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

摘要

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 LlAlH(4) 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.