Cobalt-Catalyzed Allylic Alkylation at sp3-Carbon Centers.

The rising demand and financial costs of noble transition metal catalysts have emphasized the need for sustainable catalytic approaches. Over the past few years, base-metal catalysts have emerged as ideal candidates to replace their noble-metal counterparts because of their abundance and easiness of handling. Despite the significant advancements achieved with precious transition metals, earth-abundant cobalt catalysts have emerged as efficient alternatives for allylic substitution reactions. In this review, allylic alkylations at sp3-carbon centers mediated by cobalt will be discussed, with a special focus on the mechanistic features, scope, and limitations.

Cobalt-Catalyzed Decarboxylative Allylations: Development and Mechanistic Studies.

In recent years, there has been a concerted drive to develop methods that are greener and more sustainable. Being an earth-abundant transition metal, cobalt offers an attractive substitute for commonly employed precious metal catalysts, though reactions engaging cobalt are still less developed. Herein, we report a method to achieve the decarboxylative allylation of nitrophenyl alkanes, nitroalkanes, and ketones employing cobalt. The reaction allows for the formation of various substituted allylated products in moderate-excellent yields with a broad scope. Additionally, the synthetic potential of the methodology is demonstrated by the transformation of products into versatile heterocyclic motifs. Mechanistic studies revealed an in situ activation of the Co(II)/dppBz precatalyst by the carboxylate salt to generate a Co(I)-species, which is presumed to be the active catalyst.

Photoassisted Cobalt-Catalyzed Asymmetric Reductive Grignard-Type Addition of Aryl Iodides.

Grignard addition is one of the most important methods used for syntheses of alcohol compounds and has been known for over a hundred years. However, research on asymmetric catalysis relies on the use of organometallic nucleophiles. Here, we report the first visible-light-induced cobalt-catalyzed asymmetric reductive Grignard-type addition for synthesizing chiral benzyl alcohols (>50 examples, up to 99% yield, and 99% ee). This methodology has the advantages of mild reaction conditions, good functionality tolerance, excellent enantiocontrol, the avoidance of mass metal wastes, and the use of precious metal catalysts. Kinetic realization studies suggested that migratory insertion of an aryl cobalt species into the aldehyde was the rate-determining step of the reductive addition reaction.

Direct Aroylation of Olefins through a Cobalt/Photoredox-Catalyzed Decarboxylative and Dehydrogenative Coupling with α-Oxo Acids.

Invited for the cover of this issue is the group of Jon Tunge at the University of Kansas. The image depicts the direct cross-coupling of α-oxo acids and styrenes through the release of CO2 and H2 gas in a metallaphotoredox process. Read the full text of the article at 10.1002/chem.202202781.

Direct Aroylation of Olefins through a Cobalt/Photoredox-Catalyzed Decarboxylative and Dehydrogenative Coupling with α-Oxo Acids.

A photoredox/cobalt dual catalytic procedure has been developed that allows benzoylation of olefins. Here the photoredox catalyst effects the decarboxylation of α-ketoacids to form benzoyl radicals. After addition of this radical to styrenes, the cobalt catalyst abstracts a H-atom. Hydrogen evolution from the putative cobalt hydride intermediate allows a Heck-like aroylation without the need for a stoichiometric oxidant. Mechanistic studies reveal that electronically different styrenes lead to a curved Hammett plot, thus suggesting a change in product-determining step in the catalytic mechanism.

Photoredox/Cobalt Dual-Catalyzed Decarboxylative Elimination of Carboxylic Acids: Development and Mechanistic Insight.

Recently, dual-catalytic strategies towards the decarboxylative elimination of carboxylic acids have gained attention. Our lab previously reported a photoredox/cobaloxime dual catalytic method that allows the synthesis of enamides and enecarbamates directly from N-acyl amino acids and avoids the use of any stoichiometric reagents. Further development, detailed herein, has improved upon this transformation's utility and further experimentation has provided new insights into the reaction mechanism. These new developments and insights are anticipated to aid in the expansion of photoredox/cobalt dual-catalytic systems.

Decarboxylative Acetoxylation of Aliphatic Carboxylic Acids.

Organic molecules bearing acetoxy moieties are important functionalities in natural products, drugs, and agricultural chemicals. Synthesis of such molecules via transition metal-catalyzed C-O bond formation can be achieved in the presence of a carefully chosen directing group to alleviate the challenges associated with regioselectivity. An alternative approach is to use ubiquitous carboxylic acids as starting materials and perform a decarboxylative coupling. Herein, we report conditions for a photocatalytic decarboxylative C-O bond formation reaction that provides rapid and facile access to the corresponding acetoxylated products. Mechanistic investigations suggest that the reaction operates via oxidation of the carboxylate followed by rapid decarboxylation and oxidation by Cu(OAc)2.

Photoinduced Kochi Decarboxylative Elimination for the Synthesis of Enamides and Enecarbamates from N-Acyl Amino Acids.

Decarboxylative elimination of easily accessible N-acyl amino acids to provide enamide and enecarbamate building blocks has been realized through the combination of an organophotoredox catalyst and copper acetate as the terminal oxidant. This operationally simple process utilizes inexpensive and readily available reagents without preactivation of the carboxylic acid. Enamides and enecarbamates are now accessible directly from N-acyl amino acids consequently improving upon the utility of Kochi's oxidative decarboxylation of carboxylic acids.

Palladium-Catalyzed Regiodivergent Substitution of Propargylic Carbonates.

The palladium(0)-catalyzed, ligand-controlled, regioselective addition of diaryl acetonitrile pronucleophiles to propargylic carbonates is reported. Selective formation of either terminal 1,3-dienyl or propargylated products is proposed to arise from a change in reaction mechanism controlled by the denticity of the coordinating ligand.

Photocatalytic Aminodecarboxylation of Carboxylic Acids.

Aminodecarboxylation of unactivated alkyl carboxylic acids has been accomplished utilizing an organic photocatalyst. This operationally simple reaction utilizes readily available carboxylic acids to chemoselectively generate reactive alkyl intermediates that are not accessible via conventional two-electron pathways. The organic radical intermediates are efficiently trapped with electrophilic diazo compounds to provide aminated alkanes.

Dual Catalytic Decarboxylative Allylations of α-Amino Acids and Their Divergent Mechanisms.

The room temperature radical decarboxylative allylation of N-protected α-amino acids and esters has been accomplished via a combination of palladium and photoredox catalysis to provide homoallylic amines. Mechanistic investigations revealed that the stability of the α-amino radical, which is formed by decarboxylation, dictates the predominant reaction pathway between competing mechanisms.

Decarboxylative allylation of amino alkanoic acids and esters via dual catalysis.

A combination of photoredox and palladium catalysis has been employed to facilitate the room temperature decarboxylative allylation of recalcitrant α-amino and phenylacetic allyl esters. This operationally simple process produces CO2 as the only byproduct and provides direct access to allylated alkanes. After photochemical oxidation, the carboxylate undergoes radical decarboxylation to site-specifically generate radical intermediates which undergo allylation. A radical dual catalysis mechanism is proposed. Free phenylacetic acids were also allylated utilizing similar reactions conditions.

Decarboxylative allylations of ester enolate equivalents.

A variety of ester enolate equivalents are generated in situ and undergo α-allylation in high yields via palladium-catalyzed decarboxylative allylation. The transformations are complete within very short reaction times under ambient conditions. Synthesis of α-allylated acyl derivatives provides access to other carboxylic acid and alcohol derivatives via acyl group substitution or reduction.

Transition metal-free decarboxylative olefination of carboxylic acid salts.

The cost-effective and efficient synthesis of alkenes is highly significant due to their extensive applications in both synthetic and polymer industries. A transition metal-free approach has been devised for the chemoselective olefination of carboxylic acid salts. This modular approach provides direct access to valuable electron-deficient styrenes in moderate to good yields. Detailed mechanistic studies suggest anionic decarboxylation is followed by halogen ion transfer. This halogen transfer leads to an umpolung of reactant electronics, allowing for a rate-limiting rebound elimination.

Development of asymmetric deacylative allylation.

Herein we present the development of asymmetric deacylative allylation of ketone enolates. The reaction directly couples readily available ketone pronucleophiles with allylic alcohols using facile retro-Claisen cleavage to form reactive intermediates in situ. The simplicity and robustness of the reaction conditions is demonstrated by the preparation of >6 g of an allylated tetralone from commercially available materials. Furthermore, use of nonracemic PHOX ligands allows intermolecular formation of quaternary stereocenters directly from allylic alcohols.

Cobalt-catalyzed decarboxylative difluoroalkylation of nitrophenylacetic acid salts.

The selective installation of fluorine-containing groups into biologically relevant molecules has been used as a common strategy for the development of pharmaceutically active molecules. However, the selective incorporation of gem-difluoromethylene groups next to sterically demanding secondary and tertiary alkyl groups remains a challenge. Herein, we report the first cobalt-catalyzed regioselective difluoroalkylation of carboxylic acid salts. The reaction allows for the facile construction of various difluoroalkylated products in good yields tolerating a wide range of functionalities on either reaction partner. The potential of the method is illustrated by the late-stage functionalization of molecules of biological relevance. Mechanistic studies support the in situ formation of a cobalt(i) species and the intermediacy of difluoroalkyl radicals, thus suggesting a Co(i)/Co(ii)/Co(iii) catalytic cycle.

Single-Step Synthesis of γ-Ketoacids through a Photoredox-Catalyzed Dual Decarboxylative Coupling of α-Oxo Acids and Maleic Anhydrides.

A photocatalytic methodology for the single step synthesis of γ-ketoacids from α-ketoacids has been developed. This method employs maleic anhydrides as traceless synthetic equivalents of acrylic acids, achieving a selective cross-coupling via a dual decarboxylative strategy, where molecular CO2 is released as the only waste byproduct. The method has also been expanded to incorporate a highly regioselective, 3-component coupling with various alcohols to access functionalized γ-ketoesters.

Palladium-catalyzed, pyrrolidine-mediated arylmethylation of ketones and aldehydes with coumarinyl(methyl) acetates.

We report the palladium-catalyzed, pyrrolidine-mediated α-benzylation of enamines generated from aldehydes and ketones. The method allows for direct coupling of medicinally relevant coumarin moieties with aldehydes and ketones in good yield under mild conditions. The reaction is believed to proceed via a Pd-π-benzyl complex generated from (coumarinyl)methyl acetates.

Intercepted Decarboxylative Allylations of Nitroalkanoates.

Using palladium-catalyzed decarboxylation, several cascade reactions of allyl and prenyl nitroalkanoates that lead to nitro-containing chemical building blocks are described. A nitronate Michael addition/Tsuji-Trost allylation cascade was developed, leading to functionally dense chemical building blocks. Likewise, a Tsuji-Trost/decarboxylative protonation sequence was developed for the synthesis of orthogonally functionalized 2° nitroalkanes. The latter method provides rapid access to the indolizidine core.

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles.

The palladium-catalyzed nucleophilic substitution of (coumarinyl)methyl acetates is described. The reaction proceeds though a palladium π-benzyl-like complex and allows for many different types of C-, N-, and S-nucleophiles to be regioselectively added to the biologically active coumarin motif. This new method was utilized to prepare a 128-membered library of aminated coumarins for biological screening.