Preparation of trans- and cis-2-allyl-6-alkyl(aryl)-1,2,3,6-tetrahydropyridines based on the reductive trans-2,6-dialkylation of pyridine. Synthesis of (+/-)-epidihydropinidine and (+/-)-dihydropinidine

Article abstract of DOI:10.1007/BF02495652

A general method for the preparation of unsymmetrical trans-2-allyl-6-alkyl(aryl)-1,2,3,6-tetrahydropyridine 6 based on a combination of 1,2-addition of RLi to pyridine and trans-6-allylation with triallylborane in the presence of methanol was elaborated.It was shown that trans-piperidines 6 (R = Alk, Ph) isomerize into the corresponding cis-2-allyl-6-alkyl(phenyl)-3-piperidines 14 on heating with triallylborane followed by deboronation of aminoborane (16) with methanol and an alkali.The stereochemistry of compounds 6 and 14 was determined by two-dimensional NOE spectroscopy.A possible mechanism of the formation of trans-amines 6 and their transformation into cis-isomers discussed.Alkaloids (+/-)-epidihydropinidine (trans-2-methyl-6-propylpiperidine 2a, 70percent) and (+/-)-dihydropinidine (cis-2-methyl-6-propylpiperidine 1d, 71percent) were synthesized by hydrogenation of compound 6a (R = Me) and 14a (R = Me), respectively, over Raney nickel. - Keywords: allylboration; pyridine, 1,2-addition, alkyl(aryl)lithium, triallylborane; trans- and cis-2-allyl-6-alkyl(aryl)-1,2,3,6-tetrahydropyridines; trans-cis-isomerization; stereochemistry; piperidine alkaloids; (+/-)-epidihydropinidine; (+/-)-dihydropinidine.