Rhodium‐Catalyzed CH Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3‐Diaryl‐Substituted Indoles

The direct C? H annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3‐disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3‐diaryl substituted indoles. Herein, we report the rhodium(III)‐catalyzed C? H annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3‐diaryl‐substituted N‐unprotected indoles with two different aryl groups. One of the aryl substituents is derived from N?C‐aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.     

Rhodium‐Catalyzed Regioselective C7‐Functionalization of N‐Pivaloylindoles

An efficient rhodium‐catalyzed method for direct C? H functionalization at the C7 position of a wide range of indoles has been developed. Good to excellent yields of alkenylation products were observed with acrylates, styrenes, and vinyl phenyl sulfones, whereas the saturated alkylation products were obtained in good yield with α,β‐unsaturated ketones. Both the N‐pivaloyl directing group and the rhodium catalyst proved to be crucial for high regioselectivity and conversion.     

Rhodium‐Catalyzed (5+1) Annulations Between 2‐Alkenylphenols and Allenes: A Practical Entry to 2,2‐Disubstituted 2H‐Chromenes

Readily available alkenylphenols react with allenes under rhodium catalysis to provide valuable 2,2‐disubstituted 2H‐chromenes. The whole process, which involves the cleavage of one C? H bond of the alkenyl moiety and the participation of the allene as a one‐carbon cycloaddition partner, can be considered a simple, versatile, and atom‐economical (5+1) heteroannulation. The reaction tolerates a broad range of substituents both in the alkenylphenol and in the allene, and most probably proceeds through a mechanism involving a rhodium‐catalyzed C? C coupling followed by two sequential pericyclic processes.     

Rhodium‐Catalyzed Direct Amination of Arenes with Nitrosobenzenes: A New Route to Diarylamines

A Rh^III‐catalyzed addition of aryl C?H bonds to nitrosobenzenes, followed by cleavage of the resulting hydroxylamines in situ, has been reported. Different directing groups, such as N‐based heterocycles and ketoximes, can be used in this C?H amination process, providing valuable diarylamines in excellent yields. Most importantly, this process provides a new method for attaching arylamine groups to aromatic rings.     

Rhodium‐Catalyzed Annulative Coupling of 3‐Phenylthiophenes with Alkynes Involving Double C‐H Bond Cleavages

Double C?H bond activation took place efficiently upon treatment of 3‐phenylthiophenes with alkynes in the presence of a rhodium catalyst and a copper salt oxidant to form the corresponding naphthothiophene derivatives. Dehydrogenative coupling with alkenes was also found to occur on the phenyl moiety rather than the thiophene ring. These reactions provide straightforward synthetic methods for π‐conjugated molecules involving a thiophene unit from readily available, simple building blocks.     

Rhodium‐Catalyzed Directed Sulfenylation of Arene CH Bonds

The rhodium‐catalyzed intermolecular direct C?H thiolation of arenes with aryl and alkyl disulfides was developed for the first time to provide a convenient route to aryl thioethers. This strategy is compatible with many different directing groups and exhibits excellent functional group tolerance. More significantly, mono‐ or dithiolation can be selectively achieved, thus providing a straightforward way for selective preparation of aryl thioethers and dithioethers.     

RhIII‐Catalyzed Hydroacylation Reactions between N‐Sulfonyl 2‐Aminobenzaldehydes and Olefins

Metal‐catalyzed hydroacylation of olefins represents an important atom‐economic synthetic process in C?H activation. For the first time highly efficient Rh^IIICp*‐catalyzed hydroacylation was realized in the coupling of N‐sulfonyl 2‐aminobenzaldehydes with both conjugated and aliphatic olefins, leading to the synthesis of various aryl ketones. Occasionally, oxidative coupling occurred when a silver(I) oxidant was used.     

Synthesis of Spirocyclic Enones by Rhodium‐Catalyzed Dearomatizing Oxidative Annulation of 2‐Alkenylphenols with Alkynes and Enynes

The dearomatizing oxidative annulation of 2‐alkenylphenols with alkynes and enynes proceeds with high yields and regioselectivities under Rh^III catalysis. These reactions are successful using Cu(OAc)₂ or air as the stoichiometric oxidant, and provide spirocyclic enones, the basic ring system of which appears in several natural products. Application of this process to the preparation of a highly functionalized tetracycle is also demonstrated.     

Substrate‐Directed Hydroacylation: Rhodium‐Catalyzed Coupling of Vinylphenols and Nonchelating Aldehydes

We report a protocol for the hydroacylation of vinylphenols with aryl, alkenyl, and alkyl aldehydes to form branched products with high selectivity. This cross‐coupling yields α‐aryl ketones that can be cyclized to benzofurans, and it enables access to eupomatenoid natural products in four steps or less from eugenol. Excellent reactivity and high levels of regioselectivity for the formation of the branched products were observed. We propose that aldehyde decarbonylation is avoided by the use of an anionic directing group on the alkene and a diphosphine ligand with a small bite angle.     

A [4+1] Cyclative Capture Approach to 3H‐Indole‐N‐oxides at Room Temperature by Rhodium(III)‐Catalyzed CH Activation

The rhodium(III)‐catalyzed [3+2] C? H cyclization of aniline derivatives and internal alkynes represents a useful contribution to straightforward synthesis of indoles. However, there is no report on the more challenging synthesis of pharmaceutically important N‐hydroxyindoles and 3H‐indole‐N‐oxides. Reported herein is the first rhodium(III)‐catalyzed [4+1] C? H oxidative cyclization of nitrones with diazo compounds to access 3H‐indole‐N‐oxides. More significantly, this reaction proceeds at room temperature and has been extended to the synthesis of N‐hydroxyindoles and N‐hydroxyindolines.     

Efficient Rhodium‐Catalyzed Multicomponent Reaction for the Synthesis of Novel Propargylamines

[{Rh(μ‐Cl)(H)₂(IPr)}₂] (IPr = 1,3‐bis‐(2,6‐diisopropylphenyl)imidazole‐2‐ylidene) was found to be an efficient catalyst for the synthesis of novel propargylamines by a one‐pot three‐component reaction between primary arylamines, aliphatic aldehydes, and triisopropylsilylacetylene. This methodology offers an efficient synthetic pathway for the preparation of secondary propargylamines derived from aliphatic aldehydes. The reactivity of [{Rh(μ‐Cl)(H)₂(IPr)}₂] with amines and aldehydes was studied, leading to the identification of complexes [RhCl(CO)IPr(MesNH₂)] (MesNH₂ = 2,4,6‐trimethylaniline) and [RhCl(CO)₂IPr]. The latter shows a very low catalytic activity while the former brought about reaction rates similar to those obtained with [{Rh(μ‐Cl)(H)₂(IPr)}₂]. Besides, complex [RhCl(CO)IPr(MesNH₂)] reacts with an excess of amine and aldehyde to give [RhCl(CO)IPr{MesN?CHCH₂CH(CH₃)₂}], which was postulated as the active species. A mechanism that clarifies the scarcely studied catalytic cycle of A₃‐coupling reactions is proposed based on reactivity studies and DFT calculations.     

Rhodium(III)‐Catalyzed Three‐Component Reaction of Imines,Alkynes, and Aldehydes through CH Activation

An efficient rhodium(III)‐catalyzed tandem three‐component reaction of imines, alkynes and aldehydes through C?H activation has been developed. High stereo‐ and regioselectivity, as well as good yields were obtained in most cases. The simple and atom‐economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties.     

Construction of Axial Chirality by Rhodium‐Catalyzed Asymmetric Dehydrogenative Heck Coupling of Biaryl Compounds with Alkenes

Enantioselective construction of axially chiral biaryls by direct C? H bond functionalization reactions has been realized. Novel axially chiral biaryls were synthesized by the direct C? H bond olefination of biaryl compounds, using a chiral [Cp*Rh^III] catalyst, in good to excellent yields and enantioselectivities. The obtained axially chiral biaryls were found as suitable ligands for rhodium‐catalyzed asymmetric conjugate additions.     

Rhodium‐Catalyzed CH Alkynylation of Arenes at Room Temperature

The rhodium(III)‐catalyzed ortho C? H alkynylation of non‐electronically activated arenes is disclosed. This process features a straightforward and highly effective protocol for the synthesis of functionalized alkynes and represents the first example of merging a hypervalent iodine reagent with rhodium(III) catalysis. Notably, this reaction proceeds at room temperature, tolerates a variety of functional groups, and more importantly, exhibits high selectivity for monoalkynylation.     

Diastereoselective Carbocyclization of 1,6‐Heptadienes Triggered by Rhodium‐Catalyzed Activation of an Olefinic CH Bond

The use of α,ω‐dienes as functionalization reagents for olefinic carbon–hydrogen bonds has been rarely studied. Reported herein is the rhodium(I)‐catalyzed rearrangement of prochiral 1,6‐heptadienes into [2,2,1]‐cycloheptane derivatives with concomitant creation of at least three stereogenic centers and complete diastereocontrol. Deuterium‐labeling studies and the isolation of a key intermediate are consistent with a group‐directed C? H bond activation, followed by two consecutive migratory insertions, with only the latter step being diastereoselective.     

Rhodium(II)‐Catalyzed Nondirected Oxidative Alkenylation of Arenes: Arene Loading at One Equivalent

A bimetallic Rh^II catalyst promoted the C? H alkenylation of simple arenes at 1.0 equivalent without the use of a directing group. A phosphine ligand as well as cooperative reoxidation of Rh^II with Cu(TFA)₂ and V₂O₅ proved essential in providing monoalkenylated products in good yields and selectivities, especially with di‐ and trisubstituted arenes.     

Regioselective C3 Alkenylation of 4 H‐pyrido[1,2‐a]pyrimidin‐4‐ones via Palladium‐Catalyzed CH Activation

A general and efficient palladium‐catalyzed direct C3 alkenylation of 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones using AgOAc/O₂ as the oxidant has been developed. A variety of 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones were successfully coupled with acrylate esters, styrenes, methylvinylketone, and acrylamide in moderate to excellent yields. The reaction exhibited complete regio‐ and stereoselectivity. This transformation provides an attractive new approach to functionalize 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones.     

Synthesis of Dibenzo[c,e]oxepin‐5(7H)‐ones from Benzyl Thioethers and Carboxylic Acids: Rhodium‐Catalyzed Double CH Activation Controlled by Different Directing Groups

A rhodium(III)‐catalyzed cross‐coupling of benzyl thioethers and aryl carboxylic acids through the two directing groups is reported. Useful structures with diverse substituents were efficiently synthesized in one step with the cleavage of four bonds (C? H, C? S, O? H) and the formation of two bonds (C? C, C? O). The formed structure is the privileged core in natural products and bioactive molecules. This work highlights the power of using two different directing groups to enhance the selectivity of a double C? H activation, the first of such examples in cross‐oxidative coupling.     

Highly Stereoselective Synthesis of Imine‐Containing Dibenzo[b,d]azepines by a Palladium(II)‐Catalyzed [5+2] Oxidative Annulation of o‐Arylanilines with Alkynes

A novel palladium(II)‐catalyzed [5+2] oxidative annulation of readily available o‐arylanilines with alkynes has been developed for building a seven‐membered N‐heterocyclic architecture containing a biaryl linkage. This method is applicable to a wide range of unprotected o‐arylanilines and internal alkynes, and results in the chemoselective preparation of imine‐containing dibenzo[b,d]azepines in high yields with excellent diastereoselectivity with respect to the two types of stereogenic elements.