DIASTEREOSELECTIVITY IN THE REDUCTION OF STERICALLY UNBIASED 2,2-DIARYLCYCLOPENTANONES

Reduction of sterically unbiased 2-phenyl-2-(4-X-phenyl)cyclopentanones 1 (X = NO2, Br, Cl, OCH3, OH, NH2) with either sodium borohydride in methanol or lithium borohydride in tetrahydrofuran at 0 °C produced diastereomeric cyclopentanols 2 in cis/trans ratios varying from 79:21 to 30:70 as determined by 1H and 13C NMR spectroscopy. These ratios correspond to an overall energy difference of 1.3 kcal/mol. In all cases the hydride was added opposite the more electron rich aromatic ring in support of Cieplak's theory for explaining stereoelectronic control in ketone reductions. A Hammet plot of log (cis/trans) versus the σ para parameter produced a linear relationship with a correlation coefficient of 0.98. An efficient synthesis of the diarylcyclopentanones is described. The diastereomeric alcohols were separable by preparatory thin layer chromatography. The stereochemistry of the products was determined by 2D NOE (NOESY) spectroscopy, 13C NMR chemical shift data, and direct chemical correlation between different products. © 1990, American Chemical Society. All rights reserved.