Conformational Analysis of Marine Polyhalogenated β‐Chamigrenes Through Temperature‐Dependent NMR Spectra

Temperature‐dependent 1H‐ and 13C‐NMR spectra reveal that polyhalogenated marine β‐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 Brax–C(2) and Heq–C(7) are seen to disfavour thermodynamically conformers 1b, 2b, 3b, and 4b, which can only be detected through cross‐saturation transfer, while additional steric repulsions between Meax–C(1) and OHax–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 Hax–C(14) and the axial H or halogen atoms at C(8) and C(10), are calculated and discussed with respect to well documented exocycliemethylidene‐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.