Palladium‐Catalyzed Decarboxylative ortho‐C(sp2)−H Aroylation of N‐Sulfoximine Benzamides at Room Temperature

A palladium‐catalyzed method for the decarboxylative ortho C?H acylation of N‐sulfoximine benzamides is developed at room temperature. The catalytic method enables easy access to various functionalized 2‐aroylaromatic carboxylic acid derivatives in good isolated yields. Based on our mechanistic studies, a Pd(II)/Pd(IV) catalytic cycle that involves aroyl radical intermediate is proposed for the reaction.     

Palladium‐Catalyzed Dearomative syn‐1,4‐Oxyamination

A palladium‐catalyzed dearomative syn‐1,4‐oxyamination protocol using non‐activated arenes has been developed. This one‐pot procedure utilizes arenophile chemistry, and the corresponding para‐cycloadducts are treated with oxygen nucleophiles via formal allylic substitution, providing direct access to syn‐1,4‐oxyaminated products. The reaction conditions permit a range of arenes, as well as different O‐nucleophiles, such as oximes and benzyl alcohols. Moreover, this process was established in an asymmetric fashion, delivering products with high enantioselectivity. The dearomatized products are amenable to a multitude of further derivatizations ranging from olefin chemistry to C?H activation, giving rise to a diverse set of new functionalities. Overall, this dearomative functionalization offers rapid and controlled formation of molecular complexity, enabling straightforward access to functionalized small molecules from simple and readily available arenes.     

Palladium(II)‐Catalyzed ortho‐CH Arylation/Alkylation of N‐Benzoyl α‐Amino Ester Derivatives

The palladium‐catalyzed arylation/alkylation of ortho‐C?H bonds in N‐benzoyl α‐amino ester derivatives is described. In such a system both the NH‐amido and the CO₂R groups in the α‐amino ester moieties play a role in successful C?H activation/C?C bond formation using iodoaryl coupling partners. A wide variety of functional groups and electron‐rich/deficient iodoarenes are tolerated. The yields obtained range from 20 to 95 %.     

Palladium‐Catalyzed ortho‐Selective CH Deuteration of Arenes: Evidence for Superior Reactivity of Weakly Coordinated Palladacycles

We disclose a protocol for the palladium‐catalyzed ortho‐selective C? H deuteration of arenes. Phenylacetic acids and benzoic acids are suitable substrates for this reaction. This reaction offers a catalytic route to ortho‐deuterated phenylacetic acids and benzoic acids and demonstrates the sharp difference in reactivity of palladacycle intermediates held together by weak and strong coordination.     

C‐2 Selective Arylation of Indoles with Heterogeneous Nanopalladium and Diaryliodonium Salts

A simple and efficient method to prepare synthetically useful 2‐arylindoles is presented, using a heterogeneous Pd catalyst and diaryliodonium salts in water under mild conditions. A remarkably low leaching of metal catalyst was observed under the applied conditions. The developed protocol is highly C‐2 selective and tolerates structural variations both in the indole and in the diaryliodonium salt. Arylations of both N?H indoles and N‐protected indoles with ortho‐substituted, electron‐rich, electron‐deficient, or halogenated diaryliodonium salts were achieved to give the desired products in high to excellent isolated yields within 6 to 15 h at room temperature or 40 °C.     

Towards Ideal Synthesis: Alkenylation of Aryl CH Bonds by a Fujiwara–Moritani Reaction

An overview of recent progress in the Fujiwara–Moritani reaction, which is the palladium‐catalyzed oxidative coupling of arenes with olefins to afford alkenyl arenes, is described. It is emphasized that regioselectivity on aryl ortho‐ or meta‐C?H activation could be controlled very well in the presence of Pd, Rh, or Ru catalysts with the assistance of various chelation groups on aromatic rings in this coupling reaction. Catalytic alkenylation of aryl C?H bonds from simple arenes is also discussed, especially from electron‐deficient arenes. These advanced protocols would not only make the Fujiwara–Moritani reaction more useful and applicable in organic synthesis but also light the way for the further development of the functionalization of normal C?H bonds.     

CH Oxygenation and N‐Trifluoroacylation of Arylamines Under Metal‐Free Conditions: A Convenient Approach to 2‐Aminophenols and N‐Trifluoroacyl‐ortho‐aminophenols

Direct ortho‐hydroxylation through C?H oxygenation and N‐trifluoroacylation of anilines was achieved in a single step under metal‐free conditions by using a combination of TFA and oxone. The method allowed the formation of functionalised amino phenolic compounds such as ortho‐hydroxy‐N‐trifluoroacetanilides in good yields with broad substrate scope.     

Exceedingly Fast Copper(II)‐Promoted ortho CH Trifluoromethylation of Arenes using TMSCF3

The direct ortho‐trifluoromethylation of arenes, including heteroarenes, with TMSCF₃ has been accomplished by a copper(II)‐promoted C? H activation reaction which completes within 30 minutes. Mechanistic investigations are consistent with the involvement of C? H activation, rather than a simple electrophilic aromatic substitution (S_EAr), as the key step.     

meta‐Selective C−H Arylation of Fluoroarenes and Simple Arenes

Fluorine is known to promote ortho‐C?H metalation. Based upon this reactivity, we employed an activated norbornene that traps the ortho‐palladation intermediate and is then relayed to the meta position, leading to meta‐selective C?H arylation of fluoroarenes. Deuterium experiment suggests that this meta‐arylation is initiated by ortho C?H activation and the catalytic cycle is terminated by C‐2 protonation. A dual‐ligand system is crucial for the observed high reactivity and site selectivity. Applying this approach to simple benzene or other arenes also affords arylation products with good yield and site selectivity.     

Rhodium‐Catalyzed Enantioselective Oxidative [3+2] Annulation of Arenes and Azabicyclic Olefins through Twofold C−H Activation

C?H bond activation is mostly limited to ortho selectivity. Activation of both ortho and meta C?H bonds constitutes a particularly important strategy for annulation, but has rarely been studied in enantioselective systems. Reported herein is rhodium(III)‐catalyzed asymmetric [3+2] transannulation of arenes with 7‐azabenzonorbornadienes. Two distinct classes of arenes have been identified as substrates, and the coupling proceeded with high enantioselectivity and excellent diastereoselectivity through sequential activation of ortho and meta C?H bonds.     

Visible‐Light‐Enabled Ruthenium‐Catalyzed meta‐C−H Alkylation at Room Temperature

Visible‐light‐induced ruthenium catalysis has enabled remote C?H alkylations with excellent levels of position control under exceedingly mild conditions at room temperature. The metallaphotocatalysis occurred under exogenous‐photosensitizer‐free conditions and features an ample substrate scope. The robust nature of the photo‐induced mild meta‐C?H functionalization is reflected by the broad functional group tolerance, and the reaction can be carried out in an operationally simple manner, setting the stage for challenging secondary and tertiary meta‐C?H alkylations by ruthenaphotoredox catalysis.     

Nitrone Directing Groups in Rhodium(III)‐Catalyzed C−H Activation of Arenes: 1,3‐Dipoles versus Traceless Directing Groups

Functionalizable directing groups (DGs) are highly desirable in C?H activation chemistry. The nitrone DGs are explored in rhodium(III)‐catalyzed C?H activation of arenes and couplings with cyclopropenones. N‐tert‐butyl nitrones bearing a small ortho substituent coupled to afford 1‐naphthols, where the nitrone acts as a traceless DG. In contrast, coupling of N‐tert‐butyl nitrones bearing a bulky ortho group follows a C?H acylation/[3+2] dipolar addition pathway to give bicyclics. The coupling of N‐arylnitrones follows the same acylation/[3+2] addition process but delivers different bicyclics.     

Chiral N,N′‐Dioxide–Scandium(III) Complex‐Catalyzed Asymmetric Friedel–Crafts Alkylation Reaction of ortho‐Hydroxybenzyl Alcohols with C3‐Substituted N‐Protected Indoles

The first Lewis acid catalyzed asymmetric Friedel–Crafts alkylation reaction of ortho‐hydroxybenzyl alcohols with C3‐substituted indoles is described. A chiral N,N′‐dioxide Sc(OTf)₃ complex served not only to promote formation of ortho‐quinone methides (o‐QMs) in situ but also induced the asymmetry of the reaction. This methodology enables a novel activation of ortho‐hydroxybenzyl alcohols, thus affording the desired chiral diarylindol‐2‐ylmethanes in up to 99 % yield and 99 % ee. A range of functional groups were also tolerated under the mild reaction conditions. Moreover, this strategy gives concise access to enantioenriched indole‐fused benzoxocines.     

Palladium‐Catalyzed ortho‐Selective C?H Deuteration of Arenes: Evidence for Superior Reactivity of Weakly Coordinated Palladacycles

We disclose a protocol for the palladium‐catalyzed ortho‐selective C H deuteration of arenes. Phenylacetic acids and benzoic acids are suitable substrates for this reaction. This reaction offers a catalytic route to ortho‐deuterated phenylacetic acids and benzoic acids and demonstrates the sharp difference in reactivity of palladacycle intermediates held together by weak and strong coordination.     

Photoluminescent and Liquid‐Crystalline Properties of Donor–Acceptor‐Type 2,5‐Diarylthiazoles

The synthesis of donor–acceptor‐type 2,5‐diarylthiazoles that bear electron‐donating N,N‐dialkylamine and electron‐withdrawing cyano groups at the 2‐ and 5‐position, respectively, were carried out with transition‐metal‐catalyzed C? H arylation reactions developed by us. The compounds were synthesized by the C? H arylation of unsubstituted thiazole at the 2‐position with a palladium/copper catalyst in the presence of tetrabutylammonium fluoride (TBAF) as an activator. Further C? H arylation of the 2‐arylated thiazole at the 5‐position was carried out by the palladium‐catalyzed reaction in the presence of silver(I) fluoride to afford the donor–acceptor‐type 2,5‐diarylthiazoles with N,N‐dialkylamine groups of different chain lengths. The UV/Vis absorption, photoluminescence, and electrochemical behavior were similar regardless of chain length, whereas liquid‐crystalline behavior and thermal characteristics were found to be dependent on the alkyl‐chain length. The compounds with N,N‐diethylamine or N‐butyl‐N‐methyl groups showed a stable liquid‐crystalline phase over a wide temperature range as well as higher stability to thermal decomposition.     

Direct CH Amidation of Benzoic Acids to Introduce meta‐ and para‐Amino Groups by Tandem Decarboxylation

The Ir‐catalyzed mild C?H amidation of benzoic acids with sulfonyl azides was developed to give reactions with high efficiency and functional‐group compatibility. Subsequent protodecarboxylation of ortho‐amidated benzoic acid products afforded meta‐ or para‐substituted (N‐sulfonyl)aniline derivatives, the latter being inaccessible by other C?H functionalization approaches. The decarboxylation step was compatible with the amidation conditions, enabling a convenient one‐pot, two‐step process.     

Catalytic Borylation of SCF3‐Functionalized Arenes by Rhodium(I) Boryl Complexes: Regioselective CH Activation at the ortho‐Position

An unprecedented reaction pathway for the borylation of SCF₃‐containing arenes using [Rh(Bpin)(PEt₃)₃] (pin=pinacolato) is reported. Catalytic processes were developed and the functionalizations proceed under mild reaction conditions. The C? H activations occur with a unique regioselectivity for the position ortho to the SCF₃ group, which apparently serves as directing group. Borylated SCF₃ compounds can serve as versatile building blocks.     

Cobalt‐Catalyzed C8‐Dienylation of Quinoline‐N‐Oxides

An efficient Cp*Co^III‐catalyzed C8‐dienylation of quinoline‐N‐oxides was achieved by employing allenes bearing leaving groups at the α‐position as the dienylating agents. The reaction proceeds by Co^III‐catalyzed C?H activation of quinoline‐N‐oxides and regioselective migratory insertion of the allene followed by a β‐oxy elimination, leading to overall dienylation. Site‐selective C?H activation was achieved with excellent selectivity under mild reaction conditions, and 30 mol % of a NaF additive was found to be crucial for the efficient dienylation. The methodology features high stereoselectivity, mild reaction conditions, and good functional‐group tolerance. C8‐alkenylation of quinoline‐N‐oxides was achieved in the case of allenes devoid of leaving groups as coupling partners. Furthermore, gram‐scale preparation and preliminary mechanistic experiments were carried out to gain insights into the reaction mechanism.     

CBr4‐Mediated Cross‐Dehydrogenative Coupling Reaction of Amines

A novel CBr₄‐mediated dehydrogenative Povarov/aromatization tandem reaction of glycine derivatives with alkenes, leading to complex quinoline derivatives, and a CBr₄‐mediated dehydrogenative C?H functionalization of N‐aryl tetrahydroisoquinolines with nucleophiles to form C?C and C?P bonds are reported. The reactions were performed under very simple and mild reaction conditions; only CBr₄ was used as a promoter. A plausible mechanism involving a radical process is proposed.     

Furan‐Based o‐Quinodimethanes by Gold‐Catalyzed Dehydrogenative Heterocyclization of 2‐(1‐Alkynyl)‐2‐alken‐1‐ones: A Modular Entry to 2,3‐Furan‐Fused Carbocycles

A strategy for in situ generation of furan‐based ortho‐quinodimethanes (o‐QDMs) by the gold(I)‐mediated dehydrogenative heterocyclization of 2‐(1‐alkynyl)‐2‐alken‐1‐ones in the presence of pyridine N‐oxide under mild reaction conditions was developed. These in situ furan‐based o‐QDMs were trapped by electron‐deficient olefins and alkynes, thus furnishing various 2,3‐furan‐fused carbocycles in good yields with high diastereo‐ and regioselectivities.