Regioselective Reactions of Organozinc Reagents with 2,4-Dichloroquinoline and 5,7-Dichloropyrazolo[1,5-a]pyrimidine

Strategies for controlling the regioselective reactions between 2,4-dichloroquinoline and organozinc reagents are described. 2,4-Dichloroquinoline has been found to react with benzylic zinc and phenylzinc reagents in the presence of catalytic amounts of palladium complexes to exclusively give α-substituted products. Several metal salts were examined as an additive for γ-selective coupling reactions. The most effective additive for selective coupling reaction at the γ-position has been found to be LiCl. These conditions for α- or γ-selective coupling reactions were applied to the reaction between 5,7-dichloropyrazolo[1,5- a ]pyrimidine and a biphenylmethylzinc reagent in the synthesis of the angiotensin II receptor antagonists. This regioselectivity should be generally applicable to other α,γ-dichloroazine systems.