A Versatile Enantioselective Catalytic Cyclopropanation‐Rearrangement Approach to the Divergent Construction of Chiral Spiroaminals and Fused Bicyclic Acetals

Abstract

A highly enantioselective synthesis of various chiral heterobicyclic molecules including spiroaminals and fused bicyclic acetals has been developed via a chiral copper catalyzed cyclopropanation-rearrangement (CP-RA) approach under mild reaction conditions. Remarkably, the asymmetric CP-RA for exocyclic vinyl substrates without a pro-stereogenic carbon at the b-position has been realized for the first time and a broad substrate scope with excellent results (33 examples; 34-99 % yields; > 95/5 dr and 91-99 % ee) has been achieved. An application of a successive enantioselective CP-RA approach was also described, providing a concise access to complex chiral heteropolycycles.

Nickel-Catalyzed Regiodivergent Asymmetric Cycloadditions of α,β-Unsaturated Carbonyl Compounds

“…Optically active spirocyclic moieties are important scaffolds products in many bioactive molecules and natural products. 56,57 Under the standard conditions, chiral spirocyclic products (3r-3t) were obtained in 63-81% yield, with 1:1->20:1 dr and 85-91% ee from exocyclic alkenes (2j-2l). The absolute configuration of the [2+2] cycloadducts were assigned as (1R,2R,3S) by comparison of their HPLC data and optical rotations with published data.…”