On the origins of diastereoselectivity in the alkylation of enolates derived from N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxamates: chiral Weinreb amide equivalents.
The stereochemical outcome observed upon alkylation of enolates derived from N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxamates (chiral Weinreb amide equivalents) may be rationalized by a chiral relay mechanism. Deprotonation with KHMDS leads to a nonchelated (Z)-enolate in which the oxygen atoms adopt an anti-periplanar conformation. The configuration of the N-1-(1'-naphthyl)ethyl group dictates the conformation of the O-tert-butyl group and the configuration adopted by the adjacent pyramidal nitrogen atom. Highly diastereoselective enolate alkylation then proceeds anti to both the bulky tert-butyl group (sterically driven) and the N-lone pair (stereoelectronically driven).
Davies
Stephen G
SG
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom. steve.davies@chem.ox.ac.uk
Goodwin
Christopher J
CJ
Hepworth
David
D
Roberts
Paul M
PM
Thomson
James E
JE
D000478:Alkylation; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006877:Hydroxamic Acids / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D013237:Stereoisomerism; D014466:Ultraviolet Rays
D001643:Bridged Bicyclo Compounds; D006877:Hydroxamic Acids; C549275:N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxamate; D009281:Naphthalenes