Conformational Studies of Marine Polyhalogenated α‐Chamigrenes Using Temperature‐dependent NMR spectra inverted‐chair and twist‐boat cyclohexane moieties in the presence of an axial halogen atom at C(8)

α‐Chamigren‐3‐one (+) ‐8 bearing an axial CI‐atom at C(8) exists as a largely dominant conformer with Me—C(5) at the envelope‐shaped enone ring pointing away from CI ax −C(8) at the cyclohexane ring (= B) in the ‘normal’ chair conformation, as shown by 1 H‐NMR. In contrast, the α‐chamigren‐3‐ols (+) ‐9 and (+) ‐10 , obtained from hydride reduction of (+) ‐8 , show a temperature‐dependent equilibrium of conformers where the major conformers have ring B in the inverted‐chair (and twist‐boat for (+) ‐9 ) conformation to avoid repulsions between Me−C(5) and CI ax –C(8) ( Scheme 1 ). This is in agreement with the conformation of the epoxidation product (+) ‐12 of (+) ‐9 where Me–C(5) is pushed away from CI ax –C(8) in a ring‐B chair similar to that of (+) ‐8 ( Scheme 2 ). Introduction of a pseudoequatorial Br‐atom at C(2) of (+) ‐8 , as in enone (+) ‐15 ( Scheme 3 ), does not affect the conformation; but a pseudoaxial BrC(2) experiences repulsive interactions with H eq –C(7), as shown by the 1 H‐NMR data of the isomeric enone (+) ‐16 where the ‘normal’‐chair conformer C β ‐16 is in an equilibrium with the inverted chair conformer IC β ‐16 ( Scheme 3 ). These results and the accompanying paper allow a unifying view on the conformational behavior of marine polyhalogenated α‐chamigrenes. This view is supported by the acid‐induced isomerization of α‐chamigrene (+) ‐9 (inverted chair) to β‐chamigrene (+) ‐17 (‘normal’ chair; Scheme 4 ), the driving force being the lesser space requirement of CH 2 C(5) than of Me–C(5). This explains why β‐chamigrenes are so common in nature.