STEREOCHEMISTRY OF THE IODOCARBONATATION OF CIS-3-METHYL-4-PENTENE-1,2-DIOLS AND TRANS-3-METHYL-4-PENTENE-1,2-DIOLS - THE UNUSUAL FORMATION OF SEVERAL ANTI IODO CARBONATES

A study on the stereoselective preparation of a series of 3-methyl-4,5-epoxy alcohols as an entry to polypropionates was undertaken. Initially, the opening of cis and trans TIPS-protected 2,3-epoxy butanols by propynyldiethylalane showed an excellent regioselectivity favoring the monoprotected 1,2-diol products. The resulting propargylic alcohols were stereoselectively reduced to the cis and trans 1-[(triisopropylsilyl)oxy]-3-methyl-4-hexen-2-ols. Iodocarbonatation of these four isomeric homoallylic alcohols was carried out and the stereochemistry of the intermediate iodo carbonates established. Interestingly, a complete anti selectivity (>20:1 anti:syn) was observed when both the syn 3-methyl and cis double-bond geometry were present (3b, 10, and 20). The anti relative configuration for all of the iodo carbonates was established by NMR, and that of 5b was confirmed by X-ray crystallography. This study demonstrated that the relative stereochemistry of the hydroxyl and C(3) methyl groups in combination with the cis or trans geometry of the alkene exerts a significant effect on the stereochemical outcome of the iodocarbonatation reaction. Methanolysis of the iodo carbonates produced the desired 3-methyl-4,5-epoxy alcohols. The application of this chemistry to the reiterative synthesis of polypropionates was carried out with epoxy alcohol 4a (anti isomer), producing a new homologated epoxy alcohol, 22, with six contiguous stereocenters in a highly stereoselective manner.