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. 2021 Mar 19;11(6):3749-3754.
doi: 10.1021/acscatal.1c00267. Epub 2021 Mar 9.

Visible Light-Induced Pd-Catalyzed Alkyl-Heck Reaction of Oximes

Nikita Kvasovs  1 , Valeriia Iziumchenko  1 , Vitalii Palchykov  1 , Vladimir Gevorgyan  1
Affiliations

Visible Light-Induced Pd-Catalyzed Alkyl-Heck Reaction of Oximes

Nikita Kvasovs et al. ACS Catal. .

Abstract

A visible light-induced palladium-catalyzed oxidative C-H alkylation of oximes has been developed. This mild protocol allows for an efficient atom economical C-C bond construction of alkyl-substituted oximes. A broad range of primary, secondary, and tertiary alkyl bromides and iodides, as well as a range of different formaldoximes, can efficiently undergo this transformation. The method features visible light-induced generation of nucleophilic hybrid alkyl Pd radical intermediates, which upon radical addition at the imine moiety and a subsequent β-hydrogen elimination deliver substituted imines.

Keywords: Heck reaction; alkylation; light-induced; oxime; palladium; radical.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
Radical Reactions of Imines
Scheme 2.
Scheme 2.
Synthetic Utility of Obtained Products
Scheme 3.
Scheme 3.
Impact of Base and Halide on E/Z Selectivity
Scheme 4.
Scheme 4.. Scope of Alkyl Heck-Type Coupling of Oximesa
a0.3 mmol scale, isolated yields. b3 equiv of EtI. c3 equiv of oxime. d0.5 mmol scale, 3 equiv of i-PrBr. eYield after reduction with NaBH3CN.
Scheme 5.
Scheme 5.
Proposed Mechanism
See this image and copyright information in PMC

References

    1. Friestad GK Addition of carbon-centered radicals to imines and related compounds. Tetrahedron 2001, 57, 5461–5496.
    2. Miyabe H; Ueda M; Naito T Carbon-Carbon Bond Construction Based on Radical Addition to C=N Bond. Synlett 2004, 7, 1140–1157.
    1. Halland N; Anker Jørgensen K Intermolecular addition of alkyl radicals to imines in the absence and in the presence of a Lewis acid. J. Chem. Soc., Perkin Trans 12001, 1290–1295.
    2. Yamada K-I; Fujihara H; Yamamoto Y; Miwa Y; Taga T; Tomioka K Radical Addition of Ethers to Imines Initiated by Dimethylzinc. Org. Lett 2002, 4, 3509–3511. - PubMed
    3. Lee S; Kim S Enantioselective radical addition reactions to imines using binaphthol-derived chiral N-triflyl phosphor-amides. Tetrahedron Lett. 2009, 50, 3345–3348.
    1. Garrido-Castro AF; Maestro MC; Alemán J α-Functionalization of Imines via Visible Light Photoredox Catalysis. Catalysts 2020, 10, 562.
    1. Matos JLM; Vásquez-Céspedes S; Gu J; Oguma T; Shenvi RA Branch-Selective Addition of Unactivated Olefins into Imines and Aldehydes. J. Am. Chem. Soc 2018, 140, 16976–16981. - PMC - PubMed
    1. Kim S; Lee IY; Yoon J-Y; Oh DH Novel Radical Reaction of Phenylsulfonyl Oxime Ethers. A Free Radical Acylation Approach. J. Am. Chem. Soc 1996, 118, 5138–5139.
    2. Kim S; Song H-J; Choi T-L; Yoon J-Y Tin-Free Radical Acylation Reactions with Methanesulfonyl Oxime Ether. Angew. Chem., Int. Ed 2001, 40, 2524–2526. - PubMed
    3. Rouquet G; Robert F; Méreau R; Castet F; Landais Y Allylsilanes in “Tin-free” Oximation, Alkenylation, and Allylation of Alkyl Halides. Chem. - Eur. J 2011, 17, 13904–13911. - PubMed
    4. Kamijo S; Takao G; Kamijo K; Hirota M; Tao K; Murafuji T Photo-induced Substitutive Introduction of the Aldoxime Functional Group to Carbon Chains: A Formal Formylation of Non-Acidic C(sp3)-H Bonds. Angew. Chem., Int. Ed 2016, 55, 9695–9699. - PubMed