Bifunctional Chiral Electrocatalysts Enable Enantioselective α-Alkylation of Aldehydes.

Herein, we describe an innovative approach to the asymmetric electrochemical α-alkylation of aldehydes facilitated by a newly designed bifunctional chiral electrocatalyst. The highly efficient bifunctional chiral electrocatalyst combines a chiral aminocatalyst with a redox mediator. It plays a dual role as a redox mediator for electrooxidation, while simultaneously providing remarkable asymmetric induction for the stereoselective α-alkylation of aldehydes. Additionally, this novel catalyst exhibits enhanced catalytic activity and excellent stereoselective control comparable to conventional catalytic systems. As a result, this strategy provides a new avenue for versatile asymmetric electrochemistry. The electrooxidation of diverse phenols enables the C-H/C-H oxidative α-alkylation of aldehydes in a highly chemo- and stereoselective fashion. Detailed mechanistic studies by control experiments and cyclic voltammetry analysis demonstrate possible reaction pathways and the origin of enantio-induction.

Electroreductively Induced Radicals for Organic Synthesis.

Organic electrochemistry has attracted tremendous interest within the novel sustainable methodologies that have not only reduced the undesired byproducts, but also utilized cleaner and renewable energy sources. Particularly, oxidative electrochemistry has gained major attention. On the contrary, reductive electrolysis remains an underexplored research direction. In this context, we discuss advances in transition-metal-free cathodically generated radicals for selective organic transformations since 2016. We highlight the electroreductive reaction of alkyl radicals, aryl radicals, acyl radicals, silyl radicals, fluorosulfonyl radicals and trifluoromethoxyl radicals.

Remote Enantioselective [4 + 1] Annulation with Copper-Vinylvinylidene Intermediates.

The first copper-catalyzed enantioselective [4 + 1] annulation of yne-allylic esters with 1,3-dicarbonyl compounds was realized through an elegant remote stereocontrol strategy. The very remote ε regioselective nucleophilic substitution was developed by employing a novel chiral copper-vinylvinylidene species from the new C4 synthon yne-allylic esters. Thus, greatly diverse spirocycles were obtained with ample scope and excellent levels of chemo-, regio-, and enantioselectivities. Moreover, detailed mechanistic studies suggest an yne-allylic substitution and Conia-ene cascade pathway on the remote stereochemical induction progress.

Sustainable electrochemical C(sp3) - H oxygenation using water as the oxygen source.

Electrochemical C(sp3) - H oxygenation of phenols derivatives were accomplished using H2O as the sole oxygen source. Thus, selectively oxidative 4-cresols to 4-acylphenols derivatives proved viable with the aid of indirect electrolysis, through metal- and external oxidant free environmental-friendly and safe electrocatalytic conditions. Advances of this strategy were proved by its ability to transform various sulfonamides with excellent site and regioselectivity. Detailed mechanistic studies allowed to delineate the exact profile of the generation of the oxygenation events.

Catalytic Asymmetric Vinylogous and Bisvinylogous Propargylic Substitution.

Distinct regio- and enantioselectivity control in copper-catalyzed vinylogous and bisvinylogous propargylic substitution has been accomplished by using a novel chiral N,N,P ligand. The developed method provides an efficient and selective approach to an array of highly enantioenriched alkynyl unsaturated carbonyl compounds. Salient features include excellent functional group tolerance and broad substrate scope. The synthetic utility of the developed method is further demonstrated by a gram-scale synthesis and by application to a range of transformations including enantioselective synthesis of unique challenging compounds.

Organic Electrochemistry: Molecular Syntheses with Potential.

Efficient and selective molecular syntheses are paramount to inter alia biomolecular chemistry and material sciences as well as for practitioners in chemical, agrochemical, and pharmaceutical industries. Organic electrosynthesis has undergone a considerable renaissance and has thus in recent years emerged as an increasingly viable platform for the sustainable molecular assembly. In stark contrast to early strategies by innate reactivity, electrochemistry was recently merged with modern concepts of organic synthesis, such as transition-metal-catalyzed transformations for inter alia C-H functionalization and asymmetric catalysis. Herein, we highlight the unique potential of organic electrosynthesis for sustainable synthesis and catalysis, showcasing key aspects of exceptional selectivities, the synergism with photocatalysis, or dual electrocatalysis, and novel mechanisms in metallaelectrocatalysis until February of 2021.

Iron-Electrocatalyzed C-H Arylations: Mechanistic Insights into Oxidation-Induced Reductive Elimination for Ferraelectrocatalysis.

Despite major advances, organometallic C-H transformations are dominated by precious 5d and 4d transition metals, such as iridium, palladium and rhodium. In contrast, the unique potential of less toxic Earth-abundant 3d metals has been underexplored. While iron is the most naturally abundant transition metal, its use in oxidative, organometallic C-H activation has faced major limitations due to the need for superstoichiometric amounts of corrosive, cost-intensive DCIB as the sacrificial oxidant. To fully address these restrictions, we describe herein the unprecedented merger of electrosynthesis with iron-catalyzed C-H activation through oxidation-induced reductive elimination. Thus, ferra- and manganaelectro-catalyzed C-H arylations were accomplished at mild reaction temperatures with ample scope by the action of sustainable iron catalysts, employing electricity as a benign oxidant.

Manganese(I)-Catalyzed C-H Activation/Diels-Alder/retro-Diels-Alder Domino Alkyne Annulation featuring Transformable Pyridines.

Complexity-increasing Domino reactions comprising C-H allenylation, a Diels-Alder reaction, and a retro-Diels-Alder reaction were realized by a versatile catalyst derived from earth-abundant, non-toxic manganese. The C-H activation/Diels-Alder/retro-Diels-Alder alkyne annulation sequence provided step-economical access to valuable indolone alkaloid derivatives through a facile organometallic C-H activation manifold with transformable pyridines.

MnCl2-Catalyzed C-H Alkylation on Azine Heterocycles.

Low-valent manganese-catalyzed C-H alkylation of pyridine derivatives with both primary and challenging secondary alkyl halides was established by amide assistance. The strategy provided expedient access to alkylated pyridines with wide functional group tolerance and ample scope through weak chelation. Mechanistic studies provided strong support for a rate-determining C-H activation and a SET-type C-X scission.

Arene-Ligand-Free Ruthenium(II/III) Manifold for meta-C-H Alkylation: Remote Purine Diversification.

meta-Selective C-H alkylations of bioactive purine derivatives were accomplished by versatile ruthenium catalysis. Thus, the arene-ligand-free complex [Ru(OAc)2 (PPh3 )2 ] enabled remote C-H functionalizations with ample scope and excellent levels of chemo- and positional selectivities. Detailed experimental and computational mechanistic studies provided strong support for a facile C-H activation within a ruthenium(II/III) manifold.

meta-C-H Bromination on Purine Bases by Heterogeneous Ruthenium Catalysis.

Methods for positionally selective remote C-H functionalizations are in high demand. Herein, we disclose the first heterogeneous ruthenium catalyst for meta-selective C-H functionalizations, which enabled remote halogenations with excellent site selectivity and ample scope. The versatile heterogeneous Ru@SiO2 catalyst was broadly applicable and could be easily recovered and reused, which set the stage for the direct fluorescent labeling of purines. In contrast to palladium, rhodium, iridium, or cobalt complexes, solely the ruthenium catalysis manifold provided access to meta-halogenated purine derivatives, illustrating the unique power of ruthenium C-H activation catalysis.

Ruthenium(II)-Catalyzed meta C-H Mono- and Difluoromethylations by Phosphine/Carboxylate Cooperation.

Ruthenium(II)-catalyzed meta-selective C-H (di)fluoromethylation was accomplished by phosphine and carboxylate cooperation. The remote C-H functionalization was characterized by ample substrate scope, thereby setting the stage for meta-(di)fluoromethylation through facile C-H cleavage.

Ruthenium(ii)-catalyzed C-H functionalizations on benzoic acids with aryl, alkenyl and alkynyl halides by weak-O-coordination.

C-H arylations of weakly coordinating benzoic acids were achieved by versatile ruthenium(ii) catalysis with ample substrate scope. Thus, user-friendly ruthenium(ii) biscarboxylate complexes modified with tricyclohexylphosphine enabled C-H functionalizations with aryl electrophiles. The unique versatility of the ruthenium(ii) catalysis manifold was reflected by facilitating effective C-H activations with aryl, alkenyl and alkynyl halides.

Condensation of anthranilic acids with pyridines to furnish pyridoquinazolones via pyridine dearomatization.

The unprecedented carbodiimide-mediated condensation between pyridines and anthranilic acids via pyridine dearomatization at room temperature has been developed to provide a straightforward approach to pyridoquinazolones. The value of this approach has further been demonstrated by its application to one-step, gram-scale syntheses of a series of pyridoquinazolone-based natural products and their analogues from readily available starting materials.