An efficient, general asymmetric synthesis of carbocyclic nucleosides: application of an asymmetric aldol/ring-closing metathesis strategy

A general and efficient synthesis of carbocyclic and hexenopyranosyl nucleosides has been developed. The strategy combines three key transformations: an asymmetric aldol addition to establish the relative and absolute configuration of the pseudosugar, a ring-closing metathesis to construct the pseudosugar ring, and a Trost-type palladium(0)-mediated substitution to assemble the pseudosugar and the aromatic base. Carbovir, abacavir, and their 2'-methyl derivatives as well as hexenopyranosyl nucleoside analogues have been prepared by this sequence.