Reaction between N-alkylhydroxylamines and chiral enoate esters: more experimental evidence for a cycloaddition-like process, a rationale based on DFT theoretical calculations, and stereoselective synthesis of new enantiopure beta-amino acids.
The reactions between N-benzyl- and N-methylhydroxylamine and chiral enoate esters, derived from D-glyceraldehyde and (-)-verbenone, respectively, have been investigated. Theoretical calculations show that the most favorable mechanism involves the concerted cycloaddition of the hydroxylamine to the substrate. This result is in good agreement with the stereospecificity observed when the trisubstituted olefins are used. The open-chain adducts have been isolated when the processes are carried out at low temperatures and for short reaction times. These compounds evolve to the corresponding isoxazolidinones on standing at room temperature or under acid catalysis. The high pi-facial diastereoselection has been rationalized on the basis of steric effects induced by the dioxolane ring for D-glyceraldehyde derivatives or by the cyclobutane gem-dimethyl substitution for esters prepared from (-)-verbenone. As an application of these reactions, new beta-amino acids have been synthesized in a highly efficient and stereocontrolled manner.
Moglioni
Albertina G
AG
Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Muray
Elena
E
Castillo
José A
JA
Alvarez-Larena
Angel
A
Moltrasio
Graciela Y
GY
Branchadell
Vicenç
V
Ortuño
Rosa M
RM
D000473:Alkanes / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000081008:Bicyclic Monoterpenes; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D003500:Cyclization; D003503:Cyclobutanes / Q000737:chemistry; D004952:Esters / Q000737:chemistry*; D005985:Glyceraldehyde / Q000737:chemistry; D006898:Hydroxylamines / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism; D013696:Temperature; D013729:Terpenes / Q000737:chemistry
D000473:Alkanes; D000596:Amino Acids; D000081008:Bicyclic Monoterpenes; D003503:Cyclobutanes; D004952:Esters; D006898:Hydroxylamines; D013729:Terpenes; D005985:Glyceraldehyde; C052875:verbenone