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 (> or = 94% de) gives the corresponding chiral, 2-substituted derivatives as single diastereoisomers (> 98% de) after chromatography. Reductive cleavage with LiAlH(4) allows direct access to chiral aldehydes, and treatment with MeLi gives chiral methyl ketones in excellent enantiopurity (> or = 94% ee). The auxiliary can be recovered in > 98% ee and recycled.
Chernega
Alexander N
AN
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Davies
Stephen G
SG
Goodwin
Christopher J
CJ
Hepworth
David
D
Kurosawa
Wataru
W
Roberts
Paul M
PM
Thomson
James E
JE
D000215:Acylation; D000577:Amides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019811:Hydroxylamine / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D013237:Stereoisomerism
D000577:Amides; C544843:N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine; D009281:Naphthalenes; D019811:Hydroxylamine