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

A BINOL-derived chiral phosphoric acid (<i>R</i>)-<b>1</b> was shown by kinetic profiling to be deactivated during the catalytic bromoesterification of cyclohexene. The products of the deactivation were identified as diastereoisomeric phosphates (<i>R</i>,1<i>R</i>,2<i>R</i>)-<b>3a</b> and (<i>R</i>,1<i>S</i>,2<i>S</i>)-<b>3b</b> and are formed via an alkene bromophosphatation process where the phosphate of <b>1</b> behaves as a competitive nucleophile, as confirmed by authentic preparations of <b>3a</b> and <b>3b</b> from a stoichiometric bromophosphatation reaction. HPLC separation of the diastereoisomers gave pure <b>3a</b> whose absolute and relative configurations were proven by single-crystal X-ray diffraction. The ³¹P{¹H} NMR spectrum of phosphate <b>3a</b> displayed four resonances despite <b>3a</b> 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 <b>3a</b> and <b>3b</b> formed under catalytic bromoesterification conditions was quantified, enabling tracking of the temporal catalyst <b>1</b> concentration and hence elucidation of first order kinetics in catalyst <b>1</b>. A catalytic cycle consistent with these observations is proposed.