Light Induced Radical Alkenylation and Allylation of Alkyl

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Cite This: Org. Lett. 2018, 20, 1078−1081

Palladium/Light Induced Radical Alkenylation and Allylation of Alkyl Iodides Using Alkenyl and Allylic Sulfones Shuhei Sumino,†,§ Misae Uno,† Hsin-Ju Huang,‡ Yen-Ku Wu,‡ and Ilhyong Ryu*,†,‡ †

Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan

‡

S Supporting Information *

ABSTRACT: Alkenylation and allylation of alkyl iodides with alkenyl and allyl sulfones, respectively, took place under Pd/ photoirradiation system. The initial alkyl radical, derived from a single electron transfer between Pd(0) and RI, underwent the title transformations. Pd(0) was regenerated through a reductive elimination of PhSO2PdI, which is formed by the combination of the sulfonyl radical and the palladium radical. The addition of water was effective, presumably by pushing the equilibrium through hydrolysis of PhSO2I. eq 3).4 Thus far, a number of alkenylating reagents has been examined in different types of radical alkenylation reactions, which include alkenyltins,5 alkenylsulfides,6 alkenyl sulfones,7,8 nitroalkenes,9 alkenylindiums,10 alkenylgalliums,10b alkenyl chlorides,11 and alkenyl bromides.12−14 Also, the radical allylation reactions following a related mechanistic pathway have been investigated (Scheme 1, eq 2).4,6,7e,15 As part of our research program in developing Pd/light-initiated radical reactions,16,17 we recently reported a coupling reaction of alkyl iodides and alkenyl bromides with Hanztsch ester as a reducing agent (Scheme 1, eq 4).18 In this reaction system, the single electron transfer (SET) reaction between alkyl iodides and Pd(0) under photoirradiation is responsible for the generation of the initial alkyl radical, and Hanztsch ester serves an essential role in reducing Pd(II)IBr to Pd(0) to sustain radical chain. We envisioned that if alkenyl phenyl sulfones are employed in lieu of alkenyl bromides, the reductive elimination of Pd(II)ISO2Ph would be much more facile than the case with Pd(II)IBr,19 thus obviating the need of an additional reductant for the regeneration of Pd(0) (Scheme 1, eq 6). The same concept would promisingly be extended to the allylation sequence using allyl sulfones7e,20,21 (Scheme 1, eq 5). Herein, we report the Pd/ light-induced synthesis of alkenylated or allylated alkanes from the corresponding sulfone precursors. We first studied the coupling reaction of iodocyclohexane 1a and phenyl styryl sulfone 2a (Table 1). When a benzene solution of 1a and 2a was irradiated by a xenon lamp in the presence of PdCl2, LiCl, t-BuNC, and Et3N, the desired product 3aa was obtained in 39% yield (Table 1, entry 1). Interestingly, the

T

ransition metal-catalyzed cross-coupling reactions of aryl and alkenyl halides constitute a useful means for C−C bond forming processes, and nowadays, much effort has been directed to expand the reaction scope by engaging sp3-hybridized alkyl halides.1,2 A radical-based formal Mizoroki−Heck reaction of alkyl halides involves the addition of a carbon radical to a heteroatom-substituted alkene followed by a β-scission pathway (Scheme 1, eq 1).3 In order to sustain the radical chain, the leaving radical Y • has to trigger a propagation sequence, and hexabutylditin is often used to facilitate this process (Scheme 1, Scheme 1. Radical Alkenylation and Allylation of Alkyl Halides

Received: December 29, 2017 Published: February 6, 2018 © 2018 American Chemical Society

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DOI: 10.1021/acs.orglett.7b04050 Org. Lett. 2018, 20, 1078−1081

Letter

Organic Letters Table 1. Optimization of Reaction Conditionsa

Table 2. Radical Alkenylation of Alkyl Iodides 1 with Alkenyl Sulfones 2a

entry

2a (equiv)

Et3N (equiv)

solvent (mL)

yield (%)b

1 2 3 4 5 6 7c 8d 9e

1.5 1.5 2.0 1.5 1.5 1.5 1.5 1.5 1.5

2 2 2 2 3 0 2 2 2

C6H6 (2) C6H6/H2O (2/1) C6H6/H2O (2/1) C6H6/H2O (2/2) C6H6/H2O (2/1) C6H6/H2O (2/1) C6H6/H2O (2/1) C6H6/H2O (2/1) C6H6/H2O (2/1)

− (39) 65 (73) 60 (74) 64 69 0 − (56) 0 0

a

Reaction conditions: alkyl iodide 1a (0.5 mmol), alkenyl sulfone 2a (0.75 mmol), PdCl2 (5 mol %), t-BuNC (20 mol %), LiCl (20 mol %), Et3N (1 mmol), C6H6 (2 mL), H2O (1 mL), 16 h, hν (SolarBox (Xe, 800 W/m2), Pyrex). bIsolated yield; number in parentheses refers to NMR yield. cWith Hantzsch ester (0.75 mmol). dWithout PdCl2, LiCl, or t-BuNC. eUnder dark conditions.

addition of H2O increased the yield to 65% (Table 1, entry 2). There was no further improvement of the yield by increasing the amount of 2a, water, or Et3N (Table 1, entries 3−5). Et3N was necessary for the reaction to proceed (Table 1, entry 6). The addition of Hantzsch ester did not improve the yield, in contrast to our previous report on the alkenylation with alkenyl bromides18 (Table 1, entry 7). In the absence of PdCl2, LiCl, and t-BuNC, no alkenylation reaction took place (Table 1, entry 8). The reaction did not proceed under dark conditions (Table 1, entry 9). In order to confirm the involvement of a radical chain process, the reaction of 1a with 2a was carried out in the presence of TEMPO. As our expectation, cyclohexyl-TEMPO was formed in 9% yield, and no alkenylation reaction took place. With the optimized conditions in hand, we set out to examine the scope of the radical alkenylation reaction (Table 2). The reactions of primary, secondary, and tertiary alkyl iodides 1a−f with 2a gave the corresponding alkenylated alkanes 3aa−3fa in good to moderate yields (Table 2, entries 1−6). Although the reaction of nitro-substituted sulfone 2b failed to deliver the product (Table 2, entry 7), we were delighted to find that a wide range of substituted 2-aryl alkenyl sulfones 2c−2i are compatible with the alkenylation reaction (Table 2, entries 8−14). It is noteworthy that chloro and bromo substituents on the arene moieties remain intact and therefore could be further functionalized after the radical alkenylation event (Table 2, entries 11− 14). The reaction of 1a with trans-1,2-bis(phenylsulfonyl)ethene 2j provided the conjugated sulfone 3aj albeit in moderate yield (Table 2, entry 15). The reaction of 1a with ethyl (E)-3(phenylsulfonyl)acrylate 2k furnished conjugated ester 3ak in low yield; presumably, 3ak serves as a good radical trap for undesired addition reactions thus giving rise to numerous side products (Table 2, entry 16). We next explored the radical allylation of alkyl iodides with allyl sulfones under the Pd-catalyzed photoirradiation system (Scheme 2). With either a xenon lamp (800 W/m2) (condition A) or a black light bulb (15 W, wave peak: 365 nm) (condition B) as the light source, the coupling reaction of alkyl iodides 1 and allyl sulfone 4a gave the corresponding allylation products 5aa−5ja in good yields. The wide functional group compatibility of these

a

Reaction conditions: alkyl iodide 1 (0.5 mmol), alkenyl sulfone 2 (0.75 mmol), PdCl2 (5 mol %), t-BuNC (20 mol %), LiCl (20 mol %), Et3N (1.5 mmol), C6H6 (2 mL), H2O (1 mL), 16 h, hν (SolarBox (Xe, 800 W/m2), Pyrex). bNMR yield in crude mixture.

transformations is clearly displayed in the synthesis of 5ga−5ja. 2Phenyl-substituted ally sulfone 4b was also applicable resulting in the formation of 5ab and 5bb in good yields. We then sought to integrate the radical alkenylation and allylation methods into three-component coupling reactions (Scheme 3). In the event, we showed the reaction engaging ethyl iodoacetate 1k, 1-octene 6a, and sulfone 2a gave the coupling product 7a in a yield of 59% (Scheme 3, eq 7). As for the chemoselectivity of this reaction, initially formed α-acetate radical is considered to be electrophilic and therefore preferentially adds to 1-octene 6a rather than to alkenyl sulfone 2a; the resulting 1079

DOI: 10.1021/acs.orglett.7b04050 Org. Lett. 2018, 20, 1078−1081

Letter

Organic Letters

The mechanism of the radical alkenylation with alkyl iodides 1 and alkenyl sulfones 2 is illustrated in Scheme 4. First, SET

Scheme 2. Radical Allylation of Alkyl Iodides 1 with Allyl Sulfones 4a

Scheme 4. Proposed Mechanism for the Alkenylation Reaction

proceeds from photoexcited Pd(0) to the alkyl iodide to generate an alkyl radical (R•) and a PdI radical. The alkyl radical adds to the alkene of sulfone 2, and then subsequent β-scission takes place to give concomitantly the allylated product 3 and sulfonyl radical (PhO2S•). The combination of sulfonyl radical and Pd(I) generates sulfonyl palladium iodide A. We assume that Pd(I) must be persistent, which would allow selective coupling between Pd(I) and PhSO2 radical. Reductive elimination of A resulted in the formation of PhSO2I24 and Pd(0). To facilitate the catalytic process, the addition of water and Et3N assists hydrolysis of PhSO2I, preventing the reversible reaction toward the intermediate A. In summary, we have demonstrated a new protocol for the radical alkenylation and allylation of alkyl iodides with phenyl sulfone compounds under a Pd/photoirradiation system in which radical intermediate and palladium species work cooperatively. This reaction system is also applicable to the three-component coupling reactions including the radical carbonylative transformation. Facile reductive elimination of arylsulfonyl iodide from the Pd center obviates the use of reducing agent to regenerate Pd(0). Further research to explore transition metal/ radical cooperative systems is currently underway in this laboratory.

a

Reaction conditions: condition A, alkyl iodide 1 (0.5 mmol), allyl sulfone 4 (0.75 mmol), PdCl2 (5 mol %), t-BuNC (20 mol %), LiCl (20 mol %), Et3N (1.5 mmol), C6H6 (2 mL), H2O (1 mL), 16 h, hν (SolarBox (Xe, 800 W/m2), Pyrex); condition B, alkyl iodide 1 (0.5 mmol), allyl sulfone 4 (0.75 mmol), PdCl2 (6 mol %), t-BuNC (20 mol %), LiCl (20 mol %), Et3N (1.5 mmol), MeCN (1 mL), H2O (1 mL), 6 or 12 h, hν (black light, 15 W, Pyrex). bAlkyl iodide 1a (1.1 equiv), hν (black light, 15 W × 2, Pyrex). cAllyl sulfone 4b (1.0 equiv), hν (black light, 15 W × 2, Pyrex).

Scheme 3. Three-Component Coupling Reactions

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b04050. Typical experimental procedure and full characterization data for 3aa−3aj, 5, and 7−9 (PDF)

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radical is nucleophilic and adds to electron-deficient 2a to give 7a.22 Analogously, the three-component reaction of perfluoroalkyl iodide 1l, cyclooctene 6b, and 2c gave 7b in 63% yield (Scheme 3, eq 8). Nucleophilic 2-indanyl radical derived from 1c first underwent the addition to methyl acrylate 6c, and then the resulting electrophilic radical reacted with allyl sulfone 4c to give 8 in 55% yield (Scheme 3, eq 9). A three-component radical carbonylative−alkenylation16,23 reaction of an alkyl halide was realized giving enone 9 in 41% yield (Scheme 3, eq 10).16b

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Shuhei Sumino: 0000-0002-7109-8995 Yen-Ku Wu: 0000-0002-9269-7444 Ilhyong Ryu: 0000-0001-7715-4727 1080

DOI: 10.1021/acs.orglett.7b04050 Org. Lett. 2018, 20, 1078−1081

Letter

Organic Letters Present Address

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§

Osaka Research Institute of Industrial Science and Technology, 1-6-50, Morinomiya, Osaka, Japan. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by a Grant-in-Aid for Scientific Research (A) (no. 26248031) from the JSPS and Scientific Research on Innovative Areas 2707 Middle molecular strategy (no. 15H05850) from the MEXT.

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DOI: 10.1021/acs.orglett.7b04050 Org. Lett. 2018, 20, 1078−1081