The Direct Decarboxylative N-Alkylation of Azoles, Sulfonamides, Ureas, and Carbamates with Carboxylic Acids via Photoredox Catalysis

Abstract

Herein, we describe a method for the direct decarboxylative C−N coupling of carboxylic acids with a range of nitrogen nucleophiles. This platform employs visible-light-mediated photoredox catalysis and an iodine(III) reagent to generate carbocation intermediates directly from aliphatic carboxylic acids via a radical-polar crossover mechanism. A variety of C−N bondcontaining products are constructed from a diverse array of nitrogen heterocycles, including pyrazoles, imidazoles, indazoles, and purine bases. Furthermore, sulfonamides, ureas, and carbamates can also be utilized as the nucleophile to generate a selection of N-alkylated products. Notably, a two-step approach to construct free amines directly from carboxylic acids is accomplished using Cbz-protected amine as the nucleophile.

Visible Light Photoredox-Catalyzed Decarboxylative Alkylation of 3-Aryl-Oxetanes and Azetidines via Benzylic Tertiary Radicals and Implications of Benzylic Radical Stability

“…However, tertiary benzylic radicals remain underinvestigated in photoredox catalysis and might be expected to display low reactivity in their addition reactions due to their relatively stabilized nature . Further, benzylic radicals are prone to oxidation to form stabilized carbocations through radical-polar crossover pathways . To date, there have been no reports of the reaction of 3-aryloxetane or azetidine radicals, and the effect of the four-membered ring on the reactivity and radical structure was unclear at the outset of this work.…”

Catalyst-free electroreductive carboxylic acid–nitroarene coupling

“…The representative examples are shown in Scheme 2. In general, both electron-donating and electron-withdrawing groups were tolerated under the standard conditions, producing the corresponding products in moderate to high yields (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). The substituents of nitroarenes at ortho-, meta-, and para-positions can all be reacted in this transformation.…”

“…In recent years, various methods have been developed for introducing a nitrogen atom into carboxylic acid starting materials through decarboxylative coupling reactions. [29][30][31][32][33][34][35][36] While non-activated approaches for decarboxylative C(sp 3 )-N couplings have been reported, they are often limited to specific conditions such as heterocycles, [29][30][31] specific oxidants, [32][33][34] stabilized acids 35,37 or unstable amine sources. 36 In contrast, several research groups have explored the use of redox-active acids for the construction of C(sp 3 )-N bonds.…”

Aerobic Electrochemical Csp3–N Coupling between Aliphatic Carboxylic Acids and N-heterocycles

“…Conventionally, metal complexes were often involved in the C–N coupling via decarboxylation, such as CuI/MnO 2 , CuI/Pd II , CuCl 2 , and CuSO 4 /Ag 2 CO 3 . Similarly, in photochemical syntheses, various photocatalysts (metal or metal-free) were essential to facilitate the decarboxylation and the subsequent C–N coupling. In an electrochemistry system, the oxidative decarboxylation of carboxylic acids usually occurred under applied potentials, forming carbocations that further coupled with N-containing compounds .…”