An efficient synthesis of (±)-crinane using an intramolecular azide-olefin cycloaddition

Article abstract of DOI:10.1016/0040-4020(95)01098-X

Refluxing 3-(2-azidoethyl)-3-[3,4-(methylenedioxy)phenyl]cyclohex-1-ene (2) in toluene for 24 hours afforded 3a-[3,4-methylenedioxy)phenyl]-3,3a,4,5,6,7-hexahydro-2H-indole (12) in quantitative yield. This reaction proceeds by intramolecular 1,3-dipolar cycloaddition of the azide onto the alkene followed by loss of nitrogen from the triazoline intermediate to give an imine. Reduction of the imine 12 with sodium cyanoborohydride in acetic acid/THF gave (3aR*, 7aR*)-3a-[3,4-methylenedioxy)phenyl]-2,3,3a,4,5,6,7,7a-octahydroindol e (13). Warming 13 with Eschenmoser's salt provided (±)-crinane (1). The synthesis of (±)-crinane (1) from cyclohexenone was accomplished in 8 steps in 23% overall yield.