Asymmetric Synthesis of 3-Amine-tetrahydrothiophenes with a Quaternary Stereocenter via Nickel(II)/Trisoxazoline-Catalyzed Sulfa-Michael/Aldol Cascade Reaction: Divergent Access to Chiral Thionucleosides

A generally useful Ni(II)/trisoxazoline-catalyzed asymmetric sulfa-Michael/Aldol cascade reaction is introduced to access chiral 3-amine-tetrahydrothiophene derivatives containing a quaternary stereocenter (32 examples, up to 93% yield, > 20:1 dr and 92% ee). Moreover, the novel strategy offers an efficient and convenient approach to construct chiral thionucleoside analogues.

Automated summary

This study presents a novel Ni(II)/trisoxazoline-catalyzed asymmetric cascade reaction for the synthesis of chiral 3-amine-tetrahydrothiophene derivatives with a quaternary stereocenter, with high yields and excellent enantioselectivity. This strategy offers an efficient and convenient approach for constructing chiral thionucleoside analogues.