Practical chemo-enzymatic process for the preparation of (1R, cis)-2-(2,2-dihaloethenyl)-3,3-dimethylcyclopropane carboxylic acids

A practical chemo-enzymatic process for the preparation of optically active (1R,cis)-2-(2,2-dichloro (or dibromo)ethenyl)-3,3-dimethylcyclopropane car boxylic acids (permethrinic or deltamethrinic acids) from racemic 1,1,1-tri chloro-2-acetoxy-4-methyl-3-pentene is described. The key intermediate, ena ntiopure (R)-1,1,1-trichloro-2-hydroxy-4-methyl-3-pentene, is prepared by a Lipase catalysed kinetic resolution of the racemic acetate, The reaction m ixture, containing (R)-alcohol and the unreacted (S)-acetate, is directly a cetylated by a haloacetyl halide, and the products are separated by distill ation. 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 stereoselectiv e carbenic dediazotization of the (R)diazoacetate furnishes the optically a ctive (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%.