Asymmetric synthesis of beta2-amino acids: 2-substituted-3-aminopropanoic acids from N-acryloyl SuperQuat derivatives.
Conjugate addition of lithium dibenzylamide to (S)-N(3)-acryloyl-4-isopropyl-5,5-dimethyloxazolidin-2-one (derived from l-valine) and alkylation of the resultant lithium beta-amino enolate provides, after deprotection, a range of (S)-2-alkyl-3-aminopropanoic acids in good yield and high ee. Alternatively, via a complementary pathway, conjugate addition of a range of secondary lithium amides to (S)-N(3)-(2'-alkylacryloyl)-4-isopropyl-5,5-dimethyloxazolidin-2-ones, diastereoselective protonation with 2-pyridone, and subsequent deprotection furnishes a range of (R)-2-alkyl- and (R)-2-aryl-3-aminopropanoic acids in good yield and high ee. Additionally, the boron-mediated aldol reaction of beta-amino N-acyl oxazolidinones is a highly diastereoselective method for the synthesis of a range of beta-amino-beta'-hydroxy N-acyl oxazolidinones.
Beddow
James E
JE
Department of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, UK OX1 3TA.
Davies
Stephen G
SG
Ling
Kenneth B
KB
Roberts
Paul M
PM
Russell
Angela J
AJ
Smith
Andrew D
AD
Thomson
James E
JE
D000478:Alkylation; D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D021621:Imaging, Three-Dimensional; D008094:Lithium / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry; D011522:Protons; D013237:Stereoisomerism; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000737:chemistry
D000577:Amides; D000596:Amino Acids; D010080:Oxazoles; D011522:Protons; D015091:beta-Alanine; C064210:oxazolidine; C011757:2,3-diaminopropionic acid; D008094:Lithium