Biomimetic Photoexcited Cobaloxime Catalysis in Organic Synthesis.

Drawing inspiration from nature has long been a cornerstone of chemical innovation, with natural systems offering a wealth of untapped potential for discovery. In this minireview, we delve into the burgeoning field of cobaloxime catalysis in organic synthesis, which mimics the catalytic activity of the natural organometallic alkylcobalamine enzymes. Our focus lies on elucidating the latest advancements in this area, as well as delineating the primary mechanistic pathways at play. By describing, and comparing these mechanisms, we provide a comprehensive overview of the current state-of-the-art, while also shedding light on the key unresolved challenges that await further exploration.

Photoexcited cobalt catalysed endo-selective alkyl Heck reaction.

Herein, we report an intramolecular endo-selective Heck reaction of iodomethylsilyl ethers of phenols and alkenols. The reaction leads to the formation of seven- and eight-membered siloxycycles in excellent yields, which could be further converted into the corresponding allylic alcohols upon oxidation. Thus, this method could be used for the selective (Z)-hydroxymethylation of o-hydroxystyrenes and alkenols. Rapid scan EPR experiments and DFT calculations suggest a concerted ß-hydrogen elimination event to take place in the triplet state.

Conversion of racemic alcohols to optically pure amine precursors enabled by catalyst dynamic kinetic resolution: experiment and computation.

An unprecedented base metal catalysed asymmetric synthesis of α-chiral amine precursors from racemic alcohols is reported. This redox-neutral reaction utilises a bench-stable manganese complex and Ellman's sulfinamide as a versatile ammonia surrogate. DFT calculations explain the unusual finding of the highly stereoselective transformation enabled by a catalyst that undergoes an unusual dynamic kinetic resolution.

Sustainable Alkylation of Nitriles with Alcohols by Manganese Catalysis.

A general and chemoselective catalytic alkylation of nitriles using a homogeneous nonprecious manganese catalyst is presented. This alkylation reaction uses naturally abundant alcohols and readily available nitriles as coupling partners. The reaction tolerates a wide range of functional groups and heterocyclic moieties, efficiently providing useful cyanoalkylated products with water as the only side product. Importantly, methanol can be used as a C1 source and the chemoselective C-methylation of nitriles is achieved. The mechanistic investigations support the multiple role of the metal-ligand manganese catalyst, the dehydrogenative activation of the alcohol, α-C-H activation of the nitrile, and hydrogenation of the in-situ-formed unsaturated intermediate.

C-Alkylation of Secondary Alcohols by Primary Alcohols through Manganese-Catalyzed Double Hydrogen Autotransfer.

A new Mn-catalyzed alkylation of secondary alcohols with non-activated alcohols is presented. The use of a stable and well-defined manganese pincer complex, stabilized by a PNN ligand, together with a catalytic amount of base enabled the conversion of renewable alcohol feedstocks to a broad range of higher-value alcohols in good yields with water as the sole byproduct. The strategy eliminates the need for exogenous and detrimental alkyl halides as well as the use of noble metal catalysts, making the C-alkylation through double hydrogen autotransfer a highly sustainable and environmentally benign process. Mechanistic investigations support a hydrogen autotransfer mechanism in which a non-innocent ligand plays a crucial role.

Catalytic C1 †Alkylation with Methanol and Isotope-Labeled Methanol.

A metal-catalyzed methylation process has been developed. By employing an air- and moisture-stable manganese catalyst together with isotopically labeled methanol, a series of D-, CD3 -, and 13 C-labeled products were obtained in good yields under mild reaction conditions with water as the only byproduct.

Sustainable Manganese-Catalyzed Solvent-Free Synthesis of Pyrroles from 1,4-Diols and Primary Amines.

A general and selective metal-catalyzed conversion of biomass-derived primary diols and amines to the highly valuable 2,5-unsubstituted pyrroles has been developed. The reaction is catalyzed by a stable nonprecious manganese complex (1 mol %) in the absence of organic solvents whereby water and molecular hydrogen are the only side products. The manganese catalyst shows unprecedented selectivity, avoiding the formation of pyrrolidines, cyclic imides, and lactones.

Manganese-Catalyzed Multicomponent Synthesis of Pyrroles through Acceptorless Dehydrogenation Hydrogen Autotransfer Catalysis: Experiment and Computation.

A new base metal catalyzed sustainable multicomponent synthesis of pyrroles from readily available substrates is reported. The developed protocol utilizes an air- and moisture-stable catalyst system and enables the replacement of themutagenic α-haloketones with readily abundant 1,2-diols. Moreover, the presented method is catalytic in base and the sole byproducts of this transformation are water and hydrogen gas. Experimental and computational mechanistic studies indicate that the reaction takes place through a combined acceptorless dehydrogenation hydrogen autotransfer methodology.

Sustainable Alkylation of Unactivated Esters and Amides with Alcohols Enabled by Manganese Catalysis.

The first example of manganese-catalyzed C-alkylation of the carboxylic acid derivatives is reported. The bench-stable homogeneous manganese complex enables the transformation of the renewable alcohol and carboxylic acid derivative feedstock to higher value esters and amides. The reaction operates via hydrogen autotransfer and ideally produces water as the only side product. Importantly, aliphatic-, benzylic-, and heterocyclic-containing alcohols can be used as alkylating reagents, eliminating the need for mutagenic alkyl halides.

Hydrogenation of CO2 -Derived Carbonates and Polycarbonates to Methanol and Diols by Metal-Ligand Cooperative Manganese Catalysis.

The first base-metal-catalysed hydrogenation of CO2 -derived carbonates to alcohols is presented. The reaction proceeds under mild conditions in the presence of a well-defined manganese complex with a loading as low as 0.25 mol %. The non-precious-metal homogenous catalytic system provides an indirect route for the conversion of CO2 into methanol with the co-production of value-added (vicinal) diols in yields of up to 99 %. Experimental and computational studies indicate a metal-ligand cooperative catalysis mechanism.

Cooperative Metal-Ligand Catalyzed Intramolecular Hydroamination and Hydroalkoxylation of Allenes Using a Stable Iron Catalyst.

A new iron-catalyzed chemoselective intramolecular hydroamination and hydroalkoxylation of the readily available α-allenic amines and alcohols to valuable unsaturated 5-membered heterocycles, 2,3-dihydropyrrole and 2,3-dihydrofuran, is reported. Effective selectivity control is achieved by a metal-ligand cooperative activation of the substrates. The mild reaction conditions and the use of low amounts of an air and moisture stable iron catalyst allow for the hydrofunctionalization of a wide range of allenes bearing different functional groups in good yields in the absence of base or any sensitive additives.

Experimental and Computational Study of an Unexpected Iron-Catalyzed Carboetherification by Cooperative Metal and Ligand Substrate Interaction and Proton Shuttling.

An iron-catalyzed cycloisomerization of allenols to deoxygenated pyranose glycals has been developed. Combined experimental and computational studies show that the iron complex exhibits a dual catalytic role in that the non-innocent cyclopentadienone ligand acts as proton shuttle by initial hydrogen abstraction from the alcohol and by facilitating protonation and deprotonation events in the isomerization and demetalation steps. Molecular orbital analysis provides insight into the unexpected and selective formation of the 3,4-dihydro-2H-pyran.

Asymmetric Chemoenzymatic Reductive Acylation of Ketones by a Combined Iron-Catalyzed Hydrogenation-Racemization and Enzymatic Resolution Cascade.

A general and practical process for the conversion of prochiral ketones into the corresponding chiral acetates has been realized. An iron carbonyl complex is reported to catalyze the hydrogenation-dehydrogenation-hydrogenation of prochiral ketones. By merging the iron-catalyzed redox reactions with enantioselective enzymatic acylations a wide range of benzylic, aliphatic and (hetero)aromatic ketones, as well as diketones, were reductively acylated. The corresponding products were isolated with high yields and enantioselectivities. The use of an iron catalyst together with molecular hydrogen as the hydrogen donor and readily available ethyl acetate as acyl donor make this cascade process highly interesting in terms of both economic value and environmental credentials.

Merging Iron Catalysis and Biocatalysis-Iron Carbonyl Complexes as Efficient Hydrogen Autotransfer Catalysts in Dynamic Kinetic Resolutions.

A dual catalytic iron/lipase system has been developed and applied in the dynamic kinetic resolution of benzylic and aliphatic secondary alcohols. A detailed study of the Knölker-type iron complexes demonstrated the hydrogen autotransfer of alcohols to proceed under mild reaction conditions and allowed the combination with the enzymatic resolution. Different racemic alcohols were efficiently converted to chiral acetates in good yields and with excellent enantioselectivities.

Brønsted acid catalyzed, conjugate addition of ß-dicarbonyls to in situ generated ortho-quinone methides--enantioselective synthesis of 4-aryl-4H-chromenes.

We describe herein a catalytic, enantioselective process for the synthesis of 4H-chromenes which are important structural elements of many natural products and biologically active compounds. A sequence comprising a conjugate addition of ß-diketones to in situ generated ortho-quinone methides followed by a cyclodehydration reaction furnished 4-aryl-4H-chromenes in generally excellent yields and high optical purity. A BINOL-based chiral phosphoric acid was employed as a Brønsted acid catalyst which converted ortho-hydroxy benzhydryl alcohols into hydrogen-bonded ortho-quinone methides and effected the carbon-carbon bond-forming event with high enantioselectivity.