title: Oxazinanones as chiral auxiliaries: synthesis and evaluation in enolate alkylations and aldol reactions.
abstract: Homochiral beta-amino esters (prepared on multigram scale by lithium amide conjugate addition) are readily transformed into oxazinanones. N-acyl derivatives of oxazinanones undergo stereoselective enolate alkylation reactions, with higher stereoselectivities observed for the enolate alkylation of (R)-N-propanoyl-4-iso-propyl-6,6-dimethyl-oxazinan-2-one than the corresponding Evans oxazolidin-2-one. A C(4)-iso-propyl stereodirecting group within the oxazinanone conveys higher stereoselectivity than the analogous C(4)-phenyl substituent. gem-Dimethyl substitution at C(6) within the oxazinanone framework facilitates exclusive exocyclic cleavage upon hydrolysis to furnish alpha-substituted carboxylic acid derivatives and the parent oxazinanone in good yield. Asymmetric aldol reactions of a range of aromatic and aliphatic aldehydes with the chlorotitanium enolate of (R)-N-propanoyl-4-iso-propyl-6,6-dimethyl-oxazinan-2-one proceed with excellent diastereoselectivity. Hydrolysis of the aldol products affords homochiral alpha-methyl-beta-hydroxy-carboxylic acids.
authors.affiliation: Department of Organic Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, UK OX1 3TA. steve.davies@chem.ox.ac.uk
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: A Christopher
authors.initials: AC
authors.lastname: Garner
authors.forename: Paul M
authors.initials: PM
authors.lastname: Roberts
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.forename: Miles J
authors.initials: MJ
authors.lastname: Sweet
authors.forename: James E
authors.initials: JE
authors.lastname: Thomson
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D000478:Alkylation; D010078:Oxazines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000438:Alcohols; D000447:Aldehydes; D000475:Alkenes; D010078:Oxazines; C116609:3-hydroxybutanal