Photochemical cleavage and release of carboxylic acids from α-keto amides

Article abstract of DOI:10.1021/jo050246s

In aqueous media, α-keto amides LGCH₂COCON(R)CH(R′) CH₃ (1a, R = Et, R′ = H; 1b, R = ⁱPr, R′ = Me; 1c, R = Ph, R′ = H) with various carboxylate leaving groups (LG) at the C-3 position undergo photocleavage and release of carboxylic acids with formation of diastereomeric 5-hydroxyoxazolidin-4-ones 2a,c in the cases of 1a,c or 5-methyleneoxazolidin-4-ones 3b in the case of 1b. For 1a,b, Φ(photocleavage) = 0.24-0.38, whereas Φ(photocleavage) = ca. 0.05 for 1c. The proposed mechanism involves transfer of hydrogen from an N-alkyl group to the keto oxygen to produce zwitterionic intermediates 4a-c that eliminate carboxylate anions. The resultant imminium ions, H₂C=C(OH)CON ⁺(R)=C(R′)CH₃ 5a-c, cyclize intramolecularly to 3b or undergo intermolecular addition of water followed by tautomerization and cyclization to give 2a,c. These inter- or intramolecular trapping reactions of 5 release protons that decrease the pH and cause bleaching of the 620 nm band of the pH indicator, bromocresol green. Determination of the bleaching kinetics by laser flash photolysis methods in the case of 1a gives time constants of 18-137 μs, depending on the leaving group ability of the carboxylate anion, whereas amides 1b show only a small leaving group effect. For 1a, the large leaving group effect is consistent with rate-limiting carboxylate elimination from 4a, whereas the proton release step would be largely rate determining for 1b. Photolyses of 1a (LG = CH₃CO₂^-, PhCH ₂CO₂^-) in neat CH₃CN results in carboxylate elimination to form imminium ion 5a, followed by internal return to give aminals.