Bromophosphatation as a mode of chiral phosphoric acid catalyst deactivation as elucidated by kinetic profiling
Author(s)
Braddock, David
Lancaster, Ben
Tighe, Christopher
White, andrew
Type
Journal Article
Abstract
A BINOL-derived chiral phosphoric acid (R)-1 was shown by kinetic profiling to be deactivated during the catalytic bromoesterification of cyclohexene. The products of the deactivation were identified as diastereoisomeric phosphates (R,1R,2R)-3a and (R,1S,2S)-3b and are formed via an alkene bromophosphatation process where the phosphate of 1 behaves as a competitive nucleophile, as confirmed by authentic preparations of 3a and 3b from a stoichiometric bromophosphatation reaction. HPLC separation of the diastereoisomers gave pure 3a whose absolute and relative configurations were proven by single-crystal X-ray diffraction. The 31P{1H} NMR spectrum of phosphate 3a displayed four resonances despite 3a having just one phosphorus atom, and combined VT-NMR and DFT analysis revealed this to be a consequence of rotational isomerism about the 9-phenanthrene (Ar) bearing C3,3′–Ar bonds. Moreover, kinetic studies using variable time normalization analysis (VTNA) of the catalytic cyclohexene bromoesterification showed first order kinetics in all reactants. The amount of phosphates 3a and 3b formed under catalytic bromoesterification conditions was quantified, enabling tracking of the temporal catalyst 1 concentration and hence elucidation of first order kinetics in catalyst 1. A catalytic cycle consistent with these observations is proposed.
Date Issued
2025-05-30
Date Acceptance
2025-04-28
Citation
Journal of Organic Chemistry, 2025, 90 (21), pp.6992-7002
ISSN
0022-3263
Publisher
American Chemical Society
Start Page
6992
End Page
7002
Journal / Book Title
Journal of Organic Chemistry
Volume
90
Issue
21
Copyright Statement
© 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
License URL
Identifier
10.1021/acs.joc.5c00431
Publication Status
Published
Date Publish Online
2025-05-20