Assessing the scope of reductive cyclisations of lactones using SmI2-H2O

Abstract

This report firstly describes the 5-exo-dig,6-exo-trig cascade cyclisation of 6-membered allenyl lactones for the formation of highly decorated 7,6-fused bicycles using the SmI2-H2O reducing system.Preliminary studies showed that 5-exo-dig,5-exo-trig cascade reactions successfully yield 7,5-fused bicycles. However, performance of 6-exo-trig reactions of this type with SmI2 has little literature precedent and was not known to proceed with SmI2 in combination with H2O.In order to investigate the cascade cyclisations, cis and trans allenyl lactones with alkene or alkyne chains tethered at the 2-position were successfully synthesised using a Barbier-type lactonisation reaction.Initial results using trans lactones with terminal alkene tethers yielded 5-exo-dig monocyclisation products as the major product and the corresponding 7,6-fused cascade cyclisation product as a minor component of the reaction. 5-exo-dig,6-exo-dig cascade cyclisation, as well as 5-exo-trig,6-exo-trig cyclisation attempts were not successful. Allenyl lactones containing alkene chains with a radical stabilising aryl group underwent cascade cyclisation to give the 7,6-fused ring systems as the major products.Secondly, the effect of a leaving group allowing for a beta-elimination upon reductive radical cyclisations of lactones, Meldrum's acids and barbituric acids was investigated.Using SmI2-H2O, 5-, 6-, and 7-membered lactones substituted with alkenyl radical accepting tethers containing an allylic pivalate as a leaving group successfully underwent monocyclisation to yield vinylic products. Allenyl lactones, as well as lactones with alkenyl radical acceptors at the 5-position also yielded 5-exo-dig,5-exo-trig/elimination, 5-exo-dig,6-exo-trig/elimination and 5-exo-trig,5-exo-trig/elimination products, respectively.A Meldrum's acid derivative, as well as a barbituric acid derivative decorated with the same allyl pivalate tether also gave desired vinylic cyclisation products.Manipulation of the vinyl moiety of a monocyclisation product, involving hydroboration/oxidation and Wacker oxidation, were also successfully performed.

Date of Award	6 Jan 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	David Procter (Main Supervisor) & Louise Natrajan (Co Supervisor)