Continuous Flow Preparation of Enantiomerically Pure BINOL(s) by Acylative Kinetic Resolution

A polystyrene‐immobilized isothiourea has been applied to the enantioselective acylative kinetic resolution (KR) of monoacylated BINOL(s) with inexpensive isobutyric anhydride in batch and flow. High selectivity values ( s =29 at 0 °C) and a remarkable stability of the catalytic system in the operation conditions have been recorded for unsubstituted BINOL. No significant loss of activity/selectivity is recorded after 10 consecutive KR cycles in batch. A continuous flow process has been implemented and operated with a 100 mmol (32.8 g) sample of racemic monoacetylated BINOL in dichloromethane solution in an 84 hours experiment with a packed bed reactor containing 1 g ( f =0.37 mmol.g −1 ) of the functional resin ( s =17–21). Residence time can be decreased to 10 min with the same reactor to achieve a conversion of 58% with a selectivity factor s =17 when a more highly functionalized catalyst ( f =0.88 mmol.g −1 ) is used. This translates into a remarkable combined productivity of 5.5 mmol prod  ⋅ mmol cat −1  ⋅ h −1 .