The reaction of unprotected 1,4-dihydropyridine Hantzsch esters with Grignard reagents: Preparation of unsymmetrical 1,4-dihydropyridine derivatives

Abstract

The mild bromine-magnesium exchange reaction using i-PrMgBr in THF on the 2-bromomethyl-1,4-dihydropyridine Hantzsch esters allowed the synthesis of highly functionalized magnesiated 1,4-dihydropyridines with ester groups tolerance. Treatment of the resulting anionic intermediates with hard electrophile methyl iodide gave N-methylated product 6 and pyridine derivative 7 in 60 % and 10 % yields, respectively. In trapping the reaction mixture of magnesiated 1,4-dihydropyridine with ethyl bromide, pyridine derivative 8, and dimer 9 were obtained. Also, FeCl3-catalyzed cross-coupling reaction of allylMgBr, i-PrMgBr, and n-BuMgBr Grignard reagents with 2-bromomethyl-1,4-dihydropyridine derivative 2 afforded unsymmetrical 1,4-dihydropyridine derivatives 10a-c in good yields.