CONFORMATIONAL-ANALYSIS OF MARINE POLYHALOGENATED BETA-CHAMIGRENES THROUGH TEMPERATURE-DEPENDENT NMR-SPECTRA

Temperature-dependent H-1- and C-13-NMR spectra reveal that polyhalogenated marine beta-chamigrenes or synthetic derivatives thereof which are trans-diequatorially substituted at C(8) and C(9), such as rogiolol ((-)-2), obtusol ((+)-3), and their acetates (+)-1 and (-)-4, undergo slow ring-A chair-chair inversion. Conformational equilibria and kinetics are investigated with the aid of synthetic model compounds and molecular-mechanics calculations. Thus, steric repulsions between Br(ax)-C(2) and H(eq)-C(7) are seen to disfavor thermodynamically conformers 1b, 2b, 3b, and 4b, which can only be detected through cross-saturation transfer, while additional steric repulsions between Me(ax)-C(1) and OH(ax)-C(3) make conformer 8b of obtusol epimer so scarcely populated that it can not be detected. In agreement, with (+)-9 and (+)-10, which have a trigonal C(2), two conformers can be directly observed by NMR. The kinetic barriers, which are seen to arise mainly from steric repulsions between H(ax)-C(14) and the axial H or halogen atoms at C(8) and C(10), are calculated and discussed with respect to well documented exocyclicmethylidene-substituted cyclohexane(ene) systems. This helps to rationalize why in rogiolol acetate ((+)-1) ring B is unusually inert towards Zn/Et2O/AcOH which causes bromohydrine-group elimination from ring A.