Development of the (4+1) annulation reaction between 1,3-dienes and sulfonium ylides

by Olivier Rousseau

Institution: Université Catholique de Louvain
Year: 2016
Keywords: (4+1) annulation; (4+1) cycloaddition; Sulfur ylide; Sulfonium ylide; Vinylcyclopropane; Diene; Five-membered carbocycle; Ylide; Five-membered ring
Posted: 02/05/2017
Record ID: 2126648
Full text PDF: http://hdl.handle.net/2078.1/173837


Five-membered carbocycles are key structures which are present in a large range of biologically important targets. The development of methodologies for the construction of these systems is thus a fundamental and important issue in organic chemistry. Accordingly, recent years show a growing interest in the development of a (4+1) strategy toward five-membered carbocycles. Most reported (4+1) cycloaddition strategies towards five-membered carbocycles involve addition of carbenes onto 1,3-dienes or vinylketenes. The high reactivity of carbenes is however responsible for a low functional group tolerance. In order to contribute to the development of an effective and general (4+1) annulation strategy, we decided to investigate the reaction between 1,3-diene and sulfur ylide. Indeed, sulfur ylides are known to react as carbenoids. In addition, they are easy to handle and compatible with most functionalities. In the event, we found that sulfonium ylides react with electron poor 1,3-dienes to lead selectively to the corresponding vinylcyclopropanes, with no traces of cyclopentenes. However, we found that rearrangement of these vinylcyclopropanes into cyclopentenes proceeds smoothly in the presence of a catalytic amount of magnesium iodide. A one-pot process of this methodology has been successfully developed. The use of chiral sulfonium ylides allows generating cyclopentenes with excellent enantiomeric excesses. (SC - Sciences)  – UCL, 2016 Advisors/Committee Members: UCL - SST/IMCN/MOST - Molecules, Solids and Reactivity, UCL - Faculté des Sciences, Aggarwal, Varinder Kumar, Robiette, Raphaël, Peeters, Daniel, Monbaliu, Jean-Christophe, Riant, Olivier, Singleton, Michael.