Disproportionation-Inspired Construction of Highly Functionalized Bicyclo[3.2.1]octanes.

The formation of one unavoidable byproduct in traditional disproportionation reactions limits their applications in synthesis. Inspired by convergent disproportionation, we develop an iodine-induced cyclization and oxidation of allylic alcohols to produce highly functionalized bicyclo[3.2.1]octanes through creation of six new bonds. Guided by the mechanism, we elaborated a variety of other bicyclo[3.2.1]octanes bearing distinct groups with presynthesized dienes and enones as the starting materials. This work provides a divergent access to bicyclo[3.2.1]octane frameworks.

Skeleton-Reorganizing Coupling Reactions of Cycloheptatriene and Cycloalkenones with Amines.

Skeletal reorganization reactions have emerged as an intriguing tool for converting readily available compounds into complicated molecules inaccessible by traditional methods. Herein, we report a unique skeleton-reorganizing coupling reaction of cycloheptatriene and cycloalkenones with amines. In the presence of Rh/acid catalysis, cycloheptatriene can selectively couple with anilines to deliver fused 1,2-dihydroquinoline products. Mechanistic studies indicate that the retro-Mannich type ring-opening and subsequent intramolecular Povarov reaction account for the ring reorganization. Our mechanistic studies also revealed that skeleton-reorganizing amination between anilines and cycloalkenones can be achieved with acid. The synthetic utilization of this skeleton-reorganizing coupling reaction was showcased with a gram-scale reaction, synthetic derivatizations, and the late-stage modification of commercial drugs.

Selective C-S Bond Constructions Using Inorganic Sulfurs via Photoinduced Electron Donor-Acceptor Activation.

By complementing traditional transition metal catalysis, photoinduced catalysis has emerged as a versatile and sustainable way to achieve carbon-heteroatom bond formation. This work discloses a visible-light-induced reaction for the formation of a C-S bond from aryl halides and inorganic sulfuration agents via electron donor-acceptor (EDA) complex photocatalysis. Divergent formations of organic sulfide and disulfide have been demonstrated under mild conditions. Preliminary mechanistic studies suggest that visible-light-induced intracomplex charge transfer within the monosulfide-anion-containing EDA complex permits the C-S bond construction reactivity.

Rhodium-Catalyzed Deuterated Tsuji-Wilkinson Decarbonylation of Aldehydes with Deuterium Oxide.

The recent surge in the applications of deuterated drug candidates has rendered an urgent need for diverse deuterium labeling techniques. Herein, an efficient Rh-catalyzed deuterated Tsuji-Wilkinson decarbonylation of naturally available aldehydes with D2O is developed. In this reaction, D2O not only acts as a deuterated reagent and solvent but also promotes Rh-catalyzed decarbonylation. In addition, decarbonylative strategies for the synthesis of terminal monodeuterated alkenes from α,ß-unsaturated aldehydes are within reach.

Electrochemically driven regioselective C-H phosphorylation of group 8 metallocenes.

Metallocenes are privileged backbones for synthesis and catalysis. However, the direct dehydrogenative C-H functionalization of unsymmetric metallocenes suffers from reactivity and selectivity issues. Herein, we report an electrochemically driven regioselective C-H phosphorylation of group 8 metallocenes. Mechanistic investigations indicate this dehydrogenative cross coupling occurs through an electrophilic radical substitution of the metallocene with a phosphoryl radical, facilitated by the metallocene itself. This work not only offers an efficient and divergent synthesis of phosphorylated metallocenes, but also provides a guide to interpret the reactivity and regioselectivity for the C-H functionalization of unsymmetric metallocenes.

Photo-induced catalytic halopyridylation of alkenes.

The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here we report an atom-economical cross-coupling of halopyridines and unactivated alkenes under photoredox catalysis to afford a series of alkene halopyridylation products. This protocol with mild and redox neutral conditions contributes broad substrate scope. As a complement to conventional Heck-type reaction, this radical process avoids the involvement of ß-H elimination and thus useful pyridyl and halide groups could be simultaneously and regioselectively incorporated onto alkenes. The success depends on TFA-promoted domino photocatalytic oxidative quenching activation and radical-polar crossover pathway. Plausible mechanism is proposed based on mechanistic investigations. Moreover, the reserved C - X bonds of these products are beneficial for performing further synthetic elaborations.

The serendipitous effect of KF in Ritter reaction: Photo-induced amino-alkylation of alkenes.

Ritter reaction has been recognized as an elegant strategy to construct the C-N bond. Its key feature is forming the carbocation for nucleophilic attack by nitriles. Herein, we report a complementary visible-light-induced three-component Ritter reaction of alkenes, nitriles, and α-bromo nitriles/esters, thereby providing mild and rapid access to various γ-amino nitriles/acids. Mechanistic studies indicated that traceless fluoride relay, transforming KF into imidoyl fluoride intermediate, is critical for the efficient reaction switch from atom transfer radical addition (ATRA) to the Ritter reaction. This approach to amino-alkylation of alkenes is chemoselective and operationally simple.

Orthogonal Regulation of Nucleophilic and Electrophilic Sites in Pd-Catalyzed Regiodivergent Couplings between Indazoles and Isoprene.

Depending on the reactant property and reaction mechanism, one major regioisomer can be favored in a reaction that involves multiple active sites. Herein, an orthogonal regulation of nucleophilic and electrophilic sites in the regiodivergent hydroamination of isoprene with indazoles is demonstrated. Under Pd-hydride catalysis, the 1,2- or 4,3-insertion pathway with respect to the electrophilic sites on isoprene could be controlled by the choice of ligands. In terms of the nucleophilic sites on indazoles, the reaction occurs at either the N1 - or N2 -position of indazoles is governed by the acid co-catalysts. Preliminary experimental studies have been performed to rationalize the mechanism and regioselectivity. This study not only contributes a practical tool for selective functionalization of isoprene, but also provides a guide to manipulate the regioselectivity for the N-functionalization of indazoles.

Visible Light Induced Bifunctional Rhodium Catalysis for Decarbonylative Coupling of Imides with Alkynes.

Transition metal catalyzed decarbonylation offers a distinct synthetic strategy for new chemical bond formation. However, the π-backbonding between CO π* orbitals and metal center d-orbitals impedes ligand dissociation to regenerate the catalyst under mild reaction conditions. Developed here is visible light induced rhodium catalysis for decarbonylative coupling of imides with alkynes under ambient conditions. Initial mechanistic studies suggest that the rhodium complex simultaneously serves as the catalytic center and photosensitizer for decarbonylation. This visible light promoted catalytic decarbonylation strategy offers new opportunities for reviewing old transformations with ligand dissociation as a rate-determining step.

Copper-catalyzed boroacylation of allenes to access tetrasubstituted vinylboronates.

A distinct copper-catalyzed boroacylation of allenes with acyl chlorides and bis(pinacolato)diboron is developed. For aromatic acyl chlorides, 1,2-boroacylation of allenes readily takes place, leading to the formation of tetrasubstituted vinylboronates with exclusive (E)-stereoselectivity. In comparison, the employment of alkyl acyl chlorides as electrophiles alters the selectivity to 2,3-boroacylated products. Additionally, the product can easily undergo Suzuki-Miyaura cross-coupling to afford tetrasubstituted alkene with complete retention of the configuration.

Rhodium-catalyzed regio- and enantioselective allylic alkylation of pyrazol-5-ones with alkynes.

A rhodium-catalyzed asymmetric allylic alkylation of pyrazol-5-ones with internal alkynes is illustrated. In the presence of a chiral rhodium-hydride catalyst, functionalized heterocyclic products bearing an all-carbon quaternary stereogenic center were obtained in high yields with satisfactory enantioselectivities. This protocol also features good regiocontrol and a high atom economy without stoichiometric by-product formation.

Cobalt-Catalyzed Regioselective Carboamidation of Alkynes with Imides Enabled by Cleavage of C-N and C-C Bonds.

Through the oxidative addition of cobalt into the N-C(O) bond of phthalimide and the subsequent decarbonylation, we describe an efficient cobalt-catalyzed intermolecular decarbonylative carboamidation of alkynes. High regioselectivities have been achieved for unsymmetrical alkynes (including aryl-alkyl or aryl-aryl) to deliver polysubstituted isoquinolones. To facilitate step economy, a three-component decarbonylative carboamidation of alkynes with phthalic anhydrides and amines has been demonstrated using the current cobalt catalysis.

Ruthenium(ii)-catalyzed intermolecular annulation of alkenyl sulfonamides with alkynes: access to bicyclic sultams.

A ruthenium-catalyzed allylic C(sp3)-H activation strategy has been employed to develop an intermolecular coupling of alkenyl sulfonamides with alkynes. This protocol features the diastereoselective construction of [3.3.0] and [4.3.0] bicyclic sultams in one step.

Cobalt-catalyzed hydroxymethylarylation of terpenes with formaldehyde and arenes.

Terpenes, consisting of isoprene monomer units, represent a family of naturally abundant compounds. The difunctionalization of terpenes is highly appealing yet remains challenging, since the multiple unbiased C[double bond, length as m-dash]C bonds of terpenes lead to difficulty in controlling the regioselectivity. Herein, a cobalt(iii)-catalyzed C-H activation strategy has been developed to facilitate hydroxymethylarylation of terpenes with formaldehyde and arenes with high chemo- and regio-selectivities. These (chemo- and regio-) selectivities are governed by the coordination abilities of isoprene, directing groups and the steric effect. This terpene difunctionalization also features high atom and step economy through a C-H addition pathway.