Over the past decades, N‐heterocyclic carbene (NHC) organocatalysis has undergone a flourish of development on the basis of closed‐shell reaction paths. By contrast, the emerging area of ...single‐electron transfer (SET) reactions enabled by NHC catalysis still remain underdeveloped, but offer plenty of opportunities to develop new catalytic modes and useful synthetic methods. A number of interesting transformations were triggered by the SET process from the electron‐rich Breslow intermediates to various single‐electron acceptors. In additions, recent studies revealed that the Breslow radical cations could also be generated by single‐electron reduction of the electron‐deficient acyl azolium intermediates. These discoveries open a new avenue for NHC organocatalysis to harness radical reactions. The present review will focus on the exciting advancements in the dynamic area of radical NHC organocatalysis.
NHC organocatalysis: The development of N‐heterocyclic carbene (NHC) organocatalysis presents new opportunities in radical reactions. The Breslow intermediate‐based radical cations, which could be generated through single‐electron oxidation or reduction, enabled a series of novel radical transformations. These advancements greatly extend the synthetic potential of N‐heterocyclic carbene catalysis.
Fluorinated ketones are widely prevalent in numerous biologically interesting molecules, and the development of novel transformations to access these structures is an important task in organic ...synthesis. Herein, we report the multicomponent radical acylfluoroalkylation of a variety of olefins in the presence of various commercially available aromatic aldehydes and fluoroalkyl reagents through N‐heterocyclic carbene organocatalysis. With this protocol, over 120 examples of functionalized ketones with diverse fluorine substituents have been synthesized in up to 99 % yield with complete regioselectivity. The generality of this catalytic strategy was further highlighted by its successful application in the late‐stage functionalization of pharmaceutical skeletons. Excellent diastereoselectivity could be achieved in the reactions forging multiple stereocenters. In addition, preliminary results have been achieved on the catalytic asymmetric variant of the olefin difunctionalization process.
Organocatalytic acylfluoroalkylation: A multicomponent radical acylfluoroalkylation of olefins through NHC organocatalysis was developed, and over 120 examples of fluoroketones were facilely accessed from simple materials. Moreover, a dearomative difunctionalization of indoles could be readily achieved in a highly diastereoselective manner. The generality and practicality were highlighted by the late‐stage modification of drug skeletons.
The direct functionalization of inert C(sp3)−H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote ...C(sp3)−H acylation of amides and cascade cyclization through a radical‐mediated 1,5‐hydrogen atom transfer mechanism using N‐heterocyclic carbene as the catalyst. Notably, a diversity of nitrogen‐containing substrates, including simple linear aliphatic carbamates and ortho‐alkyl benzamides, can be successfully applied to this organocatalytic system. With the established protocol, over 120 examples of functionalized δ‐amino ketones and isoquinolinones with diverse substituents were easily synthesized in up to 99 % yield under mild conditions. The robustness and generality of the organocatalytic strategy were further highlighted by the successful acylation of unactivated C(sp3)−H bonds and late‐stage modification of pharmaceutical molecules. Then, the asymmetric control of the radical reaction was attempted and proven feasible by using a newly designed chiral thiazolium catalyst, and moderate enantioselectivity was obtained at the current stage. Preliminary mechanistic investigations including several control reactions, KIE experiments, and computational studies shed light on the organocatalytic radical reaction mechanism.
An N‐heterocyclic carbene catalyzed remote C(sp3)−H acylation of amides was developed, and also combined with a cascade cyclization. Over 120 functionalized δ‐amino ketones and isoquinolinones with diverse substituents were synthesized in up to 99 % yield under mild conditions. Preliminary mechanistic investigations shed light on the organocatalytic radical reaction mechanism.
Immobilization of various nanoparticles onto complex 2D or 3D macroscopic surface is an important issue for nanotechnology, but the challenge remains to explore a facile, general and environmentally ...friendly method for achieving this goal. Taking inspiration from the adhesion of marine mussels, we reported here that oxide nanoparticles of different compositions and sizes were directly and robustly anchored on the surface of monolithic foams ranging from polymer to metals in an aqueous solution of dopamine. The effective immobilization of the nanoparticles was strongly dependent on the oxidation of dopamine, which could be tuned by either pH or by adding n-dodecanethiol. Interestingly, the thiol addition not only allowed the immobilization to take place in a wide pH range, but also led to superhydrophobicity of the resulting foams. Application of the superhydrophobic foams was illustrated by fast and selective collecting oils from water surface. Because catecholic derivatives exhibit high affinity to a variety of substances, the present strategy might be extendable to fabricate hybrid nanomaterials desirable for self-cleaning, environmental protection, sensors and catalysts, and so forth.
Since it was confirmed two decades ago that the expansion of the Universe is accelerating, it would be of theoretical interests to figure out what is the influence from cosmological constant on ...detection of stochastic gravitational wave background. This paper studies the overlap reduction functions in de-Sitter space-time for a pair of one-way tracking gravitational wave detectors. It is shown to be non-trivial in an expanding Universe, because the propagation of light along line of sight also has effect on the response of GW detectors. It is found that the expansion of the Universe can enhance the value of magnitude of the overlap reduction functions, when the detector pairs are close to each other. For nanohertz gravitational waves, this effect can dominate the values of overlap reduction functions when the galactic pulsar pairs are separated by milliarcsecond.
Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been intensively studied to lower low-density lipoprotein cholesterol (LDL-C) levels. The purpose of this meta-analysis was to ...evaluate the safety and efficacy of anti-PCSK9 antibodies in randomized, controlled trials (RCTs).
PubMed, EMBASE, CENTRAL databases, and recent conferences were searched. Safety outcomes were rates of common adverse events. Efficacy outcomes included percentages of LDL-C lowering and other lipid changes compared with placebo and ezetimibe, respectively.
Twenty-five RCTs encompassing 12,200 patients were included. The rates of common adverse events were firstly reported in our study by pooling together all evidence in RCTs, showing largely no significant difference between anti-PCSK9 antibodies and placebo (or ezetimibe), except that alirocumab was associated with reduced rates of death (relative risk (RR): 0.43, 95 % confidence interval (CI): 0.19 to 0.96, P = 0.04) and an increased rate of injection-site reactions (RR: 1.48, 95 % CI: 1.05 to 2.09, P = 0.02); evolocumab reduced the rate of abnormal liver function (RR: 0.43, 95 % CI: 0.20 to 0.93, P = 0.03), both compared with placebo. No significant difference in safety outcomes was detected between monthly 420 mg and biweekly 140 mg evolocumab treatments. Monthly 420 mg evolocumab treatment significantly reduced LDL-C by -54.6 % (95 % CI: -58.7 to -50.5 %) and by absolute -78.9 mg/dl (95 % CI: -88.9 to -68.9 mg/dl) versus placebo, and by -36.3 % (95 % CI: -38.8 to -33.9 %) versus ezetimibe, and increased high-density lipoprotein cholesterol (HDL-C) by 7.6 % (95 % CI: 5.7 to 9.5 %) versus placebo and 6.4 % (95 % CI: 4.3 to 8.4 %) versus ezetimibe. An equal or even greater change was observed following biweekly 140 mg administration. Significant and favorable changes were also detected in other lipids following evolocumab treatment. Biweekly 50 to 150 mg alirocumab lowered LDL-C by -52.6 % (95 % CI: -58.2 to -47.0 %) versus placebo, by -29.9 % (95 % CI: -32.9 to -26.9 %) versus ezetimibe, and increased HDL-C by 8.0 % (95 % CI: 4.2 to 11.7 %) versus placebo.
Evolocumab and alirocumab were safe and well-tolerated from our most-powered analyses. Both antibodies substantially reduced the LDL-C level by over 50 %, increased the HDL-C level, and resulted in favorable changes in other lipids.
The first image of a black hole in the M87 galaxy taken by the Event Horizon Telescope shows that directed observation of supermassive black holes would be a promising way to test general relativity ...in strong gravity field regime. In order to calculate the shadow of rotating black holes with respect to observers located at finite distance, orthonormal tetrads have been introduced in previous works. However, it is noticed that a different choice of tetrads does not lead to the same shape of shadow for observers in near regions. In this paper, we alternatively use the formula of astrometric observables for calculating the shadow of a general rotating black hole with respect to these observers. For the sake of intuition, we also consider Kerr-de Sitter black holes as a representative example. In this space-time, size and shape of Kerr-de Sitter black hole shadows are expressed as functions of distance between the black hole and observer. It is forecasted that the distortion of the shadow would increase with distance.
PDF
