A new convenient synthesis of 2-substituted quinolizidines was developed. Basecatalyzed cyclization of 4-(2-chloromethylpiperidin-1-yl) butyronitrile (14) afforded 2-cyanoquinolizidines (17a and 17b), which were converted to 2-ethoxycarbonyl- (18a and 18b), 2-benzoyl- (19a and 19b) and 2-thenoylquinolizidines (20a and 20b). Quinolizidine (18a) was transformed via diarylmethanol derivatives (21a and 22a) into 5-alkyl-2-diarylmethylenequinolizidinium bromides (2), which exhibit potent anticholinergic activities. 2-Ethoxycarbonyl- (18a and 18b) and 2-benzoyl-quinolizidines (19a and 19b) were also obtained by cyclization of the chloroester (15) and the chlorobenzoyl derivative (16), respectively. The stereochemistry of all 2-substituted quinolizidines synthesized here was established.
