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CC BY ND NC 4.0 · Synlett 2019; 30(04): 511-514
DOI: 10.1055/s-0037-1612230
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Photoinduced 1,2-Hydro(cyanomethylation) of Alkenes with a Cyanomethylphosphonium Ylide

,
Daisuke Moriyama
,
Yuuta Funakoshi
,
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Katsura, Kyoto 615-8510, Japan   Email: tmiura@sbchem.kyoto-u.ac.jp   Email: murakami@sbchem.kyoto-u.ac.jp
› Author Affiliations

This work was supported by JSPS KAKENHI [Scientific Research (S) (15H05756) and (C) (16K05694)]
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Publication History

Received: 22 December 2018

Accepted after revision:23.01.2019

Publication Date:
13 February 2019 (online)

 


Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue

Abstract

An efficient method has been developed for the 1,2-hydro(cyanomethylation) of alkenes, in which a cyanomethyl radical species is generated from a cyanomethylphosphonium ylide by irradiation with visible light in the presence of an iridium complex, a thiol, and ascorbic acid. The cyanomethyl radical species then adds across the C=C double bond of an alkene to form an elongated alkyl radical species that accepts a hydrogen atom from the thiol to produce an elongated aliphatic nitrile. The ascorbic acid acts as the reductant to complete the catalytic cycle.


Radical chemistry has undergone a renaissance since the introduction of photoredox catalysis,[1] and a wide variety of reagents are now available as competent precursors to radical species. We recently reported that an ester-stabilized phosphonium ylide[2] can act as a precursor to an (alkoxycarbonyl)methyl radical species[3] when irradiated with visible light in the presence of an iridium catalyst, a thiol, and ascorbic acid.[4] The radical species, substituted by an electron-withdrawing alkoxycarbonyl group, adds across the C=C double bond of an alkene to generate an elongated alkyl radical. Subsequently, the thiol delivers a hydrogen atom to the radical,[5] producing an elongated aliphatic ester.[6]

We also examined the use of a cyanomethylphosphonium ylide instead of an ester-stabilized phosphonium ylide. The former act as the precursor of a cyanomethyl radical species[7] [8] [9] [10] that, due to the electron-withdrawing nature of the cyano group, is sufficiently electrophilic to attach to a C=C double bond of an alkene, as in the case of an (alkoxycarbonyl)methyl radical.[3,4,6] The appended alkyl radical species is not as electrophilic as the original cyanomethyl radical, and can therefore abstract a hydrogen atom from a sulfanyl group[5] to form an elongated aliphatic nitrile.

Initially, we applied the conditions optimized for the reaction of an ester-stabilized phosphonium ylide[4] to the reaction of the cyanomethylphosphonium ylide 2 with 4-phenylbut-1-ene (1a), and we obtained 6-phenylhexanenitrile (3a) as expected. The yield, however, was moderate (43% by NMR), which led us to adapt the reaction conditions slightly to fit the ylide 2. The elongated nitrile 3a was produced in 94% NMR yield and 80% isolated yield when 1a (0.50 mmol) was treated with 2 (1.0 mmol, 2.0 equiv) in 1:1 CH3CN/H2O (0.1 M) under irradiation by blue light-emitting diodes (LEDs; 470 nm, 23 W) in the presence of fac-Ir(ppy)3 (1.0 mol%; ppy = 2-phenylpyridinato), C6F5SH (20 mol%), ascorbic acid (10 equiv), and KHSO4 (3.0 equiv) at room temperature for 40 hours (Scheme [1]). No product resulting from 1,2-addition in the opposite direction was observable within the detection limits of 1H NMR (400 MHz). A larger-scale experiment using 925 mg (7.0 mmol) of 1a also gave a comparable yield of 3a (83% isolated yield), indicating the scalability of the present reaction.

Zoom
Scheme 1 1,2-Hydro(cyanomethylation) of alkene 1a with phosphonium ylide 2

The formation of the product 3a can be reasonably explained by assuming the radical mechanism depicted in Scheme [2], which is similar to that proposed in the case of ester-stabilized phosphonium ylides.[4] First, an acid/base ­reaction of 2 (pK aH = 6.9)[11] with ascorbic acid (AscH2; pK a= 4.0)[12] generates the phosphonium ascorbate [Ph3PCH2CN]+[AscH] (4). This has an energetically low-lying σ* orbital for the C–P linkage. The Ir catalyst [fac-Ir(ppy)3] [Ir(III)] is photoexcited by visible light to form the excited species [Ir(III)]*. This then transfers a single electron to the σ* orbital of the phosphonium ascorbate 4, giving rise to the cyanomethyl radical species 5, along with PPh3 and [Ir(IV)]+[AscH]. Electrophilic addition of 5 to the C=C double bond of alkene 1a affords the elongated secondary alkyl radical species 6, which is less electrophilic than 5. Hydrogen-atom transfer from C6F5SH to 6 produces 3a and a thiyl radical (C6F5S).[5] The [Ir(IV)]+ species and C6F5S are reduced back to the [Ir(III)] species and C6F5SH, respectively, by the action of the ascorbate anion [AscH],[13] [14] which ultimately becomes dehydroascorbic acid (DHA).[15] The additive KHSO4 might act by suppressing undesirable formation of a thiolate anion (C6F5S) from C6F5SH.

Zoom
Scheme 2 Plausible mechanism for the formation of 3a from alkene 1a and phosphonium ylide 2

Various alkenes 1 were subjected to the 1,2-hydro(cyanomethylation) reaction with 2 (Table [1]). A wide range of functional groups were tolerated to afford the corresponding elongated aliphatic nitriles 3bg in yields ranging from 74 to 88% (Table [1], entries 1–6). Not only monosubstituted alkenes, but also polysubstituted alkenes, participated in the reaction. Geminally disubstituted alkenes 1h and 1i were suitable substrates (entries 7 and 8). Cyclic disubstituted alkenes 1j and 1k afforded the corresponding products 3j and 3k in yields of 59 and 79%, respectively (entries 9 and 10). The reaction of the acyclic vicinally disubstituted alkenes (Z)- and (E)-1l was sluggish, and the reason for the low yield of product 3l is unclear (entries 11 and 12). In the case of trisubstituted alkene 1m, a mixture of diastereomers of 3m was formed through nonstereoselective transfer of a hydrogen atom to an intermediate tertiary radical species (entry 13). Even the tetrasubstituted alkene 1n underwent the reaction (entry 14). The 1,2-adduct 3o was obtained in 18% NMR yield from styrene (1o), and the final reaction mixture contained various products, probably as a result of the high reactivity of the benzylic radical intermediates (entry 15).[16]

Table 1 1,2-Hydro(cyanomethylation) of Various Alkenes 1 with Phosphorus Ylide 2 a

Entry

Alkene 1

Product 3

Yieldb (%)

 1

76

 2

82

 3

74

 4

88

 5

77

 6

88

 7

73

 8

77

 9

59

10

79

11

28

12

29c

13

45

14

56c

15

18c

a Reaction conditions: 1 (0.50 mmol), 2 (1.0 mmol), fac-Ir(ppy)3 (1.0 mol%), C6F5SH (20 mol%), ascorbic acid (5.0 mmol), KHSO4 (1.5 mmol), 1:1 CH3CN/H2O (5.0 mL), r.t., 40 h, blue LEDs (470 nm, 23 W).

b Isolated yield.

c NMR yield with 1,1,2,2-tetrachloroethane as internal standard.

In the case of 1-benzofuran (7), the cyanomethyl radical species added regioselectively to form a benzylic radical species, giving the 2-substituted 2,3-dihydro-1-benzofuran 8 (Scheme [3]).

Zoom
Scheme 3 The addition reaction to 1-benzofuran (7)

Notably, even a branched α-cyanoethyl group was attached to the C=C double bond of 1a when α-cyanoethyl­phophorus ylide 9 was employed (Scheme 4).

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Scheme 4 The reaction with the α-cyanoethylphosphonium ylide 9

A similar reaction to form elongated aliphatic nitriles from alkenes has been reported,[8] in which a cyanomethyl radical species is generated from CH3CN by using an excess of dicumyl peroxide at a high temperature; these potentially hazardous conditions significantly limit the synthetic value of the method. The present reaction uses cyanomethylphosphonium ylide, which is stable and easily accessible, as the radical source, thereby providing a convenient method for synthesizing elongated aliphatic nitriles from alkenes.[17]


Acknowledgment

We thank Mr. H. Nikishima (Kyoto University) for his experimental contribution at a preliminary stage.

Supporting Information



Zoom
Scheme 1 1,2-Hydro(cyanomethylation) of alkene 1a with phosphonium ylide 2
Zoom
Scheme 2 Plausible mechanism for the formation of 3a from alkene 1a and phosphonium ylide 2
Zoom
Scheme 3 The addition reaction to 1-benzofuran (7)
Zoom
Scheme 4 The reaction with the α-cyanoethylphosphonium ylide 9