Site‐Selective C−S Bond Formation at C−Br over C−OTf and C−Cl Enabled by an Air‐Stable,Easily Recoverable,and Recyclable Palladium(I) Catalyst

This report widens the repertoire of emerging Pd^I catalysis to carbon–heteroatom, that is, C?S bond formation. While Pd⁰‐catalyzed protocols may suffer from the formation of poisonous sulfide‐bound off‐cycle intermediates and lack of selectivity, the mechanistically diverse Pd^I catalysis concept circumvents these challenges and allows for C?S bond formation (S–aryl and S–alkyl) of a wide range of aryl halides. Site‐selective thiolations of C?Br sites in the presence of C?Cl and C?OTf were achieved in a general and a priori predictable fashion. Computational, spectroscopic, X‐ray, and reactivity data support dinuclear Pd^I catalysis to be operative. Contrary to air‐sensitive Pd⁰, the active Pd^I species was easily recovered in the open atmosphere and subjected to multiple rounds of recycling.     

Site‐Selective C−S Bond Formation at C−Br over C−OTf and C−Cl Enabled by an Air‐Stable,Easily Recoverable,and Recyclable Palladium(I) Catalyst

This report widens the repertoire of emerging Pd^I catalysis to carbon–heteroatom, that is, C−S bond formation. While Pd⁰‐catalyzed protocols may suffer from the formation of poisonous sulfide‐bound off‐cycle intermediates and lack of selectivity, the mechanistically diverse Pd^I catalysis concept circumvents these challenges and allows for C−S bond formation (S–aryl and S–alkyl) of a wide range of aryl halides. Site‐selective thiolations of C−Br sites in the presence of C−Cl and C−OTf were achieved in a general and a priori predictable fashion. Computational, spectroscopic, X‐ray, and reactivity data support dinuclear Pd^I catalysis to be operative. Contrary to air‐sensitive Pd⁰, the active Pd^I species was easily recovered in the open atmosphere and subjected to multiple rounds of recycling.     

Trifluoromethylthiolation of Aryl Iodides and Bromides Enabled by a Bench‐Stable and Easy‐To‐Recover Dinuclear Palladium(I) Catalyst

While palladium catalysis is ubiquitous in modern chemical research, the recovery of the active transition‐metal complex under routine laboratory applications is frequently challenging. Described herein is the concept of alternative cross‐coupling cycles with a more robust (air‐, moisture‐, and thermally‐stable) dinuclear Pd^I complex, thus avoiding the handling of sensitive Pd⁰ species or ligands. Highly efficient C? SCF₃ coupling of a range of aryl iodides and bromides was achieved, and the recovery of the Pd^I complex was accomplished via simple open‐atmosphere column chromatography. Kinetic and computational data support the feasibility of dinuclear Pd^I catalysis. A novel SCF₃‐bridged Pd^I dimer was isolated, characterized by X‐ray crystallography, and verified to be a competent catalytic intermediate.     

Palladium‐Catalyzed Cascade CH Trifluoroethylation of Aryl Iodides and Heck Reaction: Efficient Synthesis of ortho‐Trifluoroethylstyrenes

A palladium‐catalyzed selective C? H bond trifluoroethylation of aryl iodides has been explored. The reaction allows for the efficient synthesis of a variety of ortho‐trifluoroethyl‐substituted styrenes. Preliminary mechanistic studies indicate that the reaction might involve a key Pd^IV intermediate, which is generated through the rate‐determining oxidative addition of CF₃CH₂I to a palladacycle; the bulky nature of CF₃CH₂I influences the reactivity. Reductive elimination from the Pd^IV complex then leads to the formation of the aryl–CH₂CF₃ bond.     

Highly Efficient CSeCF3 Coupling of Aryl Iodides Enabled by an Air‐Stable Dinuclear PdI Catalyst

Building on our recent disclosure of catalysis at dinuclear Pd^I sites, we herein report the application of this concept to the realization of the first catalytic method to convert aryl iodides into the corresponding ArSeCF₃ compounds. Highly efficient C? SeCF₃ coupling of a range of aryl iodides was achieved, enabled by an air‐, moisture‐, and thermally stable dinuclear Pd^I catalyst. The novel SeCF₃‐bridged dinuclear Pd^I complex 3 was isolated, studied for its catalytic competence and shown to be recoverable. Experimental and computational data are presented in support of dinuclear Pd^I catalysis.     

Pd‐Catalyzed Decarboxylative Cross‐Coupling of 2‐Carboxyazine N‐Oxides with Various (Hetero)aryl Halides

Decarboxylative cross‐coupling reactions of substituted 2‐carboxyazine N‐oxides, with a variety of (hetero)aryl halides, by bimetallic Pd⁰/Cu^I and Pd⁰/Ag^I catalysis are reported. Two possible pathways, a conventional bimetallic‐catalyzed decarboxylative arylation, as well as a protodecarboxylative/direct C?H arylation sequence have been considered. These methods provide the first general decarboxylative arylation methodology for the 2‐carboxyazine series.     

A Preliminary Study of Diastereoselectivity in the PdII‐Catalyzed C(sp3)‐H Alkoxylation of Cyclic Systems

Primary mechanism of a Pd^II‐catalyzed 8‐aminoquinoline‐directed C?H alkoxylation was investigated. It was understood that the Pd^II‐catalyzed C(sp³)?O bond formation proceeded through a concerted reductive elimination from the Pd^IV intermediate in the cyclic system. Deuteration experiments and related computational studies elucidate that intrinsic conformation determined the diastereoselectivity of the Pd^II‐catalyzed C?H alkoxylation of cyclic carboxylic acids.     

Palladium‐Catalyzed Arylation of Olefins by Triarylphosphines via CP Bond Cleavage

C? H Arylation of olefins by triarylphosphines via C? P bond cleavage has been achieved with either Pd⁰ or Pd^II catalysts. A variety of olefins and triarylphosphines are tolerated, and we inferred that both Pd⁰ and Pd^II could function directly without pre‐oxidation or pre‐reduction.     

Palladium‐Catalyzed Cross‐Coupling of Alkenyl Carboxylates

Carboxylate esters have many desirable features as electrophiles for catalytic cross‐coupling: they are easy to access, robust during multistep synthesis, and mass‐efficient in coupling reactions. Alkenyl carboxylates, a class of readily prepared non‐aromatic electrophiles, remain difficult to functionalize through cross‐coupling. We demonstrate that Pd catalysis is effective for coupling electron‐deficient alkenyl carboxylates with arylboronic acids in the absence of base or oxidants. Furthermore, these reactions can proceed by two distinct mechanisms for C?O bond activation. A Pd^0/II catalytic cycle is viable when using a Pd⁰ precatalyst, with turnover‐limiting C?O oxidative addition; however, an alternative pathway that involves alkene carbopalladation and β‐carboxyl elimination is proposed for Pd^II precatalysts. This work provides a clear path toward engaging myriad oxygen‐based electrophiles in Pd‐catalyzed cross‐coupling.     

Employing Aryl‐Linked Bis‐mesoionic Carbenes as a Pincer‐Type Platform to Access Ambient‐Stable Palladium(IV) Complexes

The study of palladium(IV) species has great implications for Pd^II/Pd^IV‐mediated catalysis. However, most of the Pd^IV complexes rapidly decompose under ambient conditions, which makes the isolation, characterization and further reactivity study very challenging. The reported ancillary ligand platforms to stabilize Pd^IV species are dominated by chelating N‐donors such as bipyridines. In this work, we present two Pd^IV complexes with scarcely used C‐donors as the supporting platform. The anionic aryl donor and MIC (MIC=mesoionic carbene) are combined in a [CC′C]‐type pincer framework to access a series of ambient‐stable Pd^IV tris(halido) complexes. Their synthesis, solid‐state structures, stability, and reactivity are presented. To the best of our knowledge, the work presented herein reports the first isolated Pd^IV–MIC as well as the first Pd^IV carbene‐based aryl pincer.     

Catalytic Behavior of Mono‐N‐Protected Amino‐Acid Ligands in Ligand‐Accelerated C−H Activation by Palladium(II)

Mono‐N‐protected amino acids (MPAAs) are increasingly common ligands in Pd‐catalyzed C?H functionalization reactions. Previous studies have shown how these ligands accelerate catalytic turnover by facilitating the C?H activation step. Here, it is shown that MPAA ligands exhibit a second property commonly associated with ligand‐accelerated catalysis: the ability to support catalytic turnover at substoichiometric ligand‐to‐metal ratios. This catalytic role of the MPAA ligand is characterized in stoichiometric C?H activation and catalytic C?H functionalization reactions. Palladacycle formation with substrates bearing carboxylate and pyridine directing groups exhibit a 50–100‐fold increase in rate when only 0.05 equivalents of MPAA are present relative to Pd^II. These and other mechanistic data indicate that facile exchange between MPAAs and anionic ligands coordinated to Pd^II enables a single MPAA to support C?H activation at multiple Pd^II centers.     

Manganese(I)‐Catalyzed C−H Activation: The Key Role of a 7‐Membered Manganacycle in H‐Transfer and Reductive Elimination

Manganese‐catalyzed C?H bond activation chemistry is emerging as a powerful and complementary method for molecular functionalization. A highly reactive seven‐membered Mn^I intermediate is detected and characterized that is effective for H‐transfer or reductive elimination to deliver alkenylated or pyridinium products, respectively. The two pathways are determined at Mn^I by judicious choice of an electron‐deficient 2‐pyrone substrate containing a 2‐pyridyl directing group, which undergoes regioselective C?H bond activation, serving as a valuable system for probing the mechanistic features of Mn C?H bond activation chemistry.     

Rhodium‐Catalyzed Intramolecular C−H Silylation by Silacyclobutanes

Silacyclobutane was discovered to be an efficient C?H bond silylation reagent. Under the catalysis of Rh^I/TMS‐segphos, silacyclobutane undergoes sequential C?Si/C?H bond activations, affording a series of π‐conjugated siloles in high yields and regioselectivities. The catalytic cycle was proposed to involve a rarely documented endocyclic β‐hydride elimination of five‐membered metallacycles, which after reductive elimination gave rise to a Si?Rh^I species that is capable of C?H activation.     

Stereoselective Palladium‐Catalyzed C−F Bond Alkynylation of Tetrasubstituted gem‐Difluoroalkenes

A stereoselective Pd(PPh₃)₄‐catalyzed C?F bond alkynylation of tetrasubstituted gem‐difluoroalkenes with terminal alkynes has been developed. This method gives access to a great variety of conjugated monofluoroenynes bearing a tetrasubstituted alkene moiety with well‐defined stereochemistry. Chelation‐assisted oxidative addition of Pd to the C?F bond is proposed to account for the high level of stereocontrol. An X‐ray crystal structure of a key monofluorovinyl Pd^II intermediate has been obtained for the first time as evidence for the proposed mechanism.     

Shedding Light on the Diverse Reactivity of NacNacAl with N‐Heterocycles

The aluminum(I) compound NacNacAl (NacNac=[ArNC(Me)CHC(Me)NAr]^?, Ar=2,6‐iPr₂C₆H₃, 1 ) shows diverse and substrate‐controlled reactivity in reactions with N‐heterocycles. 4‐Dimethylaminopyridine (DMAP), a basic substrate in which the 4‐position is blocked, induces rearrangement of NacNacAl by shifting a hydrogen atom from the methyl group of the NacNac backbone to the aluminum center. In contrast, C?H activation of the methyl group of 4‐picoline takes place to produce a species with a reactive terminal methylene. Reaction of 1 with 3,5‐lutidine results in the first example of an uncatalyzed, room‐temperature cleavage of an sp² C?H bond (in the 4‐position) by an Al^I species. Another reactivity mode was observed for quinoline, which undergoes 2,2′‐coupling. Finally, the reaction of 1 with phthalazine produces the product of N?N bond cleavage.     

Non‐Innocent Ligand Effects on Low‐Oxidation‐State Indium Complexes

Attempts to coordinate neutral ligands to low oxidation state indium centers are often hindered by disproportionation pathways that produce elemental indium and higher oxidation state species. In contrast, we find that reactions of the salt, InOTf (OTf=trifluoromethanesulfonate), with α‐diimine ligands yielded intensely colored compounds with no evidence of decomposition. X‐ray structural analysis of InOTf ? ^MesDAB^Me (^MesDAB^Me=N,N‐dimesityl‐2,3‐dimethyl‐diazabutadiene; 1 ) reveals a discrete molecular compound with a pyramidal coordination environment at the indium center, consistent with the presence of a stereochemically active lone pair of electrons on indium and a neutral diazabutadiene chelate ligand. The use of the less‐electron‐rich ^MesDAB^H ligand (^MesDAB^H=N,N‐dimesityl‐diazabutadiene) engenders dramatically different reactivity and produces a metallopolymer (InOTf ? ^MesDAB^H)_∞ ( 2 ) linked via C? C and In? In bonds. The difference in reactivity is rationalized by cyclic voltammetry and DFT studies that suggest more facile electron transfer from In^I to the ^MesDAB^H and bis(aryl)acenaphthenequinonediimine (BIAN) ligands. Solution EPR spectroscopy indicates the presence of non‐interacting ligand‐based radicals in solution, whereas solid‐state EPR studies reflect the presence of a thermally accessible spin triplet consistent with reversible C? C bond cleavage.     

Is PdII‐Promoted σ‐Bond Metathesis Mechanism Operative for the PdPEPPSI Complex‐Catalyzed Amination of Chlorobenzene with Aniline? Experiment and Theory

Reduction of the Pd?PEPPSI precatalyst to a Pd⁰ species is generally thought to be essential to drive Buchwald–Hartwig amination reactions through the well‐ documented Pd⁰/Pd^II catalytic cycle and little attention has been paid to other possible mechanisms. Considered here is the Pd?PEPPSI‐catalyzed aryl amination of chlorobenzene with aniline. A neat reaction system was used in new experiments, from which the potentially reductive roles of the solvent and labile ligand of the PEPPSI complex in leading to Pd⁰ species are ruled out. Computational results demonstrate that anilido‐containing Pd^II intermediates involving σ‐bond metathesis in pathways leading to the diphenylamine product have relatively low barriers. Such pathways are more favorable energetically than the corresponding reductive elimination reactions resulting in Pd⁰ species and other putative routes, such as the Pd^II/Pd^IV mechanism, single electron transfer mechanism, and halide atom transfer mechanism. In some special cases, if reactants/additives are inadequate to reduce a Pd^II precatalyst, a Pd^II‐involved σ‐bond metathesis mechanism might be feasible to drive the Buchwald–Hartwig amination reactions.     

Mechanistic Insights into the Ni‐Catalyzed Reductive Carboxylation of C−O Bonds in Aromatic Esters with CO2: Understanding Remarkable Ligand and Traceless‐Directing‐Group Effects

The mechanism of the Ni⁰‐catalyzed reductive carboxylation reaction of C(sp²)?O and C(sp³)?O bonds in aromatic esters with CO₂ to access valuable carboxylic acids was comprehensively studied by using DFT calculations. Computational results revealed that this transformation was composed of several key steps: C?O bond cleavage, reductive elimination, and/or CO₂ insertion. Of these steps, C?O bond cleavage was found to be rate‐determining, and it occurred through either oxidative addition to form a Ni^II intermediate, or a radical pathway that involved a bimetallic species to generate two Ni^I species through homolytic dissociation of the C?O bond. DFT calculations revealed that the oxidative addition step was preferred in the reductive carboxylation reactions of C(sp²)?O and C(sp³)?O bonds in substrates with extended π systems. In contrast, oxidative addition was highly disfavored when traceless directing groups were involved in the reductive coupling of substrates without extended π systems. In such cases, the presence of traceless directing groups allowed for docking of a second Ni⁰ catalyst, and the reactions proceed through a bimetallic radical pathway, rather than through concerted oxidative addition, to afford two Ni^I species both kinetically and thermodynamically. These theoretical mechanistic insights into the reductive carboxylation reactions of C?O bonds were also employed to investigate several experimentally observed phenomena, including ligand‐dependent reactivity and site‐selectivity.     

RhI‐Catalyzed Intramolecular Carbonylative C−H/C−I Coupling of 2‐Iodobiphenyls Using Furfural as a Carbonyl Source

Synthesis of fluoren‐9‐ones by a Rh‐catalyzed intramolecular C?H/C?I carbonylative coupling of 2‐iodobiphenyls using furfural as a carbonyl source is presented. The findings indicate that the rate‐determining step is not a C?H bond cleavage but, rather, the oxidative addition of the C?I bond to a Rh^I center.     

Computational Insight into Nickel‐Catalyzed Carbon–Carbon versus Carbon–Boron Coupling Reactions of Primary,Secondary, and Tertiary Alkyl Bromides

The nickel‐catalyzed alkyl–alkyl cross‐coupling (C?C bond formation) and borylation (C?B bond formation) of unactivated alkyl halides reported in the literature show completely opposite reactivity orders in the reactions of primary, secondary, and tertiary alkyl bromides. The proposed Ni^I/Ni^III catalytic cycles for these two types of bond‐formation reactions were studied computationally by means of DFT calculations at the B3LYP level. These calculations indicate that the rate‐determining step for alkyl–alkyl cross‐coupling is the reductive elimination step, whereas for borylation the rate is determined mainly by the atom‐transfer step. In borylation reactions, the boryl ligand involved has an empty p orbital, which strongly facilitates the reductive elimination step. The inability of unactivated tertiary alkyl halides to undergo alkyl–alkyl cross‐coupling is mainly due to the moderately high reductive elimination barrier.