Gold(I)‐Catalyzed Tandem Transformation with Diynes: Rapid Access to Linear Cyclopentenone‐Fused Polycyclic Molecules

An efficient and convenient synthesis of useful linear cyclopentenone‐fused polycyclic compounds has been achieved through a novel gold(I)‐catalyzed transformation of diynes. The method demonstrates high product yields and tolerates of a wide variety of important functional groups. Gold‐vinylidene formation, methoxy group migration, and Nazarov‐type cyclization are proposed to be the key steps in the reaction pathway. The synthetic utility of this method is demonstrated by converting the product to eight‐membered‐ring‐fused compound.     

Palladium‐Catalyzed Atom‐Transfer Radical Cyclization at Remote Unactivated C(sp3)−H Sites: Hydrogen‐Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates

A novel mild, visible‐light‐induced palladium‐catalyzed hydrogen atom translocation/atom‐transfer radical cyclization (HAT/ATRC) cascade has been developed. This protocol involves a 1,5‐HAT process of previously unknown hybrid vinyl palladium radical intermediates, thus leading to iodomethyl carbo‐ and heterocyclic structures.     

Nitrone Directing Groups in Rhodium(III)‐Catalyzed C−H Activation of Arenes: 1,3‐Dipoles versus Traceless Directing Groups

Functionalizable directing groups (DGs) are highly desirable in C?H activation chemistry. The nitrone DGs are explored in rhodium(III)‐catalyzed C?H activation of arenes and couplings with cyclopropenones. N‐tert‐butyl nitrones bearing a small ortho substituent coupled to afford 1‐naphthols, where the nitrone acts as a traceless DG. In contrast, coupling of N‐tert‐butyl nitrones bearing a bulky ortho group follows a C?H acylation/[3+2] dipolar addition pathway to give bicyclics. The coupling of N‐arylnitrones follows the same acylation/[3+2] addition process but delivers different bicyclics.     

Palladium(0)‐Catalyzed Intermolecular Carbocyclization of (1,n)‐Diynes and Bromophenols: An Efficient Route to Tricyclic Scaffolds

A novel palladium(0)‐catalyzed dearomative cyclization reaction of bromophenols with (1,n)‐diynes has been developed for building two new types of tricyclic architectures containing a quaternary carbon center. This method employs inexpensive bromophenols, and easily accessible tethered diynes. It exhibits a broad substrate scope and tolerates various functional groups. Preliminary results with commercially available chiral ligands indicate that enantioselective variants are feasible for both cyclization processes.     

Metal‐Free Annulation of Arenes with 2‐Aminopyridine Derivatives: The Methyl Group as a Traceless Non‐Chelating Directing Group

A novel annulation reaction between 2‐aminopyridine derivatives and arenes under metal‐free conditions is described. The presented intermolecular transformation provided straightforward access to the important pyrido[1,2‐a]benzimidazole scaffold under mild reaction conditions. The unprecedented application of the methyl group of methylbenzenes as a traceless, non‐chelating, and highly regioselective directing group is reported.     

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.     

OH‐Directed Alkynylation of 2‐Vinylphenols with Ethynyl Benziodoxolones: A Fast Access to Terminal 1,3‐Enynes

The first direct alkynylation of 2‐vinylphenols was developed. The rationally optimized hypervalent iodine reagent TIPS‐EBX* in combination with [(Cp*RhCl₂)₂] as a C? H‐activating transition metal catalyst enables the construction of a variety of highly substituted 1,3‐enynes in high yields of up to 98 %. This novel C? H activation method shows excellent chemoselectivity and exclusive (Z)‐stereoselectivity, and it is also remarkably mild and tolerates a variety of functional groups. Furthermore, synthetic modifications of the resulting 1,3‐enynes were demonstrated. To our knowledge, this is the first example for an OH‐directed C? H alkynylation with hypervalent iodine reagents.     

Radical Covalent Organic Frameworks: A General Strategy to Immobilize Open‐Accessible Polyradicals for High‐Performance Capacitive Energy Storage

Ordered π‐columns and open nanochannels found in covalent organic frameworks (COFs) could render them able to store electric energy. However, the synthetic difficulty in achieving redox‐active skeletons has thus far restricted their potential for energy storage. A general strategy is presented for converting a conventional COF into an outstanding platform for energy storage through post‐synthetic functionalization with organic radicals. The radical frameworks with openly accessible polyradicals immobilized on the pore walls undergo rapid and reversible redox reactions, leading to capacitive energy storage with high capacitance, high‐rate kinetics, and robust cycle stability. The results suggest that channel‐wall functional engineering with redox‐active species will be a facile and versatile strategy to explore COFs for energy storage.     

Sunlight‐Driven Decarboxylative Alkynylation of α‐Keto Acids with Bromoacetylenes by Hypervalent Iodine Reagent Catalysis: A Facile Approach to Ynones

A novel and practical decarboxylative alkynylation of α‐keto acids with bromoacetylenes is catalyzed by hypervalent iodine(III) reagents when irradiation by sunlight at room temperature. The product ynones are generated in good yields. Experiments show that results obtained with blue light (λ=450–455 nm) are comparable to those obtained when using sunlight. Mechanistic studies demonstrate that the sunlight‐driven decarboxylation undergoes a radical process.     

Regioselective C−H Hydroarylation of Internal Alkynes with Arenecarboxylates: Carboxylates as Deciduous Directing Groups

In the presence of catalytic [Ru(p‐cym)I₂]₂ and the base guanidine carbonate, benzoic acids react with internal alkynes to give the corresponding 2‐vinylbenzoic acids. This alkyne hydroarylation is generally applicable to diversely substituted electron‐rich and electron‐poor benzoic and acrylic acids. Aryl(alkyl)acetylenes react regioselectively with formation of the alkyl‐branched hydroarylation products, and propargylic alcohols are converted into γ‐alkylidene‐δ‐lactones. The hydroarylation can also be conducted decarboxylatively with a different choice of catalyst and reaction conditions. This reaction variant, which does not proceed via intermediate formation of 2‐vinylbenzoic acids, opens up a regioselective, waste‐minimized synthetic entry to vinylarenes.     

Design of Leaving Groups in Radical CC Fragmentations: Through‐Bond 2c–3e Interactions in Self‐Terminating Radical Cascades

Radical cascades terminated by β‐scission of exocyclic C?C bonds allow for the formation of aromatic products. Whereas β‐scission is common for weaker bonds, achieving this reactivity for carbon–carbon bonds requires careful design of radical leaving groups. It has now been found that the energetic penalty for breaking a strong σ‐bond can be compensated by the gain of aromaticity in the product and by the stabilizing two‐center, three‐electron “half‐bond” present in the radical fragment. Furthermore, through‐bond communication of a radical and a lone pair accelerates the fragmentation by selectively stabilizing the transition state. The stereoelectronic design of radical leaving groups leads to a new, convenient route to Sn‐functionalized aromatics.     

Ruthenium‐Catalyzed [2+2+2] Cycloaddition of 1,6‐Enynes and Unactivated Alkynes: Access to Ring‐Fused Cyclohexadienes

The [2+2+2] intermolecular carbocyclization reactions between 1,6‐enynes and alkynes catalyzed by [RuCl(cod)(Cp*)] (cod=1,5‐cyclooctadiene, Cp*=pentamethylcyclopentadienyl) are reported to provide bicyclohexa‐1,3‐dienes. The presented reaction conditions are compatible with internal and terminal alkynes and the chemo‐ and regioselectivity issues are controlled by the presence of substituents at the propargyl carbon center of the alkyne(s) partner(s).     

Evidence for Extensive Single‐Electron‐Transfer Chemistry in Boryl Anions: Isolation and Reactivity of a Neutral Borole Radical

Despite the synthesis of a boryl anion by Yamashita et al. in 2006, compounds that show boron‐centered nucleophilicity are still rare and sought‐after synthetic goals. A number of such boryl anions have since been prepared, two of which were reported to react with methyl iodide in apparent nucleophilic substitution reactions. One of these, a borolyl anion based on the borole framework, has now been found to display single‐electron‐transfer (SET) reactivity in its reaction with triorganotetrel halides, which was confirmed by the isolation of the first neutral borole‐based radical. The radical was characterized by elemental analysis, single‐crystal X‐ray crystallography, and EPR spectroscopy, and has implications for the understanding of boron‐based nucleophilic behavior and the emergent role of boron radicals in synthesis. This radical reactivity was also exploited in the synthesis of compounds with rare B? Sn and B? Pb bonds, the latter of which was the first isolated and structurally characterized compound with a “noncluster” B? Pb bond.     

From Reactivity and Regioselectivity to Stereoselectivity: An Odyssey of Designing PIP Amine and Related Directing Groups for C—H Activation

Improving the reactivity and selectivity is a long pursuing goal in C—H functionalization reactions. In line with this goal, a well‐designed bidentate 2‐(pyridine‐yl)isopropyl amine (PIP amine) directing group was developed by our group to achieve the activation of unbiased methylene C(sp³)–H activation, which also found its broad applications in C—H activation reactions catalyzed by base metals, such as Cu, Ni, Co and Fe, to form various C—C and C—X bonds. Moreover, PIP amine has also been applied in the strategic step toward the total synthesis of aeruginosin marine natural products. Its highly tunable structure has triggered the design of a series of chiral auxiliaries for diastereoselective C—H activation. More recently, Pd(II)‐catalyzed enantioselective functionalization of unbiased methylene C(sp³)–H bonds enabled by the cooperative effects between PIP amine and chiral ligands with axially chiral binaphthyl scaffold has also been realized. In this account, we briefly summaries the journey of developing PIP amine for C—H activation, from controlling the reactivity and regioselectivity to stereoselectivity.     

Synthesis and Reactivity of 5‐Bromopenta‐2,4‐diynenitrile (BrC5N): an Access to π‐Conjugated Scaffolds

The synthesis of 5‐bromopenta‐2,4‐diynenitrile (BrC₅N) in three steps from commercially available compounds is reported. Reacting 5‐bromopenta‐2,4‐diynenitrile with secondary amines led to the formation of stable butadiynamines or enynenitriles, depending on the nature of the amine reactant. The reaction of 5‐bromopenta‐2,4‐diynenitrile with simple terminal alkynes in the presence of secondary amines, copper, and palladium catalysts, provided a straightforward access to original polyfunctional carbon‐rich scaffolds. In this work, different alkynes and secondary amines were tested, which allowed for the preparation of a family of substituted dienes. Given the high synthetic potential of 5‐bromopenta‐2,4‐diynenitrile, we also prepared iodinated counterparts of this compound, that is, 5‐iodopenta‐2,4‐diynenitrile and its lower homologue 3‐iodopropiolonitrile. The UV‐visible spectrum of some relevant compounds was also recorded.     

Base‐Catalyzed Tandem Michael/Dehydro‐Diels–Alder Reaction of α,α‐Dicyanoolefins with Electron‐Deficient 1,3‐Conjugated Enynes: A Facile Entry to Angularly Fused Polycycles

Angularly fused carbocyclic frameworks and their heteroatom‐substituted analogues exist in many natural products that display a broad and interesting range of biological activities. Preparation of polycyclic products by cycloaddition reactions have been the long‐standing hot topic in the synthetic community. Dehydro‐Diels–Alder (DDA) reactions are one class of dehydropericyclic reactions that are derived conceptually by systematic removal of hydrogen atom pairs. A base‐promoted tandem Michael addition and DDA reaction of α,α‐dicyanoolefins with electron‐deficient 1,3‐conjugated enynes was realized in which a DDA reaction takes place between the arylalkynes and electron‐deficient tetrasubstituted olefin. The control experiments support the stepwise anionic reaction pathway rather than the concerted reaction pathway.