Auto-Tandem Copper-Catalyzed Carboxylation of Undirected Alkenyl C-H Bonds with CO2 by Harnessing ß-Hydride Elimination.

The exploration into challenging scenarios of the application of elementary reactions offers excellent opportunities for the development of unique transformations under organometallic catalysis. As a ubiquitous reaction of metal alkyl complexes, ß-hydride elimination plays a crucial role in a number of important catalytic transformations. However, its functions in these catalytic cycles are limited to either releasing alkene products or generating isomerized intermediates through further migratory insertion. Herein, we report that the precise manipulation of ß-hydride elimination enables an auto-tandem copper catalysis for the carboxylation of undirected alkenyl C-H bonds with CO2. In this transformation, ß-hydride elimination of an alkyl copper intermediate is facilitated, while its reaction with CO2 is suppressed. The resulting copper hydride in turn reacts with CO2 to provide access to a multitasking catalyst, which enables the tandem borylation/carboxylation of C-H bonds in two mechanistically distinct catalytic cycles.

Metal-free switchable ortho/ipso-cyclization of N-aryl alkynamides: divergent synthesis of 3-selenyl quinolin-2-ones and azaspiro[4,5]trienones.

A selenium radical triggered switchable ortho/ipso-cyclization cascade of N-aryl alkynamides has been devised under metal-free conditions to access 3-selenyl quinolin-2-ones and 3-selenospiro[4,5]trienones in high yields (up to 98%). The simple protocol is scalable and the mechanistic studies suggest that the radical cascade proceeds through a spirocyclic intermediate which is formed via an intramolecular ipso-cyclization route.

Copper Catalyzed C-N Cross-Coupling Reaction of Aryl Boronic Acids at Room Temperature through Chelation Assistance.

A copper-catalyzed selective C-N cross-coupling has been developed based on chelation-assisted amidation of readily available aryl boronic acids at room-temperature under open-flask conditions. The reaction is scalable and tolerates a wide spectrum of functional groups delivering fully substituted unsymmetrical amides in high yields (up to 96%). The C-N cross coupling also established with aryl silanes, extending the palette of coupling partners of this strategy.

Copper-Catalyzed 8-Amido Chelation-Induced Remote C-H Amination of Quinolines.

A copper-catalyzed 8-amide chelation-induced remote C-H amination of quinolines has been developed. This direct amination with readily available azodicarboxylates proceeded with perfect C5-regioselectivity offering amino-substituted 8-aminoquinolines, important bioactive molecular scaffolds, in very high yields (up to 96%). A single-electron transfer (SET)-mediated mechanism with kH /kD =1.1 was proposed after trapping of the radical intermediate.

Atom Transfer Oxidative Radical Cascade of Aryl Alkynoates towards 1,1-Dichalcogenide Olefins.

An oxidative trifunctionalization of aryl alkynoates has been devised via the chalcogenide radical triggered intramolecular 1,4-aryl migration/decarboxylation cascade to prepare 1,1-dichalcogenide tetrasubstituted alkenes in high yields (up to 98 %). This operationally simple reaction proceeds under metal-free conditions, can be executed on gram scale, and highlights formal 1,1-difunctionalization of alkynes. Synthetic potential of this protocol was demonstrated through a twofold cascade rearrangement to access highly conjugated tetra-selenylated alkenes along with a cross-dehydrogenative annulation to prepare fluorene derivative.

Radical Cascade Reaction of Aryl Alkynoates at Room Temperature: Synthesis of Fully Substituted α,ß-Unsaturated Acids with Chalcogen Functionality.

A radical-based cascade reaction has been devised for oxidative difunctionalization of aryl alkynoates at room temperature to access stereodefined fully substituted α,ß-unsaturated acids bearing a chalcogen functionality in high yields (up to 95%). The protocol is operationally simple, metal-free, scalable, and suppresses the usual CO2 exclusion phenomenon. The utility of this method was showcased in the synthesis of vinyl halides, vinyl selenides, and 3,3-disubstituted indanones.

Ru(II)-Catalyzed Oxidative Heck-Type Olefination of Aromatic Carboxylic Acids with Styrenes through Carboxylate-Assisted C-H Bond Activation.

A straightforward synthesis of 2-styrylbenzoic acids from aryl carboxylic acids is disclosed through a carboxylate-assisted coupling under Ru(II) catalysis. This protocol is simple and exhibits broad scope with high tolerance of common organic functional groups, providing good to excellent yields of diverse olefinated products. The efficacy of this protocol has been showcased through sequential syntheses of isochromanone, isocoumarin, and formal synthesis of anacardic acid derivative in good yields.

Ruthenium(II)-Catalyzed Hydroarylation of Maleimides Using Carboxylic Acids as a Traceless Directing Group.

An efficient Ru(II)-catalyzed hydroarylation of maleimides with ready-stock aryl carboxylic acids has been developed based on weak carboxylate-directed ortho-C-H alkylation and concomitant decarboxylation processes, fabricating 3-aryl succinimides, a recurrent scaffold in drug molecules, in high yields (up to 97%). The protocol features operational simplicity, avoids the need for precious metal additives/oxidants, and offers broad substrate scope with formal meta- and para-selectivities. It represents the first example of Ru(II)-catalyzed direct arylation of maleimides with unbiased benzoic acids.

Ru(II)-Catalyzed C-H Functionalization on Maleimides with Electrophiles: A Demonstration of Umpolung Strategy.

The unconventional nucleophilic reactivity of maleimides, innate electrophiles, has been realized under Ru(II)-catalysis such that exposure to electrophiles delivered products of C-H chalcogenation and amidation in good yields (up to 94%). This protocol features mild conditions and operational simplicity with broad substrate scope, uses an inexpensive and air-stable catalyst, and also represents the first example of Ru(II) catalyzed C-H selenylation of alkenes.

Ruthenium(II)-Catalyzed ortho-C-H Chalcogenation of Benzoic Acids via Weak O-Coordination: Synthesis of Chalcogenoxanthones.

A general protocol for direct chalcogenation of inert C-H bonds of (hetero)aromatic carboxylic acids is developed with a ruthenium(II) catalyst using readily available starting materials, offering densely substituted ortho-chalcogenyl aromatic acids in high yields (up to 96%). The strategy avoids the installation of an external directing group, use of metallic oxidants, and features operational simplicity with ample substrate scope. Synthetic application en route to biologically important chalcogenoxanthones is also demonstrated. This work represents the first example of ruthenium(II)-catalyzed direct C-H chalcogenation of benzoic acids.

Brønsted acid mediated N-O bond cleavage for α-amination of ketones through the aromatic nitroso aldol reaction.

A Brønsted acid mediated N-O bond cleavage for α-amination of ketones has been developed through the nitroso aldol reaction of less-reactive aromatic nitroso compounds and silyl enol ethers having a disilane (-SiMe2TMS) backbone. This transformation is operationally simple and scalable, offering structurally diverse α-amino ketones in high yields (up to 98%) with complete regioselectivity. It represents a mechanistically unique and rare example of a metal-free N-O bond cleavage process.

Copper-Catalyzed 8-Aminoquinoline-Directed Selenylation of Arene and Heteroarene C-H Bonds.

An efficient copper-catalyzed/-mediated and 8-aminoquinoline-assisted arylselenylation of inert C-H bonds of (hetero)arenes with readily available diselenides has been reported. The reaction is scalable and tolerates a wide spectrum of functional groups to deliver diarylselenides in very high yields (up to 98%). Application of this methodology to the facile synthesis of thiophene-fused selenochromone was demonstrated.

The Mukaiyama aldol reaction of in situ generated nitrosocarbonyl compounds: selective C-N bond formation and N-O bond cleavage in one-pot for α-amination of ketones.

A practical protocol for the α-amination of ketones (up to 99% yield) has been developed via the Mukaiyama aldol reaction of in situ generated nitrosocarbonyl compounds. The reaction with silyl enol ethers having a disilane (-SiMe2TMS) backbone proceeded not only with perfect N-selectivity but concomitant N-O bond cleavage was also accomplished. Such a cascade of C-N bond formation and N-O bond cleavage in a single step was heretofore unknown in the field of nitrosocarbonyl chemistry. A very high diastereoselectivity (dr = 19 : 1) was accomplished using (-)-menthol derived chiral nitrosocarbonyl compounds.