Stereocontrolled Total Synthesis of (−)-Kaitocephalin

This paper describes the successful implementation of a stereocontrolled strategy for the total chemical
synthesis of the pyrrolidine-based alkaloid (−)-kaitocephalin. This scalable synthetic route profits from
the strategic utilization of substrate-controlled manipulations for the iterative installation of the requisite
stereogenic centers. The key transformations include a diastereoselective modified Claisen condensation,
a chemo- and diastereoselective reduction of a β-keto ester, and the substrate-directed hydrogenation of
a dehydroamino ester derivative. During the course of our investigations, an interesting stereoconvergent
cyclization reaction was discovered for the efficient assembly of the kaitocephalin 2,2,5-trisubstituted
pyrrolidine core.