Enantioselective Construction of Anthracenylidene-Based Axial Chirality by Asymmetric Heck Reaction.

Anthracenylidene is an intriguing structural unit with potential in various fields. The study presents a novel approach to introducing axial chirality into this all-carbon core skeleton through a remotely controlled desymmetrization strategy. A palladium-catalyzed enantioselective Heck arylation of exocyclic double bond of anthracene with two distinct substituents at the C10 position is harnessed to realize such a transformation. The judicious identification of the P-centrally chiral ligand is pivotal to ensure the competitive competence in reactivity and stereocontrol when the heteroatom handle is absent from the anthracenylidene skeleton. Both C10 mono- and disubstituted substrates were compatible for the established catalytic system, and structurally diverse anthracenylidene-based frameworks were forged with good-to-high enantiocontrol. The subsequent derivatization of the obtained products yielded a valuable array of centrally and axially chiral molecules, thus emphasizing the practicality of this chemistry. DFT calculations shed light on the catalytic mechanism and provided insights into the origin of the experimentally observed enantioselectivity for this reaction.

Organocatalytic aromatization-promoted umpolung reaction of imines.

The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Strong nucleophiles are often required to react with the N-electrophiles without catalytic and stereochemical control. Here we show an effective strategy to realize umpolung of imines promoted by organocatalytic aromatization. The attachment of strongly electron-withdrawing groups to imines could enhance the umpolung reactivity by both electronegativity and aromatic character, enabling the direct amination of (hetero)arenes with good efficiencies and stereoselectivities. Additionally, the application of chiral Brønsted acid catalyst furnishes (hetero)aryl C-N atropisomers or enantioenriched aliphatic amines via dearomative amination from N-electrophilic aromatic precursors. Control experiments and density functional theory calculations suggest an ionic mechanism for the umpolung reaction of imines. This disconnection expands the options to forge C-N bonds stereoselectively on (hetero)arenes, which represents an important synthetic pursuit, especially in medicinal chemistry.

Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Brønsted Acid-Catalyzed Isomerization of BCBs.

Chiral cyclobutene units are commonly found in natural products and biologically active molecules. Transition-metal-catalysis has been extensively used in asymmetric synthesis of such structures, while organocatalytic approaches remain elusive. In this study, bicyclo[1.1.0]butanes are involved in enantioselective transformation for the first time to offer a highly efficient route toward cyclobutenes with good regio- and enantiocontrol. The utilization of N-triflyl phosphoramide as a chiral Brønsted acid promoter enables this isomerization process to proceed under mild conditions with low catalyst loading as well as good functional group compatibility. The resulting chiral cyclobutenes could serve as platform molecules for downstream manipulations with excellent reservation of stereochemical integrity, demonstrating the synthetic practicality of the developed method. Control experiments have also been performed to verify the formation of a key carbocation intermediate at the benzylic position.

Synthesis of Axially Chiral QUINAP Derivatives by Ketone-Catalyzed Enantioselective Oxidation.

QUINAPs have emerged as a pivotal class of axially chiral compounds with remarkable features in the stereoinduction of diverse enantioselective transformations. However, the confined substrate range and extravagant price still pose challenges, limiting their broader utilization. Herein, we describe the first atroposelective oxidation of an N atom using a chiral ketone catalyst, allowing the kinetic resolution of QUINAPOs to give both the unreacted substrates and their corresponding N-oxides with excellent enantioselectivity. Importantly, the enantioenriched products can be readily converted into the QUINAP targets without any loss of stereochemical integrity. Mechanistic investigations indicate that a dioxirane, generated through the oxidation of the ketone with oxone, acts as the active catalytic species. Furthermore, we have successfully extended this catalytic system to the kinetic resolution of QUINOLs and the dynamic kinetic transformation of pyridine analogues of QUINAPO possessing a labile stereogenic axis. The practicality of the developed protocol is further demonstrated by the successful application of QUINAPO N-oxide as a Lewis base catalyst in a series of enantioselective transformations.

Organocatalytic Atroposelective Cross-Coupling of 1-Azonaphthalenes and 2-Naphthols.

Atroposelective cross-coupling is one of the most appealing routes to construct axially chiral binaphthyl molecules due to the modular and succinct nature. Although transition-metal-catalyzed cross-couplings offer reliable synthetic means, alternative reaction modes that could be applied to broader substrate range without their pre-functionalization is highly desirable. Herein we show that the application of chiral Brønsted acid catalyst as organocatalyst could accomplish cross-coupling of 1-azonaphthalenes and 2-naphthols with high efficiency, exclusive C4-selectivity as well as excellent enantioselectivity and functional group compatibility. The identification of acylimidazolinone auxiliary for azo activating group, effective remote catalyst control and arene resonance effect synergistically play key roles in the development of this method. The utility is further demonstrated by transformations of the products into other binaphthyl compounds with perfectly retained axial chirality.

Modular enantioselective access to ß-amino amides by Brønsted acid-catalysed multicomponent reactions.

ß-Amino acids are structural motifs widely found in therapeutic natural products, novel biomimetic polymers and peptidomimetics. As a convergent method, the synthesis of stereoenriched ß-amino amides through the asymmetric Mannich reaction requires specialized amide substrates or a metal catalyst for enolate formation. By a redesign of the Ugi reaction, a conceptually different solution to prepare chiral ß-amino amides was established using ambiphilic ynamides as two-carbon synthons. The modulation of ynamides or oxygen nucleophiles concisely furnished three classes of ß-amino amides with generally good efficiency as well as excellent chemo- and stereo-control. The utility is verified in the preparation of over 100 desired products that bear one or two contiguous carbon stereocentres, including those that directly incorporate drug molecules. This advance also provides a synthetic shortcut to other valuable structures. The amino amides could be elaborated into ß-amino acids, anti-vicinal diamines, γ-amino alcohols and ß-lactams or undergo transamidation with amino acids and amine-containing pharmaceuticals.

Enantioselective construction of triaryl-substituted all-carbon quaternary stereocenters via organocatalytic arylation of oxindoles with azonaphthalenes.

Azonaphthalenes have been verified as a class of effective arylation reagents in a variety of asymmetric transformations. Here a highly efficient approach to construct triaryl-substituted all-carbon quaternary stereocenters through chiral phosphoric acid-catalyzed enantioselective arylation of 3-aryl-2-oxindoles with azonaphthalenes is disclosed. This chemistry is scalable and displays excellent functional group tolerance, furnishing a series of 3,3-disubstituted 2-oxindole derivatives in good yields with excellent enantiocontrol. Preliminary mechanistic data suggest that the initially formed direct addition intermediate undergoes intramolecular annulation under acidic reaction conditions.

Phosphoric Acid-Catalyzed Enantioselective Synthesis of Axially Chiral Anthrone-based Compounds.

Anthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2 -rich nature imposes inherent obstruction to introduce stereogenic element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone-derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long-range chirality control. The enantioenriched anthrones could be elaborated into dibenzo-fused seven-membered N-heterocycles containing well-defined stereogenic center via Beckmann rearrangement with axial-to-point chirality conversion.

Acid Catalyzed Stereocontrolled Ferrier-Type Glycosylation Assisted by Perfluorinated Solvent.

Described herein is the first application of perfluorinated solvent in the stereoselective formation of O-/S-glycosidic linkages that occurs via a Ferrier rearrangement of acetylated glycals. In this system, the weak interactions between perfluoro-n-hexane and substrates could augment the reactivity and stereocontrol. The initiation of transformation requires only an extremely low loading of resin-H+ and the mild conditions enable the accommodation of a broad spectrum of glycal donors and acceptors. The 'green' feature of this chemistry is demonstrated by low toxicity and easy recovery of the medium, as well as operational simplicity in product isolation.

Organocatalytic Enantioselective Synthesis of Axially Chiral Molecules: Development of Strategies and Skeletons.

The growing importance of axially chiral architectures in different scientific domains has unveiled shortcomings in terms of efficient synthetic access and skeletal variety. This account describes our strategies in answering these challenges within the organocatalytic context where the emergence of bifunctional catalysts such as chiral phosphoric acids (CPAs) has proven invaluable in controlling the sense of axial chirality. The wide occurrence of bi(hetero)aryl skeletons in privileged structures constitutes a strong motivation to devise more effective arylation methods. Our design revolves around modulating the intrinsic nucleophilicity of aromatic amines and alcohols. The first approach involves the design of an electron-withdrawing activating group which could associate with the catalyst for reactivity enhancement and selectivity control. The resonance of arenes offers the unique mechanistic possibility to select between activating sites. C2-Azo- and nitroso-substituted naphthalenes undergo atroposelective ortho C- or N-arylation with (hetero)aromatic nucleophiles. For monocyclic benzenes, programmable charge localization leads to regioselective activation by catalytic control alone or aided by substrate design. For instance, selective addition to nitroso nitrogen enables successive annulation initiated by the amine to yield axially chiral N-arylbenzimidazoles. In a biomimetic manner, a finely tuned catalyst could direct a para-selective nucleophilic approach in the atroposelective arylation of azobenzenes. The second strategy employs electrophilic arene precursors for arylation which occurs via rearomatization with central-to-axial chirality transfer. This enabled the arylation of (imino)quinones with indoles to access phenylindole atropisomers. By adapting this chemistry with an additional oxidation event to liberate the carbonyl functionalities, aryl-o-naphthoquinone and aryl-p-quinone atropisomers were attained. Along with the development of new arylation strategies, deriving new axially chiral structures has been another consistent theme of our research program. The atroposelective functionalization of alkynes provides broad entry to atropisomeric alkenes. The monofunctionalization of alkynes through the interception of an electrophilic vinylidene-quinone-methide (VQM) intermediate with 2-naphthols yielded the new EBINOL scaffolds. By designing an internal directing group, the atroposelective dihalogenation of alkynes was realized using abundant alkali halides despite their weak nucleophilicities and poor solubilities. The atroposelective N-alkylation of alkenes was pursued to prepare multifunctionalized alkene atropisomers that could be converted into 2-arylpyrroles with chirality transfer. The synthesis of B-aryl-1,2-azaborines containing a C-B chiral axis was accomplished where the CPA catalyst effects the desymmetrization and defines the configuration of the distal C-B bond. Inspired by the axially chiral scaffold of allenes, we leveraged the developed arene activation strategy to achieve para-addition and dearomatization of judiciously designed azobenzenes, which led to structurally novel cyclohexadienylidene-based hydrazones. To complement these structures, axially chiral cyclohexadienyl oxime ethers were also attained through CPA-catalyzed condensation between hydroxylamines and spiro[4.5]trienones.

Asymmetric Construction of an Aryl-Alkene Axis by Palladium-Catalyzed Suzuki-Miyaura Coupling Reaction.

The application of Suzuki-Miyaura coupling reaction to forge the atropisomeric biaryls has seen remarkable progress but exploration of this chemistry to directly forge chiral C(aryl)-C(alkene) axis is underdeveloped. The replacement of arene substrates by alkenes intensifies the challenges in terms of reactivity, configurational atropostability of product and selectivity control. By meticulous ligand design and fine-tuning of reaction parameters, we identified a highly active 3,3'-triphenylsilyl-substituted phosphite ligand to realize arene-alkene Suzuki-Miyaura coupling of hindered aryl halides and vinyl boronates under very mild conditions. The axially chiral acyclic aryl-alkenes were generated in commendable efficiency, enantioselectivity and E/Z selectivity.

ß-C-Glycosylation with 2-Oxindole Acceptors via Palladium-Catalyzed Decarboxylative Reactions.

This report describes a highly efficient ß-selective C-glycosylation of bicyclic galactals with 2-oxindoles through a palladium-catalyzed decarboxylative pathway. A variety of substrates representing both glycosyl donors and acceptors could be transformed in greater than 90% yields under mild reaction conditions. The decarboxylation intermediate of galactal could serve as an efficient base to deprotonate the enol tautomer of 2-oxindole and enhance its nucleophilicity. The ß-selective nucleophilic addition at the anomeric center originates from the steric hindrance imposed by the palladium and bulky ligand.

Towards more efficient ophthalmic disease classification and lesion location via convolution transformer.

OBJECTIVE: A retina optical coherence tomography (OCT) image differs from a traditional image due to its significant speckle noise, irregularity, and inconspicuous features. A conventional deep learning architecture cannot effectively improve the classification accuracy, sensitivity, and specificity of OCT images, and noisy images are not conducive to further diagnosis.  This paper proposes a novel lesion-localization convolution transformer (LLCT) method, which combines both convolution and self-attention to classify ophthalmic diseases more accurately and localize the lesions in retina OCT images. METHODS: A novel architecture design is accomplished through applying customized feature maps generated by convolutional neutral network (CNN) as the input sequence of self-attention network. This design takes advantages of CNN's extracting image features and transformer's consideration of global context and dynamic attention. Part of the model is backward propagated to calculate the gradient as a weight parameter, which is multiplied and summed with the global features generated by the forward propagation process to locate the lesion. RESULTS: Extensive experiments show that our proposed design achieves improvement of about 7.6% in overall accuracy, 10.9% in overall sensitivity, and 9.2% in overall specificity compared with previous methods. And the lesions can be localized without the labeling data of lesion location in OCT images. CONCLUSION: The results prove that our method significantly improves the performance and reduces the computation complexity in artificial intelligence assisted analysis of ophthalmic disease through OCT images. SIGNIFICANCE: Our method has a significance boost in ophthalmic disease classification and location via convolution transformer. This is applicable to assist ophthalmologists greatly.1.

Direct arylation of N-heterocycles enabled by photoredox catalysis.

N-Heterobiaryls are common skeletons found in biological molecules, pharmaceuticals and ligands. Herein, we document an efficient and redox-neutral photocatalytic system to obtain functionalized N-heterobiaryls under mild conditions. Substrates bearing variegated functional groups are compatible with the developed photocatalytic conditions. This method is translatable to gram-scale synthesis, with a photocatalyst loading as low as 0.1 mol% and minimal variation of the yield. The starting materials are commercially available, demonstrating the practicality and accessibility of this methodology. Interestingly, phenols can serve both as coupling partners and proton donors. Arenes without a phenolic hydroxyl group also underwent efficient coupling with HFIP as a solvent.

Facile synthesis of N-aryl phenothiazines and phenoxazines via Brønsted acid catalyzed C-H amination of arenes.

N-Aryl phenothiazines and phenoxazines are of significant importance in various disciplines throughout academia and industry. The conventional synthetic strategy for the construction of these structures centers on the transition-metal-catalyzed cross-coupling of aryl halides with phenothiazines or phenoxazines. Here we present an organocatalytic approach to access N-naphthyl phenothiazine and phenoxazine scaffolds through a straightforward C-H amination of arenes as enabled by an azo group. This reaction features operational simplicity, adequate substrate generality and excellent functional group compatibility. Notably, the efficiency of the catalyst could be perfectly preserved after 5 catalytic cycles.

Review and classification of AI-enabled COVID-19 CT imaging models based on computer vision tasks.

This article presents a systematic overview of artificial intelligence (AI) and computer vision strategies for diagnosing the coronavirus disease of 2019 (COVID-19) using computerized tomography (CT) medical images. We analyzed the previous review works and found that all of them ignored classifying and categorizing COVID-19 literature based on computer vision tasks, such as classification, segmentation, and detection. Most of the COVID-19 CT diagnosis methods comprehensively use segmentation and classification tasks. Moreover, most of the review articles are diverse and cover CT as well as X-ray images. Therefore, we focused on the COVID-19 diagnostic methods based on CT images. Well-known search engines and databases such as Google, Google Scholar, Kaggle, Baidu, IEEE Xplore, Web of Science, PubMed, ScienceDirect, and Scopus were utilized to collect relevant studies. After deep analysis, we collected 114 studies and reported highly enriched information for each selected research. According to our analysis, AI and computer vision have substantial potential for rapid COVID-19 diagnosis as they could significantly assist in automating the diagnosis process. Accurate and efficient models will have real-time clinical implications, though further research is still required. Categorization of literature based on computer vision tasks could be helpful for future research; therefore, this review article will provide a good foundation for conducting such research.

Quality factor of partially coherent Airy beams in a turbulent atmosphere.

The quality factor of a partially coherent Airy beam in a turbulent atmosphere is investigated with the help of the extended Huygens-Fresnel integral formula and the Wigner distribution. From the numerical results, based on the analytical formula, we find that increasing the inner scale or decreasing the structure constant of the refractive index fluctuations of the turbulent atmosphere tends to decrease the quality factor of a partially coherent Airy beam in a turbulent atmosphere. Moreover, it is found that increasing the scale factor and wavelength or decreasing the coherent length of a partially coherent Airy beam can also be used to decrease the quality factor of a partially coherent Airy beam in a turbulent atmosphere. However, the quality factor of a partially coherent Airy beam in a turbulent atmosphere has a maximum when the exponential truncation factor of a partially coherent Airy beam is 0.63. Our results will be useful in long-distance free-space optical communications and laser defense.

Nitrosobenzene-Enabled Chiral Phosphoric Acid Catalyzed Enantioselective Construction of Atropisomeric N-Arylbenzimidazoles.

Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N-arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed to transform two classes of 2-naphthylamine derivatives into structurally diverse N-arylbenzimidazole atropisomers with excellent chemo- and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C-N bond formation while the resulting amine performs the nucleophilic addition to form the second C-N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N-arylbenzimidazoles for their potential utilities in asymmetric catalysis.

Electrochemical phenothiazination of naphthylamines and its application in photocatalysis.

N-Phenylphenothiazine as an inexpensive, highly reductive and oxygen tolerant organophotocatalyst has exhibited potential in various challenging photochemical transformations. Here we report a general and straightforward method to access structurally diverse N-phenylphenothiazine derivatives by means of a novel electrochemical tool. The introduction of a 2-naphthylamine moiety with an extended π-system and an amine group led to the variation of spectral characterization. Photochemical verification experiments demonstrated that the formed N-arylation products with good efficacy and chemo/site-control displayed competitive catalytic activity in challenging transformations.

Organocatalyst-controlled site-selective arene C-H functionalization.

Over the past three decades, organocatalysis has emerged as a powerful catalysis platform and has gradually been incorporated into the routine synthetic toolbox to obtain chiral molecules. However, its application in the site- and enantioselective functionalization of inactive aryl C-H bonds remains in its infancy. Here, we present an organocatalyst-controlled para-selective arene C-H functionalization strategy that addresses this issue, which remains an enduring challenge in arene functionalization chemistry. By emulating enzyme catalysis, the chiral phosphoric acid catalyst offers an ideal chiral environment for stereoinduction, and the projecting substituents give control of chemo- and site-selectivity. Various types of nucleophile are compatible with this method, affording more than 100 para-selective adducts with stereodefined carbon centres or axes in viable molecular contexts. This protocol is expected to provide a general strategy for para-selective functionalization of arene C-H bonds in a controlled manner.