Smooth Photocatalyzed Benzylation of Electrophilic Olefins via Decarboxylation of Arylacetic Acids

Abstract

Arylacetic acids were used as sources of benzyl radicals under tetrabutylammonium decatungstate photocatalyzed conditions for the benzylation of electron-poor olefins. The reaction proceeds smoothly in a mixed aqueous medium (MeCN/H2O 2/1) in the presence of NaHCO3, NaClO4, and an electron transfer agent (biphenyl). The reaction tolerates a wide variety of functional groups on the aromatic ring (whether electron donating or electron withdrawing) and can be extended to heteroaromatic analogues. The olefins have the double role of radical trap and electron acceptor. The present approach can also be extended to arylpropionic acids (including the nonsteroidal anti-inflammatory drugs ibuprofen and flurbiprofen), as well as mandelic acid derivatives.

Direct Catalytic Decarboxylative Amination of Aryl Acetic Acids

“…[18c] Under the optimized reaction conditions,ah ost of alkyl amine nucleophiles and electron-poor aryl acetic acids can be decarboxylatively cross-coupled ( Figure 4). Both cyclic and acyclics econdary amines,i na ddition to primary amines, undergo benzylation in moderate to excellent yields (2,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

“…Included are examples of amines featuring unprotected alcohol groups (11,21,24), various potentially reactive amide or aniline groups (12)(13)(14)16), and electrophilic or potentially oxidizable groups (15,18). When primary amine substrates were used, bis-alkylation was not observed, enabling facile isolation of the alkylated products (22)(23)(24)(25). Marketed aminecontaining drug molecules bearing sensitive functionality, including aryl fluorides and chlorides,f unctionalized N-and S-heterocycles,a nd at etrasubstituted olefin, could be alkylated in good yields (Paroxetine,Debenzyldonepezil, Desloratadine,C rizotinib,F asudil, and Duloxetine; 3, 26-30).…”

“…To investigate the possibility of decarboxylation by CÀ CO 2 homolysis to generate ar adical intermediate, [24] the alkene functionalized substrate 59 was subjected to the standard Cu-catalyzed conditions.O nly direct amination (60,6 4% yield) and protodecarboxylation (61,2 7%)w ere observed. In contrast to photoredox-mediated pathways involving alkyl radical intermediates, [12,13] no cyclized products were obtained ( Figure 6A).…”

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst

“…To validate our proposal, we studied the Giese-type radical conjugate addition 22 to dimethyl fumarate 3a (Fig. 2b) [23][24][25][26] . The experiments were conducted in acetonitrile (CH3CN) using commercially available γ-terpinene as a cheaper and more stable surrogate of 1,4-CHD.…”

Synthesis of 3‐Benzylated Isoindolinones by Photoredox Decarboxylation of Arylacetates in the Presence of N‐Benzylphthalimide: Conductivity as a Kinetic Tool

“…From the initial slopes( 0 to 20 %c onversions)o ft he initially linear curves, relative reactivities were determined. In order to relate this data set with the mechanistic picture in Scheme 1, we used on one hand experimental data for the arylacetate oxidation potentials [15] and on the other hand computed activation barriers and reaction energies for the homolytic decarboxylation of the carboxyl radicals (UB3LYP/6-31G* -GD3BJ). [16,17] The data is summarized in Ta ble 2t ogether with the relative reactivities (s)o ft he seven reactive arylacetates as determined from the conductivity measurements.…”