Practical Chemo-Enzymatic Process for the Preparation of (1R,cis)-2-(2,2-Dinaloethenyl)-3,3-dimethylcyclopropane Carboxylic Acids

摘要

A practical chemo-enzymatic process for the preparation of optically active (1R,cis)-2-(2,2-dichloro (or dibromo) ethenyl)-3,3-dimethylcyclopropane carboxylic acids (permethrinic or deltamethrinic acids) from racemic 1,1,1-trichloro-2-acetoxy-4-methyl-3-pentene is described. The key intermediate, enantiopure (R)-1,1,1-trichloro-2-hydrocy-4-methyl-3-pentene, is prepared by a lipase catalysed kinetic resolution of the racemic acetate. The reaction mixture, containing (R)-alcohol and the unreacted (S)-acetate, is directly acetylated by a haloacetyl halide, and the products are separated by distillation. The (S)-acetate is racemized, and the (R)-haloacetate is transformed to the corresponding glycinate hydrochloride, followed by diazotization to (R)-1,1,1-trichloro-4-methyl-3-penten-2-yl diazoacetate. The stereoselective carbenic dediazotization of the (R)-diazoacetate furnishes the optically active (1R,4R,5S)-6,6-dimethyl-4-trichloromethyl-3-oxobicyclo[3.2.0] hexan-2-one, which is transformed to the desired enantiopure (1R, cis)-permethrinic or deltamethrinic acid in high optical yield (＞ 99% ee) and overall chemical yield of 10-15%.