Bond Activation Strategy Research Articles

Selective Access of Deuterated Dibenzo‐Fused ϵ‐Lactones and ϵ‐Lactams via Palladium Carbene Migratory Insertion Enabled 1,4‐Pd Shift

AbstractSince deuterated compounds have significant applications in pharmaceutical chemistry, selective incorporation of deuterium atoms onto a pharmacophore containing compounds has attracted great attention. Herein, we describe a concise method for construction of deuterated dibenzo‐fused ϵ‐lactones and ϵ‐lactams via Pd‐catalyzed carbene bridging C−D bond activation strategy. Readily available deuterated ortho‐bromobenzaldehydes were employed as reactants, and deuterium atom was selectively incorporated at the dibenylic position with high deuterated ratio.

Catalytic Net Oxidative C-C Activation and Silylation of Cyclopropanols with a Traceless Acetal Directing Group.

Redox-neutral carbon-carbon (C-C) bond activation and functionalization strategies of cyclopropanols that give metallo homoenolate have offered merits to construct a range of useful β-functionalized ketones in an inverse-polarity fashion. Discovery and identification of oxidative C-C activation reactions of cyclopropanols that generate metallo enolate-homoenolate would provide an opportunity to afford α,β-difunctionalized ketones. We report catalytic, net oxidative C-C activation, and silylation of cyclopropanols with traceless acetal directing groups under consecutive Ir and Rh catalysis in regio-, stereo-, and chemo-selective fashion. In detail, Ir-catalyzed hydrosilylation of cyclopropyl acetates provides the acetal directing group in quantitative yield. Rh-catalyzed proximal C-C silylation of the resulting cyclopropyl silyl acetal produces the metallo enolate-homoenolate equivalent, dioxasilepine, which uniquely holds an interconnected β-silyl moiety and Z-vinyl acetal. Upon sequential treatment of a silaphile that removes the acetal directing group and electrophile, the seven-membered silicon-containing heterocycle, serving as the ketone α,β-dianion equivalent, delivers α,β-difunctionalized ketones. Scope of the hitherto unexplored reactivity of cyclopropanols toward net oxidative C-C silylation and the versatility of the resulting dioxasilepines were demonstrated. These include late-stage, net oxidative C-C silylation of biologically relevant molecules and facile production of a range of α,β-difunctionalized ketones. Preliminary mechanistic studies suggest that the C-C activation harnessing the electron-rich Wilkinson-type catalyst is likely the turnover-determining step and a Rh-π interaction is the key to the efficient metal insertion to the proximal C-C bond in cyclopropanols.

Redox-active and Brønsted basic dual sites for photocatalytic activation of benzylic C–H bonds based on pyridinium derivatives

A mild and efficient photocatalytic C–H bond activation strategy has been developed by combining redox-active and Brønsted basic dual sites to offer a concerted pathway for H abstraction through concomitant proton and electron transfer.

Recent Developments in Hydrodecyanation and Decyanative Functionalization Reactions

AbstractNitrile is one of the ubiquitous functional groups in natural products and polymer industry. It is often used as a versatile building block in synthetic chemistry. Classically, nitrile group is used for alpha functionalization, ortho−C−H activation and as a precursor for amine or carbonyl functionalities. With the development of various transition metal catalyzed methods, in the last two decades, nitrile group has emerged as a source of carbon synthons through C−CN bond activation despite of its high bond energy. In this review we have summarized all recent developments involving the carbon synthons arising from the cleavage of C−CN bonds. Depending on the fate of the carbon center after cleavage, all the reactions are classified in two major categories for the ease of discussion: 1) decyanation (removal of the nitrile group) and 2) decyanative functionalization (replacement of the nitrile group). Finally, current limitations in C−CN bond activation strategies and future prospects are discussed.

Metal‐Free Synthesis of Diarylmethanes through Visible‐Light Induced Radical Reactions with Arylamines

AbstractAn efficient method for synthesis of diarylmethanes with arylamines by using a transition‐metal free photo‐induced radical Csp3‐H bond activation strategy has been achieved. This protocol proceeds under mild reaction condition and represents the first metal‐free radical strategy for synthesis of diarylmethanes with arylamines. The control experiments illustrated that the methylene radical involved in this process and play an important role in this reaction

Alkoxyl-radical-mediated synthesis of functionalized allyl tert-(hetero)cyclobutanols and their ring-opening and ring-expansion functionalizations

tert -(Hetero)cyclobutanols are important synthetic building blocks. However, previous synthesis of these compounds has mainly focused on the nucleophilic addition of organometallic reagents to (hetero)cyclobutanones. Herein, we disclose a single-electron process for preparing allyl tert -(hetero)cyclobutanols with readily available organosilicon reagents. The success of the reaction is attributed to the favored radical 1,2-silyl transfer over β-carbon elimination of the alkoxyl radicals. The mechanism of the generation of carbon radicals from alkoxyl radicals is distinct from previous photoredox-mediated oxidation of hypervalent silicates. Our reaction shows broad substrate scope and wide functional-group tolerance. With the highly functionalized allyl tert -(hetero)cyclobutanols, we have achieved ring-opening reactions to synthesize thiolated 1,4-diketones and ring-expansion reactions to prepare seven-membered ring compounds. • Radical 1,2-silyl transfer over β-carbon elimination of alkoxy radicals • Ring-opening and ring-expansion reactions have been achieved • Broad substrate scope and wide functional-group tolerance The selectivity of a transformations is usually controlled by the reactivity of the reactive intermediate. (Hetero)cyclobutoxyl radicals are well known to be prone to undergo β-carbon elimination to generate carbon radicals. Our work disclosed here shows that radical 1,2-silyl transfer of (hetero)cyclobutoxy radicals is favored over β-carbon elimination. This radical C–Si bond-activation strategy is applied in the synthesis of functionalized allyl tert -(hetero)cyclobutanols. These compounds are challenging to prepare via previous two-electron processes, such as the addition of Grignard reagents to (hetero)cyclobutanones. Moreover, with the highly functionalized allyl tert -(hetero)cyclobutanols, we have achieved ring-opening reactions to synthesize thiolated ketones and ring-expansion reactions to prepare seven-membered ring compounds. Shen and coworkers present a photoredox process for synthesizing allyl tert -(hetero)cyclobutanols with readily available organosilicon reagents. The favored radical 1,2-silyl transfer over β-carbon elimination of the alkoxyl radicals is key to the success of the reaction. The reaction shows broad substrate scope and wide functional-group tolerance. With the highly functionalized allyl tert -(hetero)cyclobutanols, the authors have achieved ring-opening reactions to synthesize thiolated 1,4-diketones and ring-expansion reactions to prepare seven-membered ring compounds.

Multiple Functional Organocatalyst-Promoted Inert C–C Activation: Mechanism and Origin of Selectivities

Although breakthroughs in the N-heterocyclic carbene (NHC)-catalyzed inert C–C bond activation strategy have been achieved, understanding the role of the catalyst as well as the origin of its chemo...

N-Tosylhydrazone as an oxidizing directing group for the redox-neutral access to isoquinolines via Cp∗Co(III)-Catalyzed C–H/N–N activation

Herein, an efficient and economic access has been revealed for the synthesis of isoquinolines via C–H bond activation strategy by using comparatively inexpensive and versatile cobalt catalyst. A hardly investigated directing group, N-tosylhydrazone has been effectively applied as an internal oxidant for an annulation reaction with internal alkynes via C–H/N–N bond functionalization. This catalytic protocol works for the extensive variety of substrates in moderate to excellent yields under external oxidant-free conditions. Additionally, the proposed protocol has advantages such as broad substrate coverage with significant product yields, readily synthesized substrates as well as scalability up to the gram quantity which further improves the competency of the methodology.

Pd(II)-Catalyzed oxidative alkenylation of 4-hydroxycoumarin with maleimide via a C-H bond activation strategy.

A Pd(ii)-catalyzed oxidative alkenylation of 4-hydroxycoumarins with maleimides for the synthesis of 4-hydroxy-3-maleimidecoumarins has been described. This methodology proceeds via C-H activation and C(sp2)-C(sp2) bond formation providing a series of alkenylated Heck-type products.

Manganese-Catalyzed N-F Bond Activation for Hydroamination and Carboamination of Alkenes.

A visible-light-promoted method for generating amidyl radicals from N-fluorosulfonamides via a manganese-catalyzed N-F bond activation strategy is reported. This protocol employs a simple manganese complex, Mn2(CO)10, as the precatalyst and a cheap silane, (MeO)3SiH, as both the hydrogen-atom donor and the F-atom acceptor, enabling intramolecular/intermolecular hydroaminations of alkenes, two-component carboamination of alkenes, and even three-component carboamination of alkenes. A wide range of valuable aliphatic sulfonamides can be readily prepared using these practical reactions.

Regioselective C-H Alkenylation and Unsymmetrical Bis-olefination of Heteroarene Carboxylic Acids with Ruthenium Catalysis in Water.

An efficient weak carboxylate-assisted oxidative cross-dehydrogenative C-H/C-H coupling (CDC) of heteroarenes with readily available olefins has been devised employing water as green solvent under ruthenium(II) catalysis. The reaction is operationally simple, accommodates a large variety of heteroaromatic carboxylic acids as well as olefins, and facilitates a diverse array of high-value olefin-tethered heteroarenes in high yields (up to 87%). The potential of this ortho-C-H bond activation strategy has also been exploited toward tunable synthesis of densely functionalized heteroarenes through challenging unsymmetrical bis-olefination process in a one-pot sequential fashion. Mechanistic investigation demonstrates a reversible ruthenation process and C-H metalation step might not be involved in the rate-determining step.

Synthesis of C4-Substituted Indoles via a Catellani and C-N Bond Activation Strategy.

This paper describes the case of a cross study between the C-N bond cleavage reaction field and the Catellani-Lautens reaction system. A series of highly functionalized C4-substituted indoles were synthesized using this strategy. By screening the alkyl groups of amines, the energy barrier of C-N bond cleavage reaction was reduced and the corresponding allenization products were avoided. Finally, the density functional theory calculation shows that the inert C-N bond activation reaction is not a concerted process; on the contrary, the coupling reaction first generates indole quaternary ammonium salt, and then C-N bond cleavage occurs via an SN2 process.

Copper-Catalyzed Direct C-H Alkylation of Polyfluoroarenes by Using Hydrocarbons as an Alkylating Source.

Construction of carbon-carbon bonds is one of the most important tools in chemical synthesis. In the previously established cross-coupling reactions, prefunctionalized starting materials were usually employed in the form of aryl or alkyl (pseudo)halides or their metalated derivatives. However, the direct use of arenes and alkanes via a 2-fold oxidative C-H bond activation strategy to access chemoselective C(sp2)-C(sp3) cross-couplings is highly challenging due to the low reactivity of carbon-hydrogen (C-H) bonds and the difficulty in suppressing side reactions such as homocouplings. Herein, we present the new development of a copper-catalyzed cross-dehydrogenative coupling of polyfluoroarenes with alkanes under mild conditions. Relatively weak sp3 C-H bonds at the benzylic or allylic positions, and nonactivated hydrocarbons could be alkylated by the newly developed catalyst system. A moderate-to-high site selectivity was observed among various C-H bonds present in hydrocarbon reactants, including gaseous feedstocks and complex molecules. Mechanistic information was obtained by performing combined experimental and computational studies to reveal that the copper catalyst plays a dual role in activating both alkane sp3 C-H bonds and sp2 polyfluoroarene C-H bonds. It was also suggested that the noncovalent π-π interaction and weak hydrogen bonds formed in situ between the optimal ligand and arene substrates are key to facilitating the current coupling reactions.

Synthesis of Dibenzosuberones Bearing an Isoxazole Group via Palladium-Catalyzed Intramolecular C–H/C–Br Bond Cross-Coupling of Ortho-Aroylated 3,5-Diarylisoxazoles

A facile and efficient synthetic methodology for preparing dibenzosuberones via a C-H bond activation strategy is presented. The ortho-aroylated 3,5-diarylisoxazole was employed as the starting substrate to undergo palladium-catalyzed intramolecular C-H/C-Br bond cross-coupling to produce a variety of dibenzosuberones bearing an isoxazole group in 24 to >99% 1H NMR yields. The dibenzosuberone structure was further confirmed by X-ray crystallography. The developed methodology exhibits very good functional group tolerance. In addition, a rational mechanism was presented for describing the reaction process. For the prepared dibenzosuberone, the use of Mo(CO)6 as the catalyst can easily transform the isoxazole ring into the β-aminoenone group. Finally, the structure of the anticipated ring-opening product, dibenzosuberenone, bearing a β-amino-α-ketone group was secured by X-ray crystallography.

Alkylation, Annulation, and Alkenylation of Organic Molecules with Maleimides by Transition‐Metal‐Catalyzed C‐H Bond Activation

AbstractMaleimide and succinimide core moieties are present in various natural products and pharmaceuticals. In addition, these derivatives can be readily modified into biologically important organic molecules including pyrrolidines and γ‐lactams. A transition‐metal‐catalyzed chelation‐assisted functionalization of inert C−H bond of organic molecules with electrophiles or nucleophiles is one of the efficient methods to construct chemical bonds in a highly atom‐ and step‐economical manner. The present review describes the recent advances in the reaction involving maleimides with organic molecules by a chelation‐assisted inert C−H bond activation methodology. The reaction involving maleimides with organic molecules having directing groups, such as ketone, acyl, pyridyl, pyrimidyl, oxime, amide, imidate, chromone, azo, N‐sulfonyl ketimine, carboxylic acids, and aldimines, were described. The scope, limitation and mechanistic investigation of the alkylation, annulation and alkenylation reactions were discussed elaborately. This review article includes the entire report on the chemical bond‐forming reaction of maleimides with organic molecules by the C−H bond activation strategy until the end of 2018.

Electrochemical C-H bond activation via cationic iridium hydride pincer complexes.

A C-H bond activation strategy based on electrochemical activation of a metal hydride is introduced. Electrochemical oxidation of ( tBu4 PCP)IrH4 ( tBu4 PCP is [1,3-( t Bu2PCH2)-C6H3]-) in the presence of pyridine derivatives generates cationic Ir hydride complexes of the type [( tBu4 PCP)IrH(L)]+ (where L = pyridine, 2,6-lutidine, or 2-phenylpyridine). Facile deprotonation of [( tBu4 PCP)IrH(2,6-lutidine)]+ with the phosphazene base tert-butylimino-tris(pyrrolidino)phosphorane, t BuP1(pyrr), results in selective C-H activation of 1,2-difluorobenzene (1,2-DFB) solvent to generate ( tBu4 PCP)Ir(H)(2,3-C6F2H3). The overall electrochemical C-H activation reaction proceeds at room temperature without need for chemical activation by a sacrificial alkene hydrogen acceptor. This rare example of undirected electrochemical C-H activation holds promise for the development of future catalytic processes.

Hydrogen bond activation strategy for cyclic carbonates synthesis from epoxides and CO2: current state-of-the art of catalyst development and reaction analysis

ABSTRACTChemical fixation of CO2 into useful organic compounds has been attracting much attention from the viewpoint of CO2 emission reduction and energy structure reformation. A useful and widely investigated chemical utilization of CO2 is the cycloaddition of CO2 to epoxides for the synthesis of cyclic carbonates. Efforts have been paid to the design and preparation of various catalyst systems that are active and selective to the production of the desired products under mild conditions and in green processes. This article is to review the current state of the catalyst development and the experimental and theoretical analysis of reaction mechanism for the cyclic carbonate synthesis from epoxides, one of currently important reactions involving CO2 as a reactant with 100% atom economy. Particular attention is given to the catalysis of multifunctional catalyst systems such as metal- and hydrogen-bond donor (HBD)-based catalysts.

Rhenium(I)-Catalyzed ortho-C-H Addition to Bicyclic Alkenes.

Hydroarylation of bicyclic alkenes has been developed using a low-valent ReI -catalyzed, directing group-assisted C-H bond activation strategy. The addition of sodium acetate significantly improves the reaction efficiency; moreover, bicyclic alkenes such as 7-oxa and aza benzonorbornadienes worked efficiently under this reaction condition. Preliminary mechanistic studies suggest that, after the alkene insertion, the rhenacycle preferentially undergoes protonolysis rather than reductive elimination.

Rhodium(iii)-catalyzed Oxidative Coupling of N-Methoxybenzamides and Ethenesulfonyl fluoride: a C–H Bond Activation Strategy for the Preparation of 2-Aryl ethenesulfonyl fluorides and Sulfonyl fluoride Substituted γ-Lactams

The synthesis of a new class of 2-aryl ethenesulfonyl fluorides was achieved via a rhodium(iii)-catalyzed sp2 C–H bond activation strategy.

Synthesis of Benzamide Derivatives by the Reaction of Arenes and Isocyanides through a C–H Bond Activation Strategy

A carbon–carbon bond formation reaction between isocyanides and benzene derivatives is reported. In contrast to traditional cross-coupling reactions, which require aryl halides or pseudohalides, we use a palladium catalyst to generate the aryl–palladium through C–H bond activation of arenes. This method offers an attractive approach to a range of benzamides from readily accessible benzene derivatives.