Generation of tosyl azide in continuous flow using an azide resin, and telescoping with diazo transfer and rhodium acetate-catalyzed O-H insertion.

O'Mahony, Rosella M.; Lynch, Denis; O'Callaghan, Katie S.; Collins, Stuart G.; Maguire, Anita R.

Generation of tosyl azide in continuous flow using an azide resin, and telescoping with diazo transfer and rhodium acetate-catalyzed O-H insertion.

dc.contributor.author	O'Mahony, Rosella M.
dc.contributor.author	Lynch, Denis
dc.contributor.author	O'Callaghan, Katie S.
dc.contributor.author	Collins, Stuart G.
dc.contributor.author	Maguire, Anita R.
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	European Regional Development Fund	en
dc.date.accessioned	2022-01-19T13:50:54Z
dc.date.available	2022-01-19T13:50:54Z
dc.date.issued	2021-11-30
dc.date.updated	2022-01-19T13:41:36Z
dc.description.abstract	Generation of tosyl azide 12 in acetonitrile in flow under water-free conditions using an azide resin and its use in diazo transfer to a series of aryl acetates are described. Successful telescoping with a rhodium acetate-catalyzed O-H insertion has been achieved, thereby transforming the aryl acetate 8 to a-hydroxy ester 10, a key intermediate in the synthesis of clopidogrel 11, without requiring isolation or handling of either tosyl azide 12 or a-aryl-a-diazoacetate 9, or indeed having significant amounts of either present at any point. Significantly, the solution of a-diazo ester 9 was sufficiently clean to progress directly to the rhodium acetate-catalyzed step without any detrimental impact on the efficiency of the O-H insertion. In addition, the rhodium acetate-catalyzed O-H insertion process is cleaner in flow than under traditional batch conditions. Use of the azide resin offers clear safety advantages and, in addition, this approach complements earlier protocols for the generation of tosyl azide 12 in flow; this protocol is especially useful with less acidic substrates.	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	O’Mahony, R., Lynch, D., O’Callaghan, K., Collins, S. and Maguire, A., (2021) ‘Generation of Tosyl Azide in Continuous Flow Using an Azide Resin, and Telescoping with Diazo Transfer and Rhodium Acetate-Catalyzed O–H Insertion’, Organic Process Research & Development, 25 (12), pp.2772-2785. doi: 10.1021/acs.oprd.1c00377	en
dc.identifier.doi	10.1021/acs.oprd.1c00377	en
dc.identifier.endpage	2785	en
dc.identifier.issn	1083-6160
dc.identifier.issued	12	en
dc.identifier.journaltitle	Organic Process Research & Development	en
dc.identifier.startpage	2772	en
dc.identifier.uri	https://hdl.handle.net/10468/12425
dc.identifier.volume	25	en
dc.language.iso	en	en
dc.publisher	American Chemical Society	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Infrastructure Programme/15/RI/3221/IE/Process Flow Spectroscopy (ProSpect); Advanced Reaction Understanding using Flow Nuclear Magnetic Resonance (NMR) and Infrared (IR) Spectroscopies, with On-Line Ultra-Performance Liquid Chromatography (UPLC) and Mass Spectrometry (MS)/	en
dc.relation.uri	https://pubs.acs.org/doi/10.1021/acs.oprd.1c00377
dc.rights	© 2021 The Authors. Published by American Chemical Society	en
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	en
dc.subject	Diazo transfer	en
dc.subject	Azide resin	en
dc.subject	Sulfonyl azide generation	en
dc.subject	α-aryl-α-diazoacetate	en
dc.subject	Rhodium catalysis	en
dc.subject	O−H insertion	en
dc.title	Generation of tosyl azide in continuous flow using an azide resin, and telescoping with diazo transfer and rhodium acetate-catalyzed O-H insertion.	en
dc.type	Article (peer-reviewed)	en