Photochemical Cleavage and Release of Carboxylic Acids from α-Keto Amides

Abstract

In aqueous media, alpha-keto amides LGCH(2)COCON(R)CH(R')CH(3) (1a, R = Et, R' = H; 1b, R = (i)()Pr, 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, Phi(photocleavage) = 0.24-0.38, whereas Phi(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, H(2)C=C(OH)CON(+)(R)=C(R')CH(3) 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 mus, 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 = CH(3)CO(2)(-), PhCH(2)CO(2)(-)) in neat CH(3)CN results in carboxylate elimination to form imminium ion 5a, followed by internal return to give aminals.

Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy

“…397 Time-resolved pH-jump experiments showed that the reaction rate is on the microsecond time scale and that carboxylate release occurs in the rate-determining step. 398 Phenolates can also be liberated from 216 . 399 Laser flash photolysis experiments demonstrated that p -substituted phenolic substituents undergo photocleavage to give the corresponding phenol with good quantum yields (0.2–0.3).…”

1-Acetylpyrene with dual functions as an environment-sensitive fluorophore and fluorescent photoremovable protecting group

“…Data are reported as follows: chemical shifts, multiplicity (s¼singlet, d¼doublet, t¼triplet, m¼multiplet), coupling constant (Hz). 13 C NMR (50 MHz) spectra were recorded on a BRUKER-AC 200 MHz Spectrometer with complete proton decoupling. Chemical shifts are reported in parts per million from tetramethylsilane with the solvent resonance as the internal standard (deuterochloroform: 77.0 ppm).…”

“…2a,3 To date several PRPGs have been developed to mask different functional groups including carboxylic acids, 4 alcohols, 5 amines, 6 phosphates, 7 aldehydes, 8 and ketones. 8 The carboxyl group containing molecules can be effectively protected by a variety of PRPGs, such as 2-(dimethylamino)-5-nitrophenol, 9 3-nitro-2-naphthalenemethanol, 10 a-carboxy nitrobenzyl, 11 p-hydroxyphenacyl, 12 a-keto amides, 13 1-acyl-nitroindolines, 14 anthracene-9-methanol, 15 and derivatives of quinoline 16 as well as coumarin. 17 Among the aforementioned PRPGs some groups are fluorescent and have greater advantage over non-fluorescent protecting groups since they not only release molecules of interest at desired location for a specific period of time, but also allow us to visualize, quantify and follow the spatial distribution, localization, and depletion of the released molecules.…”

Reversible Triplet Excitation Transfer in a Trimethylene-Linked Thioxanthone and Benzothiophene-2-Carboxanilide that Photochemically Expels Leaving Group Anions

“…Photoremovable protecting groups are used to facilitate research in biology, biochemistry, and physiology; practical applications have also emerged in materials science and synthesis. − Our research in the area has focused on photochemical rearrangements that produce putative zwitterionic intermediates, which are capable of expelling leaving group anions having a wide range of basicities. − Recent examples of such photochemistry are the anilides of benzothiophene-2-carboxamides, where various leaving groups are incorporated at the C-3 position of the thiophene ring (Scheme ). Chemical yields of the released leaving groups are typically quantitatitve, and quantum yields range from 0.1 to 0.2, depending on the leaving group basicity.…”