Yunfei Cai

Catalytic asymmetric chloroamination reaction of α,β-unsaturated γ-keto esters and chalcones.

Highly efficient catalytic chloroamination reaction of α,β-unsaturated γ-keto esters and chalcones has been developed via a chloronium-based mechanism to deliver anti-regioselective vicinal chloroamines instead of the aziridinium intermediates delivered aminochlorides. The combination of TsNCl(2) and TsNH(2) as reagents made the transformation highly efficient, delivering the γ-carbonyl-β-chloro-α-amino acid derivatives and α-chloro-β-amino-ketone derivatives in nearly quantitative yields with up to 99% ee and 99:1 dr under 0.05-0.5 mol % catalyst loading. TsNHCl was demonstrated to act as the key reactive species to form a bridged chloronium ion intermediate in the presence of a chiral scandium complex. The method might provide useful information for further realization of other haloamination reactions.

Asymmetric Catalytic Halofunctionalization of α,β-Unsaturated Carbonyl Compounds

Halofunctionalization methods enable the vicinal difunctionalization of alkenes with heteroatom nucleophiles and halogen moieties. As a fundamental transformation in organic synthesis, the catalytic asymmetric variants have only recently been reported. In sharp contrast to the asymmetric halocyclization of simple alkenes which involves a nucleophile-assisted alkene activation process, the asymmetric halofunctionalization of enones developed by our laboratory features an electrophile-assisted 1,4-addition pathway. Our work in this area has resulted in the development of several different types of regio-, diastereo-, and enantioselective processes, including inter- and intramolecular haloaminations, haloetherifications, and haloazidations. The scope, updated mechanism, limitations, and future perspective of these reactions are discussed.