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.
The known ene-type addition of thionium ions to alkenes has now been applied to the synthesis of homoallylic sulfides, from thionium ions RHC=S+Ar (R = alkyl, Ar = 4-chlorophenyl) and propene or other unactivated alkenes. Oxidation and thermal dehydrosulfenylation then lead to conjugated dienes. Because the reaction conditions are compatible with many functional groups, this method is simple and useful.a-Thio carbocations, ,2 also called "thionium" ions, are easily available and reactive intermediates which are analogous in structure and in reactivity to oxonium ions (a-alkoxy carbocations). Iminium ions (a-amino carbocations) are much less reactive. Ab initio calculations,3 as well as experimental results4 suggest that an alkylthio or arylthio group in the a position stabilises carbocations about as much as an alkoxy group does, and both are much less stabilising than a dialkylamino group.
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