Stereoselective Cyclopropanation Under Solvent Free ...

1 downloads 0 Views 765KB Size Report
lyzed by a Green and Efficient Recyclable Cu-Exchanged Bentonite ... troduced as a green catalyst. .... f Result determined by Hubert and co-workers [32].
Send Orders for Reprints to [email protected] Letters in Organic Chemistry, 2016, 13, ???-???

1

Stereoselective Cyclopropanation Under Solvent Free Conditions: Catalyzed by a Green and Efficient Recyclable Cu-Exchanged Bentonite Choukry K. Bendeddouchea, Mehdi Adjdira,b and Hadj Benhaouaa,* a

Laboratoire de Synthèse Organique Appliquée, Faculté des Sciences, Université d’Oran1 Ahmed Ben Bella, BP 1524, El Menaouar, Oran 31000, Algérie; bChemistry of Oxidic and Organic Interfaces COOI Institute of Functional Interfaces IFG Karlsruher Institute of Technology KIT, 76344 Eggenstein-Leopoldshafen, Germany Received May 20, 2015: Revised December 10, 2015: Accepted January 07, 2016

Abstract: Backrgound: The cyclopropanation reaction was inspected by addition of carbene generated from ethyl diazoacetate in the presence of a greener Cu-exchanged bentonite catalyst to olefin under solvent free condition. The cyclopropanes were obtained with good yields. Our own contribution in this area was to introduce a modified Algerian bentonite as a catalyst and microwave activation as a mode of heating.

Hadj Benhaoua

Methods: A catalytic material developed from natural type montmorillonite clays, from deposits of Maghnia (Western Algeria), by cation exchange (Cu2+) was characterized by different spectral methods. The catalytic properties of the new material were explored in cyclopropanation reaction of olefins under microwave irradiation. A comparative study with Cu-exchanged bentonite as catalyst between microwave activation and classical heating was conducted. Results: Cu2+ exchanged clay is an efficient catalyst in the generation of carbenes from diazocompounds, under microwave irradiation. The formation of carboxylate cyclopropane was performed in solvent free condition with moderate diastereoselectivity. The yields were good, and the catalyst can be reused at least three times without noticeable loss of catalytic activity. Conclusion: This work shows that the coupling "modified clay/microwave activation" is a clean and simple access to functionalized cyclopropanes. This reusable Cu exchanged clay material is shown to be as a good substitute for many sophisticated and hardly accessible catalysts.

Keywords: Bentonite-Cu2+, carbenes, cyclopropanation, diastereoselectivity, ethyl diazoacetate, microwave irradiations (MWI). INTRODUCTION Generally, two principal pathways was used to prepare cyclopropanes with diazo compounds: in absence of catalyst and in presence of olefin [pathway (a)] the diazocompound acts as 1,3-dipole to yield pyrazoline witch carry out cyclopropane by thermal extrusion of N2 [1], with a catalyst [pathway (b)] the diazocompound behaves as carbene after catalytic decomposition, which is trapped by olefin to yield cyclopropane [2] (Scheme 1). In fact, the catalytic cyclopropanation reactions were considerably developed by many researchers [3-9]. This reaction is the most commonly used approaches for the synthesis of cyclopropane carboxylates which can be also used for elaborating pharmaceuticals or natural products containing the cyclopropane moiety [10]. Transition-metal-catalyzed cyclopropanation reactions have been reported [11-14]. However, most of these catalysts *Address correspondence to this author at the Laboratoire de Synthèse Organique Appliquée, Departement de Chimie, Faculté des Sciences exactes et appliquées, Université d’Oran1 Ahmed Ben Bella, BP 1524, El Menaouar, Oran 31000, Algérie; Tel: 00 213 62 66 88 25; E-mail: [email protected] 1570-1786/16 $58.00+.00

are expensive, hardly accessible and difficult to recycle which limit their use in large scale synthesis. There is an increased interest in development of new inexpensive materiel catalysts. For their natural abundance and their higher ion exchange capacity clay seems to be an appropriate material in catalytic organic synthesis; therefore, insertion of divalent cation such as copper may enhance their catalytic properties [15] mainly in the decomposition of the diazocompounds. Generally, microwave irradiation chemistry techniques have been employed to avoid the use of dangerous solvent (dry media) and reduce reaction time. As far as we know the cyclopropanation with diazocompounds and modified clay under microwave irradiation has not been reported previously. A few works [16, 17] related to the use of modified clays as heterogeneous support catalysts were reported. In fact, the reaction was performed in presence and without solvent with the mass ratio between catalyst and Ethyldiazoacetate around 26%. The very bad result was obtained in absence of solvent. In this contribution a modified Algerian bentonite was introduced as a green catalyst. The catalytic properties of copper exchanged bentonite (BCu) were explored in cyclopro© 2016 Bentham Science Publishers

2

Letters in Organic Chemistry, 2016, Vol. 13, No. 3

Bendeddouche et al.

N (a)

-N2

R1

N R2

N2CR1R2

R1 R2

catalyst (b)

CR1R2

+ N2

Scheme 1. Cyclopropane obtained with diazocompounds using two pathways (a) and (b).

panation of olefins under microwave induction. The mass ratio reported in our contribution is reduced to ca.7% and the reaction was conducted in solvent free condition. A comparative study between microwave activation and classical heating is realized.

MWI or  80°C

(1) 2 N2CHE (1)

RESULTS AND DISCUSSION Generation of Carbene and Cyclopropanation of Various Olefins The BCu sample is applied as catalyst for generation of carbenes from ethyl diazoacetate (EDA). The synthesis of oxazoles from EDA and nitrile over BCu was studied [15]. These results led us to extend the investigation to the cyclopropanation reaction coupling BCu and microwave irradiation with the aim of getting better selectivity. The complexes are generally used as catalysts in this reaction under various experimental conditions. In previous work we used also clay from Maghnia in many synthetic applications [18-20]. In this present work the coupling modified clay / microwave activation is considered as a clean and a simple access to functionalized cyclopropanes. In order to ascertain the BCu efficiency to generate carbene, the EDA was heated with two activation modes: MWI and oil bath separately (Table 1. entry 1 and 2). In fact, the Table 1.

a

2 N2CHE

E BCu MWI or , 80°C H or RT

H E

E

H

H (3)

(2)

E= CO2Et

E +

Scheme 2. EDA investigation with and without BCu under MWI or conventional heating.

starting compound is obtained as result (the decomposition of EDA does not take place). Then, EDA was added to BCu under microwave irradiation and conventional heating. The reaction leads to ethyl maleate and ethyl fumarate which reveals the formation of intermediate carbenes (Scheme 2). Temperature, time of irradiation and the amount of used BCu were specified using further investigations (Table 1). These results show that BCu has effective catalytic properties and the optimal amount of catalyst is ca. 50mg. On the basis of the previous results the cyclopropanation reaction was investigated with styrene in the presence of BCu under MWI as reaction model. Then, the cyclopropanation reaction was extended to a range of cyclic and acyclic

Results obtained from decomposition of ethyl diazoacetate promoted by BCu. N°

BCu

Temperature

Times

Conversiona (%)

1

none

 (80°C)

16 h

-b

2

none

MWI (80°C)

20 min

-b

3

50 mg

 (80°C)

20 min

70

4

2g

Room temperature

16 h

100

5

100 mg

Room temperature

16 h

100

6

50 mg

Room temperature

16 h

100

7

2g

M.WI (80°C)

20 min

100

8

100 mg

M.W I (80°C)

20 min

100

9

50 mg

M.WI (80°C)

20 min

100

Estimated by 1H NMR. b Decomposition to ethyl maleate and ethyl fumarate does not work, only the EDA is recovered.

Stereoselective Cyclopropanation Under Solvent Free Conditions

Letters in Organic Chemistry, 2016, Vol. 13, No. 3

R1

H H

R2

H

+ R2 H

H

R1

H

R1

H

R2

E H

E N2CHE (1)

BCu MWI, 80°C 150 W

(5)

(4)

[ CHE ]

C H2

E = CO2C2H5

CH2

H n

C H2

n H

H

E

+

H

n

H

H H

E H

3

(7)

(6)

Scheme 3. Carbenes generation and cyclopropanation reaction. Table 2.

Olefins cyclopropanation with BCu as catalyst.



Alkenes

Products

R1

R2

%Yield a

% 4b

% 5b

ded

1

Styrene

(4a+5a)

Ph

H

96

70

30

40

2

-methylstyrene

(4b+5b)

Ph

Me

80

70

30

40

3

Methyl methacrylate

(4c+5c)

CO2Me

Me

90

66

34

32

4

Vinyl Acetate

(4d+5d)

OCOMe

H

70

7

93c

86

5

2,3-Dimethyl-2-butene

(4e=5e)

Me

Me

90

6

Cyclohexene

(6a+7a)

-(CH2)-

H

7

Cyclooctene

(6b+7b)

-(CH2)-

H

8

Norbornene

(6c+7c)

-(CH)-

H

% 6b

% 7b

ded

87

60

40

20

62

55

45

10

37

c

26

62

100

63

a

Isolated yield. Ratio determined by 1H NMR. diastereoisomeric excess. c Cis stereoisomer is obtained predominantly. b d

Table 3.

Physical characteristics of the maghnia bentonite before and after exchange. Samples

CEC (meq/100 g)

BET surface area (m2/g)

Raw bentonite

48

60.8

Na bentonite

85

96.5

BCu a

115.7

n.d means the CEC for BCu is not determined.

alkenes (Scheme 3). The generated carbenes are trapped by functionalized olefins and the cyclopropane was obtained in an average diastereoselectivity. The results are given in Table 2. The cyclopropanes obtained with acyclic alkenes as well as cyclic alkenes give yields ranging from 62% to 96% which demonstrate the excellent catalytic activity of the BCu, these results can be attributed to the particle size. In fact, the specific surface area of the catalyst increases due to the decrease of its particle size (Table 3). 1

n.d

a

H,

The cyclopropane structures were established using the 13 C NMR and mass spectrometry. The thermodynami-

cally stable trans (Ester group trans to bulky R1) or exo (cyclic olefins) cyclopropane is obtained as major product which is conform to literature [21-23], it is the sterically less hindered product. Unlike the cases 4 (vinyl acetate) and 8 (norbornene), the reaction is moderately trans diastereoselective. The diastereoisomeric excess (de) for both types of cyclopropanes obtained with cyclic and acyclic alkenes varies from 10% to 26% and 32% to 86% respectively. Few cis diastereoselective reactions are described, some catalysts based on cobalt and ruthenium [24-27], proved highly cis stereoselectivity. Even thought, these interesting results which are obtained by the use of expensive catalyst, the reaction remains sensitive to steric effects and their catalytic ac-

4

Letters in Organic Chemistry, 2016, Vol. 13, No. 3

Table 4.

Bendeddouche et al.

Stereoselectivity evolution of styrene and cyclohexene (comparison with literature). Styrene

Catalysts BCu c

Cu (acac)2

d

Cu (acac)2

(FCNN)Cu(Otf)

e

f

Rh2(OAc)4

Imino carbene

g

Cyclohexene

Experimental Conditions

Yield

Trans/cis

Yield

Exo/Endo

Time / Pa (eq.b)/Temperature

96

2.30

89

1.50

20min / 150 W (4 eq.)/80°C

94

3.10

62

9.00

20min / 150 W (4 eq.)/110°C

71

2.60

18

6.50

6-8h /  (10 eq.)/60°C

84

1.70

60

1.40

10h / (5 eq.)/RT

93

1.60

90

3.80

4-8h / (10 eq.)/RT

98

0.02

36

0.04

2-48h (5 eq.)/0°C

a

Irradiation power. Equivalent number of olefin. Result determined by Bendeddouche and co-workers [2]. d Result determined by Doyle and co-workers [30]. e Result determined by Cho and co-workers [31]. f Result determined by Hubert and co-workers [32]. g Result determined by Rosenberg and co-workers [28]. b c

Table 5.

Recycled BCu catalyst reused with styrene and EDA. N°

%Yield a

% 4b

% 5b

1

96

70

30

2

92

70

30

3

90

70

30

a

Isolated yield. b Ratio determined by 1H NMR.

tivities decrease significantly leading to low yields and average stereoselectivity. According to the results cited previously, the stereoselectivity appears to depend on the nature of the catalyst and olefin [17]. The results in Table 4 show the evolution of the stereoselectivity of styrene and cyclohexene chosen as a model. It is clear from this table that experimental conditions have a moderate impact on the stereoselectivity, however the nature of the catalyst plays a key role. An unexpected cis preference is observed with vinyl acetate and norbornene. It is difficult to explain the modification in selectivity, catalyst and olefins are probably responsible of this change. In case of the vinyl acetate, the reversal of the trans/cis diastereoselectivity, can be explained by an endo approach stabilized by secondary orbital interactions in the cis transition state. It is known that the trans preference is due to steric interactions between the ester of the diazoacetate and the bulky group of the alkene. This is an important outcome since the cis stereoselective cyclopropanations are rare and require sophisticated and hardly accessible catalysts [28, 29]. It should be noted that the obtained cyclopropanes are mixture of enantiomeres. The (cis) and (trans) enantiomeric excess (ee) determined on the basis of cyclopropanes resulting from styrene are 7% and 11% respectively. Comparable results are obtained by the use of chiral bis(oxazoline)-Cu II exchanged into bentonite [16].

with styrene and EDA under MWI (as a model of catalyst reusability), after filtration of the first reaction the catalyst was washed repeatedly with dichloromethane, and then dried under MWI at 650 watts for 6 min for subsequent reactions. The crude mixture of each reaction separately was analyzed by 1H NMR and then the product is purified. As results (Table 5), the BCu was reused for three times without noticeable decrease in catalytic activity. In fact, the yield was slightly diminished and the stereoselctivity did not change. Comparison study of Two Activation Modes We have carried out a series of reactions in a conventional oil bath in the same conditions as those used in microwave oven. The results obtained and the experimental conditions are listed in Table 6.

Recovery and Reusability of the Catalyst

The microwave activation enhances the yields and reduces considerably the formation of secondary product as polymerization of olefins and formation of ethyl maleate and fumarate compared to the conventional heating (Table 6). The results obtained with microwave irradiation show a specific microwave effect that is accentuated with cyclooctene 62% compared with conventional heating 31%. The comparison of results reveals a slight difference in diastereoselectivity between the two modes stimulation, with a slight trans preference under conventional heating (Table 6).

To exhibit the ability to recover the properties of the catalyst, the Cu-bentonite was successively used three times

Thus, the microwave experiments are much easier to set up and provide a clean simple and rapid alternative.

Stereoselective Cyclopropanation Under Solvent Free Conditions

Table 6.

Letters in Organic Chemistry, 2016, Vol. 13, No. 3

5

Comparison between microwave irradiation and conventional heating using BCu.

Alkenes Styrene -Methylstyrene

Microwave Irradiation %Yield a

%4b

%5 b

de

96

70

30

80

70

30

%6 b

Conventional Heating %7 b

%Yield a

%4b

%5b

de

40

70c

82

18

64

40

60

c

80

20

60

c

50

50

0

22

78

56

de

% 6b

% 7b

de

Methyl methacrylate

90

66

34

32

63

Vinyl Acetate

70

7

93

86

55 c

2,3-Dimethyl-2-butene

90

Cyclohexene

87

60

40

20

n.d

65

35

30

Cyclooctene

62

55

45

10

31d

56

44

12

Norbornene

62

37

63

26

n.dc

56

44

12

100

70

100

a

Isolated Yield. b Ratio determined by 1H NMR. c Polymerization of olefin is observed. d Ethyl maleate and fumarate are observed as majority product.

CONCLUSION 2+

This work shows that Cu exchanged clay is an efficient and recyclable catalyst in the decomposition of EDA. The formation of carboxylate cyclopropane was performed in solvent free condition with yields ranging from 62% to 96% and the diastereoselectivity is obtained in moderate ratio. However, it manifests a major cis stereoselectivity in two cases (vinyl acetate and norbornene). This green Cuexchanged bentonite is shown to be as a good substitute for many sophisticated and hardly accessible catalysts. Reusability of the catalyst and the easy work up under microwave irradiation are the most significant advantage of our method. EXPERIMENTAL Characterization Methods IR spectra were measured with a JASCO 4200 FTIR spectrometer (range 4000-400 cm-1). X-ray powder diffraction data were collected with monochromatic Cu K radiation using Philips PW 3710 diffractometer. The measurement of specific surface area is performed using a Flowsorb II society Micromeretics 2300 and the cation exchange capacity (CEC) is determined using cobalt method [33] the results are displayed in Table 3. 1H NMR and 13C spectra were recorded on Brüker CA 300 P and Brüker ARX 200 type spectrometers. The tetramethylsilane is used as internal standard with CDCl3 solvent. Mass spectra (HRMS) were measured on a Varian MAT 311 at the ionisation potential of 70 eV. Gas chromatography analysis was performed using a Varian CP-3380 equipped with a flame ionization detector, and a chiral column Chrompack (CP - chirasil - Dex CB 25 m x 0. 25 mm). Scanning Electron Microscopy-Energy Dispersive Spectrometry (SEM/EDS) is conducted using a SEM JSM 6400 equipped with an energy dispersive spectrometer allows a quantitative analysis of samples.The bulk rock fragments were previously coated with gold. The images are observed for an accelerator voltage 8 KV for sodium clay and 7 KV for BCu.

The determination of copper content was performed by inductively coupled plasma optical emission spectrometer (ICP-OES) (ICP-OES Jobin Yvon Typ JY385). Catalyst Preparation The raw bentonite was sampled from 600Km west of the capital of Algiers in Maghnia, its chemical composition was found to be as follows: 52.17% SiO2, 21.71% Al2O3, 2.68% Fe2O3, 1.14% MgO, 0.29% K2O, 1.07% CaO, 0.12% TiO2, 0.11% Na2O and 21.81% loss on ignition. It was purified by sedimentation following by pretreatment with HCl (0.01 mol/L) to remove carbonates and sulfates and the fraction less than 2 μm was treated three times with NaCl (1 mol L-1). The solution of bentonite was washed with distilled water until negative AgNO3 test. The modified bentonite thus obtained was named sodium bentonite (Na bentonite). The exchange of copper was done by a dropwise addition (12 hours) of copper chloride solution (500 mL, 1N) to a suspension of Na bentonite (50 g/L). The removal of supernatant was analyzed by ICP-OES to determine the copper content. The remained mud was washed with distilled water until negative AgNO3 test. The obtained Cu-exchanged bentonite (BCu) is irradiated at 650watts for six minutes and then analyzed. Characterization of BCu The BCu structure was confirmed by different spectral methods [FTIR, XRD (X-ray diffraction) and SEM/EDS], particularly the XRD spectra show the d001 decrease from 14.94 Å for raw bentonite to 12.5 Å for Cu-exchanged bentonite. The diminution in the interlayer spacing of exchanged bentonite was due to ionic radius of Na (r = 1. 02 Å) is larger than Cu (r = 0. 73 Å), according to literature d001 = 12.6 Å value corresponds to a copper exchanged clay with one layer of water [34, 35]. The analysis with ICP-OES unveils a percentage by weight of copper of 4.41%. This result is confirmed by SEM/EDS the percentage by weight of copper was ca. 4.35%. This is enough to give the catalytic properties. The analysis of the raw clay sample with SEM/EDS indicates the absence of copper.

6

Letters in Organic Chemistry, 2016, Vol. 13, No. 3

Synthesis of Cyclopropanes Two methods were performed: Method A (MWI): in this study a continuous focused microwave (synthewave 402 apparatus with a max power of 300 W) with refluxing and stirring option was used. The reaction temperature was reached a target temperature after 3min then maintained by device until the end of reaction. The temperature was detected by IR sensor. The mixture of the alkene (6 mmol) and the exchanged bentonite 50 mg was irradiated at 150 Watts to reach 80°C, in a quartz reactor (Ø = 1.8 cm). The temperature was maintained for 20 minutes and during that time, EDA (6 mmol) in alkene (6mmol) was added slowly by a syringe during 10 min. When the reaction was complete, the crud mixture was obtained after adding dichloromethane (3x20mL), filtration and removal of the excess of alkene and solvent. The crude was analyzed by 1H NMR and then the product is purified by short-path distillation. The obtained cyclopropane is identified by 1H NMR, 13C NMR and mass spectra. Method B (Conventional Heating): Reactions were performed in a conventional oil bath in the same conditions as those used in microwave oven, the crude was analyzed and the ratios were determined by 1H NMR. Characterization of Synthesized Derivatives Ethyl 2-phenylcyclopropanecarboxylate (4a+5a): Yield: 96%; translucent liquid; b.p.: 137-143°C/15mm Hg. 1 H NMR (200 MHz, CDCl3):  (ppm) 0.95 (t, J = 7.1 Hz, 3H, C2-H3, Z), 1.25 (t, J = 7.1 Hz, 3H, C2-H3, E); 1.50-2.60 (m, 4H, C3-H2, E + Z), 3.85 (q, J = 7.1 Hz, 2H, C1-H2, Z), 4.16 (q, J= 7.1 Hz, 2H, C1-H2, E), 7.00-7.35 (m, 10H, Ar-H, E+Z). 13C NMR (50 MHz, CDCl3): (ppm) 11.0 (C3, Z), 14.0 (C2, Z), 14.2 (C2, E), 17.0 (C3-E), 21.7 (C1, Z), 24.1 (C1, E), 25.4 (C2, Z), 26.1 (C2, E), 60.6 (C1, Z), 61.1 (C1, E), 128.0-140.0 (12C, aromatic carbons), 170.8(C=O, Z), 173.33 (C=O, E). HRMS: C12H14O2. Calculated = 190.099; Found = 190.099. Ethyl 2-methyl-2-phenylcyclopropanecarboxylate (4b+5b): Yield: 80%; translucent Liquid; b.p., 114116°C/5mm Hg. 1H NMR (200 MHz, CDCl3):  (ppm)0.92(t, J = 7.1Hz, 3H, C2-H3, Z), 1.12-1.21 (m, 4H, C3-H2, E+Z), 1.31 (t, J = 7.1Hz, 3H, C2-H3, E), 1.44 (s, 3H, C1-H3, Z), 1.52 (s, 3H, C1-H3, E), 1.8-2.1 (m, 2H, C1-H, E+Z), 3.80 (q, J = 7.1Hz, 2H, C1-H2, Z), 4.16 (q, J = 7.1Hz, 2H, C1-H2, E), 7.12-7.24 (m, 10H, Ar-H, E+Z). 13C NMR (50 MHz, CDCl3): (ppm) 13.9 (C2, Z), 14.4 (C2, E), 19.3 (C1, Z), 19.8 (C1, E), 20.7 (C3, Z), 27.8 (C3, E), 28.5 (C1, Z), 28.7 (C1, E), 30.5 (C2, Z), 31.9 (C2, E), 59.9 (C1, Z), 61.4 (C1, E), 125.4-145.8 (12C, aromatic carbons), 171.0 (C=O, Z), 172.0(C=O, E). HRMS: C13H16O2. Calculated = 204.114; Found = 204.115. Ethyl methyl 1-methylcyclopropane-1,2-dicarboxylate (4c+5c): Yield: 90%; Translucent liquid; b.p.: 120130°C/15mm Hg. 1H NMR (300 MHz, CDCl3):  (ppm) 1.24 (t, J = 7.1 Hz, 3H, C2-H3, Z), 1.27 (t, J = 7.1Hz, 3H, C2-H3 E), 1.39 (s, 6H,, C1-H3, E+Z), 1.4 -1.8 (m, 4H, C3-H2, E+Z), 2.32 (dd, J= 6,6Hz, 2H, C2-H, E+Z), 3.67 (s, 3H, C1H3, Z), 3.69 (s, 3H, C1-H3, E), 4.13 (m, 4H, C2-H2, E+Z).

Bendeddouche et al. 13

C NMR (75 MHz, CDCl3): (ppm) 12.8 (C1, Z), 14.0 (C1, E), 14.1 (C2, Z), 19.3 (C3, Z), 20.7 (C3, E), 20.8 (C2, E), 26.6 (C1, Z), 27.7 (C2, Z), 28.5 (C2, Z), 28.6 (C1, E), 51.9 (C1, Z), 52.2 (C1, E), 60.6 (C2, Z), 60.7 (C2, E), 170.1 (C=O, Z), 170.3 (C=O, E), 171.9 (C=O, Z), 173.7 (C=O, E). HRMS: C9H14O4. Calculated = 186.087; Found = 186.089. Ethyl 2-acetoxycyclopropanecarboxylate. (4d+5d): Yield: 70%; Translucent liquid; b.p.: 95°C/10mm Hg. 1 H NMR (300 MHz, CDCl3):  (ppm) 1.25 (t, J = 7,1Hz, 3H, C2H3, Z), 1.26 (t, J = 7.1Hz, 3H, C2-H3, E), 1.36-1.59 (m, 4H, C3-H2, E+Z), 1.84-2.00 (m, 2H, C1-H, Z+E), 2.05 (s, 3H, C1-H3, Z), 2.07 (s, 3H, C1-H3, E), 4.14 (q, J = 7.1Hz, 2H, C1-H2, Z), 4.25 (q, J = 7.1Hz, 2H, C1-H2, E), 4.40 (m, 2H, C2-H). 13C NMR (75 MHz, CDCl3): (ppm) 11.9(C3, Z), 13.8(C3, E), 14.0(C2, Z), 14.1(C2, E), 19.7(C1, Z), 20.3(C1, E), 20.4(C1, Z), 20.5(C1, E), 52.4(C2, Z), 54.1(C2, E), 60.6(C1, Z), 60.7(C1, E), 169.3(C=OC1, Z), 170.6(C=OC1, E), 171.2(C=OC1, Z), 171.4(C=OC1, E). HRMS: No molecular ion (m/z = 172), observation of m/z = 130 (M+.-CH2=C=O); m/z = 143 (M+.- C2H5). Ethyl 2,2,3,3-tetramethylcyclopropanecarboxylate (4e=5e): Yield: 90%; Translucent liquid; b.p.: 7173°C/12mm Hg. 1H NMR (200 MHz, CDCl3):  (ppm) 1.18 (s, 3H, CH3), 1.24(s, 3H, CH3), 1.25 (s, 1H, C1-H), 1.31 (t, J = 7.1Hz, 3H, C2-H3), 4.07 (q, J = 7.1Hz, 2H, C1-H2). 13C NMR (50 MHz, CDCl3): (ppm) 16.47 (C2), 23.46 (4CH3), 29.79 (C2, C3), 35.96 (C1), 59.45 (C1), 172.09 (C=O). HRMS: C10H18O2. Calculated = 170.1306; Found = 170.1308. Ethyl bicyclo[4.1.0]heptane-7-carboxylate. (6a+7a): Yield: 87%; Translucent liquid; b.p.: 115°C/12mm Hg. 1 H NMR (300 MHz, CDCl3):  (ppm) 1.05-1.98 (m, 11 H, C1H, C2-H2, C3-H2, C4-H2, C5-H2, C6-H, C7-H), 1.24 (t, J = 7.1Hz, 3H, C2-H3, endo), 1.27(t, J = 7,1Hz, 3H, C2-H3, exo), 4.10 (q, J = 7.1Hz, 2H, C1-H2, endo), 4.24(q, J = 7.1Hz, 2H, C1-H2, exo). 13C NMR (75 MHz, CDCl3): (ppm) 14.0 (2C2), 20.90 (2C3+2C4), 21.9 (2C1+2C6), 22.6 (2C2+2C5), 25.6 (2C7), 61.1 (2C1), 171.7 (C=O), 174.73 (C=O). HRMS: C10H16O2. Calculated = 168.115; Found = 168.114. Ethyl bicyclo[6.1.0]nonane-9-carboxylate. (6b+7b): Yield: 62%; Translucent liquid; b.p.: 105°C/1.5 mm Hg. 1 H NMR (200 MHz, CDCl3):  (ppm) 1.09 (m, 3H, C2-H, endo), 1.25 (t, 3H, J =7,1Hz, C2-H, exo), 1.29- 2.22 (m, 30H, C1-H, C2-H2, C3-H2, C4-H2, C5-H2, C6-H2, C7-H2, C8-H, C9-H), 4.09 (q, J =7.1Hz, 2H, C1-H, exo), 4.23(m, 2H, C1H, endo). 13C NMR (50 MHz, CDCl3): (ppm) 14.2 (C2), 14.3 (C2), 20.6 (C3+C6), 20.8 (C9), 24.4 (C9), 25.7 (C3+C6), 25.8 (C4+C5), 26.2 (C4+C5), 27.1 (2(C1+C8)), 29.0 (C2+C7), 29.1 (C2+C7), 59.5 (C1), 60.0 (C1), 172.23 (C=O), 174.29 (C=O). HRMS: C12H20O2. Calculated = 196.144; Found = 196.146. Ethyl Tricyclo[3.2.1.02,4] octane-3-carboxylate. (6c+7c): Yield: 62%; Translucent liquid; b.p.: 65°C/0.8 mm Hg. 1 H NMR (200 MHz, CDCl3):  (ppm) 0.6-1.9 (m, 24H, C2, C1H, C3-H, C5-H, C6-H2, C7-H2, C8-H2), 2.36 (sl, 2H, C2+C4), 2.51 (d, 2H, C2+C4), 4.03-4.13 (m, 4H, C1-H2). 13 C NMR (50 MHz, CDCl3): (ppm) 14.2 (2C2), 16.3

Stereoselective Cyclopropanation Under Solvent Free Conditions

(2C3), 25.9 (2(C2+C4)), 28.5 (2(C6+C7)), 28.7 (2C8), 35.6 (2(C1+C5)), 60.2 (2C1), 174.2 (2C=O). HRMS: C11H16O2. Calculated = 180.115; Found = 180.115. CONFLICT OF INTEREST The authors confirm that this article content has no conflict of interest.

Letters in Organic Chemistry, 2016, Vol. 13, No. 3 [17]

[18] [19]

ACKNOWLEDGEMENTS Special homage is given to the deceased Mohamed S. Ouali for his help to make a catalyst (BCu). We thank Pr. Peter G. Weidler from Karlsruhe Institute of Technology for his fruitful collaboration. Financial support by the Comité National d'Evaluation et de Programmation de la Recherche Universitaire (CNEPRU) is gratefully acknowledged.

[20] [21]

[22]

REFERENCES [1] [2] [3] [4] [5]

[6] [7] [8] [9]

[10] [11] [12] [13] [14] [15] [16]

Regitz, M.; Heydt, H. 1,3-Dipolar cycloaddition chemistry, Padwa A. Ed., John Wiley & sons, New York, 1984; Vol. 1. Bendeddouche, K.C.; Rechsteiner, B.; texier-Boullet, F.; Hamelin, J.; Benhaoua, H. Reactivity of ethyldiazoacetate towards alkenes under microwave irradiation. J. Chem. Res., 2002, 114-117. Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A.B. Stereoselective cyclopropanation reactions. Chem. Rev., 2003, 103, 977-1050. Pellissier, H. Recent developments in asymmetric cyclopropanation. Tetrahedron, 2008, 64, 7041-7095. Telalovi, S.; Hanefeld, U. Noncovalent immobilization of chiral cyclopropanation catalysts on mesoporous TUD-1: Comparison of liquid-phase and gas-phase ion-exchange. Appl. Catal., 2010, A 372, 217-223. Mloston, G.; Mucha, P.; Heimgartner H. Chiral imidazoles and imidazole N-oxides as ligands for stereoselective cyclopropanation reactions. Lett. Org. Chem., 2012, 9, 89-91. Nani, R. R.; Reisman, S. E. -Diazo--ketonitriles: Uniquely reactive substrates for arene and alkene cyclopropanation. J. Am. Chem., Soc., 2013, 135, 7304-7311. White, J. D.; Shaw, S. A new cobalt-salen catalyst for asymmetric cyclopropanation. synthesis of the serotonin-norepinephrine repuptake inhibitor (+)-synosutine. Org. Lett., 2014, 16, 3880-3883. Mugishima, N.; Kanomata, N.; Akutsu, N.; Kubota, H. Remote steric effects of C2 -symmetric planar-chiral terpyridine ligands on copper-catalyzed asymmetric cyclopropanation reactions. Tetrahedron Lett., 2015, 56, 1898-1903. Chen, D.Y.K.; Pouwer, R.H.; Richard, J.A. Recent advances in the total synthesis of cyclopropane-containing natural products. Chem. Soc. Rev., 2012, 41, 4631-4642. Doyle, M.P. Catalytic methods for metal carbene transformations. Chem. Rev., 1986, 86, 919-939. Doyle, M.P. Comprehensive Organometallic Chemistry II, Pergamon Eds., New York, 1995. Doyle, M.P.; McKervey, M.A.; Ye, T. Modern catalytic methods for organic synthesis with diazo compounds: from cyclopropanes to ylides, ed., Wiley, New York, 1998. Gnad, F.; Reiser, O. Synthesis and applications of aminocarboxylic acids containing a cyclopropane ring. Chem. Rev., 2003, 103, 1603-1624. Bendedouche, C.K.; Benhaoua, H. Copper-exchanged bentonite: a reusable catalysis for the formation of alkoxycarbonyl nitrile ylides under microwave irradiation. J. Chem. Res., 2012, 36, 149-151. Fraile, J.M.; Garcia, J.I.; Mayoral, J.A.; Tarnai, T. Asymmetric cyclopropanation catalysed by cationic bis(oxazoline)-CuII complexes exchanged into clays. Tetrahedron: Asymmetry, 1997, 8, 2089-2092.

[23] [24]

[25]

[26]

[27] [28]

[29]

[30]

[31] [32] [33] [34]

[35]

7

Fraile, J.M.; Garcia, B.; Garcia, J.I.; Mayoral, J.A.; Figueras, F. In: The use of heterogeneous copper catalysts in cyclopropanation reactions. Heterogeneous Catalysis and Fine Chemicals IV. In: Proceedings of the 4th international symposium on heterogeneous catalysis and fine chemicals. Basel, Switzerland 8-12 September 1996. Ed. Blaser, H.U.; Baiker A.; Prins R., 1997; 108; pp. 571-578. Kasmi, S.; Hamelin, J.; Benhaoua, H. Microwave-assisted solventfree synthesis of iminothiazolines. Tetrahedron Lett., 1998, 39, 8093-8096. Saoudi, A.; Hamelin, J.; Benhaoua, H. A rapid synthesis of aziridine derivatives over bentonite in 'dry media'. J. Chem. Res., 1996. 492-493. Hamelin, J.; Saoudi, A.; Benhaoua, H. Versatile transformations of ,-dibromoesters and ketones in basic media under microwave irradiation. Synthesis, 2003, 2185-2188. Maurya, R.A.; Kapure, J.S.; Adiyala, P.R.; Srikanth, P.S.; Chandrasekhar, D.; Kamal, A. Catalyst-free stereoselective cyclopropanation of electron deficient alkenes with ethyl diazoacetate. RSC Adv., 2013, 3, 15600-15603. Le Maux, P.; Abrunhosa, I.; Berchel, M.; Simonneaux, G.; Gulea, M.; Masson, S. Application of chiral 2,6-bis(thiazolinyl)pyridines in asymmetric Ru-catalyzed cyclopropanations with diazoesters. Tetrahedron: Asymmetry, 2004, 15, 2569-2573. Lowenthal, R.E.; Abiko, A.; Masamune, S. Asymmetric catalytic cyclopropanation of olefins: bis-oxazoline copper complexes Tetrahedron Lett., 1990, 31, 6005-6008. Diaz-Requejo, M.M.; Caballero, A.; Belderrain, T.R.; Nicasio, M.C.; Trofimenko, S.; Perez, P.J. Copper(I)-Homoscorpionate Catalysts for the preferential, kinetically controlled cis cyclopropanation of -olefins with ethyl diazoacetate. J. Am. Chem. Soc., 2002, 124, 978-983. Shitama, H.; Katsuki, T. Synthesis of metal-(pentadentate-Salen) complexes: Asymmetric epoxidation with aqueous hydrogen peroxide and asymmetric cyclopropanation (salenH2: N,Nbis(salicylidene)ethylene-1,2-diamine). Chem.--Eur. J., 2007, 13, 4849-4858. Bonaccorsi, C.; Bachmann, S.; Mazzetti, A. Electronic tuning of the PNNP ligand for the asymmetric cyclopropanation of olefins catalysed by [RuCl(PNNP)]+.Tetrahedron: Asymmerty, 2003, 14, 845-854. Uchida, T.; Katsuki, T. -Diazoacetates as carbene precursors: metallosalen-catalyzed asymmetric cyclopropanation. Synthesis, 2006, 1715-1723. Rosenberg, M.L.; Krivokapic, A.; Tilst, M. Highly cis-selective cyclopropanations with ethyl diazoacetate using a novel Rh(I) catalyst with a chelating N-heterocyclic iminocarbene ligand. Org. Lett., 2009, 11, 547-550. Gu, P.; Su, Y.; Wu, X.-P.; Sun, J.; Liu, W.; Xue, P.; Li, R. Enantioselective preparation of cis--azidocyclopropane esters by cyclopropanation of azido alkenes using a chiral dirhodium catalyst. Org. Lett., 2012, 14, 2246-2249. Doyle, M.P.; Dorow, R.L.; Buhro, W.E.; Griffin, J.H.; Tamblyn, W.H.; Trudell, M.L. Stereoselectivity of catalytic cyclopropanation reactions. Catalyst dependence in reactions of ethyl diazoacetate with alkenes. Organometallics, 1984, 3, 44-52. Cho, D.-J.; Jeon, S.-J.; Kim, H.-S.; Kim, T.-J. Catalytic cyclopropanation and aziridination of alkenes by a Cu(I) complex of ferrocenyldiimine. Synlett, 1998, 617-618. Hubert, A.J.; Noels, A.F.; Anciaux, A.J.; Teyssie, P. Rhodium(II) carboxylates: novel highly efficient catalysts for the cyclopropanation of alkenes with alkyl diazoacetates. Synthesis, 1976, 600-602. Rhodes, C.N.; Brown, D.R. Rapid determination of the cation exchange capacity of clays using Co(II). Clay Miner., 1994, 29, 799-801. Adams, J.M.; Ballantine, J.A.; Graham, S.H.; Laub, R.J.; Purnell, J.H.; Reid, PI.; Shaman, W.Y.M.; Thomas, J.M. Selective chemical conversions using sheet silicate intercalates: Low-temperature addition of water to 1-alkenes. J. Catal., 1979, 58, 238-252. Adams, J.M.; Clapp, T.V. Reactions of the conjugated dienes butadiene and isoprene alone and with methanol over ion-exchanged montmorillonites. Clays Clay Miner., 1986, 34, 287-294.