The Chiral Auxiliary N-1-(1′-Naphthyl)ethyl-O-tert-butylhydroxylamine: A Chiral Weinreb Amide Equivalent

The chiral auxiliary N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine is readily prepared from N-hydroxyphthalimide in four steps, with resolution giving access to both enantiomers in >98% ee, on a multigram (>25 g) scale. Conversion to a range of N-acyl derivatives, followed by highly diastereoselective alkylation (≥94% de) gives the corresponding chiral, 2-substituted derivatives as single diastereoisomers (>98% de) after chromatography. Reductive cleavage with LiAlH4 allows direct access to chiral aldehydes, and treatment with MeLi gives chiral methyl ketones in excellent enantiopurity (≥94% ee). The auxiliary can be recovered in >98% ee and recycled.