Synthesis of erythro-alpha-amino beta-hydroxy carboxylic acid esters by diastereoselective photocycloaddition of 5-methoxyoxazoles with aldehydes.
A new photoaldol route to alpha-amino-beta-hydroxy carboxylic acid esters is initiated by the photocycloaddition of aromatic or aliphatic aldehydes to 5-methoxyoxazoles. The 4-unsubstituted 5-methyloxazole 1 gave the cycloadducts 8a-f in high yields and excellent exo-diastereoselectivities. Hydrolysis of 8a-f gives the N-acetyl alpha-amino-beta-hydroxy esters 9a-f, which could be subsequently converted into the corresponding Z-didehydro alpha-amino acids 10a-f. Quartenary alpha-amino-beta-hydroxy esters 12, 14, 16, 18, and 20, which are stable against dehydration, were obtained from the 4-alkylated 5-methoxyoxazoles 2-6, in most cases highly erythro-selective due to the high degree of stereocontrol (exo) at the photocycloaddition (to give 11, 13, 15, 17, and 19) level. The relative configurations of the N-acetyl alpha-amino-beta-hydroxy esters were determined by NMR spectroscopy and comparison with chiral pool-derived compounds as well as by X-ray structure determination of the ester 23, formed by hydrolysis of the cycloadduct 22, derived from photocycloaddition of propionaldehyde to the isoleucine-derived oxazole 21.
Griesbeck
Axel G
AG
Institut für Organische Chemie der Universität zu Köln, Greinstr. 4, D-50939 Köln, Germany. griesbeck@uni-koeln.de
Bondock
Samir
S
Lex
Johann
J
D000447:Aldehydes / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry; D006880:Hydroxy Acids / Q000138:chemical synthesis; D008958:Models, Molecular; D010080:Oxazoles / Q000737:chemistry*; D010777:Photochemistry; D013237:Stereoisomerism
D000447:Aldehydes; D000596:Amino Acids; D004952:Esters; D006880:Hydroxy Acids; D010080:Oxazoles