Photoinduced Addition Reactions in Aqueous Media

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Current Organic Chemistry, 2012, 16, 2354-2364

Photoinduced Addition Reactions in Aqueous Media Sebastián Barata-Vallejo and Al Postigo* Departamento de Química Orgánica-Facultad de Farmacia y Bioquímica-Universidad de Buenos Aires-Junín 954-CP 1113-Buenos Aires-Argentina Abstract: The scope of this account on addition reactions in aqueous media is to demonstrate that the syntheses of useful targets or functionalizations can be accomplished through photoaddition reactions in benign environments. Ammination reactions of olefins and constrained cycloalkanes, addition products derived from quinonemethides, aromatic arylation reactions of furanones and alkenes, and radical addition reactions to ,!-unsaturated aldehydes performed in aqueous media constitute valuable reactions and hence interesting synthetic targets in organic syntheses. In studying these synthetic targets, different light sources are employed to achieve excitation. Also, photoinduced electron transfer sequences will account for the addition products. This account does exclude the photoaddition reactions performed by the aid of metals or metallic complexes, or the addition of perfluoroalkyl radicals to carbon-carbon and carbon-heteroatom multiple bonds in aqueous media.

Keywords: Photoaddition in aqueous media, Photoinduced electron transfer addition in aqueous media, Radical additions in aqueous media. INTRODUCTION Carbon-carbon bond formation reactions are considered seminal reactions in Organic Synthesis. The plethoras of reactions that can accomplish homologation or carbon-chain elongation are central to Organic Chemistry. The need to resort to environmentally friendlier solvents has urged chemists to move out from conventional organic solvents and replace them gradually by benign options, such as water or low-impact media. This does not only carry environmental safeguards, but also is accompanied by reduction costs, particularly in large scale and industrial syntheses. Addition reactions to carbon-carbon multiple bonds have been traditional a recourse to performing homologation or carbon extension. Lately, these reactions have been performed in water or aqueous media. In particular, radical addition reactions of carboncentered radicals to multiple carbon-carbon (and carbonheteroatom) bonds have shown a significant scope in this sense. To that effect, interesting review articles have appeared in the literature summarizing these types of reactions [1]. Radical photoaddition reactions onto carbon-carbon multiple bonds in water as solvent have been recently reported employing perfluoroalkyl radicals and electron-poor and -rich olefins and alkynes [2]. Addition reactions of perfluoroalkyl radicals in aqueous media have also been reviewed very recently [3]. Radical addition reactions mediated by metals in aqueous media have also been the subject of recent review articles [1a]. This account will deal with photoaddition reactions in aqueous media leading to carbon-carbon bond formation, with the exclusion of metal-mediated photoaddition reactions. It is interesting to note that in performing these photoaddition reactions, not only radicals are postulated as discrete intermediates, but also cations and radical ion species such as radical cations and radical anions are proposed as intermediates generated these latter through photoinduced electron-transfer reactions. In this sense, the diverse reaction pathways

*Address correspondence of this author at the Departamento de Química OrgánicaFacultad de Farmacia y Bioquímica-Universidad de Buenos Aires-Junín 954-CP 1113Buenos Aires-Argentina; Tel: 86-551-5107342; Fax: +54 011 4964-8252; E-mail: [email protected]

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that photoaddition reactions can display in aqueous media expand of indenes and dihydronaphthalenes classical methodologies. It is also interesting to point out that a parallel reactivity behavior of addition reactions in organic media and aqueous environment can be established. However, distinct aspects of regioselectivity and enantioselectivity will be highlighted when comparing the photoaddition reactions in organic solvents. 1. PHOTOSENSITISED AMINATIONS OF BENZOCYCLOALKADIENES, ARYLCYCLOPROPANES, AND QUADRICYCLANES WITH AMMONIA Dinnocenzo et al. have reported that the photoinduced nucleophilic addition of MeOH to the arylcyclopropanes in MeCN preceded via the nucleophilic attack on the cation radicals of the ringclosed cyclopropanes [4]. Roth et al. have reported the detailed product analysis for the para-dicyanobenzene-photosensitized (p-DCB-) nucleophilic addition of MeOH to arylcyclopropanes, which gave several types of the MeOH adducts [5]. Yasuda, Yamashita and collaborators [6], on the other hand, accomplished the photoamination of indenes, dihydronaphthalenes, and substituted cyclopropanes, through a redox-photosensitized reaction in the presence of ammonia [6]. The photosensitization takes place in the presence of 1,2,4tetrapehnylbenzene (1,2,4-TPB) and m-dicyanobenzene (m-DCB) as sensitizers. The 1,2,4-TPB-photosensitized amination of 2methylindene (1b), 3,4- dihydronaphthalene (1c), and 1,2-benzo1,3-cycloheptadiene (1d) with NH3 gave 2-amino-2-methylindan (2b), 2-amino-1,2,3,4-tetrahydronaphthalene (2c), and 4-amino1,2-benzocycloheptene (2d), respectively, in high yields compared with the photoamination without sensitizers, according to Scheme 1.1 [6]. The redox photosensitization was applied to the amination of arylcyclopropanes (3a-e) (Scheme 1.2). The amination of 1,2diphenylcyclopropane (3a) photosensitized by a pair of 1,2,4-TPB and m-DCB gave 1-amino-1,3-diphenylpropane (4a) in high yield compared with the use of other photosensitizers and the photoamination without the sensitizer [6]. © 2012 Bentham Science Publishers

Current Organic Chemistry, 2012, Vol. 16, No. 20

Photoinduced Addition Reactions in Aqueous Media

R1

h R1

R2NH2

+

NHR2

ArH, m-DCB MeCN-H2O 1a R1=H 1b R1=Me

2355

2a R1=H, R2=H (79%) 2b R1=Me, R2=H (83%) 2e R1=H, R2=i-Pr (52%) 2f R1=H, R2=t-Bu (49%) NH2

h +

NH3

1,2,4-TPB m-DCB MeCN-H2O

n 1c n=1 1b n=2

n

2c n=1 (63%) 2d n=2 (57%)

Scheme 1.1. Photosensitized amination in MeCN-H 2O.

NH2 h , ArH, m-DCB NH3

+ Ar

Ar

Ar

Ar Et4NBF4 MeCN-H2O

3a Ar=Ph 3b Ar=4-MeOC6H4-

4a Ar=Ph (71%) 4b Ar=4-MeOC6H4- (90%) NH2

h , ArH, m-DCB + MepOC6H4

NH3

MepOC6H4

Ph

NH2

+ Ph

MepOC6H4

Ph

Et4NBF4 MeCN-H2O 3c

4c (61%)

4c´(18%)

Scheme 1.2. Photosensitized amination of aryl-substituted cyclopropanes in MeCN-H2O.

Therefore, the initiation step should be an electron transfer from the excited singlet states of ArH (1ArH*) to mDCB, resulting in the cation radicals of ArH (ArH+•) and the anion radical of DCB (DCB • ). This mechanism is confirmed from the following experiments: the fluorescences of ArH were quenched by DCB at nearly diffusion-controlled rates, and the free energy changes ( G) for the electron transfer were calculated to be negative or slightly positive by the Rehm-Weller equation. The nucleophilic addition of NH3 at the ring-closed cation radicals of 3 gave the aminated radicals, which were reduced by DCB -• after the deprotonation and then followed by the protonation to give the aminated products (4) [6]. 2. PHOTOCHEMICAL ADDITION PRODUCTS FROM QUINOME METHIDES IN AQUEOUS SYSTEMS Quinone methides (QM) are ubiquitous intermediates in chemistry and biology [7]. The polar nature of these compounds makes them both nucleophilic and electrophilic [8]. o-QMs in particular behave chemically as !,"-unsaturated ketones. It has been suggested that QMs play a critical role in the biological action of several classes of antibiotics such as mitomycin and anthracyclines [9]. Furthermore, QMs react with nucleic acids [10] and amino acids [11]. It is now well-established that QMs can act as DNA cross-linking agents and are believed to be responsible

for the cytotoxicity of antitumor antibiotics of mitomycin C and anthracycline families [12,13]. The most common reaction of QMs is with nucleophilic solvent (e.g., water) wherein they behave as Michael systems (e.g., eq 1). Nucleophiles add to the methylene position of QMs, and the driving force of the reaction is the resulting rearomatization of the molecule. One approach for the generation of QMs under mild conditions is the use of photochemical reactions [14]. Wan et al. developed a general photochemical method for the generation of QMs by dehydration of hydroxymethylphenols (e.g., eqs 1-3) [15,16]. On excitation of phenols 5 and 5´, (eq 1), excited-state intramolecular proton transfer (ESIPT) from the phenol OH to the hydroxyl group, coupled with a loss of H2O, takes place. That delivers QM 6 and 6´ (eq 1) which react with nucleophilic solvents giving solvolysis products 7 and 7´ (eq 1), respectively [17]. A protic solvent is required to mediate the excited-state deprotonation of the phenol moiety and the protonation of the alcohol. Photolysis of phenol-adamantanes, AdPh, in MeOH should give rise to methanolysis products via QM intermediates. Wan and collaborators [8] performed photolyses (254 nm, argon-purged) of AdPh 12-14 in MeOH-H2O (3:1) and neat MeOH, according to equations 4 and 5.

2356 Current Organic Chemistry, 2012, Vol. 16, No. 20

OH

Barata-Vallejo and Al Postigo

OH

O

OH

h

CH

HNu

R

Nu CH

(1)

R

R

5 R=H 5´ R=Ph

6 R=H 6´ R=Ph

7 R=H 7´ R=Ph

OH

O

h

(2) CH

H2O

OH

CH

R

R

8 R=H 8´R=Ph

9 R=H 9 R=Ph O

OH

h (3) H2O R

CH(R)OH 10 R=H 10´R=Ph

11 R=H 11 R=Ph

OH

OH OH

h

OMe (4)

MeOH : H2O 3:1 12 o14 p-

12b o14b p-

OH

H OH

h

H

HO

OMe

OH

OH (5)

+

MeOH : H2O 3:1 13

Compounds 12 and 14 underwent methanolysis to render products 12b and 14b, respectively [8]. The authors observed formation of the rearranged alcohol 13c on photolysis of 13, irradiations of 12 and 14 were also carried out in MeCN-H2O 3:1 to check for the possibility of rearranged alcohols due to an analogous rearrangement. Formation of the rearranged alcohols 15ac, and 16ac (eq 6) suggests the intermediacy of the carbocations that could arise via an acid-catalyzed protonation of the alcohol moiety and dehydration (vide infra). It is known that in the neutral aqueous media singlet excitedstate phenols deprotonate, whereas in MeCN it does not occur since MeCN cannot solvate protons [18]. Therefore, addition of H2O to the MeCN solution of ohydroxymethylphenols can in principle change the mechanism of

13c

13d

the proton transfer from intrinsic ESIPT to H2O-mediated ESPT giving rise to phenolates. In addition, for the meta and the para derivatives, H2O-mediated ESPT giving rise to dehydration and QMs can become operative [17,19]. The influence of added H2 O and the change of the photochemical reaction mechanism was evidenced by the authors [8] from fluorescence which is being quenched [20]. The authors [8] also investigated the influence of added H2O on the photochemistry of AdPh, exploring the fluorescence titrations of the MeCN solutions of 14-16 with H2O. On addition of H2O no changes to the maxima in the absorption spectra could be detected [8]. The emission maxima shifted 2 nm batochromically due to a weak stabilization of the excited state by H-bonding. The increase of the fluorescence for the ortho derivative 14 may be ascribed to the disruption of the intramolecular H-bond between the phenol OH



2357

H

OH OMe

OMe

h

HO

(6)

H

MeOH : H2O 3:1

15a m 16a p-

15ac m16ac pOR

15 or 15a

OR

OR

h

H

H2O

H

OR HO

H

H

H !+

15+ R=H 15a+R=Me

15´+ R=H 15a´+R=Me

15´´+ R=H 15a´´+R=Me

15c R=H 15ac R=Me

Scheme 2.1. Mechanism for the rearranged product formation from 1-hydroxy-1-(3-methoxyphenyl)-adamantane 15.

O OH

h

O

O

18 X

HO

H2O

HO

OH

h 17a-c

OH HO 17a

Scheme 2.2. Formation of product 17a.

and the alcohol, which decreases quantum yield of the intrinsic ESIPT. According to the well-known meta-effect in photochemistry [21], the adamantylphenyl in the singlet excited state is probably more electron donating in the meta position than in the para. Hence, 15 is probably less acidic in the singlet excited state than 16. Thus, as the acidity of the solution of 15 is approaching the equilibrium pKa*, the phenol moiety should deprotonate less in the excited state, resulting in the increase of the fluorescence. According to the authors [8], the phenolic OH group in AdPh 8 is intramolecularly hydrogen- bonded to the oxygen atom of the alcohol OH group. The presence of the intramolecular H-bond suggests that on excitation of 12, an efficient ESIPT takes place. Indeed, it is shown that dehydration of 12 giving rise to 12QM is an efficient process. The lower limit for the quantum yield of the photochemical formation of 12QM is 0.51, as determined for the methanolysis reaction giving 12b. The authors [8] argued that the free phenolic OH is required for the efficient formation of the photosolvolysis products. Furthermore, comparing photochemical reactivity of 5, and 12, (judged by the values of the quantum yield for the QM formation), clearly shows that 12 is the most reactive. That may be ascribed to the electron-donating effect of the adamantyl substituent which stabilizes the QM structure.

The mechanism of photochemical reaction of 13and 14 clearly has to be different from 12, since the phenolic OH is further away from the alcohol moiety. Intramolecular hydrogen bonding cannot exist; hence, the presence of a protic solvent is required to ferry the proton from the acidic to the basic site. Compound 15 upon irradiation in MeOH-H2O, undergoes solvolysis to render the benzylic cation 15+ , which is transposed to secondary cation 15´´+ , which suffers ulterior attack by water to render product 15c. In another study by Popik and collaborators [22], prolonged irradiation of an aqueous solution of o-QM precursor 17a (pH 7) with 300 nm light yielded methyl-p-benzoquinone 18 as the only photoproduct. The quantum yield of the formation of 18 is 17a = 0.060 ± 0.005. Since competing hydration of the o-QM 1 regenerates the starting material 17a and thus is undetectable (Scheme 2.2). The authors [22] have explored the aqueous photochemistry of the corresponding ethyl ether 17b. Low conversion ( 15%) photolysis of 17b in aqueous biphosphate buffer solutions at pH 7 yielded diol 17a as the major product (76%) and 2-methyl-1,4-benzoquinone (18) as the minor product (19%) with quantum efficiency 3b=0.31 ( 0.01 (Scheme 2.2) [22]. Photolysis of aqueous solutions of o-QM precursor 19a with 300 nm light did not produce any detectable amounts of new products due to the rapid and efficient rehydration of QM 20 to yield



OH OH MeO OH

AcO-/AcOH

X

MeO

19c

O

h MeO

OH OAC

MeO 19a-c

20

19d

Scheme 2.3. Formation of product 19a.

N

N

N h +

+

O O

MeCN: H2O 89% O

O 21

22

23a

O

O

23b

9:1

Scheme 3.1. Photoinduced addition of naphthylamine derivatives to furanones.

back the starting material. On the other hand, irradiation of the aqueous solution of ethyl ether 19b resulted in a rapid consumption of the substrates and the formation of 19a (Scheme 2.3) [22]. The reactivity of o-QMs 20 resembles that of other o-quinone methides albeit with reduced nucleophilicity. In aqueous solution it undergoes efficient rehydration back to 19a and this reaction is catalyzed by both hydroxide and hydronium ions. In the case of o-QMs 1, addition of water to give 18a competes with tautomerization to form methyl-p-quinone (18). This is a rather unique phenomenon, as the same carbon atom shows both electrophilic (addition of water) and nucleophilic (protonation) reactivity. The ketonization reaction shows pronounced general acid catalysis. Both o-QMs readily react with other nucleophiles such as azide anion and undergo efficient Diels-Alder cycloaddition to electron-rich olefins. 3. PHOTOINDUCED ELECTRON TRANSFER-MEDIATED ADDITION IN AQUEOUS MEDIA Hoffmann and collaborators introduced the photochemical electron transfer addition of naphthylamine derivatives to electron deficient alkenes [23]. Using photochemical electron transfer, N,Ndimethylnaphthylamine derivatives are added to ,!-unsaturated carboxylates (Scheme 3.1). The addition takes place exclusively in the -position of electron-deficient alkenes and mainly in the 4position of N,N-dimethylnaphthalen-1-amine. A physicochemical study reveals that the fluorescence quenching of N,Ndimethylnaphthalen-1-amine is diffusion-controlled and that the back electron transfer is highly efficient. Therefore no transformation is observed at lower concentrations. To overcome this limitation and to induce an efficient conversion, minor amounts of water or another proton donor as well as an excess of the naphthylamine derivative are necessary [23]. A mechanism involving a contact radical ion pair is discussed. The hydrogen transfer to the furanone moiety observed in the overall reaction therefore results from an exchange with the reaction medium. An electrophilic oxoallyl radi-

cal (Scheme 3.2) generated from the furanone reacts with the naphthylamine used in excess. Concerning some mechanistic details, the reaction is compared with radical and electrophilic aromatic substitutions. The transformation was carried out with a variety of electron-deficient alkenes [23]. In electrophilic substitutions in the ground state of such naphthalene derivatives carrying an electron-donating substituent in the 1-position, the transformation in position 2 dominates over the one in position 5 [24,25]. Using the Norrish type II reaction of butyrophenone as actinometer [26,27], the authors [23] have measured a product quantum yield of 0.1 for the optimized reaction conditions (Scheme 3.1). It must be pointed out that the quantum yield decreases significantly when the naphthylamine concentration is diminished. Upon addition of 1% of bidistilled water to the fluorophorequencher solutions, no spectral changes were detected [23]. The recorded absorption and fluorescence spectra do not give any indication for complex formation in ground or excited state, so that exciplex formation is not thought to occur under the conditions applied. Within experimental error, the quenching constants determined from quantum yields and lifetime measurements are identical to the ones obtained in the case where no water was added. The observations indicate that water has no influence on the primary quenching step. In order to give further support for the ET mechanism in the addition reaction of naphthylamine derivatives to furanones, the authors [23] employed the Rhem-Weller equation (eq 7) so as to see whether the Gibbs energy change in the ET process ("GET) is spontaneous or not.

Go = E(D/D+) - E(A/A-) - E* + Z1Z2 !r12

(7)

Where E(D/D+) is the redox potential of the donor, and E(A/A-) the redox potential of the acceptor, E* the singlet excited state energy



1

N

O

N

O

2359

*

h

21

O

O

+ 22

22

1

O

N

O

N +D2O -DO-

I

2

N

2

N O Ox O -H+

O 24

D O

H O III

21

II

D

D O

Scheme 3.2. Mechanism for the PET addition of naphthylamine derivatives to furanones in MeCN : H2O.

of the aromatic amine, and the last term represents the coulombic energy necessary to form an ion pair with charges Z1 and Z2 in the medium of dielectric constant at a distance r12. The redox potentials of the substrates have been determined by cyclic voltametry (vs. ferrocene/ferrocenium): Ep(1+/1) = +0.39 V, Ep(2/2_) = _2.75 V. The energy gap between the frontier orbitals (E0_0) approximately corresponds to the excitation energy, which can be determined by UV_vis spectroscopy. Especially in cases of low Stokes shifts, a better value of the HOMO/LUMO energy difference is obtained when the 0_0 transition between the S0 and the S1 potential energy surface is determined from UV_vis absorption and fluorescence spectra. The corresponding energy of 3.39 eV is determined from the intersection ( inter = 365 nm) of the absorption and the normalized emission spectra. The value for w is +0.12 eV. This term corresponds to the free enthalpy gained by bringing the ions to encounter distance in acetonitrile as solvent [28]. In contrast, cyclic voltametry is considered to take into account free ions. The productivity of photochemical electron transfer mediated reactions frequently suffers from back electron transfer, which leads to the regeneration of the substrates. In our case, this electron transfer is efficient. To induce a chemical reaction, a competitive trapping process is needed. Protonation of the radical anion by the reaction medium fulfills this task and leads to the radical cation I and the oxoallyl radical II. Obviously, proton transfer from the radical cation to the radical anion (Scheme 3.2). Electrophilic oxoallyl radicals such as II are easily trapped by nucleophilic reaction partners [29-31]. In the present case, this occurs through addition of the naphthylamine derivative 21, which is

therefore needed in excess. Despite the trapping process and as indicated by the product quantum yield (! = 0.1) and the efficient fluorescence quenching of 21 by the furanone 22, about 90% of the radical ion pair reacts via back electron transfer to regenerate the substrates 21 and 22 (Scheme 3.2). As in the case of "-aminoalkyl radicals [32-34], the resulting intermediate III is easily oxidized, and after deprotonation, the final product 23a is obtained. In positions in which electrophilic substitution can occur, the lowest electron density is detected in position 4 (-0.106). The electron density in position 2 (-0.172) is significantly higher than that in position 5 (-0.127). A relatively low electron density is also detected in position 8 (-0.128). Most probably, due to steric hindrance, no reaction occurs in this position [35]. 4. ADDITION OF -OXY AND , -DIOXY SUBSTITUTED RADICALS TO ,!-UNSATURATED ALDEHYDES BY MEANS OF PHOTOSENSITISED HYDROGEN TRANSFER FROM ALCOHOLS AND 1,3-DIOXOLANES IN AQUEOUS MEDIA Fagnoni, Albini and collaborators [36] have accomplished the generation of alkyl radicals from precursors RH through hydrogen abstraction by an excited sensitizer (Sens*). The radical thus formed attacks the electrophilic olefin in the # position and finally yields the alkylated aldehydes. As radical sources, the authors chose 1,3-dioxolane derivatives and alcohols. As water-soluble sensitizer, benzophenone disodium disulfonate was chosen. The scope of the reaction is depicted in Scheme 4.1. The irradiation took place at 315 nm.



R1 ´R h

CHO R1

O

O

R2

5. PHOTOARYLATIONS OF ALKENES VIA PHENYL CATIONS IN AQUEOUS MEDIA

CHO

Albini and Fagnoni have introduced the photoarylation reactions via phenyl cations in the presence of excess nucleophiles [37].

R2

More recently, the same authors undertook the use of water as a (co)solvent in the photoarylation reactions employing N,Ndimethylaniline derivatives [38]. This was possible because the intermediate triplet 4-N,N-dimethylaminophenyl cation was known not to react with water or alcohols [39]. Adding water reduced the amount of organic solvents gave further advantages, that is that highly polar water both favored the photoheterolytic step [40] and buffered the acidity produced in the reaction, allowing a base to be omitted.

O O ´R 25a 25b 25c 25

R1=H, R2=H 26k R´=H R1=Me, R2=H 26l R´=Me R1=nPropyl, R2=H 26m R´=ethyl

3

Scheme 4.1. Radical Addition to unsaturated aldehydes.

Albini and collaborators had accomplished arylation reactions via phenyl cation [39,40] by using a 0.05 M solution of ArX in the presence of a large excess of the nucleophiles (0.5-1 M). Gradually, water has been employed as a (co)solvent in these reactions. By a series of elegant studies, the authors have shown that (i) the arylation reaction is effective also under solar light irradiation, (ii) aqueous acetonitrile and acetone could be likewise used as reaction media, (iii) the concentration of the starting chloride can be increased up to 0.2 M, and (iv) the molar excess of the nucleophile can be lowered. The reaction with alkenes was next tested [38], namely, with "methylstyrene (31), allyltrimethylsilane (32), 1-methoxy-1[(trimethylsilyl)oxy]propene (33), 4-pentenoic acid (34), and ethyl vinyl ether (35), Scheme 5.1 [38].

-butyrolactones were synthesized using alcohols as radical precursors, as opposed to 1,3-dioxolane [36]. The alcohols employed were 2-propanol, ethanol, and methanol, according to Scheme 4.2. The general reaction mechanism is depicted in Scheme 4.3. The excited photosensitizer (benzophenone disodium disulfonate) abstracts a H atom from the alcohol or 1,3-dioxolane, to render al alkyl radical which adds to the !-position of the aldehyde, rendering a radical adduct that abstracts H to form the product. The mild conditions of photosensitization appear well suited for the radical alkylation of such sensitive substrates as unsaturated aldehydes. Promotion of the sensitizer to the triplet state leads to hydrogen abstraction from the donors (RH) and radical R• is trapped by the unsaturated aldehydes leading to an adduct radical. The sequence is completed by hydrogen abstraction from either the ketyl radical or a reagent, such as RH, or the solvent. The first two paths do not consume the sensitizer stoichiometrically. The present reaction is efficient by using the sensitizer at a sub stoichiometric concentration (20–40%), and the relative independence of the results on the structure of R–H suggests that path a is the most important one. Path c, on the contrary, leads to stoichiometric consumption of the sensitizer and produces pinacols [36].

Another synthetic application of phenyl cations is the reaction with vinyl ethers (e.g., ethyl vinyl ether, 35, Scheme 5.1) where the stabilized cation, resulting from the attack onto the alkene, adds a nucleophilic solvent such as methanol [38]. The exploration was extended to the activation of the Ar-F bond and new arylations were found in the solar light-induced reactions of 4-fluoro-N,N-dimethyl aniline (41, Scheme 5.2) [38].

R4 CHO R1

R4 +

R2

a

R4

OH H

R3

OH R3

R3

OH

R4 b

R3

O

O

O

h R1

R2

R1

R2

28a R3=R4=Me 28b R3=Me, R4=H 28c R3=R4=H

25

O

R2

R1

29

30

Scheme 4.2. Photosensitized alkylation of unsaturated aldehydes using open-chain alcohols to afford -butyrolactones in aqueous media.

Sens*

Sens-H

[H] R

R-H

+ CHO

O R= O

R´

R4 or

OH

R3

Scheme 4.3. General mechanism for the photosensitized alkylation of unsaturated aldehydes.

R

CHO

R

CHO



36, 63%

Ar

Ar

2361

31

MeO 40, 60%

37, 51%

Ar OEt

OEt NMe2

35

SiMe3 32

Me3SiO

CO2H 34

33

MeO

Ar

O O

38, 58%

39, 71%

COOMe

Ar

Scheme 5.1. Reaction of N,N-dimethylaminophenyl cation with -methylstyrene (31), allyltrimethylsilane (32), 1-methoxy-1- [(trimethylsilyl)oxy]propene (33), 4-pentenoic acid (34), and ethyl vinyl ether (35).

NMe2 sunlight, 35

sunlight, 32 37

40 H2O:MeCN

MeOH, Cs2CO3 F 41

Scheme 5.2. Reaction of N,N-dimethylamino-4-fluorobenzene with allyltrimethylsilane (32), and ethyl vinyl ether (35).

6. PHOTOINDUCED TANDEM THREE-COMPONENT ADDITION OF PROPANEDINITRILE AND CYANOARENES TO 2,5-DIMETHYLHEXA-2,4-DIENE Mizuno and collaborators [41] achieved the tandem threecomponent coupling photoreaction consisting in a photoirradiation of MeCN/H2O solutions containing propanedinitrile (42, malononitrile), 2,5-dimethylhexa-2,4-diene (43), and polycyanoarenes in the presence of phenanthrene and carbonate, leading to selective monoalkylation of 42. The reaction proceeds via photo-NOCAS

(Nucleophile-Olefin Combination, Aromatic Substitution) type mechanism: nucleophilic attack of the anion of 42 to photogenerated 43•+ is followed by ipso-substitution on the radical anion of the polycyanoarene (Scheme 6.1). It advances under mild, safe, and environmentally friendly conditions such as proceeding at ambient temperature without metals and halogens, and in the presence of weak base [42]. Thus, photoirradiation of an aqueous acetonitrile solution containing malononitrile (42), 2,5-dimethylhexa-2,4-diene (43), and pdicyanobenzene (p-44) in the presence of phenanthrene (Phen)[42] and an excess amount of sodium carbonate gives a good yield of three-component coupling product p-45 (87% based on the amount of p-44 used) along with propanedinitrile-incorporated dimer 46 (25% based on the amount of 43 used) (Scheme 6.2). The use of odicyanobenzene (o-44) also results in the formation of corresponding photoproduct o-45 (52%) together with dimer 46 (37%), while m-dicyanobenzene (m-44) affords a better yield of 45 (47%) as the sole product. The authors [43] propose that the reaction is promoted by single electron transfer (SET) from the excited singlet state of Phen CN

CN NC

CN

+

+

h / Phen + CN

MeCN-H2O Na2CO3, rt, 20 h NC NC

42

43

44 (o, m, p)

Scheme 6.1. Three-component reaction between 42, 43, and 44.

45

CN

CN NC

46

CN



CN CN CN

-CN-

PET 44 1Phen*

CN

CN NC

Phen

CN

B-

45

NC

CN

h

44

Phen 43

dimerization

46

43 NC NC

CN A

CN

NC

NC

CN

CN

42

NC

CN

Scheme 6.2. Mechanism for the NOCAS type product from coupling of 42, 43 and 44.

(1Phen*) to 44, followed by a secondary SET from 43 to Phen•+ (Scheme 6.2) [42]. SET from Phen or 43 to 144* can also take place. These processes afford 43•+, which is trapped by the anion of 42 to form an allylic radical intermediate A• (path I). An alternative pathway might involve SET from the anion of 42 to Phen•+, followed by coupling of the resulting radical with 43 to form A• (path II, Scheme 6.3). Radical coupling between A• and 44•- takes place to give B-. Stabilization of the anion charge of B- by a cyano group on the ortho- or para-position of the former benzene ring is crucial for the success of the radical coupling. Elimination of cyanide ion from the ipso-position of B- regenerates the aromaticity of the benzene ring to afford three-component coupling product 45 [44]. If A• diffuses out of the solvent cage, it dimerizes regioselectively at its terminal position to produce 46, a result that correlates with the relative stabilities of the three possible dimers. Phen

NC

Phen

CN

NC

CN

photoinduced cross coupling under mild and safe conditions such as ambient temperature and in the presence of water and weak base, employing a cyano group as a leaving group. CONCLUSIONS Photoinduced addition reactions in aqueous media show significant applications and scope, both in accomplishing new carboncarbon bond formation in a benign environment in the absence of metals, and for bypassing significant activation energy barriers for producing necessary reaction intermediates common in non-polar reactions. Of note are the solar-activated additions of aryl cations onto unsaturated carbon-carbon centers in aqueous media, and the electron transfer-mediated addition of aryl radicals onto furanonederivatives. From these perspectives, it is apparent that these photoinduced transformations can progress through significantly different reaction mechanism, widening the synthetic applications and scope. Thus, electron transfer addition reactions involving radical cation and radical anion species, reactions through phenyl radical intermediates, and those involving discrete radicals can account for the observed addition products in aqueous media. CONFLICT OF INTEREST The author(s) confirm that this article has no conflicts of inter-

Na2CO3

est. 43

ACKNOWLEDGEMENTS Declared none. NC

CN

REFERENCES

42

[1]

NC

CN A

Scheme 6.3. Plausible Mechanism for the Formation of A• via Path II.

This tandem three-component reaction not only broadens the synthetic usability of the photochemical -monoalkylation method of 42 that we have reported [45], but also enables us to accomplish

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Received: June 26, 2012

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Revised: August 09, 2012

Accepted: August 09, 2012