Stereoselective beta-hydroxy-alpha-amino acid synthesis via an ether-directed, palladium-catalysed aza-Claisen rearrangement.
A highly diastereoselective synthesis of (2S,3S)-beta-hydroxy-alpha-amino acids has been developed from enantiopure alpha-hydroxy acids using a MOM-ether-directed, palladium(II)-catalysed, aza-Claisen rearrangement of allylic acetimidates to effect the key step. This highly stereoselective process gave allylic amides in diastereomeric ratios of up to 14 : 1. Problems associated with the isolation of 1,3-products (anti-Claisen) from sterically demanding substrates via an insitu palladium(0)-catalysed rearrangement process were overcome by the addition of a re-oxidant, p-benzoquinone, leading to cleaner reactions and improved yields of the 3,3-products (Claisen). The target beta-hydroxy-alpha-amino acids are an important class of natural products that are also components of more complex organic compounds with significant biological properties.
Fanning
Kate N
KN
WestChem, Department of Chemistry, Joseph Black Building, University of Glasgow, Glasgow, UKG12 8QQ.
Jamieson
Andrew G
AG
Sutherland
Andrew
A
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D001372:Aza Compounds / Q000737:chemistry*; D002384:Catalysis; D004987:Ethers / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
D000596:Amino Acids; D001372:Aza Compounds; D004987:Ethers; D010165:Palladium