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The detailed reaction mechanisms of rhodium-catalyzed cycloisomerization of benzylallene-terminal alkynes involving Csp2−H bond activation on the benzyl phenyl ring have been investigated with the aid of density functional theory calculations.

An alumanyl anion possessing a new skeleton with N,N'-bis(2,6-diisopropylphenyl)-1,3-propanediamine ligand was synthesized and characterized. Transmetalation of this Al anion with diaminoscandium chloride precursors afforded the corresponding Al–Sc complexes possessing an unprecedented Al–Sc bond. The Al–Sc complex having Sc[N(SiMe3)2] unit underwent intramolecular C–H cleavage to form a bridged dinuclear complex with 𝜇-hydrido and 𝜇-methylene ligands. The Al–Sc complex having Sc(NiPr2)2 unit reacted with benzene in the presence of alkyl bromide to furnish a 1,4-dialuminated cyclohexadiene product with a concomitant formation of alkyl-alkyl coupled product. Although the latter product seems to form through the radical mechanism, DFT calculations revealed an ionic mechanism involving the following four steps: (1) C–Br bond cleavage through cooperative participation of both the Al and Sc centers, (2) C–C bond formation by a nucleophilic attack of the resulting alkyl-Al intermediate, (3) addition of Al anion moiety to benzene mediated by scandium center to form anionic Meisenheimer type intermediate, (4) subsequent reaction of the resulting Meisenheimer intermediate with bromoalumane intermediate to form dialuminated cyclohexadiene product. Such bimetallic reaction pathways to react with alkyl bromide and benzene would provide new insight into the chemistry of metal-metal bonded compounds.

The development of innovative strategies and methods to provide natural product-like macrocycles not accessible by biosynthesis, but endowed with novel bioactivities and simplified structure, is highly desirable. Inspired by the key scaffolds of rapamycin and FR252921, herein, we report a Rh(III)-catalyzed C–H alkylation macrocyclization, which enables access to CF3-substituted macrolides. DFT calculations reveal that the chemoselectivity between C–H alkylation and olefination macrocyclization was highly controllable. Moreover, the unique CF3-substituted macrolides showed potent anti-inflammation activities against TNF-α, IL-6 and CCL2 mRNA expression.

Hypoxia-induced epigenetic regulation calls for more effective therapeutic targets for esophageal cancer. We used GEPIA and UALCAN databases to screen survival-related and cancer stage-associated genes. Eca109 and KYSE450 esophageal cancer cell lines were cultured under normoxia, hypoxia, or CoCl-induced hypoxia conditions, which were further transfected with plasmids expressing RB binding protein 7 (RBBP7), hypoxia-inducible factor 1 (HIF1)-α, or RBBP7 shRNA. Colony formation and MTT assays were used to detect cell proliferation. Tumor sphere formation and stemness marker detection were applied to assess cell stemness. RT-PCR and western blot analysis were used to detect the relative mRNA level and protein expression, respectively. Luciferase assay was utilized to detect the direct interaction between HIF1α and RBBP7. Up-regulated RBBP7 was identified as one of the most prominent survival-related genes, which is negatively correlated with the overall survival (OS), disease recurrence-free survival (DFS), and tumor stages. Hypoxia-induced HIF1α up-regulates RBBP7 expression, which promotes esophagus cancer cell viability, proliferation, and stemness with increased cyclin-dependent kinase 4 (CDK4) expression. Luciferase reporter assay verified that HIF1α transcriptionally regulates the expression of RBBP7. We conclude that hypoxia induces high expression of RBBP7 which is at least partially mediated by HIF1α, up-regulates the expression of downstream CDK4, and thereby promotes tumor progression in esophageal cancer cells.

The backbone linker for two ortho-bis-(9-borafluorene)s influences the LUMO at the boron centers and the reactivity of the respective compounds.

A 9-carboranyl-substituted 9-borafluorene is reported, which is capable of undergoing efficient ring expansion to 6,7-dihydroborepins by a previously unknown alkene insertion.

The delocalized nature of canonical molecular orbitals in quantum chemistry calculations is always in conflict with the localized nature of orbital interactions and derived chemical concepts. Localization of molecular orbitals has been achieved in many approaches, but sometimes they could be over-localized for complex systems, especially those with multicenter bonding. A fragment-based approach is thus proposed to eliminate the electron density contribution from substituents, ligands and other peripheral moieties such that the skeletal bonding is clearly revealed. To be specific, fragment group orbitals, as in analogy with ligand group orbitals in coordination chemistry, are eliminated from the space spanned by occupied molecular orbitals. Via this approach, the skeletal bonding orbitals of complex systems including but not limited to pi-delocalized systems and cluster compounds are recovered with a minimal contribution from surrounding moieties, making this method the ideal choice to analyze the electronic structure of complex systems and separate skeletal bonding contribution against peripheral moieties from various sum-over-orbital properties.

Derived from structurally similar precursors, two different azidodiboranes went through distinct aryl migration reactions triggered by different boron-boron separation distances. Biphenylene based diborane with a shorter boron-boron distance underwent heterolateral aryl migration to form a seven-membered azadiborepin, while xanthrene based diborane with a longer boron-boron distance afforded a stable bis-azidoborane scaffold. The pyrolysis of such a bis-azidoborane led to eight-membered oxazadiborocine through homolateral aryl migration and subsequent [3+2] cycloaddition. Density functional theory (DFT) calculations unveiled that the boron-boron separation distances were the intrinsic factors for the distinct migrations.

Among the parent borirane, benzoborirene and ortho-dicarbadodecaborane-fused borirane, the latter possesses the highest ring strain and the highest Lewis acidity according to our density functional theory (DFT) studies. The synthesis of this class of compounds is thus considerably challenging. The existing examples require either a strong π-donating group or an extra ligand for B-coordination, which nevertheless suppresses or completely turns off the Lewis acidity. The title compound, which possesses both features, not only allows the 1,2-insertion of P=O, C=O or C≡N to proceed under milder conditions, but also enables the heretofore unknown dearomative 1,4-insertion of Ar-(C=O)- into a B-C bond. The fusion of strained molecular systems to an o-carborane cage shows great promise for boosting both the ring strain and acidity.

Three-dimensional (3D) analogues of 9-borafluorenes, (C

The first enantioselective copper-catalyzed cyanation of propargylic C-H bonds via radical relay was established using novel BoxOTMS ligands, providing an efficient and straightforward tool for the construction of structurally diverse chiral allenyl nitriles in good yields with excellent enantioselectivities. This reaction features high functional group tolerance and mild conditions. In addition, the chiral allene products can be readily converted to other chiral compounds via axis-to-center chirality transfer.

The first-row transition metal catalysis often serves as a complementary strategy to traditional precious metal catalysis. Other than their advantages in abundance and sustainability, their unique electronic properties often give rise to more complicated reactivities. Co-catalyzed hydrogenation is an example of these relatively underexplored first-row transition metal catalysis. In this work, we will focus on an example of Co-catalyzed hydrogenation, which was reported to be able to selectively hydrogenate C=C but not C=O. We have performed DFT calculations on the model reactions, accompanied by a series of structure and bonding analysis, to investigate the underlying reason for the observed selectivity. We have identified the predominant σ-donating nature of phosphine and the π-accepting nature of C=C/C=O fragments upon interaction with Co(I) center, and we have also analyzed why these differences would lead to different coordination geometry, stability, and reactivity. We anticipate that all these analyses would advance our understanding in Co(I) catalysis and are beneficial for future Co-based catalyst design.

The asymmetric hydroboration of alkenes has proven to be among the most powerful methods for the synthesis of chiral boron compounds. This protocol is well suitable for activated alkenes such as vinylarenes and alkenes bearing directing groups. However, the catalytic enantioselective hydroboration of O-substituted alkenes has remained unprecedented. Here we report a Rh-catalyzed enantioselective hydroboration of silyl enol ethers (SEEs) that utilizes two new chiral phosphine ligands we developed. This approach features mild reaction conditions and a broad substrate scope as well as excellent functional group tolerance, and enables highly efficient preparation of synthetically valuable chiral borylethers.

Highly efficient and straightforward access to enantioenriched five-membered ring-fused chromanones is developed via [3+2]-cycloaddition of 3-cyanochromones with Morita-Baylis-Hillman carbonates. Densely functionalized chiral cyclopenta[

Air-stable amine- and phosphine-boranes are discovered as donors to integrate with pyridinium acceptor for generating pho-toactive electron-donor-acceptor (EDA) complexes. Experimental results and DFT calculations suggest a dihydrogen bond bridging the donor and acceptor. Illuminating the EDA complex enables an intramolecular single electron transfer to give boron-centered radical for dehydrogenative borylation with no need of external photosensitizer and oxidant. The deproto-nation of Wheland-like radical intermediate rather than its generation is believed to determine the very good ortho-selectivity based on DFT calculations. A variety of α-borylated pyridine derivatives have been readily synthesized with good functional group tolerance.

Boroles are attracting broad interest for their myriad and diverse applications, including in synthesis, small molecule activation and functional materials. Their properties and reactivity are closely linked to the cyclic conjugated diene system, which has been shown to participate in cycloaddition reactions, such as the Diels‐Alder reaction with alkynes. The reaction steps leading to boranorbornadienes, borepins and tricyclic boracyclohexenes from the thermal reaction of boroles with alkynes are seemingly well understood as judged from the literature. Herein, we question the long‐established mechanistic picture of pericyclic rearrangements by demonstrating that seven‐membered borepins (i. e., heptaphenylborepin and two derivatives substituted with a thienyl and chloride substituent on boron) exist in a dynamic equilibrium with the corresponding bicyclic boranorbornadienes, the direct Diels‐Alder products, but are not isolable products from the reactions. Heating gradually converts the isomeric mixtures into fluorescent tricyclic boracyclohexenes, the most stable isomers in the series. Results from mechanistic DFT calculations reveal that the tricyclic compounds derive from the boranorbornadienes and not the borepins, which were previously believed to be intermediates in purely pericyclic processes., New insights into the reactivity of perarylated boroles toward alkynes have been derived from both experimental and computational studies. It is shown that borepins (the formal alkyne insertion products) can readily isomerize to the thermodynamically more favorable boranorbornadienes (the formal Diels‐Alder products), thus obscuring the mechanism of product formation (see Figure). In addition, the fluorescent nature of the tricyclic boracyclohexenes, the most stable isomers of the addition reactions, has been investigated by absorption and emission spectroscopy.

QM/MM calculations have been used to elucidate the reaction mechanism of the reduction of acetylene to ethylene catalyzed by a nitrogenase-like enzyme DCCPCh with an unusual [Fe8S9] double-cubane cluster. Various plausible reaction pathways, involving different oxidation states and protonation states of the iron-sulfur cluster, have been analyzed to find the most favorable one. The acetylene substrate bridges to the [Fe8S8] cluster via its triple bond in a μ-(bis-η2) coordination mode. After a proton-coupled electron transfer reduction of the reactant complex, the acetylene reduction may be described to proceed via a special “double-electron transfer induced proton transfer” mechanism, deduced from the principal interacting orbital analysis. The anti-ferromagnetically coupled [Fe8S8] cluster delivers a pair of α- and β-electrons to the substrate, concertedly but asynchronously with a proton transfer mediated by the second-shell Lys147 residue to one of the acetylene carbon atoms. Subsequently, the second proton-coupled electron transfer proceeds, followed by protonation of the substrate to afford the ethylene product. During the two-electron reaction, the oxidation states of the [Fe8S8] cluster cycle from [FeII6FeIII2], to [FeII7FeIII], to [FeII5FeIII3], and back to [FeII6FeIII2].

Owing to an empty p orbital and a lone pair of electrons on the Si center, silylene exhibits reactivity similar to a transition-metal system capable of activating H2/C-H bonds and small molecules. In this work, with the aid of density functional theory calculations, we systematically investigated the reactions of an acyclic silylene with CO, CO2, and N2O. The detailed mechanisms obtained lead to an in-depth understanding of the silylene single-site ambiphilic reactivity.

Transition metal–boryl complexes play an important role as reactive intermediates in catalytic borylation processes and have enjoyed tremendous exploration. Over the years, it has been well establi...

Highly reactive dicoordinate (i.e., mono-base-stabilized) borylenes of the form [LBR] (L = Lewis base) have recently shown intriguing reactivity with inert small molecules, including N2. However, t...