2,5-Dimethylphenacyl carbamate: a photoremovable protecting group for amines and amino acids

Abstract

2,5-Dimethylphenacyl (DMP) carbamates (1a-c) released the corresponding free amines or amino acids in high chemical yields, albeit with quantum yields Phi of only 0.04-0.09, upon irradiation in either aprotic or protic solvents. The photoreaction proceeded principally from the triplet excited state via the E-photoenol. The lifetimes of the triplet enol and the E- and Z-enols in the ground state were determined by laser flash photolysis. The primary photoinitiated transformation liberated a carbamic acid derivative, which subsequently decarboxylated to the amino group-containing compound. Exhaustive irradiation of a DMP-protected aniline (1a) in acetonitrile did not provide aniline in quantitative chemical yields, because it was involved in reductive cleavage of the starting material as an electron donor, thereby decreasing the overall deprotection yield (86%). Phenylalanine methyl ester, liberated from 1c, was, however, obtained in excellent chemical yield (97%). It was also found that the carbamates, while thermally stable, released amines with higher quantum yields in acidic methanol solutions. The DMP chromophore is proposed as an excellent photoremovable protecting group for amino acids and, under specific conditions, for amines in organic synthesis and biochemistry.

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

“…54b Klán and Wirz later demonstrated that 2,5-dimethylphenacyl (DMP) can serve as a PPG for carboxylic acids, 57 phosphates, sulfonates, 54a alcohols (as carbonates), 58 and amines (as carbamates). 59 It was recognized that only moderately good or excellent leaving groups are released efficiently within the photoenol lifetime. Studies by laser flash photolysis showed that photolysis produces the anticipated reaction intermediates, the short-lived triplet enol 3 E , and two longer-lived, ground-state photoenols assigned to the corresponding ( Z ) - and ( E ) - photoenols.…”

“…60 Only the chloride anion was found to be eliminated from the ( Z ) - xylylenol (τ = 23 μs in methanol) obtained from 2,5-dimethylphenacyl chloride via the singlet pathway. 61 Poor leaving groups such as alcohols and amines that are not efficiently eliminated from the short-lived photoenol intermediates have been attached through a carbonate 58 or carbamate 59 linkage, respectively, which have similar leaving group properties to that of a carboxylate. For example, the galactopyranosyl carbonate 9 releases a carbonate monoester in a high chemical yield that disintegrates thermally into the corresponding alcohol 10 and CO 2 (Scheme 7) 58 on the millisecond time scale.…”

Tautomerism of4,4′-dihydroxy-1,1′-naphthaldazine studied byexperimental and theoretical methods

“…The obtained spectral curves were processed by a software for overlapping bands decomposition [7,8] and for derivative spectroscopy, developed by us [9]. Laser flash photolysis experiments were performed using a setup that has been described previously [10]. Solutions were placed in quartz cells (4.5 cm long and 1 cm wide) and excited by one of the following excitation sources: a Lambda-Physik EMG 101 excimer laser operating at 308 nm (XeCl) with a pulse energies of ca.…”

Unexpected Reaction of Oximinoacetoacetate with Amines: A Novel Synthesis of Carbamates

“…[6,7] Organic carbamates have also played an important role in the area of synthetic organic chemistry, primarily as versatile building blocks or as efficient protecting groups. [8,9] Carbamate syntheses have been accomplished by several methods including carbonization of amines or imines by chloroformate [10,11] or organic acids in the presence of azides [12,13] and organic carbonate under solvent-free conditions, [14,15] and finally by metal-mediated reductive acylation of nitriles [16] or oxime carbonates. [17] In an ongoing work studying the use of 2-oximinoacetoacetate 1 as a building block in the synthesis of pyrrole derivatives as precursors of porphyrin macromolecules, [18,19] we found that when equimolar amounts of oxime 1 and primary aromatic amine 2 were heated in a preheated oil bath at 130 C for 2-3 min, alkyl carbamate 3 was obtained in moderate yield (70-75%) (Scheme 1).…”