Oxazinanones as chiral auxiliaries: synthesis and evaluation in enolate alkylations and aldol reactions.
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.
Davies
Stephen G
SG
Department of Organic Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, UK OX1 3TA. steve.davies@chem.ox.ac.uk
Garner
A Christopher
AC
Roberts
Paul M
PM
Smith
Andrew D
AD
Sweet
Miles J
MJ
Thomson
James E
JE
D000438:Alcohols / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D000478:Alkylation; D010078:Oxazines / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D000447:Aldehydes; D000475:Alkenes; D010078:Oxazines; C116609:3-hydroxybutanal