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

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)(2)PHAL.

Automated summary

A new Lewis base-catalyzed bromochlorination strategy for unsaturated systems is described, which is mechanistically distinct and utilizes 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 strategy exhibits excellent site selectivity and can access a wide variety of vicinal bromochlorides with high regio- and diastereoselectivity. The precision installation of Br, Cl, and I in various combinations is also demonstrated.