Quinolizidines. I. Quaternization of the quinolizidine system: effect of .BETA.,.GAMMA.-unsaturation on stereoselectivity in methiodide formation.

Abstract

Quaternization of benzo [a] quinolizidine (Ib) with methyl iodide gave a 3.6 : 1 mixture of the cis- (IIb : X=I) and the trans-methiodide (IIIb : X=I). The 9, 10-dimethoxy derivative (Ia) also gave the corresponding cis- (IIa : X=I) and trans-methiodide (IIIa : X=I) in a ratio of 3.3 to 1. Treatment of enamines Va, b with methyl iodide furnished the N-methylated product (VIa, b) and the C-methylated product (VIIa, b) in a ratio of 1.2 : 1. Catalytic hydrogenation of VIa, b produced a mixture of the cis- (IIa, b) and the trans-methosalt (IIIa, b) in a rough ratio of 2.8 : 1, whereas that of VIIa, b gave the 1-methylated benzo [a] quinolizidine (VIIIa, b). Compound VIIIa was alternatively prepared from piperidone IX by the Bischler-Napieralski cyclization and subsequent hydrogenation. In the case of the simple quinolizidine system with the simplest β, γ-unsaturation (XV), the quaternization with methyl iodide produced the cis- (XVI) and the trans-methiodide (XVII) almost equally. Repetition of the known methiodide formation of XXVI and hydrogenation of enamine methiodide XIX confirmed their reported high stereoselectivity, and factors responsible for the difference in stereoselectivity between these reactions of the β, γ-unsaturated system and the saturated system have been discussed. At 250° the cis-methiodides (IIa, b, XX) isomerized to the corresponding trans-fused salts (IIIa, b, XXI) to some extent and one may roughly compare the susceptibilities of IIa, IIb, and XX, which decrease in that order.