In collaboration with Prof. Varinder Aggarwal, we have developed practical protocols for the synthesis of a range of important heterocycles. Bromoethyldiphenylsulfonium triflate 1 acts as a C-2 linker unit to cyclize substrates such as aminoalcohols. It reacts with base to form a vinylsulfonium salt 2 which is a very reactive electrophile. A nucleophilic attack generates a sulfur ylide 3, which undergoes a proton transfer to give 4 followed by a second nucleophilic attack with displacement of diphenylsulfide.
Medicinally important compounds such as morpholines, thiomorpholines and piperazines can all be formed in high yield. This work has since been extended to 4-, 5- and 7-membered rings.
As a result of our research bromoethyldiphenylsulfonium triflate 1 is now commercially available from Aldrich ((2-Bromoethyl)diphenylsulfonium trifluoromethanesulfonate – Catalogue number: T706345).