Synthesis of insect lipid using organobismuth remote stereocontrol of acyclic 1,3, 5 - trimethyl compounds

Abstract

The organometallic chemistry of the main group IV metals has been dominated by the widespread commercial exploitation of tin and lead. The high toxicity problems associated with organotin compounds has lead to the need to limit their use. Organobismuth chemistry is attracting interest. Bismuth metal is considered to be safe, as it is non-toxic and non-carcinogenic, in spite of its heavy metal status. Embodied in this thesis is a discussion concerning the use of organobismuth as a replacement for organotin compounds in remote stereoselective control by promoting coupling reactions of (2R,3E)-1-(benzyloxy)-5-bromo-2,4- dimethylpent-2-ene with aldehydes. (2R,3E)-1-(Benzyloxy)-5-bromo-2,4- dimethylpent-2-ene was synthesised from methyl (2S)-3-hydroxy-2- methylpropanoate in five steps with an overall yield of 41%. Addition of this bromide and an aldehyde to bismuth(III) iodide and zinc in THF at room temperature gave a �90:10 (1,5-anti:1,5-syn) ratio of homoallylic alcohols in ca. 70% yield. The generality of these bismuth(III) iodide promoted reactions is reported including the successful coupling of several aldehydes with consistently good yields and selectivities. Identification of the relative stereochemistry of the major isomer was achieved by means of 1H NMR. When this was not possible, inversion of the newly formed chiral centre was employed to determine the selectivity of the reaction. The absolute configuration of the hydroxyl group in the major diastereoisomer was confirmed by comparison of the 1H NMR spectra of its (R)- and (S)-Oacetylmandelates. The mechanism of these bismuth reactions has not been investigated, although it is suggested that it is similar to tin-Lewis acid reactions. Acyclic compounds with syn-and anti-disposed 1,3,5-trimethyl substituents were prepared from 1,5-stereocontrol homoallylic alcohol via stereoselective reduction of the trisubstituted alkenes. The application of this methodology to the synthesis of natural products was tested with the preliminary work on the synthesis of the cuticular hydrocarbon, 4,6,8,10,16-pentamethyldocosane isolated from the cane beetle Antitrogus parvulus.