STRUCTURAL-ANALYSIS OF CIS-[N.3.1]BICYCLIC KETONES BY X-RAY CRYSTALLOGRAPHY - IMPACT OF THE OBSERVED CONFORMATIONAL CROSSOVER ON PI-FACIALLY DIASTEREOSELECTIVE NUCLEOPHILIC ADDITIONS TO THIS CLASS OF KETONES AND ON THE STEREOCHEMICAL COURSE OF ELECTROPHILIC REACTIONS INVOLVING THEIR METHYLENE ANALOGS

X-ray crystallographic studies clearly show that cis-[n.3.1]bicyclic ketones 1 having n equal to 7 or less are conformationally predisposed such that the rigid chair cyclohexanone ring projects the polymethylene chain diaxially. In contrast, an increase in belt size to n = 9 is adequate to allow adoption of diequatorial geometry without evidence for dynamic chair-chair interconversion. These divergent ground-state characteristics are believed to persist in the methylene derivatives 2. In order to evaluate the impact of this stereochemical crossover on the facial stereoselectivity of nucleophilic attack on 1 and electrophilic capture by 2, the following reactions were examined: hydride and dissolving metal reduction, organometallic additions, condensation with dimethyloxosulfonium methylide, epoxidation, osmylation, oxymercuration, and cycloadditions involving chlorosulfonyl isocyanate and dichloroketene. The presence of an axially oriented loop strongly curtails otherwise favored axial approach by these reagents. With these systems, a strong preference for less hindered equatorial approach is observed. Although the (CH2)9 series is subject to near-identical inductive contributions from the polymethylene belt, the overwhelming diequatorial bias of this belt does not introduce a comparable steric bias and a general (although not exclusive) preference for axial attack is noted. These substitution effects are compared to those of the 4-tert-butylcyclohexyl analogues.