PREPARATION OF TRANS AND -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/
Yn. Bubnov et al., PREPARATION OF TRANS AND -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/, Russian chemical bulletin, 47(3), 1998, pp. 451-458
A general method for the preparation of unsymmetrical s-2-allyl-6-alky
l(aryl)1,2,3,6-tetrahydropyridines 6 based on a combination of 1,2-add
ition of RLi to pyridine and trans-6-allylation with triallylborane in
the presence of methanol was elaborated. It was shown that trans-pipe
rideines 6 (R = Alk, Ph) isomerize into the corresponding cis-2-allyl-
6-alkyl(phenyl)-3-piperideines 14 on heating with triallylborane follo
wed by deboronation of aminoborane (16) with methanol and an alkali. T
he stereochemistry of compounds 6 and 14 was determined by two-dimensi
onal NOE spectroscopy. A possible mechanism of the formation of trans-
amines 6 and their transformation into cis-isomers 14 is discussed. Al
kaloids (+/-)-epidihydropinidine (trans-2-methyl-6-propylpiperidine 2a
, 70%) and (+/-)-dihydropinidine (cis-2-methyl-6-propylpiperidine 1d,
71%) were synthesized by hydrogenation of compound 6a (R = Me) and 14a
(R = Me), respectively, over Raney nickel.