Unexpected cascade synthesis of 1-azabicyclo[3.3.1]nonanes by nucleophilic reaction of bis(2-aroylethyl)methanamines with dimethyl acetylenedicarboxylate

Abstract

SHORT COMMUNICATIONS Schwan and Warkentin [1] previously synthesized 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridin-4-ol in one step by reaction of 3-(dimethylamino)-1-phenylpropan-1-one with dimethyl acetylenedicarboxylate. We have studied the reaction of dimethyl acetylenedicarboxylate with 3,3′-(methylimino)bis(1-phenylpropan-1-one) (1) and 3,3′-(methylimino)bis[1-(thiophen-2-yl)propan-1-one] (2). Tertiary amines 1 and 2 each possess two reactive carbonyl groups in the β-position with respect to the nitrogen atom, which makes it difficult to predict the reaction direction.We have found that the reactions of 1 and 2 with dimethyl acetylenedicarboxylate involve a sequence of transformations eventually leading to double cyclization products 3 and 4, respectively, which have the structure of polysubstituted azabicyclo[3.3.1]nonanes. Presumably, the cascade process begins with attack by amine 1 or 2 on the activated triple bond of dimethyl 1, 3, R = Ph; 2, 4, R = thiophen-2-yl.