Stereocontrolled Synthesis of Carbon Chains Bearing Contiguous Methyl Groups by Iterative Boronic Ester Homologations:Application to the Total Synthesis of (+)-Faranal

摘要

Carbon chains bearing 1, 3, 5… n polymethyl groups are ubiquitous in natural products. Recently, effective solutions for a flexible, stereocontolled synthesis of such arrays have been achieved by the groups of Feringa-Minnaard,1 Breidt,2 and Negishi.3 Carbon chains bearing adjacent methyl groups, although less common, are also frequently encountered4 (Figure 1), but a general stereocontrolled solution to this problem has not been advanced.5 For example, in the previous syntheses of the insect pheromone (+)-faranal (1),5b one or both methyl groups originate from a carboxylic ester to enable control of relative stereochemistry during C[BOND]C bond formation (both utilize resolution to achieve absolute control).6 Introducing the methyl groups in the wrong oxidation state invariably leads to an increase in the total number of steps required.