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. 2022 Jul 27;144(29):13294-13301.
doi: 10.1021/jacs.2c04588. Epub 2022 Jul 12.

Catalytic Chemo-, Regio-, Diastereo-, and Enantioselective Bromochlorination of Unsaturated Systems Enabled by Lewis Base-Controlled Chloride Release

Alexandra E Lubaev  1 , Manjula D Rathnayake  1 , Favour Eze  1 , Liela Bayeh-Romero  1
Affiliations

Catalytic Chemo-, Regio-, Diastereo-, and Enantioselective Bromochlorination of Unsaturated Systems Enabled by Lewis Base-Controlled Chloride Release

Alexandra E Lubaev et al. J Am Chem Soc. .

Abstract

A new strategy is described for the Lewis base-catalyzed bromochlorination of unsaturated systems that is mechanistically distinct from prior methodologies. The novelty of this method hinges on the utilization of thionyl chloride as a latent chloride source in combination with as little as 1 mol % of triphenylphosphine or triphenylphosphine oxide as Lewis basic activators. This metal-free, catalytic chemo-, regio-, and diastereoselective bromochlorination of alkenes and alkynes exhibits excellent site selectivity in polyunsaturated systems and provides access to a wide variety of vicinal bromochlorides with up to >20:1 regio- and diastereoselectivity. The precision installation of Br, Cl, and I in various combinations is also demonstrated by simply varying the commercial halogenating reagents employed. Notably, when a chiral Lewis base promoter is employed, an enantioselective bromochlorination of chalcones is possible with up to a 92:8 enantiomeric ratio when utilizing only 1-3 mol % of (DHQD)2PHAL.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(a–c) Bromochlorination of alkenes.
Figure 2
Figure 2
Proposed mechanism for the Lewis base-catalyzed bromochlorination.
Figure 3
Figure 3
(a, b) Catalytic enantioselective bromochlorination of alkenes and inspiration for an alternative strategy.
See this image and copyright information in PMC

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