Bromophosphatation as a Mode of Chiral Phosphoric Acid Catalyst Deactivation as Elucidated by Kinetic Profiling

动力学分析阐明溴磷酸化作为手性磷酸催化剂失活的一种模式

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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 (31)P{(1)H} 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.

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