Asymmetric synthesis of N-protected amino acids by the addition of organolithium carboxyl synthons to ROPHy/SOPHy-derived aldoximes and ketoximes.
A new asymmetric synthesis of alpha-amino acids is described in which the key step is the highly diastereoselective addition of organolithium carboxyl synthons (2-furyllithium, phenyllithium, vinyllithium) to (R)- and (S)-O-(1-phenylbutyl) oximes to give hydroxylamines, with vinyllithium being the most satisfactory nucleophilic reagent. Subsequent reductive cleavage of the N-O bond in hydroxylamines, followed by N-protection, and oxidative cleavage of the carboxyl precursor gave a range of N-protected amino acids and esters. The method was exemplified by the synthesis of a range of derivatives of non-proteinogenic amino acids such as 4-bromophenylalanine, tert-leucine, norvaline, cyclohexyl- and aryl-glycines, 2-amino-8-oxodecanoic acid (Aoda) and alpha-methylvaline.
Cooper
Tracey S
TS
Department of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
Laurent
Pierre
P
Moody
Christopher J
CJ
Takle
Andrew K
AK
D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis*; D008094:Lithium / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D010091:Oximes / Q000737:chemistry*; D013237:Stereoisomerism
D000588:Amines; D000596:Amino Acids; D009942:Organometallic Compounds; D010091:Oximes; D008094:Lithium