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.     

Copper‐Catalyzed Reaction Cascade of Thiophenol Hydroxylation and S‐Arylation through Disulfide‐Directed C−H Activation

Copper‐catalyzed thiophenol C?H activation is described. Through an initial attempt to conduct C‐arylation with arylboronic acid, a rather surprising sequential C?H activation and S‐arylation was discovered. Mechanistic investigation revealed the disulfide intermediate as the key component in directing C?H oxidation. The overall reaction proceeded under mild conditions with molecular oxygen as the oxidant. Discovery of disulfide as the directing group provides a potential new direction for catalytic C?H functionalization under mild conditions.     

Cobalt‐Catalyzed CH Arylations with Weakly‐Coordinating Amides and Tetrazoles: Expedient Route to Angiotensin‐II‐Receptor Blockers

Cobalt‐catalyzed C?H arylations enabled the synthesis of biaryl tetrazoles, which are key structural motifs in antihypertensive angiotensin‐II‐receptor blockers. Thus, weakly‐coordinating benzamides were employed for step‐economical C?H arylations with ample scope. Further, a low‐valent NHC complex enabled first cobalt‐catalyzed C?H functionalization by tetrazole assistance.     

2‐(4‐Bromophenyl)‐1,2‐dihydropyrimido[1,2‐a]benzimidazol‐4(3H)‐one and 4‐(4‐methylphenyl)‐3,4‐dihydropyrimido[1,2‐a]benzimidazol‐2(1H)‐one form hydrogen‐bonded base‐paired dimers

The title compounds, 2‐(4‐bromo­phenyl)‐1,2‐di­hydro­pyrimido­[1,2‐a]­benzimidazol‐4‐(3H)‐one, C₁₆H₁₂Br­N₃O, (IVa), and 4‐(4‐methylphenyl)‐3,4‐dihydropyrimido[1,2‐a]benzimidazol‐2‐(1H)‐one, C₁₇H₁₅N₃O, (Vb), both form R(8) centrosymmetric dimers via N—H?N hydrogen bonds. The N?N distance is 2.943 (3) Å for (IVa) and 2.8481 (16) Å for (Vb), with the corresponding N—H?N angles being 129 and 167°, respectively. However, in other respects, the supra­molecular structures of the two compounds differ. Both compounds contain different C—H?π interactions, in which the C—H?π(centroid) distances are 2.59 and 2.47 Å for (IVa) and (Vb), respectively (the latter being a short distance), with C—H?π(centroid) angles of 158 and 159°, respectively. The supramolecular structures also differ, with a short Br?O distance of 3.117 (2) Å in bromo derivative (IVa), and a C—H?O interaction with a C?O distance of 3.2561 (19) Å and a C—H?O angle of 127° in tolyl system (Vb). The di­hydro­pyrimido part of (Vb) is disordered, with a ratio of the major and minor components of 0.9:0.1. The disorder consists of two non‐interchangeable envelope conformers, each with an equatorial tolyl group and an axial methine H atom.     

Micellar Catalysis for Ruthenium(II)‐Catalyzed C−H Arylation: Weak‐Coordination‐Enabled C−H Activation in H2O

Chemoselective C?H arylations were accomplished through micellar catalysis by a versatile single‐component ruthenium catalyst. The strategy provided expedient access to C?H‐arylated ferrocenes with wide functional‐group tolerance and ample scope through weak chelation assistance. The sustainability of the C?H arylation was demonstrated by outstanding atom‐economy and recycling studies. Detailed computational studies provided support for a facile C?H activation through thioketone assistance.     

Two‐in‐One Strategy for Palladium‐Catalyzed C−H Functionalization in Water

Transition metal catalyzed C?H functionalizations have been developed as powerful methods for C?C bond formations. Directing groups, removable directing groups, traceless directing groups, and transient directing groups (TDGs) have been successfully used to improve the reaction efficiencies. For the development of greener and more sustainable methods, C?H functionalization using a TDG that also serves as a reagent in aqueous solvent was investigated. The palladium‐catalyzed C?H functionalization of tryptamine derivatives using ketones in water successfully generated tetrahydro‐β‐carbolines with a quaternary carbon center at C1. Deuterium‐labeling experiments are discussed to provide insight into the mechanism. The C2‐position of pyridine was also successfully functionalized by this strategy.     

4‐Ethoxycarbonyl‐3‐hydroxy‐3‐phenylcyclohexanone

The title compound, ethyl 2‐hydroxy‐4‐oxo‐2‐phenyl­cyclo­hexane­carboxyl­ate, C₁₅H₁₈O₄, was obtained by a Michael–Aldol condensation and has the cyclo­hexanone in a chair conformation. The attached hydroxy, ethoxy­carbonyl and phenyl groups are disposed in β‐axial, β‐equatorial and α‐­equatorial configurations, respectively. An intermolecular hydrogen bond, with an O?O distance of 2.874 (2) Å, links the OH group and the ring carbonyl. Weak intermolecular C—H?O=C (ester and ketone), O—H?O=C (ketone) and C—H?OH hydrogen bonds exist.     

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.     

(E)‐N‐Benzyl­idene‐3‐chloro‐4‐fluoro­aniline

The title mol­ecule, C₁₃H₉ClFN, is substantially planar. The phenyl and 3‐chloro‐4‐fluoro­phenyl rings are on opposite sides of the C=N bond. There is an intermolecular C—H?F short contact with a C?F distance of 3.348 (2) Å and a C—H?F angle of 137.4 (1)°. The mol­ecules are held in layers parallel to the bc plane.     

Weak O‐Assistance Outcompeting Strong N,N‐Bidentate Directing Groups in Copper‐Catalyzed C−H Chalcogenation

A copper‐mediated C?H chalcogenation of triazoles has been achieved by weak coordination. The user‐friendly protocol showed high functional‐group tolerance and ample substrate scope, yielding fully substituted 1,2,3‐triazoles with complete positional site‐selectivity. The C?H selenylation could likewise be achieved by means of copper catalysis. Our findings highlight for the first time that weak O‐coordination can outcompete the strong N,N‐bidentate coordination mode in C?H functionalization technology.     

1,4‐Iron Migration for Expedient Allene Annulations through Iron‐Catalyzed C−H/N−H/C−O/C−H Functionalizations

C?H activation bears great potential for enabling sustainable molecular syntheses in a step‐ and atom‐economical manner, with major advances having been realized with precious 4d and 5d transition metals. In contrast, we employed earth abundant, nontoxic iron catalysts for versatile allene annulations through a unique C?H/N?H/C?O/C?H functionalization sequence. The powerful iron catalysis occurred under external‐oxidant‐free conditions even at room temperature, while detailed mechanistic studies revealed an unprecedented 1,4‐iron migration regime for facile C?H activations.     

2‐Iodo‐N‐(3‐nitrobenzyl)aniline and 3‐iodo‐N‐(3‐nitrobenzyl)aniline exhibit entirely different patterns of supramolecular aggregation

In 2‐iodo‐N‐(3‐nitro­benzyl)­aniline, C₁₃H₁₁IN₂O₂, the mol­ecules are linked into a three‐dimensional structure by a combination of C—H?O hydrogen bonds, iodo–nitro interactions and aromatic π–π‐stacking interactions, but N—H?O and C—H?π(arene) hydrogen bonds are absent. In the isomeric 3‐iodo‐N‐(3‐nitro­benzyl)­aniline, a two‐dimensional array is generated by a combination of N—H?O, C—H?O and C—H?π(arene) hydrogen bonds, but iodo–nitro interactions and aromatic π–π‐stacking interactions are both absent.     

Iron‐Carbonyl‐Catalyzed Redox‐Neutral [4+2] Annulation of N−H Imines and Internal Alkynes by C−H Bond Activation

Stoichiometric C?H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C?H transformations have not been developed. Herein, an iron‐catalyzed annulation of N?H imines and internal alkynes to furnish cis‐3,4‐dihydroisoquinolines is described, and represents the first iron‐carbonyl‐catalyzed C?H activation reaction of arenes. Remarkablely, this is also the first redox‐neutral [4+2] annulation of imines and alkynes proceeding by C?H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C?H bond activation to afford a dinuclear ferracycle and a synergetic diiron‐promoted H‐transfer to the alkyne as the turnover‐determining step.     

4‐Ethynyl‐4‐hydroxycyclohexan‐1‐one and 4‐ethynyl‐4‐hydroxy‐2,3,5,6‐tetramethylcyclohexa‐2,5‐dien‐1‐one

The title compounds, C₈H₁₀O₂, (I), and C₁₂H₁₄O₂, (II), occurred as by‐products in the controlled synthesis of a series of bis­(gem‐alkynols), prepared as part of an extensive study of synthon formation in simple gem‐alkynol derivatives. The two 4‐(gem‐alkynol)‐1‐ones crystallize in space group P2₁/c, (I) with Z′ = 1 and (II) with Z′ = 2. Both structures are dominated by O—H?O=C hydrogen bonds, which form simple chains in the cyclo­hexane derivative, (I), and centrosymmetric dimers, of both symmetry‐independent mol­ecules, in the cyclo­hexa‐2,5‐diene, (II). These strong synthons are further stabilized by C[triple‐bond]C—H?O=C, C_methylene—H?O(H) and C_methyl—H?O(H) interactions. The direct intermolecular interactions between donors and acceptors in the gem‐alkynol group, which characterize the bis­(gem‐alkynol) analogues of (I) and (II), are not present in the ketone derivatives studied here.     

1,4,4‐Tri­methyl‐9‐phenyl‐8‐oxa‐9‐aza­bi­cyclo­[3.2.2]­non‐6‐en‐2‐one

The structure of the adduct of eucarvone with nitro­so­benzene, C₁₆H₁₉NO₂, is reported. The [3.2.2] bicyclic system corresponds to two seven‐membered rings in boat and distorted chair conformations and a six‐membered ring that adopts a distorted boat conformation. No conjugation is observed between the phenyl group and the N—O system. The packing is directed mainly by a C?O hydrogen bond, C—H?O‐(1 ? x, ?y, z) and by intermolecular C—H?π interactions.     

C[triple‐bond]C—H⋯N hydrogen bonding in 3‐methylthio‐4‐propargylthioquinoline

The title compound, C₁₃H₁₁NS₂, contains a C[triple‐bond]C—H?N hydrogen bond to a pyridine‐type N atom, with a C?N distance of 3.305 (4) Å and an H?N distance of 2.28 Å. This is one of the shortest C—H?N hydrogen bonds known.     

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.     

The Effect of C4H and C5H on the Microstructure of Aqueous Solutions of 1‐Alkyl‐3‐methylimidazolium Tetrafluoroborate Ionic Liquids

As is well‐known, the C2?H proton of 1‐ethyl‐3‐methylimidazolium tetrafluoroborate ([Emim]BF₄) and 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([Bmim]BF₄) has a strong ability to form hydrogen bonds. The purpose of this work is to evaluate the effect of the interactions of the C4?H and C5?H protons on the microstructure of [Emim]BF₄ and [Bmim]BF₄ with water by using ¹H NMR spectroscopy. The differences between the relative ¹H NMR chemical shifts of C2?H, C4?H, and C5?H and between the interaction‐energy parameters obtained from these chemical shifts are minor, thus suggesting that the interactions of C4?H and C5?H may have a considerable effect on the microstructure. To confirm this, the viscosities of the systems are estimated by using the interaction‐energy parameters obtained from the ¹H NMR chemical shifts of the three studied aromatic protons and water, showing that the interactions of C4?H and C5?H also play an important role in the microstructure.     

C−H Acetoxylation‐Based Chemical Synthesis of 17 β‐Hydroxymethyl‐17 α‐methyl‐18‐norandrost‐13‐ene Steroids

Palladium‐catalyzed C?H acetoxylation has been proposed as a key transformation in the first chemical synthesis of steroids bearing a unique 17β‐hydroxymethyl‐17α‐methyl‐18‐nor‐13‐ene D ‐fragment. This C?H functionalization step was crucial for inverting the configuration at the quaternary stereocenter of a readily available synthetic intermediate. The developed approach was applied to prepare the metandienone metabolite needed as a reference substance in anti‐doping analysis to control the abuse of this androgenic anabolic steroid.     

Remote C−H Activation of Quinolines through Copper‐Catalyzed Radical Cross‐Coupling

Achieving site selectivity in carbon–hydrogen (C?H) functionalization reactions is a formidable challenge in organic chemistry. Herein, we report a novel approach to activating remote C?H bonds at the C5 position of 8‐aminoquinoline through copper‐catalyzed sulfonylation under mild conditions. Our strategy shows high conversion efficiency, a broad substrate scope, and good toleration with different functional groups. Furthermore, our mechanistic investigations suggest that a single‐electron‐transfer process plays a vital role in generating sulfonyl radicals and subsequently initiating C?S cross‐coupling. Importantly, our copper‐catalyzed remote functionalization protocol can be expanded for the construction of a variety of chemical bonds, including C?O, C?Br, C?N, C?C, and C?I. These findings provide a fundamental insight into the activation of remote C?H bonds, while offering new possibilities for rational design of drug molecules and optoelectronic materials requiring specific modification of functional groups.