Sulfa-Michael Reaction Cascade for the Synthesis of Chromans

Significance

Chen, Xiao, and colleagues identified thiourea 2 as an efficient catalyst in the double-Michael cyclization cascade of nitroolefin enoates 1 with heteroatom nucleophiles. The group’s previous exploration of non-asymmetric formal cycloaddition cascades with 1 identified it as a useful precursor to highly functionalized chromans. Using organocatalysis, the authors realized an asymmetric approach to chromans 3. As sulfur-containing chromans constitute a class of γ-secretase inhibitiors, various thiol nucleophiles were examined and found to be suitable in the ­reaction. Preliminary studies also showed that ­nitrogen nucleophiles are equally effective.