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

## TL;DR

This study explains how a chiral phosphoric acid catalyst breaks down during a chemical reaction, using detailed kinetic and structural analysis.

## Contribution

The paper identifies bromophosphatation as a new mode of catalyst deactivation and provides a detailed mechanistic explanation.

## Key findings

- Deactivation products were identified as diastereoisomeric phosphates formed via bromophosphatation.
- 31P{1H} NMR showed four resonances due to rotational isomerism in the phosphate structure.
- Kinetic studies confirmed first-order dependence on all reactants and catalyst concentration.

## 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.