?-facial diastereoselection of hydride reduction of 1,3-diheteran-5-ones: application of the exterior frontier orbital extension model

To obtain further evidence for the importance of the ground state conformational and orbital properties in π-facial diastereoselection of 1,3-diheteran-5-ones (heteroatom = O, S, Se), 2-phenyl-1,3-diselenan-5-one (3a) has been synthesized, and its π-facial diastereoselection upon hydride reduction has been examined. The experimental data of π-facial stereoselection of 3a has been successfully rationalized by the exterior frontier orbital extension model (the EFOE model). Intrinsic reaction coordinate (IRC) and natural bond orbital (NBO) analyses of transition states of LiAlH4 reduction of this ketone have strongly indicated that the transition state effects (the torsional strain of the carbonyl moieties and the antiperiplanar effects involving the incipient bond proposed by the conventional theoretical models for π-facial diastereoselection; the Felkin-Anh model and the Cieplak model) are not responsible for facial selection. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:358–368, 2001