Isomerisation of Vinyl Sulfones for the Stereoselective Synthesis of Vinyl Azides

Reported is the construction, and facile base-mediated conversation of ten differently substituted 3-azidoE-vinyl sulfones (gamma-azido-alpha,beta-unsaturated sulfones) into their isomeric vinyl azide counterparts. The requisite 3-azidoE-vinyl sulfones were prepared from 3-bromoE-vinyl sulfones, which in turn were accessed from allyl sulfones via a bromination-elimination sequence. In relation to this a one-pot azidation-isomerisation sequence was developed which enabled the direct formation of the vinyl azides from the corresponding 3-bromoE-vinyl sulfones. Similarly, a convenient one-pot Horner-Wadsworth-Emmons olefination-isomerisation approach was utilised in order to prepare some of the allylic sulfones used in this study. The vinyl azide forming process typically proceeded with high levels of Z-selectivity, although this was dependent on the vinyl sulfone substitution pattern. Thus, with either no substituent or a methyl group in the gamma- or beta-position, relative to the sulfone, good, to high levels of Z-selectivity (Z/E= 85:15 to >= 95:5) were obtained. However, incorporation of an alpha-sulfonyl methyl substituent led to anE-selective process (Z/E= 20:80). A non-bonding interaction between the azido group and the alpha-sulfonyl vinylic proton is proposed, which acts as a conformational control mechanism to help guide the stereochemical outcome.