Enantioselective Carbonylative Cyclization of Alkenes with C-H Bonds for Synthesis of γ-Lactams Bearing an α-Quaternary Carbon.

The development of effective synthetic methods to construct γ-lactams bearing a chiral α-quaternary carbon from relatively inert C(O)-H bonds with alkenes has been an elusive challenge. Herein, we used a naphthylamine-derived phosphine oxide ligating Ni and Al bimetallic catalyst to realize a carbonylative cyclization of formyl C-H bonds with alkenes, highly regio- and enantioselectively constructing γ-lactams bearing a chiral α-quaternary carbon in up to 99% yield and 98% ee. These γ-lactams proved to be versatile synthetic precursors for many biologically active molecules.

Enantioselective Ni-Catalyzed 1,2-Borylalkynylation of Unactivated Alkenes.

Enantioselective three-component difunctionalization of alkenes with boron reagents represents an attractive strategy for assembling three-dimensional chiral organoboron compounds. However, regio- and enantiocontrol comprise the pivot challenges in these transformations, which predominantly require the use of activated conjugated alkenes. Herein, by utilizing various carbonyl directing groups, including amides, sulfinamides, ketones, and esters, we succeed in realizing a nickel-catalyzed 1,2-borylalkynylation of unactivated alkenes to enable the simultaneous incorporation of a boron entity and an sp-fragment across the double bond.

Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins.

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as a straightforward and efficient tool for stereoselectively forging C-C bond. Nevertheless, the creation of acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within the domain of cross-coupling chemistry despite their prominence in various bioactive small molecules.

Pd-catalyzed asymmetric Larock reaction for the atroposelective synthesis of N─N chiral indoles.

Atropisomeric indoles defined by a N─N axis are an important class of heterocycles in synthetic and medicinal chemistry and material sciences. However, they remain heavily underexplored due to limited synthetic methods and challenging stereocontrol over the short N─N bonds. Here, we report highly atroposelective access to N─N axially chiral indoles via the asymmetric Larock reaction.

Sustainable production of triazoles from lignin major motifs.

An efficiently catalyzed synthesis of pharmaceutically relevant 1,2,3-trazoles from renewable resources is highly desirable. However, due to incompatible catalysis conditions, this endeavor remained challenging so far. Herein, a practical access protocol to 1,2,3-triazoles, starting from lignin phenolic β-O-4 with γ-OH group utilizing a vanadium-based catalyst is presented.

Diastereo- and Enantioselective Synthesis of Tetracyclic Cycloheptanols through (4+3) Annulation via C-C/C-H Activation Cascade.

Transition metal-catalyzed annulations of four-membered rings via C-C activation are powerful tools to construct complex fused and bridged ring systems. Despite significant progress in (4+1), (4+2) and (4+4) annulations, the (4+3) annulation remains unexplored. Herein, we develop an asymmetric Rh-catalyzed intramolecular (4+3) annulation of α-arylalkene-tethered benzocyclobutenols for the synthesis of dihydrofuran-annulated dibenzocycloheptanols with two discontinuous chiral carbon centers via a C-C and C-H activation cascade.

Rhodium-Catalyzed Enantioselective Formal [4+1] Cyclization of Benzyl Alcohols and Benzaldimines: Facile Access to Silicon-Stereogenic Heterocycles.

The carbon-to-silicon switch in formation of bioactive sila-heterocycles with a silicon-stereogenic center has garnered significant interest in drug discovery. However, metal-catalyzed synthesis of such scaffolds is still in its infancy. Herein, a rhodium-catalyzed enantioselective formal [4+1] cyclization of benzyl alcohols and benzaldimines has been realized by enantioselective difunctionalization of a secondary silane reagent, affording chiral-at-silicon cyclic silyl ethers and sila-isoindolines, respectively.

Nickel/Photoredox Dual-Catalyzed Regiodivergent Aminoalkylation of Unactivated Alkyl Halides.

A mild and regiodivergent aminoalkylation of unactivated alkyl halides is disclosed via a dual photoredox/nickel catalysis. Bipyridyl-type ligands without an -substituent control the site-selective coupling at the original position, while -disubstituted ligands tune the site-selectivity at a remote, unprefunctionalized position. Mechanistic studies combined with DFT calculations give insight into the mechanism and the origins of the ligand-controlled regioselectivity.

Towards bioresource-based aggregation-induced emission luminogens from lignin β-O-4 motifs as renewable resources.

One-pot synthesis of heterocyclic aromatics with good optical properties from phenolic β-O-4 lignin segments is of high importance to meet high value added biorefinery demands. However, executing this process remains a huge challenge due to the incompatible reaction conditions of the depolymerization of lignin β-O-4 segments containing γ-OH functionalities and bioresource-based aggregation-induced emission luminogens (BioAIEgens) formation with the desired properties. In this work, benzannulation reactions starting from lignin β-O-4 moieties with 3-alkenylated indoles catalyzed by vanadium-based complexes have been successfully developed, affording a wide range of functionalized carbazoles with up to 92% yield.

Stereoselective Photoredox Catalyzed (3+3) Dipolar Cycloaddition of Nitrone with Aryl Cyclopropane.

By resorting to the principle of remote activation, we herein demonstrate the first photoredox catalyzed (3+3) dipolar cycloaddition of nitrones with aryl cyclopropanes. Key to the fidelity of the reaction resides in a facile manner of substrate activation by single-electron transfer (SET) oxidation with photoredox catalysis, and the reaction takes place through a stepwise cascade encompassing a three-electron-type nucleophilic substitution triggered cyclopropane ring-opening and a diastereoselective 6-endo-trig radical cyclization manifold. The reaction proceeds under mild conditions with excellent regio- and stereoselectivity, nicely complementing the well-developed Lewis acid catalyzed cycloaddition of donor-acceptor cyclopropanes.

Rhodium-catalyzed annulative approach to N-N axially chiral biaryls C-H activation and dynamic kinetic transformation.

N-N axially chiral biaryls represent a rarely explored class of atropisomeric compounds. We hereby report rhodium-catalyzed enantioselective [4 + 2] oxidative annulation of internal alkynes with benzamides bearing two classes of N-N directing groups. The coupling occurs under mild conditions NH and CH annulation through the dynamic kinetic transformation of the directing group and is highly enantioselective with good functional tolerance.

Rhodium-catalyzed enantioselective and diastereodivergent access to diaxially chiral heterocycles.

N-N axially chiral biaryls represent a rarely explored class of atropisomers. Reported herein is construction of diverse classes of diaxially chiral biaryls containing N-N and C-N/C-C diaxes in distal positions in excellent enantioselectivity and diastereoselectivity. The N-N chiral axis in the products provides a handle toward solvent-driven diastereodivergence, as has been realized in the coupling of a large scope of benzamides and sterically hindered alkynes, affording diaxes in complementary diastereoselectivity.

Sigma-Bond Metathesis as an Unusual Asymmetric Induction Step in Rhodium-Catalyzed Enantiodivergent Synthesis of C-N Axially Chiral Biaryls.

Mechanistic understanding of asymmetric induction plays a crucial role in designing new catalytic asymmetric reactions. Reported herein is atroposelective access to C-N axially chiral isoquinolones via rhodium-catalyzed C-H activation of -alkoxy benzamides and annulation with imidoyl sulfoxonium ylides. The coupling system proceeded with excellent functional group tolerance, and different conditions were identified to afford one or the other enantiomeric product each in excellent enantioselectivity for a representative class of the sulfoxonium ylide reagent, thus making both enantiomers readily available using the same catalyst.

Ni-catalyzed benzylic β-C(sp)-H bond activation of formamides.

The development of transition metal-catalyzed β-C-H bond activation via highly-strained 4-membered metallacycles has been a formidable task. So far, only scarce examples have been reported to undergo β-C-H bond activation via 4-membered metallacycles, and all of them rely on precious metals. In contrast, earth-abundant and inexpensive 3d transition metal-catalyzed β-C-H bond activation via 4-membered metallacycles still remains an elusive challenge.

Mechanism and Origins of Diastereo- and Regioselectivities of Palladium-Catalyzed Remote Diborylative Cyclization of Dienes via Chain-Walking Strategy.

Density functional theory calculations have been performed to investigate the palladium-catalyzed remote diborylative cyclization of dienes. The computations reveal that the reaction proceeds through a rarely explored Pd(II)/Pd(IV) catalytic cycle, and the formal σ-bond metathesis between the alkylpalladium intermediate and B pin occurs via the pathway of the B-B oxidative addition/C-B reductive elimination involving the high-valent Pd(IV) species. The diastereoselectivity is determined by the migratory insertion into the Pd-C bond, which is mainly due to the combination of the torsional strain effect, steric repulsion and C-H-O hydrogen-bonding interaction.

Enantioselective C2-H Alkylation of Pyridines with 1,3-Dienes via Ni-Al Bimetallic Catalysis.

A chiral phosphine oxide-ligated Ni-Al bimetallic catalyst was used to realize an enantioselective C2-H alkylation of pyridines without the need of a C2-block. A wide range of pyridines, including unsubstituted pyridine, C3, C4, and C2-substituted pyridines, and even complex pyridine-containing bioactive molecules are well compatible with the reaction, providing up to 81% yield and up to 97% ee.

Nickel-Catalyzed Cross-Coupling of Acyl Chloride with Racemic α-Trifluoromethyl Bromide to Access Chiral α-Trifluoromethyl Ketones.

The nickel-catalyzed reductive cross-coupling reaction of acyl chloride with racemic secondary α-trifluoromethyl bromide has been developed. By this chemistry, a series of structurally interesting chiral α-CF carbonyl compounds could be accessed with great enantioselectivity and good functional group tolerance. The study of late-stage transformation indicated that this chemistry could be used as the robust method to prepare products that contain a bioactive motif.

Mechanism and Origins of Enantioselectivity of Cobalt-Catalyzed Intermolecular Hydroarylation/Cyclization of 1,6-Enynes with -Pyridylindoles.

Density functional theory calculations were performed to investigate the cobalt-catalyzed intermolecular hydroarylation/cyclization of 1,6-enynes with -pyridylindoles. The computations reveal that the reaction begins with the oxidative cyclization of 1,6-enyne to afford the five-membered cobaltacycle, from which the metal-assisted σ-bond metathesis/C-C reductive elimination led to the final hydroarylation/cyclization product. The initial oxidative cyclization constitutes the rate-determining step of the overall reaction.

Copper-Catalyzed Highly Selective Protoboration of CF -Containing 1,3-Dienes.

The copper-catalyzed highly selective protoboration of CF -containing conjugated diene with proton source and B Pin has been developed. This chemistry could suppress the well-known defluorination and provide borated reagents with an intact CF -group. Further studies indicated that the functional group tolerance of this chemistry is very well, and the products could be used as versatile precursors for different types of transformations.

Computational and Experimental Study of Turbo-Organomagnesium Amide Reagents: Cubane Aggregates as Reactive Intermediates in Pummerer Coupling.

The dynamic equilibria of organomagnesium reagents are known to be very complex, and the relative reactivity of their components is poorly understood. Herein, a combination of DFT calculations and kinetic experiments is employed to investigate the detailed reaction mechanism of the Pummerer coupling between sulfoxides and turbo-organomagnesium amides. Among the various aggregates studied, unprecedented heterometallic open cubane structures are demonstrated to yield favorable barriers through a concerted anion-anion coupling/ S-O cleavage step.

Combined Evaluation of Preoperative Serum CEA and CA125 as an Independent Prognostic Biomarker in Patients with Early-Stage Cervical Adenocarcinoma.

Purpose: There is currently a lack of research on preoperative prognostic analysis of early-stage cervical adenocarcinoma (ADC). The purpose of our study was to clarify whether preoperative serum tumor-marker levels were of prognostic value in early-stage ADC.

Patients And Methods: We performed a retrospective study of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IIA1 and pathology-proven invasive ADC.

Factors Predicting Severe Myelosuppression and Its Influence on Fertility in Patients with Low-Risk Gestational Trophoblastic Neoplasia Receiving Single-Agent Methotrexate Chemotherapy.

Purpose: To investigate the potential factors to predict severe myelosuppression among low-risk gestational trophoblastic neoplasia (GTN) patients with single-agent methotrexate (MTX) chemotherapy. To analyze reproductive outcomes of patients with or without severe myelosuppression after achieving complete remission (CR).

Patients And Methods: The retrospective study included 319 low-risk GTN patients registered from January 2008 to December 2018 in our hospital.

WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/β-catenin pathway.

Purpose: Persistent infection with high-risk human papillomavirus (HR-HPV) is thought to play a prominent role in the initiation and progression of almost all cases of cervical cancer. Previously, we and others found that microRNA 34a (miR-34a) may be regulated by HR-HPV E6 to contribute to the development of cervical cancer. Here, we aimed to identify the oncogenic potential and clinical significance of a known miR-34a target, WNT1, in cervical squamous cell carcinoma (SCC) development and to investigate the associated mechanisms underlying cervical SCC cell proliferation and invasion.

NiH-Catalyzed Migratory Defluorinative Olefin Cross-Coupling: Trifluoromethyl-Substituted Alkenes as Acceptor Olefins to Form gem-Difluoroalkenes.

We report a NiH-catalyzed migratory defluorinative coupling between two electronically differentiated olefins. A broad range of unactivated donor olefins can be joined directly to acceptor olefins containing an electron-deficient trifluoromethyl substituent in both intra- and intermolecular fashion to form gem-difluoroalkenes. This migratory coupling shows both site- and chemoselectivity under mild conditions, with the formation of a tertiary or quaternary carbon center.