Continuous-flow biocatalysed kinetic resolution of 4-fluorophenyl-furan-2-yl methanol

Abstract

Enantiomerically pure secondary alcohols are useful in the synthesis of several natural products and as active pharmaceutical intermediates (API). Due to the high demand for these chiral compounds, much progress has been made in the areas of asymmetric synthesis and catalysis. In this context, biocatalysis together with continuous flow technology can be a valuable tool for more versatile and sustainable methods, with lower cost, greater stereoselectivity and less environmental impact. This work aims to obtain an enantiomerically pure alcohol of industrial interest, (4 Fluorophenyl) (furan-2-yl) methanol (3), by performing a kinetic resolution using immobilized Candida antarctica lipase B (Novozyme 435, N435) under continuous-flow conditions. Initial study was carried out to optimize batch reaction conditions. The best results were obtained using isooctane as solvent, 37.7 mg of N435 and three equivalents of isopropenyl acetate as acyl donor at 60 °C for 24 h. Under these conditions, a conversion of 49% and 91 of enantiomeric ratio was obtained. Optimized batch conditions were translated to the continuous flow reactor leading to the desired product in 30 min of residence time, 47% conversion and an enantiomeric ratio of 61.

Keywords:

• Flow chemistry
• biocatalysis
• kinetic resolution
• continuous flow
• lipases

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

The authors acknowledge the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico – CNPq) and Carlos Chagas Filho Foundation for Support of Research of the State of Rio de Janeiro (Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro – FAPERJ) for financial support. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001.