Highly Regioselective α-Addition of Alkynyl and Alkenyl Grignard Reagents to 1-Alkoxycarbonylpyridinium Salts and Its Application to Synthesis of 1-Azabicycloalkanes and (±)-Solenopsin A

Nucleophilic addition of a variety of alkynyl and alkenyl Grignard reagents to 1-methoxycarbonylpyridinium chloride takes place at the α-position in a highly regioselective manner to give 2-substituted 1-methoxycarbonyl-1,2-dihydropyridines exclusively, while, with alkyl Grignard reagents, a lack of the regioselectivity is observed. These results may be explained by the HSAB principle. The high α-regioselectivity is preserved in the cases of 2-substituted pyridines as well, giving 2,6-disubstituted 1,2-dihydropyridines exclusively, which can be transformed stereoselectively into cis- and trans-2,6-dialkylated piperidines. These highly regioselective α-alkynylations of 1-methoxycarbonylpyridinium salts are exploited in synthesis of 1-azabicycloalkanes as well as (±)-solenopsin A.