One‐Pot Synthesis of Highly Substituted Polyheteroaromatic Compounds by Rhodium(III)‐Catalyzed Multiple C?H Activation and Annulation

A new method for the synthesis of highly substituted naphthyridine‐based polyheteroaromatic compounds in high yields proceeds through rhodium(III)‐catalyzed multiple C H bond cleavage and C C and C N bond formation in a one‐pot process. Such highly substituted polyheteroaromatic compounds have attracted much attention because of their unique π‐conjugation, which make them suitable materials for organic semiconductors and luminescent materials. Furthermore, a possible mechanism, which involves multiple chelation‐assisted ortho C H activation, alkyne insertion, and reductive elimination, is proposed for this transformation.     

Palladium(II)‐Catalyzed C?H Activation/C?C Cross‐Coupling Reactions: Versatility and Practicality

Pick your Pd partners : A number of catalytic systems have been developed for palladium‐catalyzed C? H activation/C? C bond formation. Recent studies concerning the palladium(II)‐catalyzed coupling of C? H bonds with organometallic reagents through a Pd^II/Pd⁰ catalytic cycle are discussed (see scheme), and the versatility and practicality of this new mode of catalysis are presented. Unaddressed questions and the potential for development in the field are also addressed.

     

Nano‐Cu2O‐Catalyzed Formation of C?C and C?O Bonds: One‐Pot Domino Process for Regioselective Synthesis of α‐Carbonyl Furans from Electron‐Deficient Alkynes and 2‐Yn‐1‐ols

The formation of carbon–carbon and carbon–oxygen bonds continues to be an active and challenging field of chemical research. Nanoparticle catalysis has attracted considerable attention owing to its environmentally benign and high activity toward the reactions. Herein, we described a novel and effective nano‐Cu₂O‐catalyzed one‐pot domino process for the regioselective synthesis of α‐carbonyl furans. Various electron‐deficient alkynes with 2‐yn‐1‐ols underwent this process smoothly in moderate to good yields in the presence of air at atmospheric pressure. It is especially noteworthy that a novel 2,4,5‐trisubstituted 3‐ynylfuran was formed in an extremely direct manner without tedious stepwise synthesis. Additionally, as all of the starting materials are readily available, this method may allow the synthesis of more complex α‐carbonyl furans. An experiment to elucidate the mechanism suggested that the process involved a carbene intermediate.     

Synthesis of 1,3‐Diamines Through Rhodium‐Catalyzed C?H Insertion

A grand opening : N‐Boc‐N‐alkylsulfamides are effective substrates for the title transformation. Oxidative cyclization is highly chemoselective as well as being both stereospecific and diastereoselective. With the advent of new protocols that facilitate ring opening of the six‐membered‐ring heterocyclic products, access to differentially protected 1,3‐diamines has been made possible (see scheme).

     

Synthesis of 1,3‐Diamines Through Rhodium‐Catalyzed C?H Insertion

Schließen und öffnen : N‐Boc‐N‐alkylsulfamide sind geeignete Substrate für die Titelreaktion. Die oxidative Cyclisierung im ersten Schritt ist hoch chemoselektiv sowie stereospezifisch und diastereoselektiv. Mit neuen Verfahren zur Öffnung der dabei erhaltenen Sechsringheterocyclen werden unterschiedlich geschützte 1,3‐Diamine zugänglich (siehe Schema).

     

Orchestrated Triple C?H Activation Reactions Using Two Directing Groups: Rapid Assembly of Complex Pyrazoles

A sequential triple C H activation reaction directed by a pyrazole and an amide group leads to the well‐controlled construction of sterically congested dihydrobenzo[e]indazole derivatives. This cascade reaction demonstrates that the often problematic competing C H activation pathways in the presence of multiple directing groups can be harvested by design to improve step economy in synthesis. Pyrazole as a relatively weak coordinating group is shown to direct C H activation for the first time.     

Ligand‐Promoted ortho‐C?H Amination with Pd Catalysts

2,4,6‐Trimethoxypyridine is identified as an efficient ligand for promoting a Pd‐catalyzed ortho‐C H amination of both benzamides and triflyl‐protected benzylamines. This finding provides guidance for the development of ligands that can improve or enable Pd^II‐catalyzed C H activation reactions directed by weakly coordinating functional groups.     

Amide‐Directed Tandem C?C/C?N Bond Formation through C?H Activation

The transformation of C? H bonds into other chemical bonds is of great significance in synthetic chemistry. C? H bond‐activation processes provide a straightforward and atom‐economic strategy for the construction of complex structures; as such, they have attracted widespread interest over the past decade. As a prevalent directing group in the field of C? H activation, the amide group not only offers excellent regiodirecting ability, but is also a potential C? N bond precursor. As a consequence, a variety of nitrogen‐containing heterocycles have been obtained by using these reactions. This Focus Review addresses the recent research into the amide‐directed tandem C? C/C? N bond‐formation process through C? H activation. The large body of research in this field over the past three years has established it as one of the most‐important topics in organic chemistry.     

Ligand‐Enabled Catalytic C?H Arylation of Aliphatic Amines by a Four‐Membered‐Ring Cyclopalladation Pathway

A palladium‐catalyzed C H arylation of aliphatic amines with arylboronic esters is described, proceeding through a four‐membered‐ring cyclopalladation pathway. Crucial to the successful outcome of this reaction is the action of an amino‐acid‐derived ligand. A range of hindered secondary amines and arylboronic esters are compatible with this process and the products of the arylation can be advanced to complex polycyclic molecules by sequential C H activation reactions.     

Synthesis of 2‐ and 2,7‐Functionalized Pyrene Derivatives: An Application of Selective C?H Borylation

An efficient synthetic route to 2‐ and 2,7‐substituted pyrenes is described. The regiospecific direct C? H borylation of pyrene with an iridium‐based catalyst, prepared in situ by the reaction of [{Ir(μ‐OMe)cod}₂] (cod=1,5‐cyclooctadiene) with 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine, gives 2,7‐bis(Bpin)pyrene ( 1 ) and 2‐(Bpin)pyrene ( 2 , pin=OCMe₂CMe₂O). From 1 , by simple derivatization strategies, we synthesized 2,7‐bis(R)‐pyrenes with R=BF₃K ( 3 ), Br ( 4 ), OH ( 5 ), B(OH)₂ ( 6 ), and OTf ( 7 ). Using these nominally nucleophilic and electrophilic derivatives as coupling partners in Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig cross‐coupling reactions, we obtained 2,7‐bis(R)‐pyrenes with R=(4‐CO₂C₈H₁₇)C₆H₄ ( 8 ), Ph ( 9 ), C≡CPh ( 10 ), C≡C[{4‐B(Mes)₂}C₆H₄] ( 11 ), C≡CTMS ( 12 ), C≡C[(4‐NMe₂)C₆H₄] ( 14 ), C≡CH ( 15 ), N(Ph)[(4‐OMe)C₆H₄] ( 16 ), and R=OTf, R′=C≡CTMS ( 13 ). Lithiation of 4 , followed by reaction with CO₂, yielded pyrene‐2,7‐dicarboxylic acid ( 17 ), whilst borylation of 2‐tBu‐pyrene gave 2‐tBu‐7‐Bpin‐pyrene ( 18 ) selectively. By similar routes (including Negishi cross‐coupling reactions), monosubstituted 2‐R‐pyrenes with R=BF₃K ( 19 ), Br ( 20 ), OH ( 21 ), B(OH)₂ ( 22 ), [4‐B(Mes)₂]C₆H₄ ( 23 ), B(Mes)₂ ( 24 ), OTf ( 25 ), C≡CPh ( 26 ), C≡CTMS ( 27 ), (4‐CO₂Me)C₆H₄ ( 28 ), C≡CH ( 29 ), C₃H₆CO₂Me ( 30 ), OC₃H₆CO₂Me ( 31 ), C₃H₆CO₂H ( 32 ), OC₃H₆CO₂H ( 33 ), and O(CH₂)₁₂Br ( 34 ) were obtained from 2 . These derivatives are of synthetic and photophysical interest because they contain donor, acceptor, and conjugated substituents. The crystal structures of compounds 4 , 5 , 7 , 12 , 18 , 19 , 21 , 23 , 26 , and 28 – 31 have also been obtained from single‐crystal X‐ray diffraction data, revealing a diversity of packing modes, which are described in the Supporting Information. A detailed discussion of the structures of 1 and 2 , their polymorphs, solvates, and co‐crystals is reported separately.     

Rhodium(III)‐Catalyzed C?C and C?O Coupling of Quinoline N‐Oxides with Alkynes: Combination of C?H Activation with O‐Atom Transfer

[Cp*Rh^III]‐catalyzed C H activation of arenes assisted by an oxidizing N O or N N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N O bond is well‐known to undergo O‐atom transfer (OAT) to alkynes. Despite the liability of N O bonds in both C H activation and OAT, these two important areas evolved separately. In this report, [Cp*Rh^III] catalysts integrate both areas in an efficient redox‐neutral coupling of quinoline N‐oxides with alkynes to afford α‐(8‐quinolyl)acetophenones. In this process the N O bond acts as both a directing group for C H activation and as an O‐atom donor.     

C?C Cross‐Coupling Reactions of O6‐Alkyl‐2‐Haloinosine Derivatives and a One‐Pot Cross‐Coupling/O6‐Deprotection Procedure

Reaction conditions for the C? C cross‐coupling of O⁶‐alkyl‐2‐bromo‐ and 2‐chloroinosine derivatives with aryl‐, hetaryl‐, and alkylboronic acids were studied. Optimization experiments with silyl‐protected 2‐bromo‐O⁶‐methylinosine led to the identification of [PdCl₂(dcpf)]/K₃PO₄ in 1,4‐dioxane as the best conditions for these reactions (dcpf=1,1′‐bis(dicyclohexylphosphino)ferrocene). Attempted O⁶‐demethylation, as well as the replacement of the C‐6 methoxy group by amines, was unsuccessful, which led to the consideration of Pd‐cleavable groups such that C? C cross‐coupling and O⁶‐deprotection could be accomplished in a single step. Thus, inosine 2‐chloro‐O⁶‐allylinosine was chosen as the substrate and, after re‐evaluation of the cross‐coupling conditions with 2‐chloro‐O⁶‐methylinosine as a model substrate, one‐step C? C cross‐coupling/deprotection reactions were performed with the O⁶‐allyl analogue. These reactions are the first such examples of a one‐pot procedure for the modification and deprotection of purine nucleosides under C? C cross‐coupling conditions.     

Oxindole Synthesis by Direct Coupling of C?H and C?H Centers

An sp ² /sp ³ get‐together : A novel and efficient method can be used to synthesize 3,3‐disubstitued oxindoles by the direct intramolecular oxidative coupling of an aryl C? H and a C? H center (see scheme; DMF=N,N‐dimethylformamide).