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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.

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.

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.

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.

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.

The addition of a nitrogen-based functional group to alkenes via a direct catalytic method is an attractive way of synthesizing value-added amides. The regioselective hydroamidation of unactivated alkenes is considered one of the easiest ways to achieve this goal. Herein, we report the NiH-catalyzed anti-Markovnikov intermolecular hydroamidation of unactivated alkenes enabled by using 2,9-dibutylphenathroline (diBuphen) as the ligand. This protocol provides a platform for the direct synthesis of over 90 structurally diverse N-alkyl amides using dioxazolones, which can be easily derived from abundant carboxylic acid feedstocks. This method succeeds for both terminal and internal unactivated alkenes and some natural products. Mechanistic studies including DFT calculations reveal an initial reversible insertion/elimination of the [NiH] to the alkene, followed by the irreversible amidation to furnish the N-alkyl amides. By crossover experiments and deuterium labeling studies, the observed anti-Markovnikov regioselectivities are suggested to be controlled by the sterical environment of the coupling reaction.

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 choice of backbone linker for two

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 general strategies to stabilize a boryl radical involve single electron delocalization by π-system and the steric hinderance from bulky groups. Herein, a new class of boryl radicals is reported, with intramolecular mixed-valent B

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.

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.

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...

Three-membered unsaturated rings have been widely utilized in organic synthesis due to their inherent highly strained structures. Although much research has been applied to ring-expansion reactions...

Despite the long history of research in transition metal (TM) complexes, the study of TM-aluminyl complexes is still in its early stage of development. It is expected that the presence of an electropositive Al donor atom would open up new possibilities in TM complex reactivity, and indeed TM-aluminyl has shown an early sign of success in small-molecule activation. On the other hand, the existing reports on TM-aluminyl reactivity are often explained to readers with different understanding on individual cases, and a general picture of TM-aluminyl reactivity is still not available. In this work, we have attempted to provide a systematic picture to explain some early explorations in this field, specifically a series of recently reported heteroallene insertion reactions involving unsupported TM-aluminyl complexes. Through density functional theory calculations of a number of TM-aluminyl complexes, covering both Au and Cu centers, we found that their reactivity against heteroallenes (including CO

OBJECTIVES We recently reported a high rate of nontherapeutic thymectomy. Mediastinal lymphomas (MLs) are the malignancies most likely to be confused with thymic epithelial tumours (TETs). This study aimed to establish a predictive model by evaluating clinical variables and positron emission tomography to distinguish those diseases. METHODS From 2018 to 2021, consecutive patients who were pathologically diagnosed with TETs or MLs were retrospectively reviewed. Univariable and multivariable analyses were used to identify association factors. The Akaike information criterion was used to select variables. A nomogram was developed and validated to differentiate MLs from TETs. RESULTS A total of 198 patients were included. Compared with TETs, patients with MLs were more likely to be younger with higher metabolic tumour volume (154.1 vs 74.6 cm3), total lesion glycolysis (1388.8 vs 315.2 g/ml cm3), SUVmean (9.2 vs 4.8), SUVpeak (12.9 vs 6.3) and SUVmax (14.8 vs 7.5). A nomogram was established based on the stepwise regression results and the final model containing age and SUVmax had minimal Akaike information criterion value of 72.28. Receiver operating characteristic analyses indicated that the area under the curve of predictive nomogram in differentiating MLs from TETs was 0.842 (95% CI: 0.754–0.907). The internal bootstrap resampling and calibration plots demonstrated good consistence between the prediction and the observation. CONCLUSIONS Combination of age and SUVmax appears to be a useful tool to differentiate MLs from TETs. The novel predictive model prevents more patients from receiving nontherapeutic thymectomy.

The iminoboryl

The synthesis of 9-borafluorene with an electron-withdrawing

The reactions of the rhenium(III)-phosphine complex ReCl3(PMePh2)3 with organonitriles (NCR) were studied and found to give novel addition as well as simple substitution products. Refluxing ReCl3(P...

The detailed reaction mechanisms of gold-catalyzed reactions of 2,1-benzisoxazoles with propiolates and ynamides have been investigated with the aid of density functional theory calculations. Our investigation focused on the different selectivities observed for the reactions of the two different classes of substituted alkynes. Through our systematic calculations, we found that the catalytic reactions start with a nucleophilic nitrogen atom attacking one coordinated alkyne carbon. Then, an N–O bond cleavage takes place to give two different gold carbenoid intermediates, from which four possible pathways lead to different products (7-acylindolyl derivatives and quinolone oxides). In the reaction of 2,1-benzisoxazole (anthranil) with the propiolate PhCCCOOMe, the relevant N–O bond cleavage leading to the 7-acylindolyl product is only slightly less favorable than that leading to the quinolone oxide product. The steps following the N–O bond cleavage are all very facile. Therefore, the N–O bond cleavage step is responsible for the selective outcome observed experimentally. In the reaction of 2,1-benzisoxazole (anthranil) with the ynamide PhCCNMeMs, the N–O bond cleavages leading to the 7-acylindolyl product and the quinolone oxide have comparable barriers. However, the C–N coupling that followed has a very high barrier, making the pathway leading to the quinolone oxide product unfavorable. As a result, only the 7-acylindolyl product is experimentally observed.

A metal-free access to 3-allyl-2-alkoxychromanones by PPh3-catalyzed alkoxy allylation of chromones with MBH carbonates and alcohols is described. This reaction is performed under mild conditions and it shows good functional group tolerance, providing a series of functionalized chromanones in moderate to high yields with excellent diastereoselectivities. Deuterium-labeling experiments to probe a possible mechanism and scale-up reaction were also conducted.

Anthranilic acids (AAs) are significant basic chemicals used in pharmaceuticals, agrochemicals, dyes, fragrances, etc. Superfluous steps are always involved in obtaining AAs. Herein, we demonstrate a straightforward strategy to transform abundant o-nitrotoluenes into biologically and pharmaceutically significant AAs without any extra reductants, oxidants and protecting groups. Various sensitive groups, such as halogens, sulfide, aldehyde, pyridines, quinolines, etc., can be tolerated in this transformation. A hundred-gram-scale operation is realized efficiently with almost quantitative selenium recycling. Further mechanistic studies and DFT calculations disclosed the proposed atom-exchange processes and the key roles of the selenium species.

A di(o-tolyl)borylgold complex was synthesized via the metathesis reaction of a gold alkoxide with tetra(o-tolyl)diborane(4). The resulting diarylborylgold complex exhibited a Lewis acidic boron center and a characteristic visible absorption that arises from its HOMO–LUMO excitation, which is narrower than that of a previously reported dioxyborylgold complex. The diarylborylgold complex reacted with isocyanide in a stepwise fashion to afford single- and double-insertion products and a C–C coupled product. Reactions of this diarylborylgold complex with C Created by potrace 1.16, written by Peter Selinger 2001-2019 O/N double bond species furnished addition products under concomitant formation of Au–C and B–O/N bonds, which suggests nucleophilic reactivity of the gold metal center. DFT calculations provided details of the underlying reaction mechanism, which involves an initial coordination of the CO/N bond to the boron vacant p-orbital of the diarylboryl ligand followed by a migration of the gold atom from the tetracoordinate sp3-hybridized boron center, which is analogous to the reactivity of the conventional sp3-hybridized borate species. The DFT calculations also suggested a stepwise mechanism for the reaction of this diarylborylgold complex with isocyanide, which afforded three different reaction products depending on the applied reaction conditions., A di(o-tolyl)borylgold complex added to CO/N double bond to form Au–C and B–O/N bonds. DFT calculations revealed a two-step mechanism consisting of the coordination of O/N atom to B atom followed by nucleophilic migration of Au atom.

Transition metal-free direct and base-catalyzed 1,2-diborations of arylacetylenes using pinB-BMes2 provided a syn/anti-isomeric mixture of diborylalkenes. The kinetic analysis showed that the reaction rate and isomer ratio were affected by reaction conditions and substituents on the aryl ring. DFT calculations indicated that direct addition proceeded via the interaction of acetylene-π with the BMes2 fragment. In contrast, for the base-catalyzed diboration, the previously isolated sp2–sp3 diborane and borataallene were confirmed as stable intermediates by calculations. The whole reaction pathways can be divided into the Bpin-migration and deprotonation steps, where the borataallene should be considered as a common intermediate. It should be noted that the deprotonation step is reversible and affords the kinetically less favoured isomer under the thermodynamic conditions. As a result, the composition of isomeric products, in the base-catalyzed diboration, is attributed to the small difference of activation barriers between direct and base-catalyzed systems.

DFT calculations have been performed to study the relative preference of different unsaturated organic molecules (CO2, PhCHO and styrene) for insertion into different Cu–X (X = B, C, O) bonds, which are competing processes in copper-catalyzed three-component boracarboxylation reactions involving CO2 and B2pin2. In this work, the variations in the insertion barriers and in the relative stability of the insertion products have been systematically analyzed and discussed in-depth. Our DFT calculations also allow us to make a prediction that when both aldehyde and styrene are present with CO2 and B2pin2, styrene will undergo the three-component boracarboxylation reaction rather than the aldehyde.

First-row transition-metal catalysis has been attracting great attention in recent years, partly due to its low toxicity and low cost, as well as a wide variety in reactivities. However, the theore...

The rhodium-catalyzed deoxygenation and borylation of ketones with B2pin2 have been developed, leading to efficient formation of alkenes, vinylboronates, and vinyldiboronates. These reactions feature mild reaction conditions, a broad substrate scope, and excellent functional-group compatibility. Mechanistic studies support that the ketones initially undergo a Rh-catalyzed deoxygenation to give alkenes via boron enolate intermediates, and the subsequent Rh-catalyzed dehydrogenative borylation of alkenes leads to the formation of vinylboronates and diboration products, which is also supported by density functional theory calculations.