Solid-phase synthesis of cyclic sulfonamides and sulfamides employing a ring-closing metathesis cleavage strategy

Moriggi, Jean-Dominique Francois Michel (2001) Solid-phase synthesis of cyclic sulfonamides and sulfamides employing a ring-closing metathesis cleavage strategy. University of Southampton, Doctoral Thesis.

Abstract

A series of novel 7-membered cyclic sulfonamides and sulfamides were prepared in good to excellent yields using a ring-closing metathesis (RCM) approach. Model studies in solution indicated the sulfonamides were suitable substrates for RCM and they were thus employed on the solid-phase. A strategy that involved simultaneous cyclisation and cleavage from the resin was developed and applied to the synthesis of cyclic sulfonamides. The solid supports used included commercially available Merrifield resin and a carboxyethyl resin derived from the former. The effect of three different linkers upon the efficiency of the reaction was investigated: a relatively inflexible allylic linker, a flexible linker and a novel double armed linker. Whereas the RCM cleavage strategy failed when using the inflexible linker, cyclisative release from the more flexible single and double armed linkers proceeded efficiently using 5 mol% of catalyst. In fact, the double armed linker was successfully employed even with 1 mol% of catalyst. Following a similar strategy, the synthesis of 7-membered cyclic sulfamides met with success in the solution-phase but preliminary efforts to transfer it to the solid-phase failed in part due to lack of time. Methods for hydroxylation of the double bond on the sulfamides were developed leading to potential HIV protease inhibitors.

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