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. 2019 Feb 4;58(6):1794-1798.
doi: 10.1002/anie.201812398. Epub 2019 Jan 17.

Aliphatic Radical Relay Heck Reaction at Unactivated C(sp3 )-H Sites of Alcohols

Padon Chuentragool  1 , Dongari Yadagiri  1 , Taiki Morita  1 , Sumon Sarkar  1 , Marvin Parasram  1 , Yang Wang  1 , Vladimir Gevorgyan  1
Affiliations

Aliphatic Radical Relay Heck Reaction at Unactivated C(sp3 )-H Sites of Alcohols

Padon Chuentragool et al. Angew Chem Int Ed Engl. .

Abstract

The Mizoroki-Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that allows a Heck reaction to occur at a specific nonfunctionalized C(sp3 )-H site is desirable. Reported here is a radical relay Heck reaction which allows selective remote alkenylation of aliphatic alcohols at unactivated β-, γ-, and δ-C(sp3 )-H sites. The use of an easily installed/removed Si-based auxiliary enables selective I-atom/radical translocation events at remote C-H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible-light-mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks.

Keywords: C−H activation; Heck reaction; palladium; photochemistry; radicals.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Scheme 1.
Scheme 1.
Development of radical relay Heck reaction.
Scheme 2.
Scheme 2.
Scope of radical relay Heck reaction. Experimental details are provided In the supplementary material, a) γ-Heck reactions, b) β-Heck reactions. c) δ-Heck reactions, d) Heck reaction at secondary C–H sites, d.r. = diastereomeric ratio, e) Inefficient substrates, R = iPr for 1a–z, 1ad–am, 1 ao, 1 ap, 1 au, R = Me for 1 aa–ac, 1 an, 1 aq–at, [a] Different deprotection procedures were applied depending on the products: TBAF in THF; CSA in MeOH; or AcCI and Montmorillonite K10 in CH2Cl2, See the Supporting Information for details, [b] Methyl vinyl ketone was used in the radical relay Heck reaction followed by reduction with NaBH4 [c] Premature coupling product was observed as a major product (66%), [d] Desaturation product was observed as a major product (57%), CSA = camphorsulfonic acid, TBAF = tetra-n-butylammonium fluoride, THF = tetrahydrofuran.
Scheme 3.
Scheme 3.
Transformations of alkenol products. Experimental details are provided in the Supporting Information. a) 10 mol% OsO4, 1.2 equiv NMO, acetone/water. b) 1.5 equiv mCPBA, CH2Cl2. c) 2 equiv LiBr, 0.5 equiv NaIO4, CH3CN. d) O3, 2 equiv Me2S, acetone. e) O3, 2 equiv Me2S, acetone, then NaBH4 in MeOH. f) 5 equiv HBr, CHCI3/DMSO. g) 1.2 equiv LiAlH4, Et2O. h) 10 mol% NiCl2, 7 equiv NaBH4, MeOH. *≈1:1 d.r. DMSO = dimethylsulfoxide, mCPBA=m-chloroperbenzoic acid, NMO = N-methylmorpholine N-oxide.
Scheme 4.
Scheme 4.
Proposed mechanism.
See this image and copyright information in PMC

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