Diastereoselective Synthesis of Cephalotaxus Esters via Asymmetric Mukaiyama Aldol Reaction

We report a protocol
for efficient stereoselective installation
of the chiral oxygen-containing tetrasubstituted tertiary carbon stereocenter
of the side chain of cephalotaxus esters by means of highly diastereoselective
Mukaiyama aldol reactions between α-keto esters (2) and a (Z)-α-chloro ketene silyl acetal.
This protocol permitted synthesis of cephalotaxus esters including
six natural products in good to excellent yields (up to 94%) with
high diastereoselectivities (dr up to 97:3) and could be performed
on a multigram scale.