Visible Light‐Induced Decarboxylative Alkylation of Heterocyclic Aromatics with Carboxylic Acids via Anthocyanin as a Photocatalyst

A visible light‐induced decarboxylative alkylation of heterocyclic aromatics with aliphatic carboxylic acids was developed by using anthocyanins as a photocatalyst under mild conditions. A series of alkylated heterocyclic compounds were obtained in moderate to good yields by using the metal‐free decarboxylative coupling reaction under blue light. This strategy uses cheap and readily available carboxylic acids as alkylation reagents with good functional group tolerance and environmental friendliness. It is worth noting that this is the first time that anthocyanin has been used to catalyze the Minisci‐type C?H alkylation. The mechanism of decarboxylation alkylation was studied by capturing the adduct of alkyl radical and hydroquinone, thus confirming a radical mechanism. This protocol provides an alternative visible light‐induced decarboxylative alkylation for the functionalization of heterocyclic aromatics.     

Rhenium‐Catalyzed Decarboxylative Tri‐/Difluoromethylation of Styrenes with Fluorinated Carboxylic Acid‐Derived Hypervalent Iodine Reagents

Herein, unprecedented rhenium‐catalyzed decarboxylative oxytri‐/difluoromethylation and Heck‐type trifluoromethylation of styrenes have been developed by using hypervalent iodine(III) reagents derived from cheap, stable, and easy‐handling fluorinated carboxylic acids. Mechanistic studies revealed a radical decarboxylative trifluoromethylation pathway occurring in these reactions.     

Decarboxylative Conjunctive Cross-coupling of Vinyl Boronic Esters using Metallaphotoredox Catalysis

The synthesis of complex alkyl boronic esters through conjunctive cross-coupling of vinyl boronic esters with carboxylic acids and aryl iodides is described. The reaction proceeds under mild metallaphotoredox conditions and involves an unprecedented decarboxylative radical addition/cross-coupling cascade of vinyl boronic esters. Excellent functional-group tolerance is displayed, and application of a range of carboxylic acids, including secondary α-amino acids, and aryl iodides provides efficient access to highly functionalized alkyl boronic esters. The decarboxylative conjunctive cross-coupling was also applied to the synthesis of sedum alkaloids.     

Nickel‐Catalyzed Decarboxylative Difluoroalkylation of α,β‐Unsaturated Carboxylic Acids

The first example of nickel‐catalyzed decarboxylative fluoroalkylation of α,β‐unsaturated carboxylic acids has been developed with commonly available fluoroalkyl halides. This novel transformation has demonstrated broad substrate scope, excellent functional‐group tolerance, mild reaction conditions, and excellent stereoselectivity. Mechanistic investigations indicate that a fluoroalkyl radical is involved in the catalytic cycle.     

Decarboxylative Conjunctive Cross‐coupling of Vinyl Boronic Esters using Metallaphotoredox Catalysis

The synthesis of complex alkyl boronic esters through conjunctive cross‐coupling of vinyl boronic esters with carboxylic acids and aryl iodides is described. The reaction proceeds under mild metallaphotoredox conditions and involves an unprecedented decarboxylative radical addition/cross‐coupling cascade of vinyl boronic esters. Excellent functional‐group tolerance is displayed, and application of a range of carboxylic acids, including secondary α‐amino acids, and aryl iodides provides efficient access to highly functionalized alkyl boronic esters. The decarboxylative conjunctive cross‐coupling was also applied to the synthesis of sedum alkaloids.     

Decarboxylative radical azidation using MPDOC and MMDOC esters

An efficient radical-mediated decarboxylative azidation of aliphatic carboxylic acids has been developed. The success of this transformation hinges on the use of a new type of thiohydroxamate esters (MPDOC esters). These esters are more stable than the classical Barton esters and less prone to rearrange under radical conditions. In the case of alpha-alkoxy and alpha-amino acids, optimal results are obtained with the even more stable MMDOC esters developed recently by Kim.     

Visible‐Light‐Mediated Decarboxylative Radical Additions to Vinyl Boronic Esters: Rapid Access to γ‐Amino Boronic Esters

The synthesis of alkyl boronic esters by direct decarboxylative radical addition of carboxylic acids to vinyl boronic esters is described. The reaction proceeds under mild photoredox catalysis and involves an unprecedented single‐electron reduction of an α‐boryl radical intermediate to the corresponding anion. The reaction is amenable to a diverse range of substrates, including α‐amino, α‐oxy, and alkyl carboxylic acids, thus providing a novel method to rapidly access boron‐containing molecules of potential biological importance.     

Radical decarboxylative bromination of aromatic acids

Thiohydroxamic esters (mixed anhydrides) of aromatic and α,β-unsaturated carboxylic acids undergo clean decarboxylative bromination on treatment with bromotrichloromethane in the presence of a radical initiator.     

Silver-catalyzed decarboxylative C–H functionalization of cyclic aldimines with aliphatic carboxylic acids

Silver-catalyzed decarboxylative C–H alkylation of cyclic aldimines with abundant aliphatic carboxylic acids has been realized under mild reaction conditions generating the corresponding products in moderate to good yields (32%–91%). In addition, a gram-scale reaction, late-stage modification of drug, synthetic transformation of the product, and further application of the catalytic strategy were also performed. Preliminary studies indicate that the reaction undergoes a radical process.     

Palladium-catalyzed highly regioselective and stereoselective decarboxylative arylation of unactivated olefins with aryl carboxylic acids

Palladium(II)-catalyzed highly regioselective and stereoselective decarboxylative arylation of unactivated olefins with aryl carboxylic acids has been developed. This method is applicable to a variety of unactivated olefins, including allylamides, long chain functionalized olefins and purely aliphatic olefins, leads to the formation of linear E-configured products in high yields. Both electron-rich and electron-deficient aryl carboxylic acids are suitable arylation reagents. It was found that the choice of solvent, catalyst precursor and oxidant had an important influence on reaction efficiency. As a co-solvent and ligand, DMSO is critical to catalysis. This chemistry expands the scope of decarboxylative arylation of olefins with aryl carboxylic acids, and provides a rapid access to useful linear arylation products of unactivated olefins.     

C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation

We report the first decarboxylative alkynylation of the C‐terminus of peptides starting from free carboxylic acids. The reaction is fast, metal‐free, and proceeds cleanly to afford alkynylated peptides with a broad tolerance for the C‐terminal amino acid. By the use of hypervalent iodine reagents, the introduction of a broad range of functional groups was successful. C‐terminal selectivity was achieved by differentiation of the oxidation potentials of the carboxylic acids based on the use of fine‐tuned organic dyes.     

Visible Light‐Promoted Decarboxylative Di‐ and Trifluoromethylthiolation of Alkyl Carboxylic Acids

Described herein is a new and straightforward decarboxylative di‐ and trifluoromethylthiolation of alkyl carboxylic acids promoted by visible light. This approach enables the synthesis of biologically relevant alkyl SCF₂H and SCF₃ compounds from cheap and abundant carboxylic acids. The method is operationally simple, using irradiation from household light sources, and its mild reaction conditions make it tolerant of a range of functional groups. The strategy employs electrophilic phthalimide‐derived di‐ and trifluoromethylthiolation reagents and exploits the ability of the imidyl radical to carry a radical chain.     

Advances in Electrochemical Decarboxylative Transformation Reactions

Owing to their non-toxic, stable, inexpensive properties, carboxylic acids are considered as environmentally benign alternatives as coupling partners in various organic transformations. Electrochemical mediated decarboxylation of carboxylic acid has emerged as a new and efficient methodology for the construction of carbon-carbon or carbon-heteroatom bonds. Compared with transition-metal catalysis and photoredox catalysis, electro-organic decarboxylative transformations are considered as a green and sustainable protocol due to the absence of chemical oxidants and strong bases. Further, it exhibits good tolerance with various functional groups. In this Minireview, we summarize the recent advances and discoveries on the electrochemical decarboxylative transformations on C−C and C−heteroatoms bond formations.     

Ag/Cu-mediated decarboxylative cyanation of aryl carboxylic acids with K4Fe(CN)6 under aerobic conditions

A method for facile synthesis of aryl nitriles has been well established via Ag/Cu-mediated decarboxylative cyanation of benzoic acids with K₄Fe(CN)₆ under aerobic conditions. The approach of using readily accessible aryl carboxylic acids and green K₄Fe(CN)₆ as starting material provides a feasible alternative to previous cyanation protocols. Control experiments revealed the key role of Cu for the process and excluded the possibility of a radical mechanism for the transformation.     

Decarboxylative Alkynylation and Carbonylative Alkynylation of Carboxylic Acids Enabled by Visible‐Light Photoredox Catalysis

Visible‐light‐induced photocatalytic decarboxylative alkynylations of carboxylic acids have been developed for the first time. The reaction features extremely mild conditions, broad substrate scope, and avoids additional oxidants. Importantly, a decarboxylative carbonylative alkynylation has also been carried out in the presence of carbon monoxide (CO) under photocatalytic conditions, which affords valuable ynones in high yields at room temperature.     

Direct Catalytic Decarboxylative Amination of Aryl Acetic Acids

The decarboxylative coupling of a carboxylic acid with an amine nucleophile provides an alternative to the substitution of traditional organohalide coupling partners. Benzoic and alkynyl acids may be directly aminated by oxidative catalysis. In contrast, methods for intermolecular alkyl carboxylic acid to amine conversion, including amidate rearrangements and photoredox‐promoted approaches, require stoichiometric activation of the acid unit to generate isocyanate or radical intermediates. Reported here is a process for the direct chemoselective decarboxylative amination of electron‐poor arylacetates by oxidative Cu catalysis. The reaction proceeds at (or near) room temperature, uses native carboxylic acid starting materials, and is compatible with protic, electrophilic, and other potentially complicating functionality. Mechanistic studies support a pathway in which ionic decarboxylation of the acid generates a benzylic nucleophile which is aminated in a Chan–Evans–Lam‐type process.     

Sodium Dithionite-Mediated Decarboxylative Sulfonylation: Facile Access to Tertiary Sulfones

A straightforward multicomponent decarboxylative cross coupling of redox-active esters (N-hydroxyphthalimide ester), sodium dithionite, and electrophiles was established to construct sterically bulky sulfones. The inorganic salt sodium dithionite not only served as the sulfur dioxide source, but also acted as an efficient radical initiator for the decarboxylation. Notably, diverse naturally abundant carboxylic acids and artificially prepared carboxyl-containing drugs with multiple heteroatoms and sensitive functional groups successfully underwent this decarboxylative sulfonylation to provide sterically bulky tertiary sulfones. Mechanistic studies further demonstrated that decarboxylation was the rate-determining step and occurred via a single-electron transfer (SET) process with the assistance of sodium dithionite.     

C(sp<Superscript>3</Superscript>)–H bond functionalization of non-cyclic ethers by decarboxylative oxidative coupling with α,β-unsaturated carboxylic acids

A copper-catalyzed decarboxylative oxidative coupling of α,β-unsaturated carboxylic acids with non-cyclic ethers is developed. This method provides a new approach for C(sp³)–H bond functionalization of non-cyclic ethers. Mechanism study shows the reaction involves a radical process.     

Visible‐Light‐Induced Decarboxylative Functionalization of Carboxylic Acids and Their Derivatives

Visible‐light‐induced radical decarboxylative functionalization of carboxylic acids and their derivatives has recently received considerable attention as a novel and efficient method to create C? C and C? X bonds. Generally, this visible‐light‐promoted decarboxylation process can smoothly occur under mild reaction conditions with a broad range of substrates and an excellent functional‐group tolerance. The radical species formed from the decarboxylation step can participate in not only single photocatalytic transformations, but also dual‐catalytic cross‐coupling reactions by combining photoredox catalysis with other catalytic processes. Recent advances in this research area are discussed herein.     

Targeted Fluorination with the Fluoride Ion by Manganese‐Catalyzed Decarboxylation

We describe the first catalytic decarboxylative fluorination reaction based on the nucleophilic fluoride ion. The reported method allows the facile replacement of various aliphatic carboxylic acid groups with fluorine. Moreover, the potential of this method for PET imaging has been demonstrated by the successful ¹⁸F labeling of a variety of carboxylic acids with radiochemical conversions up to 50 %, representing a targeted decarboxylative ¹⁸F labeling method with no‐carrier‐added [¹⁸F]fluoride. Mechanistic probes suggest that the reaction proceeds through the interaction of the manganese catalyst with iodine(III) carboxylates formed in situ from iodosylbenzene and the carboxylic acid substrates.