title: The chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine: a chiral Weinreb amide equivalent.
abstract: 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.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Chernega
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Goodwin
authors.forename: David
authors.initials: D
authors.lastname: Hepworth
authors.forename: Wataru
authors.initials: W
authors.lastname: Kurosawa
authors.forename: Paul M
authors.initials: PM
authors.lastname: Roberts
authors.forename: James E
authors.initials: JE
authors.lastname: Thomson
mesh_terms: D000215:Acylation; D000577:Amides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019811:Hydroxylamine / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000577:Amides; C544843:N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine; D009281:Naphthalenes; D019811:Hydroxylamine