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.

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.

Reactivity of ynamides in catalytic intermolecular annulations.

Ynamides are unique alkynes with a carbon-carbon triple bond directly attached to the nitrogen atom bearing an electron-withdrawing group. The alkyne is strongly polarized by the electron-donating nitrogen atom, but its high reactivity can be finely tempered by the electron-withdrawing group. Accordingly, ynamides are endowed with both nucleophilic and electrophilic properties and their chemistry has been an active research field. The catalytic intermolecular annulations of ynamides, featuring divergent assembly of structurally important amino-heterocycles in a regioselective manner, have gained much attention over the past decade. This review aims to provide a comprehensive summary of the advances achieved in this area involving transition metal and acid catalysis. Moreover, the intermolecular annulations of ynamide analogs including ynol ethers and thioalkynes are also discussed, which can provide insights into the reactivity difference caused by the heteroatoms.

Bioinspired and Ligand-Regulated Unnatural Prenylation and Geranylation of Oxindoles with Isoprene under Pd Catalysis.

In nature, prenylation and geranylation are two important metabolic processes for the creation of hemiterpenoids and monoterpenoids under enzyme catalysis. Herein, we have demonstrated bioinspired unnatural prenylation and geranylation of oxindoles using the basic industrial feedstock isoprene through ligand regulation under Pd catalysis. Pentenylated oxindoles (with C5 added) were attained with high selectivity when using a bisphosphine ligand, whereas upon switching to a monophosphine ligand, selectivity toward geranylated oxindoles (with C10 added) was achieved. Moreover, the head-to-head product could be further isomerized to an internal skipped diene under Pd-H catalysis. No stoichiometric by-product was formed in the process.

Production of Copolyester Monomers from Plant-Based Acrylate and Acetaldehyde.

PCTA is an important copolyester that has been widely used in our daily necessities. Currently, its monomers are industrially produced from petroleum-derived xylene. To reduce the reliance on fossil energy, we herein disclose an alternative route to access PCTA monomer (terephthalate/isophthalate=2.4/1) in 61 % overall yield using plant-based acrylate and acetaldehyde as the feedstocks. The process includes Morita-Baylis-Hillman (MBH) reaction of acetaldehyde with acrylate, subsequent one-step dehydration/Diels-Alder reaction with acrylate over H2 SO4 /SiO2 catalyst, and final Pd/C-catalyzed dehydrogenation. Besides, when varying the final step to hydrogenation, another important monomer UNOXOL™ diol (1,4-trans/1,4-cis/1,3-trans/1,3-cis=5.2/2/2.5/1) can be produced in 67 % overall yield.

Redox-Divergent Construction of (Dihydro)thiophenes with DMSO.

Thiophene-based rings are one of the most widely used building blocks for the synthesis of sulfur-containing molecules. Inspired by the redox diversity of these features in nature, we demonstrate herein a redox-divergent construction of dihydrothiophenes, thiophenes, and bromothiophenes from the respective readily available allylic alcohols, dimethyl sulfoxide (DMSO), and HBr. The redox-divergent selectivity could be manipulated mainly by controlling the dosage of DMSO and HBr. Mechanistic studies suggest that DMSO simultaneously acts as an oxidant and a sulfur donor. The synthetic potentials of the products as platform molecules were also demonstrated by various derivatizations, including the preparation of bioactive and functional molecules.

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.

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.

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.

Ligand-Regulated Regiodivergent Hydrosilylation of Isoprene under Iron Catalysis.

A method for the regiodivergent and stereoselective hydrosilylation of the basic industrial feedstock isoprene with unactivated silanes has been developed using earth-abundant iron catalysts. The manipulation of regioselectivity relies on fine modification of the coordination geometry of the iron center. While a bidentate pyridine imine ligand promoted the formation of allylic silanes through 4,1-addition, selectivity for the 3,4-adduct homoallylic silanes was observed with a tridentate nitrogen ligand. Experimental studies and analysis were carried out to elucidate the reaction mechanism and the factors enabling manipulation of the regioselectivity. This study contributes to the art of regioselectivity control in alkene hydrofunctionalization.

Catalytic Prenylation and Reverse Prenylation of Indoles with Isoprene: Regioselectivity Manipulation through Choice of Metal Hydride.

The basic industrial feedstock isoprene was employed as a building block to install prenyl and reverse-prenyl groups onto indoles. The regioselectivity can be manipulated by the choice of metal hydride. Reverse-prenylated indoles were attained with high selectivity when using Rh-H. By switching to a Pd-H catalyst, selectivity toward prenylated indoles was achieved. This regiodivergent method also features high atom economy without stoichiometric byproduct formation.

Synthesis of 1,4-Cyclohexanedimethanol, 1,4-Cyclohexanedicarboxylic Acid and 1,2-Cyclohexanedicarboxylates from Formaldehyde, Crotonaldehyde and Acrylate/Fumarate.

Valuable polyester monomers and plasticizers-1,4-cyclohexanedimethanol (CHDM), 1,4-cyclohexanedicarboxylic acid (CHDA), and 1,2-cyclohexanedicarboxylates-have been prepared by a new strategy. The synthetic processes involve a proline-catalyzed formal [3+1+2] cycloaddition of formaldehyde, crotonaldehyde, and acrylate (or fumarate). CHDM is produced after a subsequent hydrogenation step over a commercially available Cu/Zn/Al catalyst and a one-pot hydrogenation/oxidation/hydrolysis process yields CHDA, whereas 1,2-cyclohexanedicarboxylate is obtained by a Pd/C-catalyzed tandem decarbonylation/hydrogenation step.

Tf2NH-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with Dioxazoles: A Metal-Free Approach to Polysubstituted 4-Aminooxazoles.

An unprecedented Tf2NH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.

Tf2NH-catalyzed formal [3 + 2] cycloaddition of oxadiazolones with ynamides: a simple access to aminoimidazoles.

Oxadiazolones are first employed as the three-atom coupling partners in the Tf2NH-catalyzed cycloaddition with ynamides. This formal [3 + 2] cycloaddition allows a rapid synthesis of aminoimidazoles with a broad substrate scope. The approach also features a metal-free catalytic cycloaddition process, which may find applications in the synthesis of bioactive molecules. Besides, the resulting N-methyl products can further be readily converted to free N-H aminoimidazoles.

Transition-Metal Controlled Diastereodivergent Radical Cyclization/Azidation Cascade of 1,7-Enynes.

A strategy for achieving diastereodivergent azidations of enynes has been developed, employing azide transfer from the M-N3 complex to alkyl radicals. Following this concept, the diastereoselectivity has been switched by modulating the transition metals and the ligands. The Mn(III)-mediated radical cyclization/azidation cascade of 1,7-enynes afforded trans-fused pyrrolo[3,4-c]quinolinones, whereas the Cu(II)/bipyridine system gave cis-products.

From propargylamides to oxazole derivatives: NIS-mediated cyclization and further oxidation by dioxygen.

NIS-mediated iodocyclization of N-sulfonyl propargylamides for the synthesis of various oxazolidines and iodoalkylidenedihydrooxazoles via a 5-exo-dig process is developed. The resulting iodoalkylidenedihydrooxazoles can be further transformed into the corresponding oxazoles in the presence of dioxygen.

Synthesis of functionalized oxazoles via silver-catalyzed cyclization of propargylamides and allenylamides.

Silver(I)-catalyzed [3,3] rearrangement of N-sulfonyl propargylamides affords functionalized oxazoles with highly regioselective migration of the sulfonyl group by the introduction of acyloxy groups. The allenylamides, generated from the corresponding propargylamides, can also undergo the silver-catalyzed cyclization to give various 5-vinyloxazoles.

Catalytic Undirected Meta-Selective C-H Borylation of Metallocenes.

Metallocenes are privileged backbones in the fields of synthetic chemistry, catalysis, polymer science, etc. Direct C-H functionalization is undoubtedly the simplest approach for tuning the properties of metallocenes. However, owing to the presence of multiple identical C(sp2 )-H sites, this protocol often suffers from low reactivity and selectivity issues, especially for the regioselective synthesis of 1,3-difunctionalized metallocenes. Herein, an efficient iridium-catalyzed meta-selective C-H borylation of metallocenes is reported. With no need of preinstalled directing groups, this approach enables a rapid synthesis of various boronic esters based on benzoferrocenes, ferrocenes, ruthenocene, and related half sandwich complex. A broad range of electron-deficient and -rich functional groups are all compatible with the process. Notably, C-H borylation of benzoferrocenes takes place exclusively at the benzene ring, which is likely ascribed to the shielding effect of pentamethylcyclopentadiene. The synthetic utility is further demonstrated by easy scalability to gram quantities, the conversion of boron to heteroatoms including N3 , SePh, and OAc, as well as diverse cross-coupling reactions.

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.