Intramolecular CH Activation through Gold(I)‐Catalyzed Reaction of Iodoalkynes

The cycloisomerization reaction of 1‐(iodoethynyl)‐2‐(1‐methoxyalkyl)arenes and related 2‐alkyl‐substituted derivatives gives the corresponding 3‐iodo‐1‐substituted‐1H‐indene under the catalytic influence of IPrAuNTf₂ [IPr=1,3‐bis(2,6‐diisopropyl)phenylimidazol‐2‐ylidene; NTf₂=bis(trifluoromethanesulfonyl)imidate]. The reaction takes place in 1,2‐dichloroethane at 80 °C, and the addition of ttbp (2,4,6‐tri‐tert‐butylpyrimidine) is beneficial to accomplish this new transformation in high yield. The overall reaction implies initial assembly of an intermediate gold vinylidene upon alkyne activation by gold(I) and a 1,2‐iodine‐shift. Deuterium labeling and crossover experiments, the magnitude of the recorded kinetic primary isotopic effect, and the results obtained from the reaction of selected stereochemical probes strongly provide support for concerted insertion of the benzylic C? H bond into gold vinylidene as the step responsible for the formation of the new carbon–carbon bond.     

Gold‐Catalyzed CH Annulation of Anthranils with Alkynes: A Facile,Flexible, and Atom‐Economical Synthesis of Unprotected 7‐Acylindoles

The gold‐catalyzed C? H annulation of anthranil derivatives with alkynes offers a facile, flexible, and atom‐economical one‐step route to unprotected 7‐acylindoles. An intermediate α‐imino gold carbene, generated by an intermolecular reaction, promotes ortho‐aryl C? H functionalization to afford the target products. The transformation proceeds with a broad range of substrates under mild conditions. Moreover, the obtained functionalized indole products represent a versatile platform for the construction of diverse indolyl frameworks.     

Enantioselective Synthesis of Spiroindenes by Enol‐Directed Rhodium(III)‐Catalyzed CH Functionalization and Spiroannulation

Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol‐directed C(sp²)‐H functionalization and oxidative annulation with alkynes to give spiroindenes containing all‐carbon quaternary stereocenters. High selectivity between two possible directing groups, as well as control of the direction of rotation in the isomerization of an O‐bound rhodium enolate into the C‐bound isomer, appear to be critical for high enantiomeric excesses.     

Ruthenium‐Catalyzed Cascade CH Functionalization of Phenylacetophenones

Three orthogonal cascade C? H functionalization processes are described, based on ruthenium‐catalyzed C? H alkenylation. 1‐Indanones, indeno indenes, and indeno furanones were accessed through cascade pathways by using arylacetophenones as substrates under conditions of catalytic [{Ru(p‐cymene)Cl₂}₂] and stoichiometric Cu(OAc)₂. Each transformation uses C? H functionalization methods to form C? C bonds sequentially, with the indeno furanone synthesis featuring a C? O bond formation as the terminating step. This work demonstrates the power of ruthenium‐catalyzed alkenylation as a platform reaction to develop more complex transformations, with multiple C? H functionalization steps taking place in a single operation to access novel carbocyclic structures.     

CH Functionalization/Asymmetric Michael Addition Cascade Enabled by Relay Catalysis: Metal Carbenoid Used for CC Bond Formation

A combination of either ruthenium(II) or rhodium(II) complexes and quinine‐derived squaramide enables 3‐diazooxindoles, indoles, and nitroalkenes to undergo highly efficient asymmetric three‐component reactions, thus affording optically active 3,3′‐bis(indole)s through a consecutive C? C bond‐forming sequence, which turned out to be applicable to the facile total synthesis of (?)‐folicanthine.     

Acylsilanes in Rhodium(III)‐Catalyzed Directed Aromatic C–H Alkenylations and Siloxycarbene Reactions with CC Double Bonds

Acylsilanes are known to undergo a 1,2‐silicon‐to‐oxygen migration under thermal or photochemical conditions to form siloxycarbenes. However, there are few reports regarding the application of siloxycarbenes in organic synthesis and surprisingly, their reaction with C? C double or triple bonds remains virtually unexplored. To facilitate such a study, previously inaccessible aromatic acylsilanes containing an ortho‐tethered C? C double bond were identified as suitable substrates. To access these key intermediates, we developed a new synthetic method utilizing a rhodium‐catalyzed oxidative Heck‐type olefination involving the application of an acylsilane moiety as a directing group. When exposed to visible‐light irradiation, the ortho‐olefinated acylsilanes underwent a smooth intramolecular cyclization process to afford valuable indanone derivatives in quantitative yields. This result paves the way for the development of new transformations involving siloxycarbene intermediates.     

Rhodium‐Catalyzed CS and CN Functionalization of Arenes: Combination of CH Activation and Hypervalent Iodine Chemistry

Rhodium‐catalyzed sulfonylation, thioetherification, thiocyanation, and other heterofunctionalizations of arenes bearing a heterocyclic directing group have been realized. The reaction proceeds by initial Rh^III‐catalyzed C?H hyperiodination of arene at room temperature followed by uncatalyzed nucleophilic functionalization. A diaryliodonium salt is isolated as an intermediate, which represents umpolung of the arene substrate, in contrast to previous studies that suggested umpolung of the coupling partner.     

Rhodium(I)‐Catalyzed Cycloisomerization of Benzylallene‐Alkynes through CH Activation

The efficient Rh^I‐catalyzed cycloisomerization of benzylallene‐alkynes produced the tricyclo[9.4.0.0^3,8]pentadecapentaene skeleton through a C? H bond activation in good yields. A plausible reaction mechanism proceeds via oxidative addition of the acetylenic C? H bond to Rh^I, an ene‐type cyclization to the vinylidenecarbene–Rh^I intermediate, and an electrophilic aromatic substitution with the vinylidenecarbene species. It was proposed based on deuteration and competition experiments.     

Copper(I)‐Catalyzed Alkylation of Polyfluoroarenes through Direct CH Bond Functionalization

The copper(I)‐catalyzed alkylation of electron‐deficient polyfluoroarenes with N‐tosylhydrazones and diazo compounds has been developed. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of C(sp²)? C(sp³) bonds with polyfluoroarenes through direct C? H bond functionalization. Mechanistically, copper(I) carbene formation and subsequent migratory insertion are proposed as the key steps in the reaction pathway.     

Zinc‐Catalyzed Alkyne Oxidation/CH Functionalization: Highly Site‐Selective Synthesis of Versatile Isoquinolones and β‐Carbolines

An efficient zinc(II)‐catalyzed alkyne oxidation/C? H functionalization sequence was developed, thus leading to highly site‐selective synthesis of a variety of isoquinolones and β‐carbolines. Importantly, in contrast to the well‐established gold‐catalyzed intermolecular alkyne oxidation, over‐oxidation can be completely suppressed in this system and the reaction most likely proceeds by a Friedel–Crafts‐type pathway. Mechanistic studies and theoretical calculations are described.     

Ruthenium(II)‐Catalyzed Synthesis of Isochromenes by CH Activation with Weakly Coordinating Aliphatic Hydroxyl Groups

Cationic ruthenium(II) complexes have been employed for the highly effective oxidative annulation of alkynes with benzyl alcohols to deliver diversely decorated isochromenes. The hydroxyl‐directed C?H/O?H functionalization process proceeded efficiently under an atmosphere of air. Detailed mechanistic studies were indicative of a kinetically relevant C?H metalation.     

Synthesis of Highly Substituted N‐(Furan‐3‐ylmethylene)benzenesulfonamides by a Gold(I)‐Catalyzed Oxidation/1,2‐Alkynyl Migration/Cyclization Cascade

A variety of N‐(furan‐3‐ylmethylene)benzenesulfonamides were obtained by a gold(I)‐catalyzed cascade reaction from easily accessible starting materials. The reaction pathway involves a rarely observed 1,2‐alkynyl migration onto a gold carbenoid. This observation further enriches gold carbenoid chemistry with regard to group migration.     

Synthesis of Cyclic Amine Boranes through Triazole‐Gold(I)‐Catalyzed Alkyne Hydroboration

The first catalytic alkyne hydroboration of propargyl amine boranecarbonitriles is accomplished with triazole‐Au^I complexes. While the typical [L‐Au]⁺ species decomposes within minutes upon addition of amine boranecarbonitriles, the triazole‐modified gold catalysts (TA‐Au) remained active, and allowed the synthesis of 1,2‐BN‐cyclopentenes in one step with good to excellent yields. With good substrate tolerability and mild reaction conditions (open‐flask), this new method provides an alternative route to reach the interesting cyclic amine borane with high efficiency.     

Synthesis of Polycyclic Indole Skeletons by a Gold(I)‐Catalyzed Cascade Reaction

The conversion of simple, easily available urea‐substituted 3‐phenylpropargyl alcohols catalyzed by a simple IPr–gold(I) catalyst in a gold(I)‐catalyzed cascade reaction composing of a gold‐catalyzed nucleophilic addition and a subsequent gold‐catalyzed substitution reaction delivers 1H‐imidazo[1, 5?a]indol‐3(2 H)‐ones. Other gold(I) catalysts or silver catalysts gave lower yields and often gave other side products. Gold(III) and copper(II) catalysts decomposed the starting material. Twelve examples, including donor and acceptor substituents on the distal nitrogen of the urea substructure, are provided. An X‐ray crystal structure analysis confirmed the structural assignment. The mechanistic investigation including isolation and further conversion of intermediates and reactions with enantiopure starting materials indicated that after the nucleophilic‐addition step, the substrate undergoes an S_N1‐type benzylic substitution reaction at the indolyl alcohol intermediate or an intramolecular hydroamination reaction of the 2‐vinylindole intermediate.     

A Palladium(II)‐Catalyzed CH Activation Cascade Sequence for Polyheterocycle Formation

Polyheterocycles are found in many natural products and are useful moieties in functional materials and drug design. As part of a program towards the synthesis of Stemona alkaloids, a novel palladium(II)‐catalyzed C? H activation strategy for the construction of such systems has been developed. Starting from simple 1,3‐dienyl‐substituted heterocycles, a large range of polycyclic systems containing pyrrole, indole, furan and thiophene moieties can be synthesized in a single step.     

Rhodium(I)‐Catalyzed Reductive Cyclocarbonylation of Internal Alkynes: Atom‐Economic Process for Synthesis of 2‐Cyclopenten‐1‐ones, 5‐Alkylidenefuran‐2(5 H)‐ones and Indan‐1‐ones

Economical atoms : 2‐Cyclopenten‐1‐ones, 5‐alkylidenefuran‐2(5 H)‐ones and indan‐1‐ones have been synthesized by atom‐economic reductive cyclocarbonylation of internal alkynes with carbon monoxide catalyzed by [{RhCl(CO)₂}₂]/CO(NH₂)₂ in the presence of water (see scheme).

     

Rhodium(I)‐Catalyzed Decarbonylative Spirocyclization through CC Bond Cleavage of Benzocyclobutenones: An Efficient Approach to Functionalized Spirocycles

The rhodium‐catalyzed formation of all‐carbon spirocenters involves a decarbonylative coupling of trisubstituted cyclic olefins and benzocyclobutenones through C? C activation. The metal–ligand combination [{Rh(CO)₂Cl}₂]/P(C₆F₅)₃ catalyzed this transformation most efficiently. A range of diverse spirocycles were synthesized in good to excellent yields and many sensitive functional groups were tolerated. A mechanistic study supports a hydrogen‐transfer process that occurs through a β‐H elimination/decarbonylation pathway.     

All‐Carbon [3+3] Oxidative Annulations of 1,3‐Enynes by Rhodium(III)‐Catalyzed CH Functionalization and 1,4‐Migration

1,3‐Enynes containing allylic hydrogens cis to the alkyne function as three‐carbon components in rhodium(III)‐catalyzed, all‐carbon [3+3] oxidative annulations to produce spirodialins. The proposed mechanism of these reactions involves the alkenyl‐to‐allyl 1,4‐rhodium(III) migration.