Enantioselective Construction of β-Substituted γ-Lactone through Catalytic Asymmetric Oshima-Utimoto Reaction: Divergent Total Syntheses of (-)-Podophyllotoxin and Its Eleven Congeners.

We report the first highly enantioselective Oshima-Utimoto reaction, which is combined with subsequent one-pot oxidation to construct synthetically important enantioenriched β-substituted γ-lactones with high enantioselectivity (up to 97% ee) from two chemical feedstocks (allylic alcohols and vinyl ethers). Significantly, the absolute configuration of chiral β-substituted γ-lactones can be precisely controlled by strategically selecting - or -allylic alcohol substrates, thereby providing an alternative access to both enantiomers of chiral γ-lactones. Capitalizing on this catalytic asymmetric transformation as a key step, we have achieved a concise and stereodivergent total synthesis of the natural aryltetralin lignan drug (-)-podophyllotoxin and its 11 structural congeners in only 6-8 steps from commercial materials through the combination of chemical and chemoenzymatic strategies.

Transition-metal-free α-arylation of nitroketones with diaryliodonium salts for the synthesis of tertiary α-aryl, α-nitro ketones.

Transition-metal-free α-arylation of α-nitroketones with diaryliodonium salts has been realized for the first time. As an application of this methodology, a concise synthesis of the clinical drug tiletamine was also achieved via a three-step procedure from 2-nitrocyclohexanone without the isolation of intermediates.