Csp3 Bond Research Articles

Reductive C-O, C-N, and C-S Cleavage by a Zirconium Catalyzed Hydrometalation/β-Elimination Approach.

A zirconium catalyzed reductive cleavage of Csp3 and Csp2 carbon-heteroatom bonds is reported that makes use of a tethered alkene functionality as a traceless directing group. The reaction is successfully demonstrated on C-O, C-N, and C-S bonds and proposed to proceed via a hydrozirconation/β-heteroatom elimination sequence of an in situ formed zirconium hydride catalyst. The positional isomerization of the catalyst further enables the cleavage of homoallylic ethers and the removal of terminal allyl and propargyl groups.

Synthesis of 9-biarylfluorenes by one-pot, three-step reactions of N-tosylhydrazones, p-bromobenzeneboronic acid, and arylboronic acids

A one-pot, three-step reaction of N-tosylhydrazones, p-bromobenzeneboronic acid, and arylboronic acids is established for the synthesis of 9-biarylfluorenes. Sequential formation of Csp3–Csp2 bond and Csp2–Csp2 bonds using readily available starting materials leads to the 9-biarylfluorene products in good yields. The present transformation features a broad substrate scope and good functional group tolerance.

Planar‐Chiral [2.2]Paracyclophane‐Based Pyridonates as Ligands for Tantalum‐Catalyzed Hydroaminoalkylation

AbstractBy using planar chiral [2.2]paracyclophane‐containing N,O‐chelating ligands for tantalum‐catalyzed hydroaminoalkylation, one of the most versatile catalytic systems for this reaction to date was obtained. Convenient Csp3−Csp3 bond formation of amines with terminal and internal alkenes was enabled by the same in situ synthesized catalytic system of [2.2]paracyclophane‐based pyridonates and Ta(CH2TMS)3Cl2 that shows also very promising results for N‐containing heterocycles.

TBAB‐Catalyzed Csp3–N Bond Formation by Coupling Pyridotriazoles with Anilines: A New Route to (2‐Pyridyl)alkylamines

A new metal‐free procedure allowing Csp3–N bond formation through coupling of pyridotriazoles and weakly nucleophilic anilines has been developed. This sustainable reaction shows high tolerance towards functional groups (ketones, free alcohols) leading to 2‐picolylamine derivatives. The key to our success is the use of a catalytic amount of TBAB and water as a co‐solvent leading to the formation of pyridylalkylamine derivatives. As this coupling tolerates the presence of Csp2–Br bond on both partners of the reaction, we performed a sequential one‐pot reaction between functionalized triazolopyridines and anilines followed by a second coupling with N‐tosylhydrazones leading to the formation of Csp3–N and Csp2–Csp2 bonds.

Chiral Anion‐Induced Catalytic Asymmetric Direct Dehydrative Coupling of 3‐Vinylindoles and 3‐Indolylmethanols

AbstractThe catalytic direct dehydrative coupling of an alkene with an alcohol is one of the most straightforward and green strategies for the formation of Csp2−Csp2 bonds. However, previously reported studies have only dealt with achiral reactions. Here, we describe chiral Brønsted acid‐catalyzed direct catalytic asymmetric dehydrative coupling reactions of 3‐vinylindoles and 3‐indolylmethanols. Various structurally diverse indole compounds were prepared in good to excellent yields, with good to excellent stereoselectivities.magnified image

Tandem Remote Csp3–H Activation/Csp3–Csp3 Cleavage in Unstrained Aliphatic Chains Assisted by Palladium(II)

We report here a proof-of-concept for the cleavage of unstrained remote Csp3–Csp3 bonds at room temperature assisted by a directing group, opening up new possibilities to use aliphatic carboxylic acids as suitable alkenyl coupling partners. This strategy involves the Pd-mediated Csp3–H activation directed by a tethered 8-aminoquinoline group, followed by a concerted asynchronous carbene insertion into the Pd–C bond, and an unexpected β-carbon–carbon bond splitting. The insertion of a coupling partner into a Pd–C bond is a novel route to promote C–C bond cleavage, which in contrast to most common methodologies does not rely on the use of strained carbocycles.

Selective bonding effect on microstructure and mechanical properties of (Al,N)-DLC composite films by ion beam-assisted cathode arc evaporation

Using weak-carbide metal Al and carbide non-metal N elements as co-dopant, (Al,N)-DLC composite films were prepared by DC- and pulse cathode arc technique. Microstructure, compositions, morphology and mechanical properties of (Al,N)-DLC films were investigated in the dependence of pulse frequency and target current by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force microscopy, nanoindentation, surface profilometer and nano-scratch. Raman and XPS results showed that the size of Csp2 clusters decreases and the content of Csp3 bonds increases for the (Al,N)-DLC films at the low pulse frequency with low target current or the high target current with high frequency. The contents of C–N and N–sp3C bonds increase with the target current increases. The (Al,N)-DLC films at higher target current contained a high content of N atoms and Al–N bonds. Low pulse frequency with high target current improved the hardness and toughness of (Al,N)-DLC films corresponding to the variation of microstructure parameters (the size and ordering of Csp2 clusters) and compositions (N–sp3C and Al–N bonds).

Ta-Catalyzed Hydroaminoalkylation of Alkenes: Insights into Ligand-Modified Reactivity Using DFT

Density functional theory (DFT) calculations were performed to probe the mechanism of tantalum-catalyzed hydroaminoalkylation, a reaction that affords Csp3–Csp3 bond formation via α-alkylation of a secondary amine with an alkene. Electronic effects in catalyst design were probed to reveal key features in the energy profile of the proposed mechanism, corroborating experimental trends in which electrophilic metal centers demonstrate enhanced reactivity. Modeling of the energy profile with an N,O-chelating amidate Ta catalyst (I) revealed profound differences in relative energetics, rationalizing improvements that have been observed using sterically and electronically varied ligands. N,O-Chelating ligands electronically promote preferential reactivity in the equatorial plane. The turnover-limiting step can be completely changed depending upon the ligand; for sterically bulky monoamidate complexes, the protonolysis of an intermediate metallacycle is the turnover-limiting step rather than C–H activation, as ha...

Environmentally Benign Metal-Free Reduction of GO Using Molecular Hydrogen: A Mechanistic Insight.

A simple yet effective methodology to obtain high-quality reduced graphene oxide (RGO) using a tetrahydrofuran suspension of GO under hydrogen at moderate pressure has been demonstrated. The extent of reduction as a function of the pressure of hydrogen gas, temperature, and time was studied, where the abstraction of oxygen is achievable with least mutilation of C-sp2 bonds, hence upholding the integrity of the graphene sheet. Herein, the formation of a short-lived species is proposed, which is possibly responsible for such reduction. A detailed theoretical calculation along with in situ UV–visible experiments reveals the existence of a transient solvated electron species in the reaction medium. The hydrogen RGO (HRGO) achieved a C/O atomic ratio of 11.3. The conductivity measurements show that HRGO reached as high as 934 S/m, which indicates a high quality of RGO. The process is hassle-free, environmentally benign, and can be scaled up effortlessly without compromising the quality of the material.

Metal‐Free Csp−Csp and Csp−Csp3 Bond Cleavages of N,S‐Enynes toward Thiophene‐Fused N‐Heterocycles

AbstractAlkylthio‐functionalized, o‐anilide‐embedded enynes, that is, N,S‐1,6‐enynes, were efficiently reacted with elemental sulfur to afford thiophene‐fused N‐heterocycles. The one‐pot sulfur incorporation/cascade cyclization strategy offers a straightforward route to 4H‐thieno[3,2‐b]indoles and thieno[3,4‐c]quinoline‐4(5H)‐thiones through the tunable Csp−Csp and Csp−Csp3 bond cleavages of the N,S‐1,6‐enynes, forming both a N‐heterocycle and a fused thiophene ring. The five‐ring π systems azacyclopenta[f,g]tetracene scaffolds were also obtained from the cascade cyclization of 2‐halogen‐functionalized thieno[3,4‐c]quinoline‐4(5H)‐thiones. The present synthetic protocol avoids use of prefunctionalized indole and thiophene derivatives as the building blocks for the construction of thiophene‐fused N‐heterocycles under metal‐free conditions.magnified image

Formal enantioconvergent substitution of alkyl halides via catalytic asymmetric photoredox radical coupling

Classic nucleophilic substitution reactions (SN1 and SN2) are not generally amenable to the enantioselective variants that use simple and racemic alkyl halide electrophiles. The merging of transition metal catalysis and radical chemistry with organometallic nucleophiles is a versatile method for addressing this limitation. Here, we report that visible light-driven catalytic asymmetric photoredox radical coupling can act as a complementary and generic strategy for the enantioconvergent formal substitution of alkyl haldies with readily available and bench-stable organic molecules. Single-electron reductive debrominations of racemic α-bromoketones generate achiral alkyl radicals that can participate in asymmetric Csp3–Csp3 bonds forming cross-coupling reactions with α-amino radicals derived from N-aryl amino acids. A wide range of valuable enantiomerically pure β2- and β2,2-amino ketones were obtained in satisfactory yields with good-to-excellent enantioselectivities by using chiral phosphoric acid catalysts to control the stereochemistry and chemoselectivity. Fluoro-hetero-quaternary and full-carbon quaternary stereocenters that are challenging to prepare were successfully constructed.

Visible Light Mediated, Redox Neutral Remote 1,6-Difunctionalizations of Alkenes

A photoinduced cascade strategy is presented here for the remote functionalization of alkenes under redox neutral conditions. A broad portfolio of alkyl groups has been added to double bonds to produce, upon 1,5-HAT, remote C-centered radicals which can be harvested in the presence of O- or C-nucleophiles to efficiently form Csp3–O and Csp3–Csp2 bonds at room temperature.

Ketone C–C Bond Activation Meets the Suzuki-Miyaura Cross-coupling

In a recent issue of the Journal of the American Chemical Society, Dong and coworkers report that ketones can participate as electrophiles in the Suzuki-Miyaura cross-coupling reaction under Rh(I) catalysis. They show that activation of C–C bonds of unstrained ketones is a versatile process that can engage in cross-coupling reaction with aryl boronates.

Catalytic and Atom-Economic Csp3 -Csp3 Bond Formation: Alkyl Tantalum Ureates for Hydroaminoalkylation.

Atom-economic and regioselective Csp3 -Csp3 bond formation has been achieved by rapid C-H alkylation of unprotected secondary arylamines with unactivated alkenes. The combination of Ta(CH2 SiMe3 )3 Cl2 , and a ureate N,O-chelating-ligand salt gives catalytic systems prepared in situ that can realize high yields of β-alkylated aniline derivatives from either terminal or internal alkene substrates. These new catalyst systems realize C-H alkylation in as little as one hour and for the first time a 1:1 stoichiometry of alkene and amine substrates results in high yielding syntheses of isolated amine products by simple filtration and concentration.

Pd-Catalyzed reductive heck reaction of olefins with aryl bromides for Csp2-Csp3 bond formation.

We developed a Pd-catalyzed intermolecular reductive Heck reaction to construct Csp2-Csp3 bonds between aryl bromides and olefins. Various styrene derivatives, acyclic and cyclic alkenes, were well tolerated to couple with varied aryl bromides in linear selectivity. Kinetic and deuterium labeling experiments suggested that i-PrOH provides a hydride through β-H elimination.

Csp2-Csp2 and Csp2-N Bond Formation in a One-Pot Reaction between N-Tosylhydrazones and Bromonitrobenzenes: An Unexpected Cyclization to Substituted Indole Derivatives.

A novel, sequential, palladium-catalyzed, cross-coupling reaction using N-tosylhydrazone and bromonitrobenzene derivatives followed by reductive cyclization has been developed. This transformation providing an efficient route to unexpected N-arylindole derivatives involves, in a one-pot reaction, the formation of one Csp2-Csp2 bond and two Csp2-N bonds together with the cleavage of one Csp2-heteroatom bond. Evaluation of the biological activity led to the identification of compound 5a, which displays potent activity at nanomolar concentrations against human colon carcinoma cell line.

Transition-Metal-Free Cleavage of CO.

Tertiary silane 1H, 2‐[(diphenylsilyl)methyl]‐6‐methylpyridine, reacts with tris(pentafluorophenyl)borane (BCF) to form the intramolecular pyridine‐stabilized silylium 1+‐HBCF. The corresponding 2‐[(diphenylsilyl)methyl]pyridine, lacking the methyl‐group on the pyridine ring, forms classic N(py)→B adduct 2H‐BCF featuring an intact silane Si−H fragment. Complex 1+‐HBCF promotes cleavage of the C≡O triple bond in carbon monoxide with double C−Csp2 bond formation, leading to complex 3 featuring a B‐(diarylmethyl)‐B‐aryl‐boryloxysilane fragment. Reaction with pinacol generates bis(pentafluorophenyl)methane 4 as isolable product, proving the transition‐metal‐free deoxygenation of carbon monoxide by this main‐group system. Experimental data and DFT calculations support the existence of an equilibrium between the silylium–hydroborate ion pair and the silane–borane mixture that is responsible for the observed reactivity.

Regioselective Direct C-Alkenylation of Indoles.

The direct introduction of alkenyl groups into the indole framework avoiding its preliminary functionalization can be carried out using different synthetic strategies. Transition-metal complexes facilitate the C-H activation of indoles or alkenes allowing an efficient Csp2 - Csp2 bond formation. The hydroindolation of alkynes catalyzed by the same metal complexes or various acidic promoters can also be pursued for the alkenylation process. Conjugate addition of electron-poor alkenes and direct condensation of carbonyl derivatives with indoles are also of interest for this purpose. The regiochemical control can be exploited using the intrinsic C-3 reactivity of the indole ring. The introduction of a suitable directing group at the nitrogen atom allows the preparation of C-2 alkenylated derivatives by transition metal catalyzed reactions. This review collects the fundamental contributions in this field reported in literature during the last fifteen years.

Haloselective Cross-Coupling via Ni/Photoredox Dual Catalysis.

The chemoselective functionalization of polyfunctional aryl linchpins is crucial for rapid diversification. Although well-explored for Csp2 and Csp nucleophiles, the chemoselective introduction of Csp3 groups remains notoriously difficult and is virtually undocumented using Ni catalysts. To fill this methodological gap, a “haloselective” cross-coupling process of arenes bearing two halogens, I and Br, using ammonium alkylbis(catecholato)silicates, has been developed. Utilizing Ni/photoredox dual catalysis, Csp3–Csp2 bonds can be forged selectively at the iodine-bearing carbon of bromo(iodo)arenes. The described high-yielding, base-free strategy accommodates various protic functional groups. Selective electrophile activation enables installation of a second Csp3 center and can be done without the need for purification of the intermediate monoalkylated product.

Nickel-Promoted Reductive Cyclization Cascade: A Short Synthesis of a New Aromatic Strigolactone Analogue

A stereospecific synthesis of the tetrahydro-2H-indeno[1,2-b]furan skeleton, which is embedded in bioactive aromatic strigolactones such as GR24, is realized by a nickel-mediated tandem cross-coupling for the first time. The observed cis-stereoselectivity during the intramolecular formation of the Csp3–Csp2 bond is rationalized through conformation analysis and DFT calculations.