Lipase-Mediated Dynamic Kinetic Resolution of 1-Phenylethanol Using Niobium Salts as Racemization Agents

Abstract

In this work, a racemization method of (S)-1-phenylethanol by niobium salts was developed. Among the salts available, the niobium phosphate hydrate (NbOPO4.nH2O) reduced the enantiomeric excess (ee) of the chiral alcohol from 95 to 0% after 24 h at 60 ºC in toluene. This new racemization agent was combined with a lipase (CALB) in order to achieve a chemoenzymatic dynamic kinetic resolution (DKR). Experiments demonstrated that the DKR process is feasible and the corresponding (R)-1-phenylethyl acetate was obtained with 92% conversion and 85% ee.

Kinetic and Dynamic Kinetic Resolution by Dual Catalysis

“…This system permitted the chemoenzymatic DKR of rac ‐1‐phenylethanol (Scheme 4). [43] The racemization ability was examined with various niobium salts such as NbOPO 4 ⋅ n H 2 O, Nb 2 O 5 ⋅ n H 2 O, NbCl 5 and NH 4 [NbO(C 2 O 4 )(H 2 O) x ] ⋅ n H 2 O. Among those, Nb 2 O 5 ⋅ n H 2 O showed excellent racemization activity.…”

“…This system permitted the chemoenzymatic DKR of rac-1-phenylethanol (Scheme 4). [43] The racemization ability was examined with various niobium salts such as NbOPO The same year, the group of Kim utilized a dual Ru-lipase catalyzed DKR in the asymmetric synthesis of biaryl diols. [44] The same group also reported a base-free DKR protocol using the combined action of a ruthenium-lipase dual catalytic system for the resolution of secondary alcohols (Table 8).…”

Ammonium Niobium Oxalate (ANO)

“…Four niobium compounds were tested, including ANO, and the enantiomeric excess (ee) of which reaction was measured after 3 and 24 h. Unfortunately, the racemization results using ANO were quite disappointing: 94 and 76% of ee after 3 and 24 h, while the best racemization results were found with niobium phosphate, with complete racemization resulting after 24 h. Starting from racemic 1-phenylethanol, using niobium phosphate as catalyst and CAL-B, vinyl acetate in toluene at 60 °C, (R)-1-phenylethyl acetate was obtained with 92% conversion and 85% ee. 10…”