CHEMOENZYMATIC SYNTHESIS OF (S)-ALPHA-CYANO-3-PHENOXYBENZYL ALCOHOL

A chemo-enzymatic process for the preparation of (S)-alpha-cyano-3-phe noxybenzyl alcohol (S-CPBA), an important intermediate in the synthesi s of many pyrethroids, was developed. The process consists of four sta ges, including lipase-mediated resolution. The first stage, the synthe sis of racemic alpha-cyano-3-phenoxybenzyl acetate (CPBAc) from m-phen oxybenzaldehyde (m-PBA) and sodium cyanide in the presence of phase tr ansfer catalyst, resulted in a 75 % yield with 95 % purity. The second key step is the resolution of the racemic ester by a highly enantiose lective lipase from Pseudomonas sp. The immobilized enzyme carried out the transesterification reaction to nearly full conversion (46 % out of 50 %) with an enantiomeric excess of > 96 %. The enzymatic reaction was accomplished in a batch system as well as in a fluidized bed colu mn. The reaction was found to be inhibited by accumulation of the prod uct and to a lesser extent, by the aldehyde. The separation of the ena ntiomerically pure alcohol from the undesired ester was performed by c hromatographic techniques, as well as by extraction with hexane. The f inal racemization step of the (R)-ester was easily attained with the u se of triethylamine in diisopropyl ether or toluene. The process was s hown to be feasible on a gram scale and shows potential for scale up. (C) 1998 Elsevier Science Ltd. All rights reserved.