Cieplaks Model for Diastereoselectivity

The reduction of 4-ferf-butylcyclohexanone by LiAlH4 in THF at 0 °C affords a mixture of the tram- and ris-alcohols in 88.5 11.5 ratio (Table 1) [9]. The predominant attack takes place obviously from the axial direction as predicted above by the Cieplak model. This selectivity is expected to diminish when the ring carries an equatorial methyl group on C3 because it will (a) not introduce an element of steric interaction during the course of the nucleophilic addition, and (b) raise 

The effect of a gradual increase in the bulk of a given type of nucleophile on the facial selectivity of a given cyclohexanone could also be gleaned from a measurement of the relative axial approach. The axial selectivity decreases in the order 45 % 31% 18% 0 % on changing the nucleopohilic reagent from 

CH3MgI CH3CH2MgI — (CH3)2CHMgI — (CH3)3CMgCl in the reaction with 4-ferf-butylcyclohexanone as shown in Table 2. The steric effect arising from (CH3)3CMgCl is so significant that absolutely no reaction occurs on the axial face and, hence, the civ-alcohol is isolated as the sole product. 

Let us now consider 2-phenyl-1,3-dioxan-5-one and compare its selectivity profile with that of 4-ferf-butylcyclohexanone in reactions with Grignard reagents, see Table 2. In 2-phenyl-1,3-dioxan-5-one, ctC4 o3 — tt c=o and crC6 (,i jt c=G 

The electron-donating power of ctC2 C3 and ctC5 c6 bonds in cyclohexanone could also be modified by incorporating equatorial electron-withdrawing substituents at C3 and C5 positions. The consequent decrease in cr(2 C3 — cr and CTcs-ce ct interactions imply more axial attack of the nucleophile than the equatorial attack. This explains the opposite effects of the methyl and cyano 

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