Two-Stage Coupling Process and Its Application to Syntheses of Macrolide Antibiotics

For the purpose of synthesizing effectively the optically active natural products which contain a long chain consisting of many consecutive chiral carbon atoms, it is indispensable to realize the highly diastereoselective connections between the selected chiral segments. “Two-stage coupling process” is one of the solutions, It consists of the first stage (stage I) of addition reaction of chiral vinyllithium compounds to 2-methyl-substituted aldehydes and the second stage (stage II) of homogeneous hydrogenation of exo-methylene group in the major Cram (syn) type of addition products with Wilkinson's catalyst. This article describes the mechanism of diastereoselective first stage of this process on the basis of the conformational analysis of transition states and the successful application of this process to syntheses of macrolide antibiotics.