMoV

ArH

CO2Et

+

Pd(OAc)2 (6.67 mol%) H7PMo8V4O40 (1.33 mol%)

CO2Et

+ O2 propionic acid, NaOAc

Ar

Entry

Ar

Temp, time

Yield (%)

1

Ph

90 °C, 3 h

72

2

MeC6H4

90 °C, 2 h

69a

3

ClC6H4

90 °C, 6 h

68a

4

2-furyl

30 °C, 12 h

62

a

Regioisomeric product mixtures were obtained.

Scheme 37

+

R

Pd(OAc)2 (5 mol%) Cu(OAc)2 (5 mol%) NaOAc (50 mol%)

H2 O

PdIIL2

[HPMoV]red.

Ar-H HL

[HPMoV]ox. 2 HL

Ar-PdII-L

Pd(0) R NSO2Ar

4 Å MS air (1 atm) DMF, 100 °C

NHSO2Ar

1/2 O2

HL

R = CO2Et, CN, CONMe2

Y

37–100%

Scheme 38

Y

Ar

H-PdII-L

PdII-L

The reactions of benzoic acid with butyl acrylate and styrene can also give vinylation products with a degree of ortho selectivity. These products can be subsequently converted into very important products. In these cases, the neighboring groups played an important role in directing the initial carbon–hydrogen bond activation to the ortho position (Scheme 39). COOH +

R

Pd(OAc)2 (10 mol%) Cu(OAc)2 (10 mol%)

O

COOH O Pd

R

4 Å MS N2/air (5:1900 mL) DMF, 100 °C

Scheme 39

Another interesting catalytic method for the oxidative coupling of arenes with alkenes through an aromatic carbon–hydrogen bond activation was reported by Ishii and co-workers.104 In this protocol, oxidative coupling of benzene with acrylates was accomplished by palladium(II) acetate combined with molybdovanadophosphoric acid (HPMoV) as reoxidation catalyst under an atmosphere of molecular oxygen as the terminal oxidant (Table 43). Later, the Ishii research group also carried out a detailed study of the reaction mechanism (Scheme 40).105

Synthesis 2010, No. 9, 1399–1427


Ar

Y

Scheme 40

In 2003, Jacobs and co-workers106 reported a 100% atomefficient and solvent-free system for the oxidative arylation of olefins, with water as the sole by-product. They showed that molecular oxygen can be used for palladium(0) reoxidation as the most effective oxidant for a Fujiwara coupling reaction. The palladium–benzoic acid catalyst appeared to be considerably stable, and much higher turnover number and turnover frequency (762 and 73 h-1, respectively) were obtained when compared with those given in previous reports. However, the regioselectivity of this arylation was quite low (Scheme 41). OMe +

Ph

Ph

Pd(OAc)2 (1 mol%) PhCO2H (20 mol%)

O OEt

O2 (8 atm), 90 °C 98%

O OEt

MeO

Scheme 41

The first oxidative coupling reaction of arenes with an a,b-unsaturated aldehyde catalyzed by the combined catalytic system of palladium(II) acetate with HPMoV was presented in 2005.107 The reaction of benzene with cinnamaldehyde under dioxygen (1 atm) with catalytic


Similarly, they described that N-(2¢-phenylphenyl) benzenesulfonamides or benzoic and naphthoic acids reacted efficiently with activated alkenes such as acrylate esters via cleavage of an aromatic carbon–hydrogen bond under palladium catalysis in high yields (Scheme 38).103

amounts of palladium(II) acetate and H4PMo11VO40·26H2O in the presence of dibenzoylmethane as a ligand in propionic acid at 90 °C for two hours afforded b-phenylcinnamaldehyde in 61% yield (Scheme 42).

Table 45 Oxidative Heck Coupling of Anilides with Olefins under an Oxygen Atmosphere H H R2

N

O PhH + H

Ph

R1

Pd(OAc)2 (0.5 mol%) H4PMo11VO40.26H2O (0.1 mol%) Na2CO3 (0.25 mol%) + O2

Ph

O

Ph

dibenzoylmethane, EtCO2H 90 °C, 2 h, 61%

H

Scheme 42

In this study, the authors showed that the use of acetylacetone (AA) instead of dibenzoylmethane (DBM) required a longer reaction time but benzoylacetone (BA) led to a result similar to that of dibenzoylmethane (Table 44). On the basis of this result, a variety of arenes were functionalized via the direct oxidative coupling through carbon–hydrogen bond activation.

Pd(OAc)2 (6.67 mol%) H4PMo11VO40.26H2O (1.34 mol%)

+

H

O2, EtCOOH, 90 °C

R3

R1

R2

R3

Yield (%)

1

H

Ph

CO2Bu

79

2

MeO

Me

CO2Bu

89

3

Me

Me

CO2Bu

91

4

Br

Me

CO2Bu

14

CF3

CF3 CO2Me +

Ph

F3 C

Pd(OAc)2 (10 mol%) 46 (10 mol%) F3 C

Ac2O (1.0 equiv) O2, 90 °C, 24 h

CO2Me Ph

52% (E/Z = 5:9) H

Ph

O

O

R1

Entry

Oxidative Heck Coupling of Benzene under Various Con-

O PhH

p-TsOH, AcOH–PhMe O2 (1 atm), 80 °C, 16 h

O

R2

N

Pd(OAc)2 (3 mol%) Cu(OAc)2 (3 mol%)

R3

+

Table 44 ditions

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O

H

N

H

H

+ Ph

H

Bu

H

Ph

44

Et

45

Entry

Ligand

Time, conv.

Yield (%) Yield (%) of 44 of 45

1

DBM

1.5 h, 94%

59

5

2

DBM

2 h, 96%

45

18

3

BA

1.5 h, 92%

52

6

4

AA

1.5 h, 85%

48

1

5

AA

2 h, 96%

54

8

In 2007, Guo and co-workers reported a new method for the palladium/copper-catalyzed aerobic oxidative coupling of anilides with olefins.108 Table 45 illustrates the scope and generality of such a reaction under optimized conditions in the presence of p-toluenesulfonic acid in acetic acid and toluene at 80 °C. The method is superior to previous work with regard to chemical yield.88,89 As can be understood from the above-mentioned studies, the use of monosubstituted arenes as the substrate in the C–H activation reaction leads to mixtures of the ortho-, meta-, and para-olefinated products. It was Yu and coworkers109 who first developed the meta-selective olefination reaction of highly electron-poor arenes. They screened a series of 2,6-dialkylpyridine ligands. In the palladium-catalyzed reaction of 1,3-bis(trifluoromethyl)benzene as an unreactive substrate, ligand 46 gave the highest yield (52%), with meta selectivity, in the presence of acetic anhydride under an atmosphere of molecular oxygen (Scheme 43).

Et

Bu

46

Scheme 43

The optimized conditions were applied in the reaction of different electron-poor arenes to give their corresponding coupling products (Table 46). In most cases, the products were obtained with meta-regioselectivity. In the reaction of various arenes with cinnamate, the E-isomers were observed as the major product. Quite recently, an oxidative Heck-type reaction was developed for the coupling of furans with styrenes.110 This reaction was conducted using palladium(II) acetate (10 mol%) as catalyst in the presence of benzoquinone (25 mol%), copper(II) acetate (50 mol%), and molecular oxygen as oxidants at 60 °C. A number of furans and styrenes were used as the substrates and gave coupling products with high regio- and stereoselectivity for the trans-isomers (Table 47). 3.1.2

Intramolecular Reactions

3.1.2.1 Anaerobic In 1994, Knölker79 described a short synthesis of hydroxy-substituted benzo[b]carbazoloquinone cyanamides based on a palladium-promoted oxidative coupling as the key step. This was the first example of an anaerobic catalytic intramolecular oxidative Heck cyclization. Using copper(II) acetate as the stoichiometric reoxidant, 5H-benzo[b]carbazoloquinone was cyclized to afford carbazole-1,4-quinone (Scheme 44). While the yield was moderate, this reaction was remarkable because it demonSynthesis 2010, No. 9, 1399–1427



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Table 46

meta-Selective Olefination Reactions of Electron-Poor Arenes

+

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Pd(OAc)2 (10 mol%) 46 (10 mol%)

R2

R

product

3

Ac2O (1.0 equiv) O2, 90 °C, 2–36 h

R1

Entry

R1

R2

R3

1

CO2Et

H

CO2Et

Product

Yield (%)

CO2Et

70 (m/p = 78:22) CO2Et

CF3

2

CF3

H

72 (m/p = 78:22)

CO2Et CO2Et CF3

1-CF3-4-Me

3

H

CO2Et

68 CO2Et CO2Et

4

CO2Et

Ph

81a (m/p = 85:15)

CO2Me CO2Me

NH2

5

Ph

NO2

73a (m/p = 84:16)

CO2Me CO2Me Ph CO2Me

1-CO2Me-3-CF3

6

65a

CO2Me

Ph

F3 C

CO2Me Ph

a

Yield after hydrogenation.

Table 47

Oxidative Heck Coupling of Furans with Styrenes R2 R3

R2

O

Pd(OAc)2 (10 mol%) BQ (25 mol%) Cu(OAc)2 (50 mol%)

R1

R1

R3 O

EtCO2H, THF, 60 °C O2, 24 h

Entry

R1

R2

R3

Yield (%)

1

Me

CO2Me

3-Me

66

2

CH2OAc

H

H

50

3

CH2OAc

H

4-OAc

53

The catalytic cycle for palladium-catalyzed cyclization of the 5H-benzo[b]carbazoloquinone is outlined in Scheme 45. In the first step, the o-arylpalladium(II) complex is obtained upon electrophilic attack of the palladium(II) species at the aromatic ring. In the second step, insertion of the quinone double bond gives the o-alkylpalladium(II) complex, and finally reductive b-elimination leads to the corresponding benzo[b]carbazoloquinone. O

O

N H

OMe

O MeO

H N

O

Pd(OAc)2 (12 mol%) Cu(OAc)2 (1.1 equiv)

MeO

N H

AcOH, 117 °C O O

O 84%

Pd L

Scheme 44

O

N H

OMe

[Pd(0)] OMe

O

N H

OMe


[Cu(I)]

Scheme 45

AcOH

[Cu(II)]

OAc [Pd(II)]

strated the potential application of a palladium-catalyzed intramolecular oxidative Heck reaction. Synthesis 2010, No. 9, 1399–1427

L

O

O

H N

OAc Pd

[Pd(II)]

O

L


Ph

REVIEW


After this significant result, Åkermark et al.111 carried out the same cyclization reaction using tert-butyl hydroperoxide instead of copper(II) acetate as a stoichiometric reoxidant. Moderate to good yields of the corresponding products were obtained under these conditions (Scheme 46, Table 48). O

R3 R4

rivatives afforded the corresponding b-carbolinones or pyrazino[1,2-a]indoles derivatives, respectively. Complete regioselectivity was observed under different reaction conditions (Scheme 48). PdCl2(MeCN)2 (10 mol%) benzoquinone (1 equiv)

R3

O

R2

NR

THF–DMF (2:1), 80 °C

N H

O

R2

R4

1423

O

EtOH, r.t., 98 h R5

H2 N

O

R5

R1

O

N H

N H

NR Pd(OAc)2 (5 mol%) n-Bu4NCl (1 equiv) Na2CO3 (1 equiv)

R1 R = Me, allyl, Ph

R4

90 °C, AcOH, 26–30 h

R5

DMF, 100 °C

R3

O

Pd(OAc)2 (5 mol%) TBHP (2.5 equiv)

N H

Scheme 48

Table 48 Palladium-Catalyzed Cyclization of 5H-Benzo[b]carbazoloquinone Derivatives R3

N H

O

N R

R1

Scheme 46

R3

O R2

N

R2

O

O

O

Pd(OAc)2 (5 mol%) TBHP (2.5 equiv)

R2

In 2004, a palladium-catalyzed intramolecular oxidative carbon–carbon bond formation for the synthesis of functionalized benzofurans and dihydrobenzofurans was developed by Stoltz and co-workers.115 The optimal reoxidant in this reaction was determined to be benzoquinone, while molecular oxygen was also found to be suitable (Table 49). Table 49

90 °C, AcOH, 26–30 h R1

O

N H

OMe

R1

Entry

R1

R2

R3

Time (h)

Yield (%)

1

OMe

H

H

27

74

2

H

OMe

H

27

66

3

OMe

H

Me

26

65

Oxidant Optimization

MeO

O

O

24 h, 80 °C tert-amyl alcohol–AcOH (4:1)

OMe

MeO

An efficient and novel oxidative Heck cyclization using a palladium(II) acetate/copper(II) acetate system was reported by Knölker et al. for the synthesis of carbazoquinocin.112 The key step in their synthesis was the palladiumcatalyzed oxidative cyclization of an anilinobenzoquinone intermediate (Scheme 47).

Pd(OAc)2 (10 mol%) ethyl nicotinate (40 mol%) oxidant (1 equiv)

OMe

O

MeO

O

Entry

Oxidant

Yield (%)

1

O2 (1 atm)

56

2

BQ

62

3

Cu(OAc)2

31

4

AgOAc

29

O

MeO

MeO

MeOH MeO

H2 N

25 °C, 1 h

MeO

O (2 equiv)

O

N H

O Pd(OAc)2 (0.3 equiv) Cu(OAc)2 (2.5 equiv) AcOH, 117 °C, 3–4 d

MeO MeO O

N H

Scheme 47

In 2003, Beccalli and co-workers demonstrated that the PdCl2(MeCN)2 catalyst system can be used in the oxidative cyclization of indoles. In this process benzoquinone was used as the stoichiometric reoxidant.113,114 Under the described reaction conditions, indole-2-carboxamide de-

In 2005, Youn and Eom used the same catalytic system to synthesize benzofuran and chromene derivatives in dioxane as solvent.116 The method was quite compatible with functional groups such as methoxy, methylenedioxy, and free hydroxy groups under the described reaction conditions (Table 50). In 2006, a direct synthesis of carbazoles based on palladium-catalyzed intramolecular oxidative cyclization of 3(alk-3-en-1-yl)indoles was reported by Lu and co-workers. A number of carbazole derivatives were successfully obtained in high yields (Table 51).117

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Table 50 atives

Oxidative Synthesis of Benzofuran and Chromene Deriv-

Table 52

Enantioselective Intramolecular Oxidative Heck Reaction Pd(OAc)2, 47 PhCO3t-Bu

PdCl2(MeCN)2

Entry

BQ, Na2CO3 dioxane, 1–5 h

n

O

R

N

or O

R

Substrate

O

R

n=1

n=2

Product

Yield (%)

OMe

OMe

1

Me

N

tert-amyl alcohol–AcOH 80 °C

50

Me

Entry

Ligand

Yield (%)

ee (%)

1

47

28

51

2

48

49

32

3

49

49

28

60 MeO

O

O

2

Various oxidants, including 1,4-benzoquinone, tert-butyl peroxybenzoate, and molecular oxygen, were tested in this intramolecular process, and it was found that tert-butyl peroxybenzoate was better suited as final oxidant. Enantioinduction was also influenced by alkene configuration: (Z)-50 gave a significantly higher enantiomeric excess than (E)-50 (57% ee vs. 20% ee).

57

O O

OMe

3

62 O

MeO

O

OH

4

Quite recently, Trauner and Bowie demonstrated the application of a palladium-catalyzed oxidative Heck reaction in the synthesis of (±)-rhazinal. The intermediate tetrahydroindolizine, with a quaternary stereocenter, was obtained from the N-alkylated pyrrole by using 10 mol% of palladium(II) acetate in the presence of a mixed solvent system and tert-butyl hydroperoxide in 69% yield (Scheme 49).119

57 O

HO

O

5

O

O

O

59

O

O

O

Table 51 Direct Synthesis of Carbazoles Using Palladium-Catalyzed Intramolecular Oxidative Cyclization R2

R2

R1

R3 N Me

Pd(OAc)2 (5 mol%) BQ (2.1 equiv) toluene, AcOH, 8 h 80 °C

dioxane, AcOH, DMSO 45 °C, 69%

R3

R1

N

Pd(OAc)2 (10 mol%) t-BuOOH

N

EtO

O

O OEt

OHC

N Me

N

Entry

R1

R2

R3

Yield (%)

1

H

H

Me

88

2

OMe

H

Me

80

3

H

Ph

Me

86

4

H

H

Bu

82

N

Very recently, Oestreich and co-workers reported an interesting enantioselective version of the intramolecular oxidative Heck reaction using modified PyOX ligands (Figure 8).118 The optimized reaction conditions are illustrated in Table 52.

O

R=H R = CO2Me R = CO2Et

47 48 49

N Pri

Figure 8

Synthesis 2010, No. 9, 1399–1427

O

MOM-rhazinal

Scheme 49

3.1.2.2 Aerobic In 1999, Åkermark and co-workers120 used an anilinoquinone species in a typical oxidative Heck reaction using molecular oxygen as oxidant to produce coupling products in good yields and selectivities. In 2003, a palladium-catalyzed oxidative Heck coupling was reported by Ferreira and Stoltz to produce annulated indoles, which are biologically active moieties in several natural compounds.121 The indole was initially used as substrate under mild oxidative conditions involving palladium(II) acetate, pyridine, and molecular oxygen in toluene at 80 °C. The effect of a number of substituted pyridine ligands was investigated and it was demonstrated that ligands containing electron-rich groups suppressed

R N

MOM



MeO


reactivity (Table 53, entries 1 and 2), whereas electronpoor ligands increased the overall reactivity (Table 53, entries 3 and 4). Table 53 Palladium-Catalyzed Intramolecular Oxidative Heck Coupling of Indole Pd(OAc)2 (10 mol%) pyridine ligand (40 mol%) PhMe (0.1 M), O2 (1 atm) 80 °C, 12 h

N Me

N Me

Entry

Pyridine ligand

pKa

Conv. (%)

1

4-MeOC5H4N

6.47

3

2

4-t-BuC5H4N

5.99

1

3

4-EtO2CC5H4N

3.45

52

4

3-EtO2CC5H4N

3.35

76

Stoltz and co-workers illustrated the synthesis of the [3.3.1] bicycle 51 via aerobic intramolecular oxidative Heck reaction with an excellent selectivity (Scheme 50).122 AcO

AcO Pd(OAc)2 (20 mol%), DMSO

H

t-BuOH, AcOH, O2, 80 °C, 6.5 h

HO

HO

N SEM

O

N SEM

O 51

Scheme 50

The intramolecular palladium(II)-catalyzed aerobic oxidative reaction on various types of substituted furan and thiophene rings was used to synthesize carbazole derivatives in 2008. The bicyclic compounds were synthesized in moderate yield, by cyclization of various carbamates in the presence of PdCl2(MeCN)2 and copper(II) chloride, as catalyst and oxidant, respectively, in N,N-dimethylformamide or methanol as solvent (Scheme 51).123 R2 R1

PdCl2(MeCN)2 (15 mol%) X

N CO2Et

CuCl2 (15 mol%) O2, DMF

R2 R1

X = S, R1 = R2 = H X = S, R1 = H, R2 = Me X = O, R1 = Ph, R2 = H

X

NCO2Et

48–62%

Scheme 51

4

Conclusion and Outlook

Since the first discovery of Mizoroki–Heck reaction by Heck et al., this process has been used extensively in many syntheses of significant intermediates in the fields of asymmetric chemistry, and pharmaceutical, polymer and herbicide production. The oxidative Heck reaction, in

1425

particular, has been explored to increase the efficiency of this chemical transformation. In this review, we have mainly discussed the latest developments in the area of oxidative Heck coupling reactions by both organometallic and C–H activation approaches. These two approaches have been successfully applied for the intermolecular, intramolecular, nonsymmetrical, asymmetrical, ligand-free, and ligand-based oxidative Heck couplings in the presence of different types of organometallic complexes under aerobic and anaerobic conditions. Several oxidants, including benzoquinone, copper(II) acetate, silver nitrate, tert-butyl hydroperoxide, molecular oxygen, air, and a number of metal-based complexes such as those based on palladium, ruthenium, rhodium and iridium have been reported in this regard in both stoichiometric and catalytic processes. In addition, different important coupling products have been obtained with high selectivities and good yields under a variety of conditions. Since the substrate scope of these oxidative transformations is still extremely limited and the majority of reactions are performed under anaerobic conditions, there is much room for the development of newer methods that working well under more convenient reaction conditions. Thus, it is anticipated that, due to the remarkable character of this interesting transformation in the world of carbon– carbon bond formation, the design of new systems to solve these problems will likely be the next goals. The use of efficient, recoverable catalysts has also been largely ignored in this area; hence, the design of new innovative and economically friendly systems using recoverable supported catalysts might soon become the focus in this field.

References (1) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971, 44, 581. (2) Heck, R. F.; Nolley, J. P. J. Org. Chem. 1972, 37, 2320. (3) Grips, G. T. Chem. Soc. Rev. 1998, 27, 427. (4) Gabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2. (5) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33, 2379. (6) (a) Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Tetrahedron 2001, 57, 7449. (b) Polshettiwar, V.; Molnar, A. Tetrahedron 2007, 63, 6949. (c) Karimi, B.; Enders, D. Org. Lett. 2006, 8, 1237. (7) The Mizoroki–Heck Reaction; Oestreich, M., Ed.; Wiley & Sons: Chichester, 2009. (8) Heck, R. F. J. Am. Chem. Soc. 1969, 91, 6707. (9) Dieck, H. A.; Heck, R. F. J. Org. Chem. 1975, 40, 1083. (10) Yoshida, J.; Tamao, K.; Yamamoto, H.; Kakui, T.; Uchida, T.; Kumada, M. Organometallics 1982, 1, 542. (11) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5531. (12) Cho, C. S.; Uemura, S. J. Organomet. Chem. 1994, 465, 85. (13) Cho, C. S.; Itotani, K.; Uemura, S. J. Organomet. Chem. 1993, 443, 253. (14) Du, X.; Suguro, M.; Hirabayashi, K.; Mori, A. Org. Lett. 2001, 3, 3313. (15) Andappan, M. M. S.; Larhed, P. N. M. Mol. Diversity 2003, 7, 97. (16) Karabelas, K.; Westerlund, C.; Hallberg, A. J. Org. Chem. 1985, 50, 3896.

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(17) Madin, A.; Overman, L. E. Tetrahedron Lett. 1992, 33, 4859. (18) Pan, D.; Chen, A.; Su, Y.; Zhou, W.; Li, S.; Jia, W.; Xiao, J.; Liu, Q.; Zhang, L.; Jiao, N. Angew. Chem. Int. Ed. 2008, 47, 4729. (19) Su, Y.; Jiao, N. Org. Lett. 2009, 11, 2980. (20) Bernocchi, E.; Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetrahedron Lett. 1992, 33, 3073. (21) Kang, S.-K.; Lee, H.-W.; Jang, S.-B.; Kim, T.-H.; Pyun, S.-J. J. Org. Chem. 1996, 61, 2604. (22) Jung, Y. C.; Mishra, R. K.; Yoon, C. H.; Jung, K. W. Org. Lett. 2003, 5, 2231. (23) Yoon, C. H.; Yoo, K. S. W.; Mishra, R. K.; Jung, K. W. Org. Lett. 2004, 6, 4037. (24) Kabalka, G. W.; Guchhait, S. K.; Naravane, A. Tetrahedron Lett. 2004, 45, 4685. (25) Kabalka, G. W.; Guchhait, S. K. Tetrahedron Lett. 2004, 45, 4021. (26) Yoo, K. S.; Yoon, C. H.; Jung, K. W. J. Am. Chem. Soc. 2006, 128, 16384. (27) Andappan, M. M. S.; Nilsson, P.; Larhed, M. Chem. Commun. 2004, 218. (28) Enquist, P. A.; Lindh, J.; Nilsson, P.; Larhed, M. Green Chem. 2006, 8, 338. (29) Andappan, M. M. S.; Nilsson, P.; Von Schenck, H.; Larhed, M. J. Org. Chem. 2004, 69, 5212. (30) Enquist, P. A.; Nilsson, P.; Sjberg, P.; Larhed, M. J. Org. Chem. 2006, 71, 8779. (31) Suzuki, A. In Modern Arene Chemistry; Astruc, D., Ed.; Wiley-VCH: Weinheim, 2002, 53. (32) Lindh, J.; Enquist, P. A.; Pilotti, K.; Nilsson, P.; Larhed, M. J. Org. Chem. 2007, 72, 7957. (33) (a) Karimi, B.; Zamani, A. J. Iran. Chem. Soc. 2008, 5, 1. (b) Karimi, B.; Zamani, A.; Clark, J. H. Organometallics 2005, 24, 4695. (c) Karimi, B.; Zamani, A.; Abedi, S.; Clark, J. H. Green Chem. 2009, 11, 109. (34) O’Neill, J.; Yoo, K. S.; Jung, K. W. Tetrahedron Lett. 2008, 49, 7307. (35) Lindh, J.; Sävmarker, J.; Nilsson, P.; Sjçberg, P. J. R.; Larhed, M. Chem. Eur. J. 2009, 15, 4630. (36) Ruan, J.; Li, X.; Saidi, O.; Xiao, J. J. Am. Chem. Soc. 2008, 130, 2424. (37) Delcamp, J. H.; Brucks, A. P.; White, M. C. J. Am. Chem. Soc. 2008, 130, 11270. (38) Diederich, F.; Stang, P. J. Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 1999. (39) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945. (40) Guiry, P. J.; Kiely, D. Curr. Org. Chem. 2004, 8, 781. (41) Akiyama, K.; Wakabayashi, K.; Mikami, K. Adv. Synth. Catal. 2005, 347, 1569. (42) Trost, B. M.; Jiang, C. H. Synthesis 2006, 369. (43) Dodd, D. W.; Toews, H. E.; Carneiro, F.; Jennings, M. C.; Jones, N. D. Inorg. Chim. Acta 2006, 359, 2850. (44) Penn, L.; Shpruhman, A.; Gelman, D. J. Org. Chem. 2007, 72, 3875. (45) (a) Ozawa, F.; Kubo, A.; Hayashi, T. Tetrahedron Lett. 1992, 33, 1485. (b) Trabesinger, G.; Albinati, A.; Feiken, N.; Kunz, R. W.; Pregosin, P. S.; Tschoerner, M. J. Am. Chem. Soc. 1997, 119, 6315. (46) (a) Jutand, A.; Mosleh, A. Organometallics 1995, 14, 1810. (b) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009. (47) (a) Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 13978. (b) Navarro, O.; Kelly, R. A.; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194. (c) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 14726.

Synthesis 2010, No. 9, 1399–1427


(48) Amatore, C.; Jutand, A. J. Organomet. Chem. 1999, 576, 254. (49) (a) Samsel, E. G.; Norton, J. R. J. Am. Chem. Soc. 1984, 106, 5505. (b) Ashimori, A.; Overman, L. E. J. Org. Chem. 1992, 57, 4571. (c) Grigg, R.; Loganathan, V.; Santhakumar, V.; Sridharan, V.; Teasdale, A. Tetrahedron Lett. 1991, 32, 687. (d) Brown, J. M.; Perez-Torrente, J. J.; Alcock, N. W.; Clase, H. J. Organometallics 1995, 14, 207. (50) (a) Fryzuk, M. D.; Bosnich, B. J. Am. Chem. Soc. 1977, 99, 6262. (b) Brunkan, N. M.; White, P. S.; Gagne, M. R. Angew. Chem. Int. Ed. 1998, 37, 1579. (51) Yoo, K. S.; Park, C. P.; Yoon, C. H.; Sakaguchi, S.; O’Neill, J.; Jung, K. W. Org. Lett. 2007, 9, 3933. (52) (a) Sakaguchi, S.; Yoo, K. S.; O’Neill, J.; Lee, J. H.; Stewart, T.; Jung, K. W. Angew. Chem. Int. Ed. 2008, 47, 9326. (b) Yoo, K. S.; O’Neill, J.; Sakaguchi, S.; Giles, R.; Lee, J. H.; Jung, K. W. J. Org. Chem. 2010, 75, 95. (53) Xiong, D. C.; Zhang, L. H.; Ye, X. S. Org. Lett. 2009, 11, 1709. (54) Likhar, P. R.; Roy, M.; Roy, S.; Subhas, M. S.; Kantam, M. L.; Sreedhar, B. Adv. Synth. Catal. 2008, 350, 1968. (55) (a) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou, K.; MartínMatute, B. J. Am. Chem. Soc. 2001, 123, 5358. (b) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169. (56) Lautens, M.; Mancuso, J.; Grover, H. Synthesis 2004, 12, 2006. (57) Amengual, R.; Michelet, V.; Genêt, J.-P. Tetrahedron Lett. 2002, 43, 5905. (58) Zou, G.; Wang, Z.; Zhu, J.; Tang, J. Chem. Commun. 2003, 2438. (59) Martinez, R.; Voica, F.; Genêt, J.-P.; Darses, S. Org. Lett. 2007, 9, 3213. (60) Faller, J. W.; Chase, K. J. Organometallics 1995, 14, 1592. (61) Ritleng, V.; Sutter, J. P.; Pfeffer, M.; Sirlin, C. Chem. Commun. 2000, 129. (62) Ritleng, V.; Pfeffer, M.; Sirlin, C. Organometallics 2003, 22, 347. (63) Farrington, E. J.; Brown, J. M.; Barnard, C. F. J.; Rowsell, E. Angew. Chem. Int. Ed. 2002, 41, 169. (64) Farrington, E. J.; Barnard, C. F. J.; Rowsell, E.; Brown, J. M. Adv. Synth. Catal. 2005, 347, 185. (65) Hirabayashi, K.; Nishihara, Y.; Mori, A.; Hiyama, T. Tetrahedron Lett. 1998, 39, 7893. (66) Mori, A.; Danda, Y.; Fujii, T.; Hirabayashi, K.; Osakada, K. J. Am. Chem. Soc. 2001, 123, 10774. (67) Zhou, H.; Xu, Y. H.; Chung, W.-J.; Loh, T.-P. Angew. Chem. Int. Ed. 2009, 48, 5355. (68) Hirabayashi, K.; Ando, J. I.; Nishihara, Y.; Mori, A.; Hiyama, T. Synlett 1999, 99. (69) Parrish, J. P.; Jung, Y. C.; Shin, S.; Jung, K. W. J. Org. Chem. 2002, 67, 7127. (70) Matoba, K.; Motofusa, S. I.; Cho, C. S.; Ohe, K.; Uemura, S. J. Organomet. Chem. 1999, 574, 3. (71) Nunn, M.; Sowerby, D. B.; Wesolek, D. M. J. Organomet. Chem. 1983, 251, 45. (72) Moritani, I.; Fujiwara, Y. Tetrahedron Lett. 1967, 1119. (73) Fujiwara, Y.; Moritani, I.; Matsuda, M. Tetrahedron 1968, 4819. (74) Itahara, T.; Ikeda, M.; Sakakibara, T. J. Chem. Soc., Perkin Trans. 1 1983, 1361. (75) Itahara, T.; Kawasaki, K.; Ouseto, F. Synthesis 1984, 236. (76) Asano, R.; Moritani, I.; Fujiwara, Y.; Teranishi, S. J. Chem. Soc., Chem. Commun. 1970, 1293. (77) Yogo, M.; Ito, C.; Furukawa, H. Chem. Pharm. Bull. 1991, 39, 328. (78) Knölker, H. J.; O’Sullivan, N. Tetrahedron Lett. 1994, 35, 1695.


1426

(79) Knölker, H. J.; O’Sullivan, N. Tetrahedron 1994, 50, 10893. (80) Baran, P. S.; Corey, E. J. J. Am. Chem. Soc. 2002, 124, 7904. (81) Baran, P. S.; Guerrero, C. A.; Corey, E. J. J. Am. Chem. Soc. 2003, 125, 5628. (82) Garg, N. K.; Caspi, D. D.; Stoltz, B. M. J. Am. Chem. Soc. 2004, 126, 9552. (83) Garg, N. K.; Caspi, D. D.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 5970. (84) Tsuji, J.; Nagashima, H. Tetrahedron 1984, 40, 2699. (85) Hirota, K.; Isobe, Y.; Kitade, Y.; Maki, Y. Synthesis 1987, 495. (86) Jia, C.; Lu, W.; Kitamura, T.; Fujiwara, Y. Org. Lett. 1999, 1, 2097. (87) Mikami, K.; Hatano, M.; Terada, M. Chem. Lett. 1999, 28, 55. (88) Boele, M. D. K.; van Strijdonck, G. P. F.; de Vries, A. H. M.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. W. N. M. J. Am. Chem. Soc. 2002, 124, 1586. (89) Zaitsev, V. G.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 4156. (90) Capito, E.; Brown, J. M.; Ricci, A. Chem. Commun. 2005, 1854. (91) Grimster, N. P.; Gauntlett, C.; Godfrey, C. R. A.; Gaunt, M. J. Angew. Chem. Int. Ed. 2005, 44, 3125. (92) Beck, E. M.; Grimster, N. P.; Hatley, R.; Gaunt, M. J. J. Am. Chem. Soc. 2006, 128, 2528. (93) Houlden, C. E.; Bailey, C. D.; Ford, J. G.; Gagné, M. R.; Lloyd-Jones, G. C.; Booker-Milburn, K. I. J. Am. Chem. Soc. 2008, 130, 10066. (94) Li, J.-J.; Mei, T.-S.; Yu, J.-Q. Angew. Chem. Int. Ed. 2008, 47, 6452. (95) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am. Chem. Soc. 2008, 130, 9254. (96) Rauf, W.; Thompson, A. L.; Brown, J. M. Chem. Commun. 2009, 3874. (97) Cheng, D.; Gallagher, T. Org. Lett. 2009, 11, 2639. (98) Koubachi, J.; Raboin, S. B.; Mouaddib, A.; Guillaumet, G. Synthesis 2009, 271. (99) Fujiwara, Y.; Moritani, I.; Matsuda, M.; Teranishi, S. Tetrahedron Lett. 1968, 3863. (100) Shue, R. S. J. Chem. Soc., Chem. Commun. 1971, 1510.


1427

(101) Maruyama, O.; Yoshidomi, M.; Fujiwara, Y.; Taniguchi, H. Chem. Lett. 1979, 8, 1229. (102) Miura, M.; Tsuda, T.; Satoh, T.; Nomura, M. Chem. Lett. 1997, 26, 1103. (103) Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63, 5211. (104) Yokota, T.; Tani, M.; Sakaguchi, S.; Ishii, Y. J. Am. Chem. Soc. 2003, 125, 1476. (105) Tani, M.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2004, 69, 1221. (106) Dams, M.; De Vos, D. E.; Celen, S.; Jacobs, P. A. Angew. Chem. Int. Ed. 2003, 42, 3512. (107) Yamada, T.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2005, 70, 5471. (108) Wang, J. R.; Yang, C. T.; Liu, L.; Guo, Q. X. Tetrahedron Lett. 2007, 48, 5449. (109) Zhang, Y. H.; Shi, B. F.; Yu, J. Q. J. Am. Chem. Soc. 2009, 131, 5072. (110) Aouf, C.; Thiery, E.; Bras, J. L.; Muzart, J. Org. Lett. 2009, 11, 4096. (111) Åkermark, B.; Oslob, J. D.; Heuschert, U. Tetrahedron Lett. 1995, 36, 1325. (112) Knölker, H. J.; Reddy, K. R.; Wagner, A. Tetrahedron Lett. 1998, 39, 8267. (113) Beccalli, E. M.; Broggini, G. Tetrahedron Lett. 2003, 44, 1919. (114) Abbiati, G.; Beccalli, E. M.; Broggini, G.; Zoni, C. J. Org. Chem. 2003, 68, 7625. (115) Zhang, H.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem. Int. Ed. 2004, 43, 6144. (116) Youn, S. W.; Eom, J. I. Org. Lett. 2005, 7, 3355. (117) Kong, A.; Han, X.; Lu, X. Org. Lett. 2006, 8, 1339. (118) Schiffner, J. A.; Machotta, A. B.; Oestreich, M. Synlett 2008, 2271. (119) Bowie, A. L. Jr.; Trauner, D. J. Org. Chem. 2009, 74, 1581. (120) Hagelin, H.; Oslob, J. D.; Åkermark, B. Chem. Eur. J. 1999, 5, 2413. (121) Ferreira, E. M.; Stoltz, B. M. J. Am. Chem. Soc. 2003, 125, 9578. (122) Garg, N. K.; Caspi, D. D.; Stoltz, B. M. Synlett 2006, 3081. (123) Beccalli, E. M.; Borsini, E.; Broggini, G.; Rigamonti, M.; Sottocornola, S. Synlett 2008, 1053.

Synthesis 2010, No. 9, 1399–1427



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