STEREOSELECTIVITIES OF NUCLEOPHILIC ADDITIONS TO CYCLOHEXANONES SUBSTITUTED BY POLAR GROUPS - EXPERIMENTAL INVESTIGATION OF REDUCTIONS OF TRANS-DECALONES AND THEORETICAL-STUDIES OF CYCLOHEXANONE REDUCTIONS - THE INFLUENCE OF REMOTE ELECTROSTATIC EFFECTS

A series of nine 4-substituted trans-decalones have been synthesized and submitted to hydride reduction by NaBH4. Equatorial electron-withdrawing substituents have very little effect on the stereoselectivity, while axial substituents have a large effect. Ab initio molecular orbital calculations on the reaction of cyclohexanone with lithium hydride gave a 1.8-kcal/mol preference for the axial transition state at the RHF/6-31G* level. Substituent effects were studied by calculations with substituents at the C4 position in the transition structure. The effects of OH and NH2 substitutions on the stereoselectivity are strongly dependent upon group orientation, indicating the importance or long-range electrostatic effects on stereoselectivity. Cyclohexanone, 4-ax-, 4-eq-, and 3-eq-fluorocyclohexanones, and 5-fluoroadamantanone were optimized with the 3-21 G basis set. The distortion about the C(sp2)-C-alpha bonds and the pyrimidalization at the C(sp2) center are both enhanced by the fluoro substitution. The transition structures of the reactions of sodium hydride with propanal, 3-fluoropropanal, and 3-silylpropanal were located with the 3-21G and 6-31G* basis sets. Fluoro substitution was calculated to cause a notable stabilization of the outside transition structure. Electrostatic effects are shown to be an additional factor, along with torsional and steric effects, that influence nucleophilic addition stereoselectivities.