Generation of tosyl azide in continuous flow using an azide resin, and telescoping with diazo transfer and rhodium acetate-catalyzed O-H insertion.
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Date
2021-11-30
Authors
O'Mahony, Rosella M.
Lynch, Denis
O'Callaghan, Katie S.
Collins, Stuart G.
Maguire, Anita R.
Journal Title
Journal ISSN
Volume Title
Publisher
American Chemical Society
Published Version
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.
Description
Keywords
Diazo transfer , Azide resin , Sulfonyl azide generation , α-aryl-α-diazoacetate , Rhodium catalysis , O−H insertion
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