Sivaraman Raghu

Asymmetric Synthesis: Synthesis of (S) 2,3,5,6-Tetrahydro-6-Phenylimidazo[2,1-b]Thiazole (Levamisole)

Reduction of 1-(2-methoxyethyl)-3acyl-4-phenyl-4-imidazolin- 2-ones 7 (a-f) with (+) DIOP-Rh(COD)Cl as catalyst and hydrogen provide the corresponding optically active 1-(2-methoxyethyl)-3- acyl-4-phenyl-2-imidazolidones 8 (a-f) in greater than 90 percent yield and in up to 33 percent enantiomeric excess. The latter were hydrolyzed to l-(2-methoxyethyl)-4-phenyl-2-imidazolidone 5b. Further reaction of 5b with phosphorus pentasulfide followed by cyclization with hydrochloric acid provides the same degree of enantiomeric excess of the anthelmintic (S) 2,3,5,6-tetrahydro-6- phenylimidazo[2,1-b]thiazole (levamisole).