Preparation of a privileged silicon-stereogenic silane:: Classical versus kinetic resolution

The 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.