Concise racemic and highly enantioselective approaches to key intermediates for the syntheses of carbocyclic nucleosides and pseudo-ribofuranoses: formal syntheses of carbovir

Abstract

A regio- and stereo-specific synthesis of cis-(±)-3-acetoxy-5-(acetoxymethyl)cyclopentene 3 from cyclopent-3-enecarboxylic acid 4via a bromolactonisation strategy is described. Pd-catalysed coupling of the cis-(±)-diacetate 3 with 2-amino-6-chloropurine or 2,6-diaminopurine leads to the formal syntheses of carbovir 1. A synthesis of the (1R)-cis-diacetate 15(R = Ac) is described via a highly enantioselective rearrangement of cis-6-oxabicyclo[3.1.0]hexane-3-methanol 13(also prepared from the acid 4) using the dilithium salt of (1S,2R)-norephedrine.