STEREOCONTROLLED PREPARATION OF CIS-2,6-DIALKYLPIPERIDINE AND TRANS-2,6-DIALKYLPIPERIDINE VIA 1-ACYLDIHYDROPYRIDINE INTERMEDIATES - SYNTHESIS OF (+/-)-SOLENOPSIN-A AND (+/-)-DIHYDROPINIDINE

The stereoselective reduction of 1-(tert-butoxycarbonyl)-4-chloro-2,6-dialkyl-1,2-dihydropyridines 6 and 22 was studied. Reduction of 6 with Et3SiH/TFA gave the cis-2,6-dialkyl-1,2,5,6-tetrahydropyridine 7 as the major product. The stereoselectivity was reversed by reducing 6 with NaBH3CN/TFA, which gave predominantly the trans-2,6-dialkyltetrahydropyridine 10. Catalytic hydrogenation of 7 and 10 gave the corresponding N-Boc-cis(or trans)-2,6-dialkylpiperidines. Regioselective hydrogenation of 6 gave the 1,2,3,4-tetrahydropyridine 18, which on treatment with NaBH3CN/TFA provided a 90:10 mixture of trans- and cis-piperidines 15 and 16. More vigorous hydrogenation of 6 afforded the cis-piperidine 15 with 96% stereoselectivity. Similar stereoselective reductions of dihydropyridine 22 were carried out. Stereoselective reductions of dihydropyridines 6 and 22 were utilized in the synthesis of (+/-)-solenopsin A and (+/-)-dihydropinidine from 4-chloropyridine in six and five steps, respectively.