Practical method for crystalline-liquid resolution of chrysanthemic acids utilizing chiral 1,1′-binaphthol monoethyl ethers directed for process chemistry

Abstract

We have developed an efficient practical resolution method for (1 R,3 R)- trans-chrysanthemic acid 1 and (1 R,3 S)- trans-2,2-dimethyl-3-(2,2-dichloroethenyl)cyclopropanecarboxylic acid 2, based on the preliminary results of the simpler analogues, (1 R)-2,2-dichlorocyclopropanecarboxylic acid 3 and (1 R)-2,2-dimethylcyclopropanecarboxylic acid 4, using a crystalline-liquid separation procedure (without column chromatography) with chiral 1,1′-binaphthol monoethyl ethers ( R)- 5b as the key auxiliary. Direct esterifications of 1, 2, 3, and 4 with ( R)- 5b gave four sets of (1 R)- and (1 S)-diastereomeric esters 8, 9, 6, and 7, respectively, with markedly different melting points. All of these diastereomers were easily obtained using a simple and one-step crystalline-liquid separation. The separated diastereomers 8 and 9 were easily hydrolyzed to the desired enantiopure acids 1 (>98%) and 2 (>99%), respectively, with recovery of ( R)- 5b (>90%).