Methods for direct carbon-carbon bond formation and their application to natural product synthesis.

摘要

Direct carbon--carbon bond formation via soft enolization and in situ enolate formation provides a straightforward approach to certain key transformations of synthetic organic chemistry. Reactions are generally operationally simple and proceed under mild conditions using untreated, reagent--grade solvent open to the air. Using this direct approach as a basis, we have developed methods for the synthesis of beta-hydroxy thioesters, beta-keto thioesters, and 1,3-diketones, which are key intermediates for the synthesis of natural products, pharmaceuticals, and other biologically relevant compounds. In particular, four methodology projects are described: (1) a direct aldol addition of simple thioesters, (2) a direct synthesis of 1,3 diketones, (3) a direct crossed-Claisen reaction, and (4) an anti-selective four component direct aldol cascade reaction.;Progress toward the total synthesis of apratoxin D is described. The key steps of the synthesis involve the asymmetric alkylation via chiral N-amino cyclic carbamate (ACC) hydrazones, a new technology recently developed by our group.