Synthetic Studies on (+)-Biotin, Part 15: A Chiral Squaramide-Mediated Enantioselective Alcoholysis Approach toward the Total Synthesis of (+)-Biotin

摘要

An efficient stereocontrolled total synthesis of (+)-biotin ( 1 ) has been achieved via the intermediacy of Roche's lactone 5 starting from cis -1,3-dibenzyl-2-imidazole-4,5-dicarboxylic acid ( 2 ). The bifunctional cinchona alkaloid-derived squaramide-promoted enantioselective alcoholysis was utilizing as a tool for the construction of two contiguous stereocenters of C-3a and C-6a in biotin molecular with excellent enantioselectivity. In addition, the 4-carboxybutyl side chain was assembled by first using C4+C1 approach via a novel tricyclic thiophanium salt intermediate.