Syntheses of (-)-Isocitric Acid Lactone and (-)-Homoisocitric Acid. A New Method of Conversion of Alkynylsilanes into the Alkynyl Thioether and Corresponding Carboxylic Acids

A simple, stereoselective synthesis of natural isocitric and homoisocitric acids from a common alkynylsilane correlates the stereochemistry of these acids. Starting with dimethyl D-malate dianion, methyl 2-hydroxy-3-carbomethoxy-6-(trimethylsilyl)-5-hexynoate (6a) was prepared with a good stereoselectivity (threo/erythro 90/10). Oxidative cleavage of the triple bond provided isocitric acid lactone (8') in 15% overall yield starting from D-malic acid diester 1. The synthesis of homoisocitric acid relied on a new method of conversion of alkynylsilane to alkynyl thioether, which is converted to the carboxylic acid of the same chain length. Addition of benzenesulfenyl chloride to (trimethylsilyl)alkyne 6b and elimination of trimethylsilyl chloride gave the corresponding thioether 10, which by acid hydrolysis gave homoisocitric acid (11) in a 24% yield from D-malic acid ester. This novel method of conversion of alkynylsilane to the corresponding acid was illustrated with several other alkynyltrimethylsilanes.