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Multi-component multi-functionalization reactions involving active intermediates are powerful tools for rapidly generating a wide array of compounds. Metal carbynoids, with their distinct reactivity, hold great promise for developing synthetic methodologies. However, their application in catalytic transfer reactions has been hindered by the limited availability of suitable precursors. In this study, we investigate the catalytic potential of α-halo Rh-carbenes, leveraging the concept of metal carbynoids in multi-functionalization reactions. Through a chiral phosphoric acid-catalyzed asymmetric trifunctionalization, we have developed a method for synthesizing a variety of chiral α-cyclic ketal β-amino esters with high yields and excellent enantioselectivity. Our extensive experimental and computational studies reveal that α-halo Rh-carbenes exhibit carbynoid properties, which facilitate the transformation into functionalized Fischer-type Rh-carbenes through the decomposition of the C-halo bond. The application of metal carbynoids in catalytic transfer reactions has been hindered by the limited availability of suitable precursors. Here, the authors report a chiral phosphoric acid-catalyzed asymmetric trifunctionalization, utilizing situ-generated α-Halo Rh-Carbenes as metal carbynoids, synthesizing chiral α-cyclic ketal amino esters.

Th17 cells are quite heterogeneous. Treating Th17-related inflammatory disorders requires understanding the functionally diverse subtypes in the context of tissue homeostasis, which is shaped by nutrient availability among other factors. Here, we show that increased consumption of fructose exacerbates colitis and experimental autoimmune encephalomyelitis (EAE), via pathogenic Th17 cells. Fructose selectively enhances the differentiation and function of this pathogenic subtype of Th17 cells, which are induced by a combination of IL1β, IL-6 and IL-23 (pTh17). In contrast, TGFβ1and IL-6-induced homeostatic, non-pathogenic Th17 cells remain unaffected. Notably, fructose enhances metabolic activity in pTh17 cells, leading to increased ROS production and subsequently promoting pathogenic-Th17 cell differentiation. N-acetyl cysteine (NAC), a ROS scavenger, specifically impaired pathogenic-Th17 cell immunity and mitigated high-fructose regulated colitis and EAE disease. Mechanistically, ROS accumulation results in elevated EGFR expression and phosphorylation, which leads to increased nuclear translocation. Nuclear EGFR binds to STAT3, enhancing its transcriptional activity at the CNS6 and CNS9 regions of Rorc . In summary, our work describes here a mechanism through which high fructose intake specifically exacerbates pathogenic Th17-cell-related pathologies and provides potential therapeutic targets for pTh17-mediated diseases. Th17 cells play roles in maintaining immune homeostasis but also potentially harmful inflammatory processes. Here, authors show that homeostatic and pathological Th17 cells are distinct subtypes, responding to different cytokine combinations and metabolic cues, with high fructose intake stimulating exclusively the pathological Th17 cells in vitro and in tissues.

Enantioselective α -aminomethylation of carbonyl compounds constitutes a powerful protocol for introducing aminomethyl groups to simple organic molecules. However, current strategies rely on nucleophile-based enantioselective activation with inherently activated substrates only, and enantioselective protocol based on the activation of in situ-generated unstable formaldimines remains elusive, probably owing to their unstable nature and the lack of steric environment for efficient stereocontrols. Here, based on a rhodium/chiral phosphoric acid cooperative catalysis, we achieved an enantioselective three-component reaction of α -diazo ketones with alcohols and 1,3,5-triazines. A dual hydrogen bonding between the chiral phosphoric acid catalyst and two distinct active intermediates was proposed to be crucial for the efficient electrophile-based enantiocontrol. A series of chiral β -amino- α -hydroxy ketones including those derived from simple aliphatic alcohols, allylic alcohol, propargyl alcohol, complicated natural alcohols and water could all be prepared in high efficiency and enantioselectivity. Strategies for enantioselective α -aminomethylation of carbonyl compounds rely on the chiral activation of stable ketones substrate. Here, the authors report a rhodium/chiral phosphoric acid cooperative catalysis for the three-component reaction of α -diazo ketones with alcohols and 1,3,5-triazines via imine chiral activation.

Chemical bond cleavage and reconstruction are common processes in traditional rearrangement reactions. In contrast, the process that involves bond cleavage, fragment modification and then reconstruction of the modified fragment provides an efficient way to build structurally diversified molecules. Here, we report a palladium(II)/chiral phosphoric acid catalysed three-component reaction of aryldiazoacetates, enamines and imines to afford α-amino-δ-oxo pentanoic acid derivatives in good yields with excellent diastereoselectivities and high enantioselectivities. The stereoselective reaction went through a unique process that involves cleavage of a C–N bond, modification of the resulting amino fragment and selective reassembly of the modified fragment. This innovative multi-component process represents a highly efficient way to build structurally diversified polyfunctional molecules in an atom and step economic fashion. A keto-iminium is proposed as a key intermediate and a chiral palladium/phosphate complex is proposed as an active catalyst. Multi-component reactions allow complex structures to be rapidly built from simple starting materials. Here, the authors report an enantioselective three-component coupling of imines, enamines and aryldiazoacetates catalysed by a phosphinic acid and palladium(II).

Metal carbene is an active synthetic intermediate, which has shown versatile applications in synthetic chemistry. Although a variety of catalytic methods have been disclosed for the generation of carbene species from different precursors, there is an increasing demand for the development of efficient and practical approaches for the in-situ formation of metal carbene intermediates with structural diversity and unrevealed reactivity. Herein we report a gold-catalyzed cascade protocol for the assembly of polycarbocyclic frameworks in high yields under mild reaction conditions. Mechanistic studies indicate that the unique β-aryl gold-carbene species, generated via gold-promoted 6- endo - dig diazo-yne cyclization, is the key intermediate in this reaction, followed by a [4 + 2]-cycloaddition with external alkenes. In comparison to the well-documented metal carbene cycloadditions, this carbene intermediate serves as a 4-C synthon in a cycloaddition reaction. A variety of elusive π-conjugated polycyclic hydrocarbons (CPHs) with multiple substituents are readily accessible from the initially generated products by a mild oxidation procedure. Metal carbene is usually employed as a 1-carbon synthon or 3-carbon synthon in a variety of cycloaddition reactions. Here, the authors report a gold-catalyzed cascade protocol for the assembly of polycarbocyclic frameworks via a β-aryl gold-carbene intermediate which reacts as a 4-carbon synthon with alkenes in [4 + 2]-cycloadditions.

The utilization of high-risk test cases constitutes an effective approach to enhance the safety testing of autonomous vehicles (AVs) and enhance their efficiency. This research paper presents a derivation of 2052 high-hazard pre-crash scenarios for testing autonomous driving, which were based on 23 high-hazard cut-in accident scenarios from the National Automobile Accident In-Depth Investigation System (NAIS) through combining importance sampling and combined testing methods. Compared to the direct combination of the original distribution after sampling, the proposed method has a 2.92 times higher crash rate of 69.32% for the test case set in this paper. It also has a 5.8 times higher rate of triggering Automatic Emergency Braking (AEB), improving hazardous scenario coverage. Using the proposed method, the generated parameters of the cut-in accident scenario test set were compared with those of the cut-in test scenarios included in existing Chinese autonomous driving test protocols and standards. The velocity of the ego-vehicle obtained using the proposed method matched those in the existing protocols, whereas the velocity, time gap, and time to collision of the target vehicle were significantly lower than those existing protocols indicating scenarios obtained from accident data can enrich the selection of testing scenarios for autonomous driving.

Cyclobutanone is a strained motif with broad applications, while direct assembly of the aromatic ring fused cyclobutanones beyond benzocyclobutenone (BCB) skeletons remains challenging. Herein, we report a Rh-catalyzed formal [3+2] annulation of diazo group tethered alkynes involving a 4-exo-dig carbocyclization process, providing a straightforward access to furan-fused cyclobutanones. DFT calculations disclose that, by comparison to the competitive 5- endo - dig process, 4- exo - dig carbocyclization is mainly due to lower angle strain of the key sp -hybridized vinyl cationic transition state in the cyclization step. Using less reactive catalysts Rh 2 (carboxylate) 4 is critical for high selectivity, which is explained as catalyst-substrate hydrogen bonding interaction. This method is proved successful to direct access previously inaccessible and unknown furan-fused cyclobutanone scaffolds, which can participate in a variety of post-functionalization reactions as versatile synthetic blocks. In addition, preliminary antitumor activity study of these products indicates that some molecules exhibite significant anticancer potency against different human cancer cell lines. Aromatic ring fused cyclobutanone is a strained motif with broad applications. Here, the authors report a catalytic 4- exo-dig process, which proved successful to access furan-fused cyclobutanones that can serve as versatile synthetic blocks.

Metallaphotocatalysis has been recognized as a pivotal catalysis enabling new reactivities. Traditional metallaphotocatalysis often requires two or more separate catalysts and exhibits flaw in cost and substrate-tolerance, thus representing an await-to-solve issue in catalysis. We herein realize metallaphotocatalysis with a bifunctional dirhodium tetracarboxylate ([Rh 2 ]) alone. The [Rh 2 ] shows an photocatalytic activity of promoting singlet oxygen ( 1 O 2 ) oxidation. By harnessing its photocatalytic activity, the [Rh 2 ] catalyzes a photochemical cascade reaction (PCR) via combination of carbenoid chemistry and 1 O 2 chemistry. The PCR is characterized by high atom-efficiency, excellent stereoselectivities, mild conditions, scalable synthesis, and pharmaceutically interesting products. DFT calculations-aided mechanistic study rationalizes the reaction pathway and interprets the origin of stereoselectivities of the PCR. The products show inhibitory activity against PTP1B, being promising in the treatment of type II diabetes and cancers. Overall, here we show the bifunctional [Rh 2 ] merges Rh-carbenoid chemistry and 1 O 2 chemistry. Traditional metallaphotocatalysis often requires two or more separate catalysts and is considered to be costly and not tolerant towards a wide substrate scope. Here the authors realize metallaphotocatalysis with a bifunctional dirhodium tetracarboxylate as single catalyst component to merge carbenoid chemistry and 1 O 2 chemistry.

A reaction intermediate is a key molecular entity that has been used in explaining how starting materials converts into the final products in the reaction, and it is usually unstable, highly reactive, and short-lived. Extensive efforts have been devoted in identifying and characterizing such species via advanced physico-chemical analytical techniques. As an appealing alternative, trapping experiments are powerful tools in this field. This trapping strategy opens an opportunity to discover multicomponent reactions. In this work, we report various highly diastereoselective and enantioselective four-component reactions (containing alcohols, diazoesters, enamines/indoles and aldehydes) which involve the coupling of in situ generated intermediates (iminium and enol). The reaction conditions presented herein to produce over 100 examples of four-component reaction products proceed under mild reaction conditions and show high functional group tolerance to a broad range of substrates. Based on experimental and computational analyses, a plausible mechanism of this multicomponent reaction is proposed. The interception of one chemical intermediate with another intermediate is very challenging, as intermediates may be incompatible or too reactive, but could result in a streamlined method of organic synthesis. Here, the authors demonstrate enantioselective four-component reactions via the coupling of two intermediates.

Giant panda Ailuropoda melanoleuca exhibits are popular attractions for zoos and wildlife parks. However, it remains to be investigated whether such exhibits enhance visitor knowledge about pandas and broader conservation issues. We conducted questionnaire surveys at giant panda exhibits at three city zoos and five wildlife parks in China. Although visitors were generally interested in the giant panda, this was not reflected in their post-exhibit knowledge of giant panda biology. Socio-demographically, men were more knowledgeable of giant panda biology than women. Knowledge correlated positively with respondent level of education. Younger respondents (< 45 years) knew most about giant pandas and expressed an interest in learning more about them using social media. The most informed respondents had visited other giant panda exhibits previously. Respondents were generally satisfied with the giant panda exhibits (mean score 4.44/5). Wildlife parks delivered a better educational outcome than city zoos. We recommend approaches to improve the visitor experience further and to leverage public interest in broader conservation engagement and action in China.