Stereoselectivity in reductions of carbonyl compounds by a chiral reagent prepared by adding the amino alcohol (+)-(2S,3ñ)-4-dimethylammo-3-methyl-l,2-diphenyI-2-butanol (6) to lithium aluminum hydride in ether is reasonably high and shows remarkable reversal depending upon age of the reagent from predominantly R product to predominantly S product. Reduction of acetophenone gives either (fi)-(+)or (S)-( -)-methylphenylcarbinol in 80-70% enantiomeric purity depending upon use of the reagent either immediately after its preparation (procedure A) or upon aging overnight or refluxing for a few minutes (procedure B). This reversal in stereoselectivity with age of reagent was observed with five different carbonyl substrates. The reduction of phenyltrifluoromethyl ketone did not show this reversal phenomenon, however. Procedure A for asymmetric reduction of phenyl alkyl ketones gives the R carbinol in excess in each case. Representative enantiomeric purities (% e.e., R isomer
We have found that the reaction of methylmagnesium iodide in ether with (S)-( -)-«-butyl-ier?-butylcarbinyl benzoylformate preferentially attacks the re face of the -keto group to give a 7.5% excess of the (S)-atrolactate diastereomer. Based on the premise that ieri-butyl acts as a larger group than «-butyl this result is in accord with Prelog's generalization concerning the course of this reaction. In tetrahydrofuran, however, the stereoselectivity was essentially zero. On the other hand, reduction of this same substrate by lithium tri-ieri-butoxyaluminohydride in either tetrahydrofuran or ether resulted in preferential attack on the si face of the a-keto group to give the (if)-mandelate diastereomer in excess (13 and 8%, respectively). This reversal in stereoselectivities between the Grignard addition and lithium tri-ierf-butoxyalummohydride reductions emphasizes the caution necessary in extrapolating stereoselectivities from one seemingly closely related reaction to another, especially when the stereoselectivities are low and the nature of steric differences are not clearly evident. Stereochemical analysis of the reaction mixtures was greatly facilitated by the use of the nmr enantiomer reagent, amethoxy-a-trifluoromethylphenylacetic acid, alone and in conjunction with europium nmr shift reagents.
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