A chiral bis(oxazoline)-Cu(II) complex-catalyzed asymmetric 1,4-conjugate addition of β-ketoesters to in situ generated 3-indole imine methides (3-IIMs) has been developed. The synergistic Lewis acid/Brønsted acid catalytic system enables the efficient construction of enantioenriched 3-indolyl derivatives featuring congested adjacent quaternary and tertiary stereocenters with excellent efficiency (up to >20:1 dr, 99% ee). This work not only provides a complementary and robust alternative to existing organocatalytic strategies for accessing chiral 3-indolyl scaffolds but also significantly enriches the synthetic chemistry of 3-indolylmethanols by expanding their asymmetric transformation repertoires.
Zhai et al. (Tue,) studied this question.