Csp2 Csp3 Bond Research Articles

A tandem dearomatization/rearomatization strategy: enantioselective N-heterocyclic carbene-catalyzed α-arylation.

In this study, the first example of the carbene-catalyzed tandem dearomatization/rearomatization reaction of azonaphthalenes with α-chloroaldehydes is described. This protocol enables the efficient assembly of chiral dihydrocinnolinone derivatives in good yields with excellent enantioselectivities (up to 99% ee). Moreover, this strategy enables not only the highly enantioselective NHC-catalyzed nucleophilic aromatic substitution, but also a formal Csp2-Csp3 bond formation.

Metal-free TBAI-catalyzed oxidative Csp3[sbnd]S bond formation through Csp2[sbnd]Csp2 bond and S[sbnd]N bond cleavage: A new route to β-keto-Sulfones

A novel TBAI-catalyzed radical sulfonylation of readily available N,N-dimethylenaminones with sulfonylhydrazides to afford functionalized β-keto-sulfones has been developed. Various functional groups were tolerated well under the present oxidative conditions and the corresponding β-keto-sulfone compounds were obtained in moderate to good yields. Importantly, this transformation offered the first protocol for Csp3S bond formation by oxidative Csp2Csp2 bond cleavage in one step.

Crystal structure of limonoid TS3, isolated from Trichilia rubescens.

The title limonoid compound, C26H28O5·0.5H2O (TS3) [systematic name: (3aS,3bS,4aS,5aS,6S,7aR,8aR,8bS,11aR)-6-(furan-3-yl)-3a,5a,8b,11a-tetra-methyl-3a,4a,5,5a,6,7,7a,8b,11,11a-deca-hydro-oxireno[2',3':4b,5]oxireno[2'',3'':2',3']cyclo-penta-[1',2':7,8]phenanthro[10,1-bc]furan-3(3aH)-one hemihydrate], crystallizes with two independent mol-ecules (1 and 2) in the asymmetric unit and one water mol-ecule. TS3 is composed of three six-membered rings (A, C and D), three five-membered rings (B, E and F) and two epoxide rings. A group of five fused rings (A-E) is bonded to a furan ring (F) with a Csp3-Csp2 bond [1.500 (3) Å in mol-ecule 1 and 1.499 (3) Å in mol-ecule 2]. The absolute structures of the mol-ecules in the crystal were determined by resonant scattering; Flack parameter = 0.05 (5). In the crystal, the individual mol-ecules stack in columns along the b-axis direction. The water mol-ecule bridges mol-ecules 1 and 2 via Owater-H⋯O and C-H⋯Owater hydrogen bonds. Together with further C-H⋯O hydrogen bonds, linking mol-ecules 1 and 2, the columns are linked to form slabs parallel to the ab plane. Within each column, mol-ecules are also linked via C-H⋯π inter-actions involving the five-membered furan (F) rings.

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.

Silver-Mediated Oxidative Decarboxylative Intramolecular Asymmetric Radical Cyclization (Csp3-Csp2) via Memory of Chirality: Access to Circumdatin Alkaloids.

A novel silver-mediated oxidative decarboxylative intramolecular asymmetric radical cyclization has been developed to form a Csp3-Csp2 bond via memory of chirality. The application of the process has been demonstrated for the synthesis of the circumdatin class of alkaloids in high enantiopurity with retention of the configuration. The developed protocol is mild and works with an inexpensive silver catalyst in the absence of ligand, base, or additives. The involvement of a monoradical in the reaction has been established by trapping the radical intermediate.

A Copper-Catalyzed Reductive Defluorination of β-Trifluoromethylated Enones via Oxidative Homocoupling of Grignard Reagents.

An efficient copper-catalyzed reductive defluorination of β-trifluoromethylated enones via an oxidative homocoupling of Grignard reagents is reported. The reaction proceeded smoothly with a wide range of substrates, including the ones bearing aromatic heterocycles, such as furyl and thienyl ring systems in high yields (80-92%, except one example) under mild conditions. This provides a practical method for synthesis of gem-difluoroolefin ketones. It is also worth noting that this homocoupling process of Grignard reagents using β-trifluoromethylated enones as "oxidizing reagents" is effective for both the Csp2-Csp2 and Csp3-Csp3 bond formations, including for substrates whose β-hydride elimination of the corresponding transition metal alkyl complex is particularly facile, affording coupling products with high yields (83-95%), simultaneously.

Generation of Diversity Sets with High sp3 Fraction Using the Photoredox Coupling of Organotrifluoroborates and Organosilicates with Heteroaryl/Aryl Bromides in Continuous Flow.

The photoredox cross-coupling of aryl halides and potassium alkyl trifluoroborates is a very effective means to form Csp3-Csp2 bonds. However, this transformation is inefficient for the coupling of unactivated primary trifluoroborates. We have developed a generally useful, continuous flow Csp3-Csp2 coupling procedure for the synthesis of diverse product sets that is compatible with both trifluoroborates and silicate reagents. This universal protocol provides diversity sets from both primary and secondary coupling partners. This easily scalable procedure widens the substrate scope of the coupling reaction and is efficient for producing a greater range of analogues bearing a high sp3 fraction.

A Domino Process toward Functionally Dense Quaternary Carbons through Pd-Catalyzed Decarboxylative C(sp3)-C(sp3) Bond Formation.

An efficient protocol was developed to construct functionally dense quaternary carbons with concomitant formation of a new Csp3-Csp3 bond via Pd-catalyzed decarboxylative transformation of vinyl cyclic carbonates. This redox-neutral catalytic system features stereocontrolled formation of multisubstituted allylic scaffolds with an aldehyde functionality generated in situ, and it typically can be performed at room temperature without any additives. DFT calculations provide a rationale toward the selective formation of these compounds and reveal a complex mechanism that with the help of microkinetic models is able to reproduce the nontrivial dependence of the identity of the product on the nature of the substituents in the substrate.

Early transition metal-catalyzed C-H alkylation: hydroaminoalkylation for Csp3-Csp3 bond formation in the synthesis of selectively substituted amines.

Hydroaminoalkylation is a 100% atom economic method for forming Csp3-Csp3 bonds through C-H activation α to an amine and subsequent reaction with an alkene. When catalyzed by early transition metals, this reaction allows for alternative disconnections for the synthesis of structurally complex amines. This method avoids the installation of protecting groups or directing groups and does not require added oxidants, or photoredox catalysts. In this feature article, we discuss the various selectively substituted amines that can be accessed by hydroaminoalkylation, with a special focus on the development of early transition metal catalysts for their rapid, step and atom efficient assembly.

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.

Mn(OAc)3-Promoted Oxidative Csp3-P Bond Formation through Csp2-Csp2 and P-H Bond Cleavage: Access to β-Ketophosphonates.

The Mn(OAc)3-promoted oxidative phosphonylation of N,N-dimethylenaminones with H-phosphonates, involving a chemo- and regioselective Csp2-Csp2 bond cleavage and Csp3-P bond formation in one step, provided successfully functionalized β-ketophosphonates under mild reaction conditions. Oxidative Csp3-H/P-H cross-coupling reactions via Csp3-C(C═O) bond cleavage and mechanistic studies are conducted preliminarily, and a possible mechanism is proposed. This novel method proceeds in good to excellent yields, shows operational simplicity, broad substrate scope, and large-scale preparation.

Carbon-carbon bond forming reactions via Pd-catalyzed detellurative homocoupling of diorganyl tellurides

A simple and highly efficient method for the constructions of Csp-Csp, Csp2-Csp2 and Csp3-Csp3 bonds is reported. The symmetrical diaryl tellurides undergo detellurative homocouplings to afford symmetrical biaryl products. The reactions are carried out at ambient temperature using PdCl2 as a catalyst in the presence of Ag2O and Na2CO3. Similarly, the detellurative homocouplings of dibenzyl telluride and bis(phenylethynyl)telluride give bibenzyl and the conjugated diyne, respectively.

Nickel-Catalyzed Reductive Dicarbofunctionalization of Alkenes.

An intermolecular, three-component reductive dicarbofunctionalization of alkenes is presented here. The combination of Ni catalysis with TDAE as final reductant enables the direct formation of Csp3-Csp3 and Csp3-Csp2 bonds across a variety of π-systems using two different electrophiles that are sequentially activated with exquisite selectivity under mild reaction conditions.

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.

Recent Developments in Cobalt Catalyzed Carbon–Carbon and Carbon–Heteroatom Bond Formation via C–H Bond Functionalization

Cobalt catalysts have evolved to be seen as versatile eco-compatible and economical catalysts in organic synthesis in recent years. Cobalt-catalyzed reactions are undoubtedly a classic in synthetic chemistry for the formation of carbon–carbon and carbon–heteroatom bonds. Another important aspect in this field is catalyst variants, such as low-valent and high-valent cobalt catalysts. This review summarizes the recent progress and synthetic utility of low-valent and high-valent cobalt catalysts towards C–H functionalization processes achieving C–C, C–O, C–N and C–B bond formation. Mechanistic insight is also discussed, with the goal of serving as a stepping stone for further development in this field. In addition, Csp3–H bond functionalization reactions provide many opportunities for novel synthesis approaches. 1 Introduction 2 Carbon–Carbon Bond Formation 2.1 Csp2–Csp3 Bond Formation 2.2 Csp2–Csp2 Bond Formation 3 Carbon–Nitrogen Bond Formation 4 Csp3–H Bond Functionalization 5 Carbon–Oxygen Bond Formation 6 Carbon–Boron Bond Formation 7 Conclusion

Preparation of visible-light-activated metal complexes and their use in photoredox/nickel dual catalysis.

Visible-light-activated photoredox catalysts provide synthetic chemists with the unprecedented capability to harness reactive radicals through discrete, single-electron transfer (SET) events. This protocol describes the synthesis of two transition metal complexes, [Ir{dF(CF3)2ppy}2(bpy)]PF6 (1a) and [Ru(bpy)3](PF6)2 (2a), that are activated by visible light. These photoredox catalysts are SET agents that can be used to facilitate transformations ranging from proton-coupled electron-transfer-mediated cyclizations to C-C bond constructions, dehalogenations, and H-atom abstractions. These photocatalysts have been used in the synthesis of medicinally relevant compounds for drug discovery, as well as the degradation of biological polymers to access fine chemicals. These catalysts are prepared from IrCl3 and RuCl3, respectively, in three chemical steps. These steps can be described as a series of two ligand modifications followed by an anion metathesis. Using the cost-effective, scalable procedures described here, the ruthenium-based photocatalyst 2a can be synthesized in a 78% overall yield (∼8.1 g), and the iridium-based photocatalyst 1a can be prepared in a 56% overall yield (∼4.4 g). The total time necessary for the complete protocols ranges from ∼2 d for 2a to 5-7 d for 1a. Procedures for applying each catalyst in representative photoredox/Ni cross-coupling to form Csp3-Csp2 bonds using the appropriate radical precursor-organotrifluoroborates with 1a and bis(catecholato)alkylsilicates with 2a-are described. In addition, more traditional photoredox-mediated transformations are included as diagnostic tests for catalytic activity.

Palladium-catalyzed cascade metallo-ene/Suzuki coupling reaction of allenamides.

A new type of cascade metallo-ene/Suzuki coupling reaction of allenamides catalyzed by palladium is described. A variety of polyfunctionalized 2,3-dihydropyrrole derivatives, which are important structural motifs for bioactive molecules, were furnished with excellent yields. Two new Csp3-Csp2 bonds were constructed in one pot efficiently. The reductive elimination from π-allyl palladium complex presented excellent regioselectivity to the terminal C1 position. The unique terminal alkene was one of the most easily functionalized groups, providing these molecules with a potential transformation to much more complicated molecules.

A deciduous directing group approach for the addition of aryl and vinyl nucleophiles to maleimides.

A Rh(iii)-catalyzed C-H activation followed by conjugate addition to maleimides, using carboxylic acid as a traceless/deciduous directing group, to formally furnish a Csp2-Csp3 bond is presented. For the first time, derivatives of acrylic acid have been shown as surrogates for the unstable and expensive alkenyl boronic acids.

Application of the Photoredox Coupling of Trifluoroborates and Aryl Bromides to Analog Generation Using Continuous Flow.

A method for the coupling of aryl bromides with potassium alkyl trifluoroborates, via nickel/photoredox dual catalysis, has been developed for use in continuous flow. This operationally simple protocol is able to form Csp3-Csp2 bonds with significantly reduced reaction times and a broader substrate scope than when conducted in batch. The utility of this method for rapid analog synthesis has been demonstrated by the synthesis of a small library of alkyl-substituted quinazolines.

Copper-Catalyzed Cascade Radical Addition–Cyclization Halogen Atom Transfer between Alkynes and Unsaturated α-Halogenocarbonyls

A Cu-catalyzed cascade radical addition/cyclization/halogen atom transfer between alkynes and α-halogeno-γ, δ-unsaturated carbonyl compounds for the synthesis of various substituted cyclopentenes is described. Since up to four Csp3–Csp2 bonds, two Csp3–Br bonds, and two carbocycles can be established in a single reaction, this 100% atom-efficient reaction exhibits the advantages of wide substrate scope, high functional group tolerance, and step-economics, and it offers an entry of the atom transfer radical addition/cyclization (tandem ATRA-ATRC) process to the synthesis of substituted cyclopentenes.