Stereoconvergent,Redox‐Neutral Access to Tetrahydroquinoxalines through Relay Epoxide Opening/Amination of Alcohols

We present an economical catalytic procedure to convert readily available 1,2‐diaminobenzenes and terminal epoxides into valuable 1,2,3,4‐tetrahydroquinoxalines in a highly enantioselective fashion. This procedure operates through relay zinc and iridium catalysis, and achieves redox‐neutral and stereoconvergent production of valuable chiral heterocycles from racemic starting materials with water as the only side product. The use of commercially available reagents and catalysts and a convenient procedure also make this catalytic method attractive for practical application.     

Manganese‐Catalyzed Hydrogen‐Autotransfer C−C Bond Formation: α‐Alkylation of Ketones with Primary Alcohols

A novel catalytic hydrogen‐autotransfer protocol for the atom‐efficient α‐alkylation of ketones with readily available alcohols is presented. The use of manganese complexes bearing non‐innocent PNP pincer ligands enabled the functionalization of a broad range of valuable ketones, including 2‐oxindole, estrone 3‐methyl ether, and testosterone. Mechanistic investigations suggest the participation of an intramolecular amidate‐assisted alcohol‐dehydrogenation process.     

Metallaphotoredox Difluoromethylation of Aryl Bromides

Herein, we report a convenient and broadly applicable strategy for the difluoromethylation of aryl bromides by metallaphotoredox catalysis. Bromodifluoromethane, a simple and commercially available alkyl halide, is harnessed as an effective source of difluoromethyl radical by silyl‐radical‐mediated halogen abstraction. The merger of this fluoroalkyl electrophile activation pathway with a dual nickel/photoredox catalytic platform enables the difluoromethylation of a diverse array of aryl and heteroaryl bromides under mild conditions. The utility of this procedure is showcased in the late‐stage functionalization of several drug analogues.     

Highly Enantioselective Nucleophilic Dearomatization of Pyridines by Anion‐Binding Catalysis

The asymmetric dearomatization of N‐heterocycles is an important synthetic method to gain bioactive and synthetically valuable chiral heterocycles. However, the catalytic enantio‐ and regioselective dearomatization of the simplest six‐membered‐ring N‐heteroarenes, the pyridines, is still very challenging. The first anion‐binding‐catalyzed, highly enantioselective nucleophilic dearomatization of pyridines with triazole‐based H‐bond donor catalysts is presented. Contrary to other more common NH‐based H‐bond donors, this type of organocatalyst shows a prominent higher C2‐regioselectivity and is able to promote high enantioinductions via formation of a close chiral anion‐pair complex with a preformed N‐acyl pyridinium ionic intermediate. This method offers a straightforward and useful synthetic approach to chiral N‐heterocycles from abundant and readily available pyridines.     

Iodine Catalyzed One‐pot Synthesis of 3,4‐Dihydroquinazolin‐4‐ones from Anthranilic Acids,Ortho Esters and Amines under Solvent‐free Conditions

A simple and efficient procedure has been developed for the one‐pot synthesis of 3,4‐dihydroquinazolin‐4‐ones from anthranilic acids, ortho esters and amines using a catalytic amount of iodine under solvent‐free conditions to afford the corresponding products in excellent yields. The direct use of commercially available catalyst, mild and solvent‐free reaction conditions, short reaction time, easy workup and excellent yields are the advantages of the present protocol.     

Direct Regiospecific and Highly Enantioselective Intermolecular α‐Allylic Alkylation of Aldehydes by a Combination of Transition‐Metal and Chiral Amine Catalysts

The first direct intermolecular regiospecific and highly enantioselective α‐allylic alkylation of linear aldehydes by a combination of achiral bench‐stable Pd⁰ complexes and simple chiral amines as co‐catalysts is disclosed. The co‐catalytic asymmetric chemoselective and regiospecific α‐allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2‐alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2‐alkyl substituted hemiacetals, 2‐alkyl‐butane‐1,4‐diols, and amines. The concise co‐catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed.     

Enantio‐ and Diastereoselective Synthesis of Chiral Allenes by Palladium‐Catalyzed Asymmetric [3+2] Cycloaddition Reactions

A protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium‐catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM (trimethylenemethane) donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio‐, enantio‐, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.     

KOtBu‐Catalyzed Michael Addition Reactions Under Mild and Solvent‐Free Conditions

Designed transition metal complexes predominantly catalyze Michael addition reactions. Inorganic and organic base‐catalyzed Michael addition reactions have been reported. However, known base‐catalyzed reactions suffer from the requirement of solvents, additives, high pressure and also side‐reactions. Herein, we demonstrate a mild and environmentally friendly strategy of readily available KO^tBu‐catalyzed Michael addition reactions. This simple inorganic base efficiently catalyzes the Michael addition of underexplored acrylonitriles, esters and amides with (oxa‐, aza‐, and thia‐) heteroatom nucleophiles. This catalytic process proceeds under solvent‐free conditions and at room temperature. Notably, this protocol offers an easy operational procedure, broad substrate scope with excellent selectivity, reaction scalability and excellent TON (>9900). Preliminary mechanistic studies revealed that the reaction follows an ionic mechanism. Formal synthesis of promazine is demonstrated using this catalytic protocol.     

Copper‐Catalyzed Propargylic Substitution of Dichloro Substrates: Enantioselective Synthesis of Trisubstituted Allenes and Formation of Propargylic Quaternary Stereogenic Centers

An easy and versatile Cu‐catalyzed propargylic substitution process is presented. Using easily prepared prochiral dichloro substrates, readily available Grignard reagents together with catalytic amount of copper salt and chiral ligand, we accessed a range of synthetically interesting trisubstituted chloroallenes. Substrate scope and nucleophile scope are broad, providing generally high enantioselectivity for the desired 1,3‐substitution products. The enantioenriched chloroallenes could be further transformed into the corresponding trisubstituted allenes or terminal alkynes bearing all‐carbon quaternary stereogenic centers, through the copper‐catalyzed enantiospecific 1,1/1,3‐substitutions. The two successive copper‐catalyzed reactions could be eventually combined into a one‐pot procedure and different desired allenes or alkynes were obtained respectively with high enantiomeric excesses.     

A Catalytic SEAr Approach to Dibenzosiloles Functionalized at Both Benzene Cores

A general procedure for the catalytic preparation of dibenzosiloles functionalized at one or both benzene rings starting from readily available ortho‐silylated biphenyls is reported. This method provides rapid access to silole building blocks substituted with chlorine atoms at both phenylene groups, thereby allowing catalytic access to directly polymerizable dibenzosiloles. Moreover, it is shown that, despite the involvement of highly electrophilic intermediates, a considerable range of Lewis‐basic, for example, oxygen‐ and nitrogen‐containing, functional groups is tolerated. The mechanism of this intramolecular electrophilic aromatic substitution (S_EAr) proceeds through a sulfur‐stabilized silicon cation, generated catalytically from the hydrosilane precursor.     

Nickel‐Catalyzed Allylmethylation of Alkynes with Allylic Alcohols and AlMe3: Facile Access to Skipped Dienes and Trienes

We present herein an unprecedented allylative dicarbofunctionalization of alkynes with allylic alcohols. This simple catalytic procedure utilizes commercially available Ni(COD)₂, triphenylphosphine, and inexpensive reagents, and delivers valuable skipped dienes and trienes with an all‐carbon tetrasubstituted alkene unit in a highly stereoselective fashion. Preliminary mechanistic studies support the reaction pathway of allylnickelation followed by transmetalation in this dicarbofunctionalization of alkynes.     

Nanosheet‐Enhanced Enantioselectivity in the Vanadium‐Catalyzed Asymmetric Epoxidation of Allylic Alcohols

The use of suitable chiral ligands is an efficient means of producing highly enantioselective transition‐metal catalysts. Herein, we report a facile, economic, and effective strategy for the design of chiral ligands that demonstrate enhanced enantioselectivity and catalytic efficacy. Our simple strategy employs naturally occurring or synthetic inorganic nanosheets as huge and rigid planar substituents for, but not limited to, naturally available α‐amino‐acid ligands; these ligands were successfully used in the vanadium‐catalyzed asymmetric epoxidation of allylic alcohols. The crucial role of the inorganic nanosheets as planar substituents in improving the enantioselectivity of the reaction was clearly revealed by relating the observed enantiomeric excess with the distribution of the catalytic centers and the accessibility of the substrate molecules to the catalytic sites. DFT calculations indicated that the LDH layer improved the enantioselectivity by influencing the formation and stability of the catalytic transition states, both in terms of steric resistance and H‐bonding interactions.     

Heterogeneously Catalyzed Direct CH Thiolation of Heteroarenes

The first general methodology for the direct thiolation of electron‐rich heteroarenes was developed by employing Pd/Al₂O₃, a recoverable and commercially available heterogeneous catalyst, and CuCl₂. This method represents an operationally simple approach for the synthesis of these valuable compounds. Preliminary mechanistic studies indicate a heterogeneous catalytic system, in which both metals play a complementary role in the formation of the thiolated products.     

Gold Nanoparticles Supported on a Layered Double Hydroxide as Efficient Catalysts for the One‐Pot Synthesis of Flavones

Flavones are a class of natural products with diverse biological activities and have frequently been synthesized by step‐by‐step procedures using stoichiometric amounts of reagents. Herein, a catalytic one‐pot procedure for the synthesis of flavone and its derivatives is developed. In the presence of gold nanoparticles supported on a Mg‐Al layered double hydroxide (Au/LDH), various kinds of flavones can be synthesized starting from 2′‐hydroxyacetophenones and benzaldehydes (or benzyl alcohols). The present one‐pot procedure consists of a sequence of several reactions, and Au/LDH can catalyze all these different types of reactions. The catalysis is shown to be truly heterogeneous, and Au/LDH can be readily recovered and reused.     

Zirconium oxide complex anchored on boehmite nanoparticles as highly reusable organometallic catalyst for C–S and C–O coupling reactions

Boehmite nanoparticles were prepared by a simple and inexpensive procedure in water using commercially available materials without inert atmosphere. Then, the surface of the boehmite nanoparticles was modified using 3‐mercaptopropyltrimethoxysilane and subsequently zirconium oxide was supported on the modified surface. Zirconium oxide supported on boehmite nanoparticles (Pr.S‐ZrO@boehmite) was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and inductively coupled plasma technique. The catalytic application of Pr.S‐ZrO@boehmite was studied in C–O and C–S coupling reactions for synthesis of valuable compounds such as ether and sulfide derivatives. All products were obtained in good to excellent yields and the catalyst could be recovered and reused several times without significant loss of catalytic efficiency. Furthermore, zirconium oxide is rarely used as catalyst for cross‐coupling reactions.     

Selective synthesis of 3‐Selanylindoles from Indoles and Diselenides using IK/mCPBA system

In the presence of a catalytic amount of KI combined with oxidant m CPBA, a convenient catalytic procedure is developed for the preparation of 3‐selanylindoles from indoles and diselenides. In this protocol, KI is first oxidized by m CPBA into hypoiodous acid, which reacts with diselenide to cleave Se‐Se bond. The in situ generated active electrophilic selenium species then reacts with indole, affording 3‐selanylindole via an electrophilic substitution mechanism. This catalytic selenation of indoles has mild reaction conditions and is a simple procedure, which extends the synthetic application of KI in organic synthesis.     

Synthesis of β‐Substituted γ‐Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis

β‐Substituted chiral γ‐aminobutyric acids feature important biological activities and are valuable intermediates for the synthesis of pharmaceuticals. Herein, an efficient catalytic enantioselective approach for the synthesis of β‐substituted γ‐aminobutyric acid derivatives through visible‐light‐induced photocatalyst‐free asymmetric radical conjugate additions is reported. Various β‐substituted γ‐aminobutyric acid analogues, including previously inaccessible derivatives containing fluorinated quaternary stereocenters, were obtained in good yields (42–89 %) and with excellent enantioselectivity (90–97 % ee). Synthetically valuable applications were demonstrated by providing straightforward synthetic access to the pharmaceuticals or related bioactive compounds (S)‐pregabalin, (R)‐baclofen, (R)‐rolipram, and (S)‐nebracetam.     

Direct Synthesis of an α,ω‐Diester from 2,7‐Octadienol as Bulk Feedstock in Three Tandem Catalytic Steps

A new tandem catalytic process was designed and developed as a tool for the direct conversion of the widely available feedstock 2,7‐octadienol into an α,ω‐diester. This innovative auto‐tandem catalysis is atom efficient and consists of three consecutive palladium‐catalysed reactions: ether formation, ether carbonylation and alkoxycarbonylation. By using the design of experiments (DoE) approach, significant parameters were determined and the yield of the desired α,ω‐diester was optimised. Model substrates allowed deeper insight into the progress of the reaction to be gained and, as a result, the reaction sequence was uncovered. Furthermore, by simply applying other ligands, a different reaction path was followed, allowing other, new tandem catalytic sequences to be explored and enabling new compounds to be obtained.     

Use of an efficient polystyrene‐supported cerium catalyst for one‐pot multicomponent synthesis of spiro‐piperidine derivatives and click reactions in green solvent

One‐pot multicomponent reactions are very demanding in synthetic organic chemistry. Here we report a new polystyrene‐supported cerium catalyst (PS‐Ce‐amtp) obtained via an easy two‐step procedure, which was thoroughly characterized using various techniques. PS‐Ce‐amtp catalyses the environmentally benign one‐pot multicomponent synthesis of spiro‐piperidine derivatives through the reaction of substituted aniline, cyclic active methylene compound and formaldehyde at room temperature. The catalyst also exhibits excellent catalytic activity in one‐pot synthesis of 1,4‐disubstituted 1,2,3‐triazoles via click reaction between in situ generated azides (derived from anilines and amines) and terminal alkynes. The catalyst can be recovered easily after reaction and reused five times without significant loss in its catalytic activity. The advantageous features of this catalyst are atom economy, operational simplicity, short reaction times, easy handling and high recycling efficiency.     

Catalytic,Asymmetric Synthesis of Phosphonic γ‐(Hydroxyalkyl)butenolides with Contiguous Quaternary and Tertiary Stereogenic Centers

A procedure that enables high yielding access to phosphonic γ‐(hydroxyalkyl)butenolides with excellent regio‐, diastereo‐ and enantiocontrol is reported. The simultaneous construction of up to two adjacent quaternary stereogenic centers by a catalytic asymmetric vinylogous Mukaiyama aldol reaction unites biologically and medicinally relevant entities, namely α‐hydroxy phosphonates and γ‐(hydroxyalkyl)butenolides. This is achieved by utilizing a readily available chiral copper‐sulfoximine catalyst showing a broad functional group tolerance for both the electrophilic and nucleophilic reactants. A discussion about potential factors affecting the observed level of enantioselectivity, which stems from the enantiopure sulfoximine ligand, is also included.