This Review summarizes the development of catalytic asymmetric dearomatization (CADA) reactions. The CADA reactions discussed herein include oxidative dearomatization reactions, dearomatization by ...Diels–Alder and related reactions, the alkylative dearomatization of electron‐rich arenes, transition‐metal‐catalyzed dearomatization reactions, cascade sequences involving asymmetric dearomatization as the key step, and nucleophilic dearomatization reactions of pyridinium derivatives. Asymmetric dearomatization reactions with chiral auxiliaries and catalytic asymmetric reactions of dearomatized substrates are also briefly introduced. This Review intends to provide a concept for catalytic asymmetric dearomatization.
Breaking up the party: Arenes can be transformed efficiently into enantiomerically enriched, versatile ring systems by catalytic asymmetric dearomatization reactions. Known reaction types include oxidative dearomatization, dearomatization by Diels—Alder reactions, alkylative dearomatization of electron‐rich arenes, transition‐metal‐catalyzed dearomatization reactions (see example), and cascade reaction sequences involving asymmetric dearomatization as the key step.
Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress ...to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.
From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.
Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.
LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Dearomatization reactions provide rapid access to structurally complex three-dimensional molecules from simple aromatic compounds. Plenty of reports have demonstrated their utilities in the synthesis ...of natural products, medicinal chemistry, and materials science in the last decades. Recently, visible-light mediated photocatalysis has emerged as a powerful tool to promote many kinds of transformations. The dearomatization reactions induced by visible-light have also made significant progress during the past several years. This review provides an overview of visible-light induced dearomatization reactions classified based on the manner in which aromaticity is disrupted.
Phenols are widely used as starting materials in both industrial and academic society. Dearomatization reactions of phenols provide an efficient way to construct highly functionalized ...cyclohexadienones. The main challenge to make them asymmetric by catalytic methods is to control the selectivity while overcoming the loss of aromaticity. In this tutorial review, an up to date summary of recent progress in CADA reactions of phenol and aniline derivatives is presented.
A stereodivergent synthesis of tetrahydrofuroindoles through palladium‐catalyzed asymmetric dearomative formal 3+2 cycloaddition of nitroindoles with epoxybutenes was developed. The polarity of the ...solvent was found to play a key role in the diastereoselectivity. In toluene, good to excellent yields (70–99 %), diastereoselectivity (87/13‐>95/5 d.r.), and enantioselectivity (85/15–94/6 e.r.) were obtained, regardless of the properties of the substituents on nitroindoles. In acetonitrile, tetrahydrofuroindoles of a different diastereoisomer were produced with good to excellent yields (75–98 %) and stereoselectivity (78/22–93/7 d.r., 93/7–99/1 e.r.). Mechanistic studies were conducted to illustrate the origin of the diastereodivergency. The kinetic experiments indicate that the rate‐determining step of this reaction is different in different solvents. ESI‐MS experiments also support the existence of key palladium complex intermediates and the catalytic cycle of the reaction.
Two roads diverged: A stereodivergent synthesis of tetrahydrofuroindoles through palladium‐catalyzed asymmetric dearomative formal 3+2 cycloaddition of nitroindoles with epoxybutenes was developed. The polarity of the solvent was found to play a key role in the diastereoselectivity, with toluene giving one diastereoisomer and acetonitrile giving another.
Exhaustion of cytotoxic effector natural killer (NK) and CD8
T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic ...hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/O
mice permissive for persistent HCV infection, that NK and CD8
T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8
T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8
T cell functions to prevent persistent HCV infection.
Herein we report visible‐light‐induced intramolecular double dearomative cycloaddition of arenes. Compared with the well‐known photodimerization of arenes under ultraviolet irradiation, the current ...reactions are carried out under mild conditions and feature wide substrate scope. A large array of structurally‐diverse polycyclic indoline derivatives is afforded in high yields (up to 98 %) with exclusive diastereoselectivity (>20:1 dr) via dearomative 4+2 or 2+2 pathway.
The visible‐light‐induced intramolecular double dearomative cycloaddition of arenes is reported. The reactions are carried out under mild conditions and feature a wide substrate scope. A large array of polycyclic indoline derivatives is afforded via dearomative 4+2 or 2+2 cycloaddition pathways in high yields with exclusive diastereoselectivity.
An intramolecular dearomatization of indole derivatives based on visible-light-promoted 2+2 cycloaddition was achieved via energy transfer mechanism. The highly strained cyclobutane-fused angular ...tetracyclic spiroindolines, which were typically unattainable under thermal conditions, could be directly accessed in high yields (up to 99%) with excellent diastereoselectivity (>20:1 dr) under mild conditions. The method was also compatible with diverse functional groups and amenable to flexible transformations. In addition, DFT calculations provided guidance on the rational design of substrates and deep understanding of the reaction pathways. This process constituted a rare example of indole functionalization by exploiting visible-light-induced reactivity at the excited states.
High‐performance thermal insulating aerogels are attractive candidates for thermal protection in extreme environments. However, inorganic aerogels’ brittleness and poor machinability limit their ...applications, while organic aerogels suffer from severe strength degradation and structural collapse at high temperatures. Herein, for the first time, a thermo‐responsive self‐ceramifiable aerogel is demonstrated with exceptional strengthening and thermal insulation at high temperatures. This aerogel exhibits excellent toughness and processability like polymers under normal conditions but spontaneously transforms into high‐strength semi‐crystalline hard ceramics upon exposure to high temperatures. After prolonged thermal attack at 800 °C, the strength of the aerogels does not decrease but significantly increases several‐fold (from 0.739 to 2.726 MPa). The self‐ceramization behavior and mechanism of the aerogel are illustrated in detail. The unique self‐ceramifiable capacity enables aerogels to provide fire resistance, high‐strength support, and excellent thermal insulation at ultrahigh temperatures. Even with continuous burning at 1300 °C for 60 min, the 15 mm thick aerogel shows low backside temperature below 300 °C, crack‐free overall structure, and invariant porous morphology. This self‐ceramifiable aerogel opens up a new avenue for developing thermal‐protection materials with toughness, machinability, high strength, and thermal insulation in extreme environments.
A new thermo‐responsive self‐ceramifiable aerogel is for the first time reported with exceptional strengthening and thermal insulation at high temperatures. Under normal conditions, the aerogel exhibits excellent toughness and machinability. Upon exposure to high temperatures, the aerogel spontaneously and rapidly transforms into robust semi‐crystalline hard ceramics, thus leading to fire resistance, high strength, and thermal insulation in extreme environments.
Dearomatization of indoles provides efficient synthetic routes for substituted indolines. In most cases, indoles serve as nucleophiles. Reported here is an asymmetric dearomatization reaction of ...indole derivatives that function as electrophiles. The combination of a photocatalyst and chiral phosphoric acid open to air unlocks the umpolung reactivity of indoles, enabling their dearomatization with N‐hydroxycarbamates as nucleophiles. A variety of fused indolines bearing intriguing oxy‐amines were constructed in excellent yields with moderate to high enantioselectivities. Mechanistic studies show that the realization of two sequential single‐electron transfer oxidations of the indole derivatives is key, generating the configurationally biased carbocation species while providing the source of stereochemical induction. These results not only provide an efficient synthesis of enantioenriched indoline derivatives, but also offer a novel strategy for further designing asymmetric dearomatization reactions.
Unlocked: Dearomatization of indoles and their derivatives provides efficient synthetic routes for substituted indolines. For this asymmetric dearomatization reaction the indoles function as electrophiles. The combined utilization of a photocatalyst and chiral phosphoric acid (CPA) open to air unlocks the umpolung reactivity of indoles, enabling enantioselective dearomatization of indoles with N‐hydroxycarbamates as nucleophiles.
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