Preparation of a Privileged Silicon‐Stereogenic Silane: Classical versus Kinetic Resolution

Abstract

AbstractThe cyclic silicon‐stereogenic silane (SiR)‐5 decorated with three different substituents of distinct steric demand is an exceptionally useful chiral reagent in asymmetric organosilicon chemistry. Several approaches for its large‐scale preparation in optically pure form have been investigated. These hinge upon the resolution of racemic silane rac‐5 which, in turn, is accessible in multi‐gram quantities by a straightforward one‐pot two‐step reaction sequence. For this, a classical as well as a novel kinetic resolution via its diastereomeric silyl ethers derived from enantiopure secondary alcohols as resolving agents has been elaborated: (1) the use of (−)‐menthol [(−)‐7] allowed for a quantitative separation of silyl ethers (SiS)‐10 and (SiR)‐10 by practical fractional crystallization and (2) a diastereoselective copper‐catalyzed dehydrogenative silicon‐oxygen coupling using pyridyl alcohols (S)‐16 or (R)‐16 capable of two‐point binding has been devised and assessed as a novel kinetic resolution strategy for the synthesis of a silane with silicon‐centered chirality. Subsequent stereospecific reductive cleavage of the silicon‐oxygen bond enabled the preparation of (SiR)‐5 and (SiS)‐5 in excellent enantiomeric excesses of up to 99 % ee.