A unified asymmetric approach to substituted hexahydroazepine and 7-azabicyclo[2.2.1]heptane ring systems from D(-)-quinic acid: Application to the formal syntheses of (-)-balanol and (-)-epibatidine

Article abstract of DOI:10.1016/S0040-4020(97)10139-9

3,4-O-Isopropylidene-3(R),4(S)-dihydroxycyclohexanone 7, a chiron easily prepared through a five step sequence from D(-)-quinic acid 1, has been efficiently utilized as the starting building block for the enantioselective syntheses of (3R,4S)-N-p-toluenesulfonyl-3,4-epoxy-hexahydroazepine 17 and (1R,4S)-N-tert-butoxycabonyl-7-azabicyclo[2.2.1]heptan-2-one 43, advanced intermediates already taken to (-)-balanol and (-)-epibatidine respectively. While the nitrogen atom ring insertion via Beckmann rearrangement was the key step for the construction of the hexahydroazepine ring of 17, a regio- and stereospecific intramolecular nucleophilic ring opening of an intermediate cyclic sulfate featured the approach to the substituted 7-azabicyclo[2.2.1]heptane nucleus of 43.