Synthesis of 4- and 5-membered nitrogen-containing heterocycles from homoallyl amines

Bird, Harry ORCID: 0000-0003-4820-198X (2023). Synthesis of 4- and 5-membered nitrogen-containing heterocycles from homoallyl amines. University of Birmingham. Ph.D.

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Abstract

Nitrogen-containing heterocycles are important structural motifs for the pharmaceutical industry with a least one nitrogen-containing heterocycle found in 640 out of 1086 FDA approved drugs. Our group have previously reported the synthesis of cis-azetidine and cis-pyrrolidine derivatives via the iodine mediated cyclisation of homoallyl amines with thermally controlled regioselectivity. More recently the group has developed the electrochemical mediated cyclisation of γ-aminoalkenes into phenylselanyl pyrrolidines with selectivity controlled by the addition or omission of sodium methoxide.

Herein is reported the exploration of new methodologies towards the synthesis of azetidine and pyrrolidine compounds from homoallylic amine starting materials. Three approaches are discussed: palladium-catalysed carboamination, hypervalent iodine mediated cyclisation and electrochemical mediated cyclisation. Although no azetidines were isolated from these methodologies, pyrrolidine products were obtained from hypervalent iodine and electrochemical mediated cyclisations. Despite achieving regioselective synthesis of pyrrolidine product with hypervalent iodine reaction conditions, the method is limited by poor yields at its current state. The electrochemical method had the greatest success with excellent yield of 96% obtained for one compound. However, synthesis of 3-iodopyrrolidines with the electrochemical reaction conditions were low yielding and therefore the previously reported iodine mediated synthesis of iodopyrrolidines remains superior.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):