Heterocycles

We have developed methods for the synthesis of bipyridines based on organosulfur chemistry. See the OrganoSulfur Chemistry page for more details.

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).

We have reviewed the topic in a recent book chapter:

Targets in Heterocyclic Systems, Vol 25, p78-99; Eds O A Attanasi, B Gabriele, P Merino, D Spinelli; Società Chimica Italiana; Rome, 2021. V K Duong, E M McGarrigle — Application of vinylsulfonium salts to the synthesis of heterocycles. Open Access: https://www.soc.chim.it/en/libri_collane/ths/vol_25_2021

Org Lett 2015, 17, 5044–5047. J V Matlock, T D Svejstrup, P Songara, S Overington, E M McGarrigle,* V K Aggarwal* — Synthesis of 6- and 7-Membered N-Heterocycles Using α-Phenylvinylsulfonium Salts. DOI: 10.1021/acs.orglett.5b02516

See All Publications for more details.

This research was supported by funding from EPSRC and GSK.