Multiple roles of aryloxide leaving groups in enantioselective annulations employing α,β-unsaturated acyl ammonium catalysis

Mark Greenhalgh, Shen Qu, Alexandra Slawin, Andrew D. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

An isothiourea-catalysed Michael addition-annulation process using β-fluoroalkyl-substituted α,β-unsaturated aryl esters and a range of 2-acylbenzazoles is reported for the enantioselective synthesis of dihydropyranone and dihydropyridinone products bearing polyfluorinated stereocentres (29 examples, up to 98% yield, > 99:1 er). The choice of aryl group of the aryl ester proved essential in determining reaction enantioselectivity and dihydropyranone:dihydropyridinone product selectivity. The aryloxide leaving group is shown to play a number of essential additional roles, operating (i) as a Brønsted base, circumventing the need for an auxiliary base; and (ii) as a Lewis base to catalyse the isomerisation of dihydropyranone products into thermodynamically-favoured dihydropyridinones. After optimisation, this isomerisation process was exploited for the selective synthesis of dihydropyridinone products using acylbenzothiazoles, and either dihydropyranone or dihydropyridinone products using acylbenzoxazoles. Finally, the phenol derivative, produced following protonation of the aryloxide, is proposed to act as a Brønsted acid, which promotes an isothiourea-catalysed kinetic resolution of benzoxazole-derived dihydropyranones.
Original languageEnglish
Pages (from-to)4909-4918
Number of pages10
JournalChemical Science
Volume9
Issue number21
Early online date4 May 2018
DOIs
Publication statusPublished - 7 Jun 2018

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