Scalable Rhodium(III)‐Catalyzed Aryl C−H Phosphorylation Enabled by Anodic Oxidation Induced Reductive Elimination

Transition metal catalyzed C?H phosphorylation remains an unsolved challenge. Reported methods are generally limited in scope and require stoichiometric silver salts as oxidants. Reported here is an electrochemically driven Rh^III‐catalyzed aryl C?H phosphorylation reaction that proceeds through H₂ evolution, obviating the need for stoichiometric metal oxidants. The method is compatible with a variety of aryl C?H and P?H coupling partners and particularly useful for synthesizing triarylphosphine oxides from diarylphosphine oxides, which are often difficult coupling partners for transition metal catalyzed C?H phosphorylation reactions. Experimental results suggest that the mechanism responsible for the C?P bond formation involves an oxidation‐induced reductive elimination process.     

Rhodium(I)‐Catalyzed Tertiary Phosphine Directed C−H Arylation: Rapid Construction of Ligand Libraries

Modification of commercially available monophosphine ligands with either aryl bromides or chlorides by rhodium(I)‐catalyzed, tertiary phosphine directed C−H activation is described. A series of ligand libraries containing mono‐ and diaryl‐substituted groups, having different steric and electronic properties, were obtained in high yields. Based on the outstanding properties of their parent scaffolds, the modified ligands have been found to be powerful in organic reactions.     

C−O Activation by a Rhodium Bis(N‐Heterocyclic Carbene) Catalyst: Aryl Carbamates as Arylating Reagents in Directed C−H Arylation

Despite recent progress in the catalytic transformation of inert phenol derivatives as alternatives to aryl halides and triflates, attempts at the cross‐coupling of inert phenol derivatives with the C−H bonds of arenes have met with limited success. Herein, we report the rhodium‐catalyzed cross‐coupling of aryl carbamates with arenes bearing a convertible directing group. The key to success is the use of an in situ generated rhodium bis(N‐heterocyclic carbene) species as the catalyst, which can promote activation of the inert C(sp²)−O bond in aryl carbamates.     

Rhodium(III)‐Catalyzed Enantiotopic C−H Activation Enables Access to P‐Chiral Cyclic Phosphinamides

Compounds with stereogenic phosphorus atoms are frequently used as ligands for transition‐metal as well as organocatalysts. A direct catalytic enantioselective method for the synthesis of P ‐chiral compounds from easily accessible diaryl phosphinamides is presented. The use of rhodium(III) complexes equipped with a suitable atropochiral cyclopentadienyl ligand is shown to enable an enantiodetermining C−H activation step. Upon trapping with alkynes, a broad variety of cyclic phosphinamides with a stereogenic phosphorus(V) atom are formed in high yields and enantioselectivities. Moreover, these can be reduced enantiospecifically to P ‐chiral phosphorus(III) compounds.     

Ruthenium‐Catalyzed ortho C−H Borylation of Arylphosphines

Efficient, phosphine‐directed ortho C?H borylation of arylphosphine derivatives was achieved using Ru catalysts for the first time. The reaction is applicable to various tertiary arylphosphine and arylphosphinite derivatives to give (o‐borylaryl)phosphorus compounds in high yields. This reaction enables easy access to a variety of functionalized phosphine ligands and ambiphilic phosphine boronate compounds, thus realizing a new late‐stage modification of phosphorus compounds.     

Synthesis of [5,6]‐Bicyclic Heterocycles with a Ring‐Junction Nitrogen Atom: Rhodium(III)‐Catalyzed C−H Functionalization of Alkenyl Azoles

The first syntheses of privileged [5,6]‐bicyclic heterocycles, with ring‐junction nitrogen atoms, by transition metal catalyzed C−H functionalization of C‐alkenyl azoles is disclosed. Several reactions are applied to alkenyl imidazoles, pyrazoles, and triazoles to provide products with nitrogen incorporated at different sites. Alkyne and diazoketone coupling partners give azolopyridines with various substitution patterns. In addition, 1,4,2‐dioxazolone coupling partners yield azolopyrimidines. Furthermore, the mechanisms for the reactions are discussed and the utility of the developed approach is demonstrated by iterative application of C−H functionalization for the rapid synthesis of a patented drug candidate.     

Methylenecyclopropane Annulation by Manganese(I)‐Catalyzed Stereoselective C−H/C−C Activation

C−H/C−C functionalizations with methylenecyclopropanes (MCPs) were accomplished with a versatile base‐metal catalyst. A robust manganese(I) complex enabled the expedient annulation of MCPs by synthetically meaningful ketimines to deliver, upon one‐pot hydroarylation, densely substituted polycylic anilines in a step‐economical fashion. Mechanistic studies provided strong support for a facile organometallic C−H manganation, while typical cobalt, ruthenium, rhodium, and palladium catalysts were found completely ineffective.     

meta‐Selective C−H Activation of Arenes at Room Temperature Using Visible Light: Dual‐Function Ruthenium Catalysis

Ruthenium‐catalyzed meta‐C?H activation of arenes at room temperature is reported to proceed under blue‐light irradiation. A variety of heteroarenes are compatible with this photochemical process, which leads to the corresponding meta C?C coupling products in good to very good yields. Initial mechanistic studies suggest a single‐electron transfer process occurs between a photoexcited Ru^II‐cyclometalated complex and alkyl halides, enabling meta‐C?H functionalization reaction via carbon‐centered radicals.     

Rhodium‐Catalyzed C−H Activation Enabled by an Indium Metalloligand

Rhodium complexes with an indium metalloligand were successfully synthesized by utilizing a pyridine‐tethered cyclopentadienyl ligand as a support for an In?Rh bond. The indium metalloligand dramatically changes the electronic and redox properties of the rhodium metal, thereby enabling catalysis of sp²C?H bond activation.     

Rhodium‐Catalyzed meta‐C−H Functionalization of Arenes

Rhodium‐catalyzed ortho ‐C−H functionalization is well known in the literature. Described herein is the Xphos‐supported rhodium catalysis of meta ‐C−H olefination of benzylsulfonic acid and phenyl acetic acid frameworks with the assistance of a para ‐methoxy‐substituted cyano phenol as the directing group. Complete mono‐selectivity is observed for both scaffolds. A wide range of olefins and functional groups attached to arene are tolerated in this protocol.     

Ligand‐Promoted Rhodium(III)‐Catalyzed ortho‐C−H Amination with Free Amines

Ligand development for rhodium(III)‐catalyzed C−H activation reactions has largely been limited to cyclopentadienyl (Cp) based scaffolds. 2‐Methylquinoline has now been identified as a feasible ligand that can coordinate to the metal center of Cp*RhCl to accelerate the cleavage of the C−H bond of N ‐pentafluorophenylbenzamides, providing a new structural lead for ligand design. The compatibility of this reaction with secondary free amines and anilines also overcomes the limitations of palladium(II)‐catalyzed C−H amination reactions.     

Practical Alkoxythiocarbonyl Auxiliaries for Iridium(I)‐Catalyzed C−H Alkylation of Azacycles

The development of new and practical 3‐pentoxythiocarbonyl auxiliaries for Ir^I‐catalyzed C−H alkylation of azacycles is described. This method allows for the α‐C−H alkylation of a variety of substituted pyrrolidines, piperidines, and tetrahydroisoquinolines through alkylation with alkenes. While the practicality of these simple carbamate‐type auxiliaries is underscored by the ease of installation and removal, the method's utility is demonstrated in its ability to functionalize biologically relevant l ‐proline and l ‐trans ‐hydroxyproline, delivering unique 2,5‐dialkylated amino acid analogues that are not accessible by other C−H functionalization methods.     

An Enantioselective CpxRh(III)‐Catalyzed C−H Functionalization/Ring‐Opening Route to Chiral Cyclopentenylamines

A chiral Cp^xRh^III catalyst system in situ generated from a Cp^xRh^I(cod) precatalyst and bis(o‐toluoyl) peroxide as activating oxidant was developed for a C?H activation/ring‐opening sequence between aryl ketoxime ethers and 2,3‐diazabicyclo[2.2.1]hept‐5‐enes. This transformation provides access to densely functionalized chiral cyclopentenylamines in excellent yields and enantioselectivities of up to 97:3 er. The reported method is also well suitable for asymmetric alkenyl C?H functionalizations of α,β‐unsaturated oxime ethers, furnishing skipped dienes with high levels of enantiocontrol.     

Rhodium‐Catalyzed PIII‐Directed ortho‐C−H Borylation of Arylphosphines

Transition‐metal‐mediated metalation of an aromatic C?H bond that is adjacent to a tertiary phosphine group in arylphosphines via a four‐membered chelate ring was first discovered in 1968. Herein, we overcome a long‐standing problem with the ortho‐C?H activation of arylphosphines in a catalytic fashion. In particular, we developed a rhodium‐catalyzed ortho‐selective C?H borylation of various commercially available arylphosphines with B₂pin₂ through P^III‐chelation‐assisted C?H activation. This discovery is suggestive of a generic platform that could enable the late‐stage modification of readily accessible arylphosphines.     

C−H and C−F Bond Activation Reactions of Fluorinated Propenes at Rhodium: Distinctive Reactivity of the Refrigerant HFO‐1234yf

The reaction of [Rh(H)(PEt₃)₃] ( 1 ) with the refrigerant HFO‐1234yf (2,3,3,3‐tetrafluoropropene) affords an efficient route to obtain [Rh(F)(PEt₃)₃] ( 3 ) by C?F bond activation. Catalytic hydrodefluorinations were achieved in the presence of the silane HSiPh₃. In the presence of a fluorosilane, 3 provides a C?H bond activation followed by a 1,2‐fluorine shift to produce [Rh{(E)‐C(CF₃)=CHF}(PEt₃)₃] ( 4 ). Similar rearrangements of HFO‐1234yf were observed at [Rh(E)(PEt₃)₃] [E=Bpin ( 6 ), C₇D₇ ( 8 ), Me ( 9 )]. The ability to favor C?H bond activation using 3 and fluorosilane is also demonstrated with 3,3,3‐trifluoropropene. Studies are supported by DFT calculations.     

Enantioselective Synthesis of C−N Axially Chiral N‐Aryloxindoles by Asymmetric Rhodium‐Catalyzed Dual C−H Activation

The first enantioselective Satoh–Miura‐type reaction is reported. A variety of C?N axially chiral N‐aryloxindoles have been enantioselectively synthesized by an asymmetric rhodium‐catalyzed dual C?H activation reaction of N‐aryloxindoles and alkynes. High yields and enantioselectivities were obtained (up to 99 % yield and up to 99 % ee). To date, it is also the first example of the asymmetric synthesis of C?N axially chiral compounds by such a C?H activation strategy.     

Rhodium(II)‐Catalyzed Dehydrogenative Silylation of Biaryl‐Type Monophosphines with Hydrosilanes

A rhodium‐catalyzed system is introduced for in situ modification of biaryl‐type monophosphines with hydrosilanes through a P^III‐chelation‐assisted dehydrogenative silylation reaction. A series of ligands containing silyl groups with different steric and electronic properties were obtained with excellent regioselectivities. This method offers many advantages, including the use of commercially available phosphines, no requirement for an external ligand or oxidant, a broader substrate scope, high efficiency, and access to a single regioisomer. Based on the outstanding properties of the parent scaffolds, the silyl‐substituted phosphines serve as excellent ligands in Pd‐catalyzed asymmetric Suzuki coupling reactions.     

Rhodium(III)‐Catalyzed Enantioselective Coupling of Indoles and 7‐Azabenzonorbornadienes by C−H Activation/Desymmetrization

Chiral rhodium(III) cyclopentadienyl catalysts (Cp^XRh^III) play significant roles in asymmetric arene C?H activation. Rh/Ir‐catalyzed couplings of arenes and strained rings have been well‐studied, but they have been limited to racemic systems. Reported in this work is the Cp^xRh^III/AgSbF₆‐catalyzed enantioselective desymmetrizative C?C coupling of N‐pyrimidylindoles and 7‐azabenzonorbornadienes with high efficiency and enantioselectivity. The role of AgSbF₆ has been established by mechanistic studies. AgSbF₆ enhances the catalytic activity by suppressing the C3?H activation of the indoles, activation which would otherwise lead to catalytically inactive species.     

Cross‐Coupling of α‐Carbonyl Sulfoxonium Ylides with C−H Bonds

The functionalization of carbon–hydrogen bonds in non‐nucleophilic substrates using α‐carbonyl sulfoxonium ylides has not been so far investigated, despite the potential safety advantages that such reagents would provide over either diazo compounds or their in situ precursors. Described herein are the cross‐coupling reactions of sulfoxonium ylides with C(sp²)−H bonds of arenes and heteroarenes in the presence of a rhodium catalyst. The reaction proceeds by a succession of C−H activation, migratory insertion of the ylide into the carbon–metal bond, and protodemetalation, the last step being turnover‐limiting. The method is applied to the synthesis of benz[c]acridines when allied to an iridium‐catalyzed dehydrative cyclization.