Oxazinanones as chiral auxiliaries: synthesis and evaluation in enolate alkylations and aldol reactions.

Journal article

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: Davies, S; Garner, A; Roberts, P; Smith, A; Sweet, M

• Publication status: Published
• Journal: Organic and biomolecular chemistry
• Volume: 4
• Issue: 14
• Pages: 2753-2768
• Publication date: 2006-07-01
• DOI: 10.1039/b604073j
• EISSN: 1477-0539
• ISSN: 1477-0520
• Language: English
• Keywords: Aldehydes; Stereoisomerism; Oxazines; Alkylation; Alkenes; Alcohols