INTRAMOLECULAR SCHMIDT REACTIONS OF AZIDES WITH CARBOCATIONS - SYNTHESIS OF BRIDGED-BICYCLIC AND FUSED-BICYCLIC TERTIARY-AMINES

Aliphatic azides were captured intramolecularly by carbocations, producing aminodiazonium ion intermediates. Carbon-to-nitrogen rearrangement then occurred, generating bridged- or fused-bicyclic alpha-amino carbocations or iminium ions, depending on the geometry about the C(+)-N bond. In the bridged systems, rapid elimination of the alpha-amino carbocations produced twisted enamines with 1-azabicyclo[3.2.2]nonene, 1-azabicyclo[2.2.2]octene, and 1-azabicyclo[3.2.1]octene skeletons. In the fused systems, the iminium ions were reduced with sodium borohydride to give 1-azabicyclo[n.3.0]alkanes, where n = 4 or 5. The carbocations for these intramolecular Schmidt reactions were generated by treatment of alkenes or alcohols with trifluoromethanesulfonic acid. In some cases, carbocation rearrangement was found to be fast relative to capture by the azide. The regioselectivity of the carbon-to-nitrogen shift was proposed to be due to both electronic and stereoelectronic factors. The aminodiazonium ion intermediates were modeled by a combination of molecular mechanics and AM1 semiempirical molecular orbital calculations. Alkaloids indolizidine 167B and indolizidine 209D were synthesized using this methodology.