Unique oxidation reaction of amides with pyridine-N-oxide catalyzed by ruthenium porphyrin: direct oxidative conversion of N-acyl-L-proline to N-acyl-L-glutamate.
Oxidations of alkanes, alkenes, and aromatic rings with pyridine N-oxides are efficiently catalyzed by ruthenium porphyrins under mild conditions. We show here that the oxidation of N-acyl cyclic amines with RuIVtetraarylporphyrin dichloride-2,6-substituted pyridine N-oxides directly gives N-acyl amino acids in modest to good yield via oxidative C-N bond cleavage. N-Acylpyrrolidines and N-acylpiperidines were converted to N-acyl-gamma-aminobutyric acids and N-acyl-delta-aminovaleric acids, respectively. This type of reaction is a novel one in which the C-N bond is cleaved selectively at the less substituted carbon. Notably, the proline residue in proline-containing peptides was selectively converted to glutamate. A large intramolecular kinetic isotope effect (kH/kD = 9.8) was observed in the oxidation of N-benzoyl[2,2,-d2]pyrrolidine, indicating that the reaction should involve an alpha-hydrogen atom abstraction process as the rate-determining step. N-Acylcarbaldehyde, the putative intermediate ring-opened form of alpha-hydroxylated N-acyl cyclic amine, was readily oxidized with the oxidizing system to afford the corresponding N-acylamino acid in good yield. Further, lactams (1-methyl-2-pyrrolidone and 1-methyl- 2-piperidone) were also oxidized to give the corresponding imides (1-methylsuccinimide and 1-methylpiperidine-2,6-dione).
Ito
Rina
R
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Japan.
Umezawa
Naoki
N
Higuchi
Tsunehiko
T
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D018698:Glutamic Acid / Q000031:analogs & derivatives*; D007769:Lactams / Q000737:chemistry; D008665:Metalloporphyrins / Q000737:chemistry*; D010084:Oxidation-Reduction; D011392:Proline / Q000031:analogs & derivatives*; D011725:Pyridines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*
D000588:Amines; D007769:Lactams; D008665:Metalloporphyrins; D011725:Pyridines; D018698:Glutamic Acid; D012428:Ruthenium; C013229:pyridine N-oxide; D011392:Proline