Hydroxyl-directed reduction of β-hydroxycycloalkanones as a stereoselective route to 1,3-diols: X-ray crystal structure and structural features of (1R*,2R*,6S*)-2-[hydroxy(phenyl)methyl]cyclopentanol

Abstract

syn and anti Aldol adducts 4/5 and 6/7 undergo reduction using NaBH(OAc)₃ to give 1,3-diols with good to excellent levels of diastereoselectivity. Reduction using NaBH₄ is generally less selective but, in the cyclohexyl series, reduction of the syn aldol adduct 6 does afford a complementary stereochemical outcome in relation to the product 1,3-diols obtained. 12vs.13. The structure of the diol 9 has been determined by X-ray crystallographic analysis, thereby providing proof of the stereochemical course of the reduction of the aldol 4. Additionally, the diol 9 is shown to pack in the solid state as columnar stacks of independent hexamers with each pillar comprising a central (OH)₆ core, incorporating a network of hydrogen bonds, with a hydrophobic exterior.