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

Article abstract of DOI:10.1002/hlca.19910740411

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 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.