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

Abstract

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 of long-range electrostatic effects on stereoselectivity. Cyclohexanone, 4-ax-, 4-eq-, and 3-eq-fluorocyclohexanones, and 5-fluoroadamantanone were optimized with the 3–21G basis set. The distortion about the C_sp2-C_a 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.