An (S)-(+)-lactic acid route to (2S,6R,8S)-2,8 dimethyl-1,7-dioxaspiro[5,5]undecane and (2S,6R,8S)-2-ethyl-8-methyl-1,7-dioxaspiro[5,5]undecane and demonstration of their presence in the rectal glandular secretion of Bactrocera nigrotibialis(Perkins)

Abstract

The chiral iodide resulting from reduction and iodination of the tetrahydropyran-2-yl ether of ethyl (S)-(+)-lactate has been engaged in a free-radical addition to acrylonitrile. The resulting protected hydroxy nitrite, on reaction with pent-4-enylmagnesium bromide afforded (S)-2-tetrahydropyran-2-yloxyundec-10-en-6-one. Oxymercuriation of this hydroxy enone, under reversible conditions, employing aqueous acid–tetrahydrofuran, effected simultaneous deprotection and cyclisation, and in situ biphasic demercuriation with sodium borohydride provided essentially stereochemically pure (2S,6R,8S)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane [i.e.the (E,E)-diastereoisomer only]. Epoxidation of the protected hydroxy enone, followed by dimethylcuprate ring-opening and cyclisation, provided a mixture of the (E,E)and the two possible (E,Z)-diastereoisomers of 2-ethyl-8-methyl-1,7-dioxaspiro[5.5]undecane with the former being the (2S,6R,8S) stereoisomer. Separation of the (E,E)from the two (E,Z)isomers was achieved by preparative gas chromatography. GC analysis of these samples and of the rectal glandular secretion of male Bactrocera nigrotibialis, using a cyclodextrin-based phase, demonstrated that the (2S,6R,8S)-stereoisomers of the 2,8-dimethyl- and 2-ethyl-8-methyl-1,7-dioxaspiro[5.5]undecanes were the natural products, with no detectable level of the antipodes.