Selective Perhydroxylation of Squalene: Taming the Arithmetic Demon

Abstract

Osmium-catalyzed asymmetric dihydroxylation, which produces 1,2-diols of high enantiopurity from prochiral olefins, is an example of the synthetic catalysts that have been developed that rival enzymes in their efficiency and high enantioselectivity. Although the asymmetric dihydroxylation catalyst lacks an enzyme's ability to effectively distinguish among the subtly different olefinic sites in a polyolefin such as squalene, this very inability permits it to bring about the "exhaustive" polyhydroxylation of squalene to give a dodecahydroxy derivative. Twelve chemical and stereochemical events proceed in tandem with a remarkable average yield of 98 percent per step, giving 1 out of the 36 possible stereoisomers in (0.98)12 = 78.9 percent overall yield.