Selective Functionalization of Aromatic C(sp2)−H Bonds in the Presence of Benzylic C(sp3)−H Bonds by Electron‐Deficient Carbenoids Generated from 4‐Acyl‐1‐Sulfonyl‐1,2,3‐Triazoles

A rhodium(II)‐catalyzed reaction of newly prepared 4‐acyl‐1‐sulfonyl‐1,2,3‐triazoles with benzene, and its derivatives, is investigated. Acceptor/acceptor carbenoids generated from 4‐acyltriazoles undergo selective insertion at aromatic C(sp²)−H bonds in the presence of benzylic C(sp³)−H bonds to produce N ‐sulfonylenaminones.     

Rhodium‐Catalyzed Defluorinative Vinylation of gem‐Difluoroalkenes for the Synthesis of 2‐Fluoro‐1,3‐dienes

Herein, we present a strategy for the formation of 2‐fluoro‐1,3‐diene derivatives via rhodium‐catalyzed direct C(sp²)—C(sp²) cross‐coupling of gem‐difluoroalkenes and acrylamides. By merging Rh(III)‐catalyzed C(sp²)–H bond activation and nucleophilic addition/F‐elimination of gem‐difluoroalkene, an efficient defluorinative vinylation reaction is uncovered, which leads to the generation of 2‐fluoro‐1,3‐dienes in moderate to good yields with excellent stereoselectivity under mild conditions. Preliminary mechanistic study suggests unique effects of fluorine substituents which allow the reactivity profile not observed with the congeners bearing heavier halides.     

Intramolecular Metal‐Free Oxidative Aryl–Aryl Coupling: An Unusual Hypervalent‐Iodine‐Mediated Rearrangement of 2‐Substituted N‐Phenylbenzamides

Hypervalent‐iodine‐mediated oxidative coupling of the two aryl groups in either 2‐acylamino‐N‐phenyl‐benzamides or 2‐hydroxy‐N‐phenylbenzamides, with concomitant insertion of the ortho‐substituted N or O atom into the tether, has been described for the first time. This unusual metal‐free rearrangement reaction involves an oxidative C(sp²)? C(sp²) aryl–aryl bond formation, cleavage of a C(sp²)? C(O) bond, and a lactamization/lactonization. Furthermore, unsymmetrical diaryl compounds can be easily obtained by removing the tether within the cyclized product.     

Redox‐Neutral Coupling between Two C(sp3)−H Bonds Enabled by 1,4‐Palladium Shift for the Synthesis of Fused Heterocycles

The intramolecular coupling of two C(sp³)?H bonds to forge a C(sp³)?C(sp³) bond is enabled by 1,4‐Pd shift from a trisubstituted aryl bromide. Contrary to most C(sp³)?C(sp³) cross‐dehydrogenative couplings, this reaction operates under redox‐neutral conditions, with the C?Br bond acting as an internal oxidant. Furthermore, it allows the coupling between two moderately acidic primary or secondary C?H bonds, which are adjacent to an oxygen or nitrogen atom on one side, and benzylic or adjacent to a carbonyl group on the other side. A variety of valuable fused heterocycles were obtained from easily accessible ortho‐bromophenol and aniline precursors. The second C?H bond cleavage was successfully replaced with carbonyl insertion to generate other types of C(sp³)‐C(sp³) bonds.     

Amine‐Catalyzed Highly Regioselective and Stereoselective C(sp2)–C(sp2) Cross‐Coupling of Naphthols with trans‐α,β‐Unsaturated Aldehydes

A metal‐free C(sp²)–C(sp²) cross‐coupling approach to highly congested (E)‐α‐naphtholylenals from simple naphthols and enals is described. The mild reaction conditions with pyridine hydrobromideperbromide (PHBP) as the bromination reagent in the presence of piperidine or diphenylprolinol trimethylsilyl (TMS) ether as promoters enable the process in good yields and with high chemoselectivity, regioselectivity, and stereoselectivity. The process involves an unprecedented pathway of in situ regioselective 4‐bromination of 1‐naphthols and the subsequent unusual aromatic nucleophilic substitution of the resulting 4‐bromo‐1‐naphthols with the α‐C(sp²) of enals through a Michael‐type Friedel–Crafts alkylation–dearomatization followed by a cyclopropanation ring‐opening cascade process. The noteworthy features of this strategy are highlighted by the highly efficient creation of a C(sp²)–C(sp²) bond from readily available unfunctionalized naphthols and enals catalyzed by non‐metal, readily available cyclic secondary amines under mild reaction conditions.     

Surface oxidation process of a diamond‐like carbon film analyzed by difference X‐ray photoelectron spectroscopy

Difference X‐ray photoelectron spectroscopy (D‐XPS) revealed the surface oxidation process of a diamond‐like carbon (DLC) film. Evaluation of surface functional groups on DLC solely by the C 1s spectrum is difficult because the spectrum is broad and has a secondary asymmetric lineshape. D‐XPS clarified the subtle but critical changes at the DLC surface caused by wet oxidation. The hydroxyl (C―OH) group was dominant at the oxidized surface. Further oxidized carbonyl (C?O) and carboxyl (including carboxylate) (COO) groups were also obtained; however, the oxidation of C?O to COO was suppressed to some extent because the reaction required C―C bond cleavage. Wet oxidation cleaved the aliphatic hydrogenated and non‐hydrogenated sp² carbon bonds (C―H sp² and C―C sp²) to create a pair of C―OH and hydrogenated sp³ carbon (C―H sp³) bonds. The reaction yield for C―H sp² was superior at the surface, suggesting that the DLC film was hydrogen rich at the surface. Oxidation of aromatic sp² rings or polycyclic aromatic hydrocarbons such as nanographite to phenols did not occur because of their resonance stabilization with electron delocalization. Non‐hydrogenated sp³ carbon (C―C sp³) bonds were not affected by oxidation, suggesting that these bonds are chemically inert. Copyright © 2014 John Wiley & Sons, Ltd.     

Transition‐metal‐free Chemoselective Oxidative C−C Coupling of the sp3 C−H Bond of Oxindoles with Arenes and Addition to Alkene: Synthesis of 3‐Aryl Oxindoles,and Benzofuro‐ and Indoloindoles

A transition‐metal (TM)‐free and halogen‐free NaOt Bu‐mediated oxidative cross‐coupling between the sp³ C−H bond of oxindoles and sp² C−H bond of nitroarenes has been developed to access 3‐aryl substituted and 3,3‐aryldisubstituted oxindoles in DMSO at room temperature in a short time. Interestingly, the sp³ C−H bond of oxindoles could also react with styrene under TM‐free conditions for the practical synthesis of quaternary 3,3‐disubstituted oxindoles. The synthesized 3‐oxindoles have also been further transformed into advanced heterocycles, that is, benzofuroindoles, indoloindoles, and substituted indoles. Mechanistic experiments of the reaction suggests the formation of an anion intermediate from the sp³ C−H bond of oxindole by tert ‐butoxide base in DMSO. The addition of nitrobenzene to the in‐situ generated carbanion leads to the 3‐(nitrophenyl)oxindolyl carbanion in DMSO which is subsequently oxidized to 3‐(nitro‐aryl) oxindole by DMSO.     

A study of the planarity of the pyrrolone fragment in 2‐isopropyl‐2,3‐dihydro‐1H‐isoindol‐1‐one

Orthophthalaldehyde (o‐phthalaldehyde, OPA) is an aromatic dialdehyde bearing two electron‐withdrawing carbonyl groups. The reactions of OPA with primary amines are broadly applied for the synthesis of important heterocyclic compounds with biological relevance. A number of such reactions have been investigated recently and several structures of condensation products have been reported, however, the complex reaction mechanism is still not fully understood and comprises concurrent as well as consecutive reactions. The reaction products depend on the primary amine which reacts with OPA, the reaction environment (solvent) and the proportion of the reactants. The title molecule, C₁₁H₁₃NO, the product of the reaction of OPA with isopropylamine, contains a five‐membered pyrrole C₄N ring with a carbonyl substituent, which forms part of the isoindolinone unit. Though this pyrrole ring contains one C atom in the sp³‐hybridized state, it is fairly planar. The title molecule has been compared with similar structures retrieved from the Cambridge Structural Database in order to study this phenomenon. The planarity of this fragment has been explained by the presence of partially delocalized C—C, C—N and C—O bonds, and by an inner angle in the planar pentagonal ring (∼108°), which is close to the ideal tetrahedral value for the sp³‐hybridized state of the constituent C atom. Due to this propitious angle, this C atom can be present in states intermediate between sp³‐ and sp²‐hybridized in different structures, while still maintaining the planarity of the ring. There are only weak intermolecular C—H…O hydrogen bonds and C—H…π‐electron ring interactions in the structure. In particular, it is the pyrrole ring which is involved in these interactions.     

Gas‐phase functionalized carbon‐carbon coupling reactions catalyzed by Ni (II) complexes

Gas‐phase C―C coupling reactions mediated by Ni (II) complexes were studied using a linear quadrupole ion trap mass spectrometer. Ternary nickel cationic carboxylate complexes, [(phen)Ni (OOCR¹)]⁺ (where phen = 1,10‐phenanthroline), were formed by electrospray ionization. Upon collision‐induced dissociation (CID), they extrude CO₂ forming the organometallic cation [(phen)Ni(R¹)]⁺, which undergoes gas‐phase ion‐molecule reactions (IMR) with acetate esters CH₃COOR² to yield the acetate complex [(phen)Ni (OOCCH₃)]⁺ and a C―C coupling product R¹‐R². These Ni(II)/phenanthroline‐mediated coupling reactions can be performed with a variety of carbon substituents R¹ and R² (sp³, sp², or aromatic), some of them functionalized. Reaction rates do not seem to be strongly dependent on the nature of the substituents, as sp³‐sp³ or sp²‐sp² coupling reactions proceed rapidly. Experimental results are supported by density functional theory calculations, which provide insights into the energetics associated with the C―C bond coupling step.     

Di‐tert‐Butyl Peroxide‐Mediated Atom‐Transfer Radical Addition of 2‐Chlorodithiane to Aryl Alkynes under Mild Conditions

Atom transfer radical addition (ATRA) of 2‐chlorodithiane onto aryl alkynes through the use of di‐tert‐butyl peroxide as an oxidant at room temperature directly affords a variety of synthetically valuable β‐chloro‐(Z)‐vinyl dithianes in good yields with high regioselectivities and without the assistance of any transition metals. It provides an operationally simple pathway to access vinyl dithianes with controlled formation of a new C(sp²)?C bond and a C(sp²)?Cl bond.     

2,5‐Bis(methylthio)‐1,4‐benzo­quinone and 2‐methyl‐3‐(methylsulfonyl)benzo[b]thiophene

The structure of 2,5‐bis­(methyl­thio)‐1,4‐benzo­quinone, C₈H₈O₂S₂, is composed of an essentially planar centrosymmetric benzo­quinone substituted with two methyl­thio groups. The important bond distances are S—Csp³ 1.788 (2) and S—Csp² 1.724 (2) Å, and the two Csp²—Csp² distances are 1.447 (3) and 1.504 (3) Å, which differ significantly. There are short S?S interactions of 3.430 (1) Å and Csp²—H?O‐type contacts forming a dimeric motif with graph set R₂²(8). The structure of 2‐methyl‐3‐(methyl­sulfonyl)­benzo­[b]­thio­phene, C₁₀H₁₀O₂S₂, is composed of an essentially planar benzo­thio­phene moiety substituted with methyl and methyl­sulfonyl groups. The mean values of the important bond distances are endocyclic S—Csp² 1.734 (3), S=O 1.434 (4) and C—C_aromatic 1.389 (10) Å. The exocyclic S—Csp² and S—Csp³ distances are 1.759 (4) and 1.763 (5) Å, respectively.     

TMSCl Promoted Direct sp3 C‐H Alkenylation to Construct (E)‐2‐Styryl‐tetrahydrobenzo[d]thiazoles

A high‐efficient and stereo‐specific approach for the preparation of biologically important (E)‐2‐styryl‐tetrahydrobenzo[d]thiazoles has been developed via TMSCl promoted direct sp³ C‐H alkenylation of 2‐methyl‐5,6‐dihydrobenzo[d]thiazol‐7(4H)‐one under metal‐free conditions. Seventeen target compounds were synthesized in excellent yields of 82% –98% under the optimal conditions of 300 mol% TMSCl at 110°C for 2 h, and their chemical structures were elucidated by IR, NMR, ESI‐MS, elemental analyses and X‐ray crystallography analysis. A plausible mechanism was also proposed, and this method provided a good functional group conversion for the sp³ C‐H substrates.     

Metal‐Free Radical [2+2+1] Carbocyclization of Benzene‐Linked 1,n‐Enynes: Dual C(sp3)?H Functionalization Adjacent to a Heteroatom

A new metal‐free oxidative radical [2+2+1] carbocyclization of benzene‐linked 1,n‐enynes with two C(sp³) H bonds adjacent to the same heteroatom is described. This method achieves two C(sp³) H oxidative functionalizations and an annulation, thus providing efficient and general access to a variety of fused five‐membered carbocyclic hydrocarbons.     

3,17‐Dioxoandrost‐4‐en‐4‐yl acetate

The title compound, C₂₁H₂₈O₄, has a 4‐acetoxy substituent positioned on the steroid α face. The six‐membered ring A assumes a conformation intermediate between 1α,2β‐half chair and 1α‐sofa. A long Csp³—Csp³ bond is observed in ring B and reproduced in quantum‐mechanical ab initio calculations of the isolated molecule using a molecular‐orbital Hartree–Fock method. Cohesion of the crystal can be attributed to van der Waals interactions and weak C—H...O hydrogen bonds.     

Visible‐Light‐Driven Palladium‐Catalyzed Radical Alkylation of C−H Bonds with Unactivated Alkyl Bromides

Reported herein is a novel visible‐light photoredox system with Pd(PPh₃)₄ as the sole catalyst for the realization of the first direct cross‐coupling of C(sp³)−H bonds in N‐aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra‐ and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp³)−C(sp³) and C(sp²)−C(sp³) bonds in moderate to excellent yields. These redox‐neutral reactions feature broad substrate scope (>60 examples), good functional‐group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible‐light photocatalyst and radicals are involved in the process.     

Transition‐Metal‐Free Deconstructive Lactamization of Piperidines

One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp³)–C(sp³) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3‐alkoxyamino‐2‐piperidones, which were prepared from piperidines through a dual C(sp³)–H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3‐alkoxyamino‐2‐piperidones to 3‐keto‐2‐piperidones, followed by a regioselective Baeyer–Villiger oxidation to give N‐carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.     

Regioselective Ruthenium‐Catalyzed Carbonylative Direct Arylation of Five‐Membered and Condensed Heterocycles

A ruthenium‐catalyzed carbonylative C?H bond arylation process for the three‐component synthesis of complex aryl–(hetero)aryl ketones in an aqueous solution has been developed. By exploiting the ortho‐activating effect of nitrogen‐containing directing groups, a regioselective, successive twofold C(sp²)?C(sp²) bond formation has been achieved. This straightforward catalytic process provides access to versatile products prevalent in multiple bioactive compounds and supplies a valuable functional group for subsequent transformations.     

(2S,3S)‐2,6‐Dimethylheptane‐1,3‐diol,the oxygenated side chain of 22(S)‐hydroxycholestrol,and its synthetic precursor (R)‐4‐benzyl‐3‐[(2R,3S)‐3‐hydroxy‐2,6‐dimethylheptanoyl]‐1,3‐oxazolidin‐2‐one

(2S,3S)‐2,6‐Dimethylheptane‐1,3‐diol, C₉H₂₀O₂, (I), was synthesized from the ketone (R)‐4‐benzyl‐3‐[(2R,3S)‐3‐hydroxy‐2,6‐dimethylheptanoyl]‐1,3‐oxazolidin‐2‐one, C₁₉H₂₇NO₄, (II), containing C atoms of known chirality. In both structures, strong hydrogen bonds between the hydroxy groups form tape motifs. The contribution from weaker C—H...O hydrogen bonds is much more evident in the structure of (II), which furthermore contains an example of a direct short Osp³...Csp² contact that represents a usually unrecognized type of intermolecular interaction.     

Radical Cation Salt‐initiated Aerobic C−H Phosphorylation of N‐Benzylanilines: Synthesis of α‐Aminophosphonates

A radical cation salt‐initiated phosphorylation of N‐benzylanilines was realized through an aerobic oxidation of the sp³ C?H bond, providing a series of α‐aminophosphonates in high yields. An investigation of the reaction scope revealed that this mild catalyst system is superior in good functional group tolerance and high reaction efficiency. The mechanistic study implied that the cleavage of the sp³ C?H bond was involved in the rate‐determining step.     

Cu‐Catalyzed [4+1] Annulation toward Indolo[2,1‐a]isoquinolines through Oxidative C(sp3)/C(sp2)−H Bond Bifunctionalization

A Cu‐catalyzed [4+1] annulation of N‐aryl‐1,2,3,4‐tetrahydroisoquinolines (N‐aryl THIQs) with α‐diazoketones has been established under oxidative conditions, leading to the construction of a series of indolo[2,1‐a]isoquinolines with generally good yields. The reaction enables dediazotized dicarbonylation of α‐diazoketones, creating direct C(sp³)/C(sp²)?H bond bifunctionalization to access tetracyclic aza‐heterocyclic skeletons.