The radical-involved 1,2-difunctionalization of alkenes has developed into a robust tool for preparation of complex organic molecules. Despite significant advances in this area, the catalytic ...asymmetric version still remains a challenging task mainly due to the difficulty in the stereocontrol of the highly reactive radical intermediates. Recently, owing to the good single-electron transfer ability and coordination with chiral ligands of copper catalysts, remarkable achievements in radical-involved asymmetric alkene difunctionalization have been made
via
synergistic combination of copper and chiral ligands. This tutorial review highlights the recent progress in copper-catalysed radical-involved asymmetric 1,2-difunctionalization of alkenes and the mechanistic scenarios governing the stereocontrol, with an emphasis on utilization of chiral ligands.
This tutorial review highlights the recent progress in copper-catalysed radical asymmetric 1,2-difunctionalization of alkenes.
A novel radical 1,2‐formylfunctionalization of alkenes involving 1,2(4,5)‐formyl migration triggered by addition of various carbon‐ and heteroatom‐centered radicals to alkenes has been developed for ...the first time, thus providing straightforward access to diverse β‐functionalized aldehydes with good efficiency, remarkable selectivity, and excellent functional group tolerance. Analogous transformations mediated by a keto‐carbonyl migration have also been effected under similar conditions. This method was used to access ring systems including various benzannulated nine‐, ten‐, and eleven‐membered rings, complex 6‐5(6,7)‐6(5) fused rings, and bridged rings with diverse functionalities.
The old 1,2: A novel 1,2‐formyl functionalization of unactivated alkenes involving formyl migration and addition of radicals to alkenes has been developed for access to synthetically important β‐functionalized aldehydes. The analogous keto‐carbonyl migration has been performed to synthesize challenging medium‐sized diketones, which were additionally transformed into complex fused rings.
Radical‐involved enantioselective oxidative C−H bond functionalization by a hydrogen‐atom transfer (HAT) process has emerged as a promising method for accessing functionally diverse enantioenriched ...products, while asymmetric C(sp3)−H bond amination remains a formidable challenge. To address this problem, described herein is a dual CuI/chiral phosphoric acid (CPA) catalytic system for radical‐involved enantioselective intramolecular C(sp3)−H amination of not only allylic positions but also benzylic positions with broad substrate scope. The use of 4‐methoxy‐NHPI (NHPI=N‐hydroxyphthalimide) as a stable and chemoselective HAT mediator precursor is crucial for the fulfillment of this transformation. Preliminary mechanistic studies indicate that a crucial allylic or benzylic radical intermediate resulting from a HAT process is involved.
Radical control: The first radical‐involved intramolecular enantioselective oxidative C−H amination of not only allylic substrates, but also benzylic substrates, by a hydrogen atom transfer process with a CuI/chiral phosphoric acid catalytic system is reported. Critical to the success is the use of 4‐methoxy‐PINO as a stable and chemoselective hydrogen or.
Recently, with the boosted development of radical chemistry, enantioselective functionalization of C(sp
)-H bonds via a radical pathway has witnessed a renaissance. In principle, two distinct ...catalytic modes, distinguished by the steps in which the stereochemistry is determined (the radical formation step or the radical functionalization step), can be devised. This Perspective discusses the state-of-the-art in the area of catalytic enantioselective C(sp
)-H functionalization involving radical intermediates as well as future challenges and opportunities.
Age‐associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation ...leads to the redistribution of fat to the intra‐abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β‐oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro‐inflammatory cytokines. In turn, these muscle‐secreted cytokines may exacerbate adipose tissue atrophy, support chronic low‐grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full‐blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the ‘obesity paradox’, could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full‐blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.
In contrast to the wealth of asymmetric transformations for generating central chirality from alkyl radicals, the enantiocontrol over the allenyl radicals for forging axial chirality represents an ...uncharted domain. The challenge arises from the unique elongated linear configuration of the allenyl radicals that necessitates the stereo‐differentiation of remote motifs away from the radical reaction site. We herein describe a copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes via the coupling of allenyl radicals with terminal alkynes, providing diverse synthetically challenging tetrasubstituted chiral allenes. A chiral N,N,P‐ligand is crucial for both the reaction initiation and the enantiocontrol over the highly reactive allenyl radicals. The reaction features a broad substrate scope, covering a variety of (hetero)aryl and alkyl alkynes and 1,3‐enynes as well as radical precursors with excellent functional group tolerance.
A copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes is realized, providing diverse tetrasubstituted chiral allenes. The utilization of the copper/chiral N,N,P‐ligand is crucial for the enantiocontrol over the allenyl radicals, which is difficult due to their elongated linear configuration that necessitates the stereo‐differentiation of remote motifs away from the reaction site.
The intermolecular asymmetric radical oxidative C(sp3)−C(sp) cross‐coupling of C(sp3)−H bonds with readily available terminal alkynes is a promising method to forge chiral C(sp3)−C(sp) bonds because ...of the high atom and step economy, but remains underexplored. Here, we report a copper‐catalyzed asymmetric C(sp3)−C(sp) cross‐coupling of (hetero)benzylic and (cyclic)allylic C−H bonds with terminal alkynes that occurs with high to excellent enantioselectivity. Critical to the success is the rational design of chiral oxazoline‐derived N,N,P(O)‐ligands that not only tolerate the strong oxidative conditions which are requisite for intermolecular hydrogen atom ion (HAA) processes but also induce the challenging enantiocontrol. Direct access to a range of synthetically useful chiral benzylic alkynes and 1,4‐enynes, high site‐selectivity among similar C(sp3)−H bonds, and facile synthesis of enantioenriched medicinally relevant compounds make this approach very attractive.
Chiral benzylic alkynes and 1,4‐enynes can be obtained in a straightforward approach from commercially available terminal alkynes and a diverse range of compounds containing benzylic and allylic C−H bonds by using the title reaction. The success of this approach lies in newly designed anionic N,N,P(O)‐ligands bearing a stable chiral oxazoline and a pentavalent phosphine oxide that are generated in situ.
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Conformal truncation is a powerful numerical method for solving generic strongly-coupled quantum field theories based on purely field-theoretic technics without introducing lattice ...regularization. We discuss possible speedups for performing those computations using quantum devices, with the help of near-term and future quantum algorithms. We show that this construction is very similar to quantum simulation problems appearing in quantum chemistry (which are widely investigated in quantum information science), and the renormalization group theory provides a field theory interpretation of conformal truncation simulation. Taking two-dimensional Quantum Chromodynamics (QCD) as an example, we give various explicit calculations of variational and digital quantum simulations in the level of theories, classical trials, or quantum simulators from IBM, including adiabatic state preparation, variational quantum eigensolver, imaginary time evolution, and quantum Lanczos algorithm. Our work shows that quantum computation could not only help us understand fundamental physics in the lattice approximation, but also simulate quantum field theory methods directly, which are widely used in particle and nuclear physics, sharpening the statement of the quantum Church-Turing Thesis.
An asymmetric intermolecular, three-component radical-initiated dicarbofunctionalization of 1,1-diarylalkenes with diverse carbon-centered radical precursors and electron-rich heteroaromatics by a ...copper(I) and chiral phosphoric acid cooperative catalysis strategy has been developed, providing straightforward access to chiral triarylmethanes bearing quaternary all-carbon stereocenters with high efficiency as well as excellent chemo- and enantioselectivity. The key to success is not only the introduction of a sterically demanding chiral phosphoric acid to favor radical difunctionalization over the otherwise remarkable side reactions but also the in situ generation of carbocation intermediates from benzylic radical to realize asymmetric induction with the aid of a removable hydroxy directing group via cooperative interactions with chiral phosphate. Density functional theory calculations elucidated the critical chiral environment created by the hydrogen-bonding and ion-pair interactions between the chiral phosphoric acid catalyst and substrates, which leads to the enantioselective C–C bond formation.
A copper‐catalyzed asymmetric radical oxytrifluoromethylation of alkenyl oxime and Togni's reagent has been successfully developed, thereby providing straightforward access to CF3‐containing ...isoxazolines bearing α‐tertiary stereocenters with excellent yield and enantioselectivity. The key to success is the rational design of cinchona‐alkaloid‐based sulfonamides as neutral/anionic hybrid ligands to effectively control the stereochemistry in copper‐catalyzed reactions involving free alkyl radical species. The utility of this method is illustrated by efficient transformation of the products into useful chiral CF3‐containing 1,3‐aminoalcohols.
Powerful hybrid ligand: Cinchona‐alkaloid‐based sulfonamides were designed as effective hybrid ligands for copper, which enabled catalytic asymmetric radical oxytrifluoromethylation of alkenyl oximes to give CF3‐containing isoxazolines bearing α‐tertiary stereocenters with excellent yield and enantioselectivity.
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