Transition-Metal-Free Decarboxylative Photoredox Coupling of Carboxylic Acids and Alcohols with Aromatic Nitriles

Abstract

A transition-metal-free protocol for the redox-neutral light-induced decarboxylative coupling of carboxylic acids with (hetero)aromatic nitriles at ambient temperature is presented. A broad scope of acids and nitriles is accepted, and alcohols can be coupled in a similar fashion through their oxalate half esters. Various inexpensive sources of UV light and even sunlight can be used to achieve this C-C bond formation proceeding through a free radical mechanism.

The Persistent Radical Effect in Organic Synthesis

“…Enamine hydrolysis finally leads to the corresponding β‐arylated ketone. Transient radicals generated by oxidative decarboxylation of carboxylic (Figure c) and oxalic acids (Figure d) were selectively coupled with simultaneously cogenerated cyanoarene radical anions. An elegant method to introduce silyloxy benzyl radicals in this transformation was presented by Smith III (Figure e) .…”

“…[85] Furthermore,ketones in combination with an amine cocatalyst can be utilized in this reaction by radical arylation of the corresponding enamine.A fter enamine oxidation and subsequent deprotonation, the enaminyl radical generated acts as cross-coupling partner (Figure 19 b). [86] Enamine hydrolysis finally leads to the corresponding b-arylated ketone.T ransient radicals generated by oxidative decarboxylation of carboxylic (Figure 19 c) [87] and oxalic acids (Figure 19 d) [88] were selectively coupled with simultaneously cogenerated cyanoarene radical anions.Anelegant method to introduce silyloxy benzyl radicals in this transformation was presented by Smith III (Figure 19 e). [89] In analogy to the Brook rearrangement, the authors start with a-silylcarbinol, which cyclizes to ap entavalent silicon species.R ing opening and oxidation deliver the a-silyloxybenzyl radical.…”

“…Radical-radical cross-couplingreaction with cyanoarenes 66 using photoredox catalysis. [85][86][87][88][89][90][91][92][93] desired cross-coupling product can be achieved if an excess of the precursor of the radical showing the longer-lifetime-the cyanoarene (10 equiv [98a] and 5equiv [98b] )-is used.…”

Decarboxylative couplings as versatile tools for late‐stage peptide modifications

“…In 2016, Opatz and coworkers reported a phenanthrene (phen)‐based photochemical strategy for the arylation of α‐amino acid derivatives (Scheme ) . The methodology exploits the phen/1,4‐DCB organic photocatalyst system employed by Yoshimi and coworkers for intermolecular Giese reactions (see Scheme ), taking advantage of the authors’ observation that 1,4‐DCB itself was capable of coupling to a tripeptide substrate 124 in the absence of other radical acceptors .…”

“…The methodology exploits the phen/1,4‐DCB organic photocatalyst system employed by Yoshimi and coworkers for intermolecular Giese reactions (see Scheme ), taking advantage of the authors’ observation that 1,4‐DCB itself was capable of coupling to a tripeptide substrate 124 in the absence of other radical acceptors . Armed with this knowledge, Opatz and coworkers successfully coupled a variety of aromatic nitriles to α‐amino acid derivatives, including Fmoc‐protected dipeptide 122 to afford pyridine substituted peptide 123 …”