A novel enzymatic tandem process: utilization of biocatalytic promiscuity for high stereoselective synthesis of 5-hydroxyimino-4,5-dihydrofurans

A lipase-catalyzed protocol for the synthesis of 5-hydroxyimino-4,5-dihydrofurans via tandem coupling between β-nitrostyrenes and 1,3-dicarbonyl compounds was developed in a ‘one-pot’ strategy. A series of β-nitrostyrenes were employed to expand the scope of this new biocatalytic promiscuity with high stereoselectivity (Z/E up to 99:1) and moderate to good yields. The reaction activity of 1,3-cyclohexanedione was found to be better than linear 2,4-pentanedione, while ethyl acetoacetate and diethylmalonate were not suitable for this reaction under the same conditions. Single-crystal X-ray diffraction analysis indicated that the reaction was stereoselective and Z-stereomer was found to be the major product. A reaction mechanism was supposed to elucidate the biocatalytic process.

Graphical abstractA tandem process for the preparation of 5-hydroxyimino-4,5-dihydrofurans derivatives via the reaction between β-nitrostyrene and 1,3-dicarbonyl compounds utilizing biocatalytic promiscuity was developed. A series of β-nitrostyrenes were employed to expand the scope of this new biocatalytic promiscuity with high stereoselectivity (Z/E up to 99:1) and moderate to good yields.Figure optionsDownload full-size imageDownload as PowerPoint slide