Chemoselective functionalizations of intrinsically less reactive C(sp3)–H bonds of alkyl nitriles are of particular interest to the chemical community because these strategies provide opportunities ...for the introduction of important cyanoalkyl groups onto target frameworks in a step-economical fashion. In recent years, the introduction of nitrile-containing alkyl radicals in tandem radical additions and oxidative couplings has inarguably brought chemists a new radical reaction platform for the diverse synthesis of natural products and pharmaceuticals. Compared with the wide applications of various C-centered radicals adjacent to a heteroatom, however, nitrile-containing alkyl radicals remain largely unexplored. New methods for C(sp3)–H bond oxidative functionalization of alkyl nitriles and new mechanistic manifolds would result in the development of a broad range of novel reactions. Therefore, this review will give an overview of various types of radical cyanoalkylation using the key alkyl nitrile reactants, which lie beyond traditional coupling chemistry.
Abstract A tandem carbonyl reduction and hydrodefluorination of β‐trifluoromethyl enones with hydrosilanes under transition‐metal‐free conditions was developed for the synthesis of a variety of ...valuable gem ‐difluorovinyl alcohols. The hydrosilane could act as both a reductive agent and a C(sp 3 )‐F bond‐breaking promoter under mild reaction conditions. Synthetically useful organofluorides, such as gem ‐fluorophosphine alkene, gem ‐difluorovinyl ketone, and fluorinated dihydrofuran derivatives could be readily constructed by further transformations of the obtained gem ‐difluorovinyl alcohols. Moreover, the method features mild reaction conditions, operational simplicity, excellent functional group tolerance, and scalability.
A step‐economical and operationally simple nickel‐catalyzed cross‐electrophile coupling of aryl phosphates with aryl bromides through C−O bond cleavage, which precluded the employment of relatively ...moisture‐labile and unreadily available organometallics, was developed. The reaction proceeded smoothly in the presence of magnesium turnings and lithium chloride in THF to afford the corresponding biaryls in moderate to good yields with reasonable functionality tolerance.
An efficient copper-catalyzed three-component cyclization for the construction of highly functionalized pyrimidine derivatives from readily available amidines, styrenes and fluoroalkyl halides is ...developed. This protocol distinguishes itself by the formation of three new C-C/C-N bonds and a new six-membered ring through a radical addition/oxidation/cyclization sequence in a one-pot manner.
An efficient palladium-catalyzed carbonylation of aryl fluorosulfates with aryl formates for the facile synthesis of esters was developed. The cross-coupling reactions proceeded effectively in the ...presence of a palladium catalyst, phosphine ligand, and triethylamine in DMF to produce the corresponding esters in moderate to good yields. Of note, functionalities or substituents, such as nitro, cyano, methoxycarbonyl, trifluoromethyl, methylsulfonyl, trifluoromethoxy, fluoro, chloro, bromo, methyl, methoxy,
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-dimethyl, and 1,3dioxolyl, were well-tolerated in the reactions, which could be kept for late-stage modification. The reactions employing readily available and relatively robust aryl fluorosulfates as coupling electrophiles could potentially serve as an attractive alternative to traditional cross-couplings with the use of aryl halides and pseudohalides as substrates.
The strong and unreactive C−F bond makes polyfluorocarbons extremely long‐lived and potentially toxic. A successive selective and controllable C(sp3)−F functionalization of polyfluoroalkylated ...ketones with S‐ and O‐nucleophiles to enable efficient synthesis of pharmaceutically important fluorine‐ and sulfur‐containing polycyclic furan and chromene derivatives under transition metal‐free conditions is demonstrated here. The combination of C−S/C−O coupling, aromatization, and cyclization cascade contribute to the accurate four/five C(sp3)−F bond cleavage at two different sites of perfluoroalkyl chain. The formation of reactive quinoid intermediates and the necessity of using TBAB (tetrabutylammonium bromide) as additive and Cs2CO3 as base were identified by detailed mechanistic studies.
Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with ...coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.
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•Spatial proteome maps of COVID-19 myocardia and microvessels are established•SARS-CoV-2-driven inflammation leads to region-resolved dysfunction of the heart•Mechanisms of dysregulated contraction, conduction, and circulation are elaborated•Myocardia and microvessels of the left atrium are affected by inflammation the most
Leng et al. establish a region-resolved proteome map of the inflammatory myocardia and microvessels of COVID-19 hearts. The myocardia and microvessels of the left atrium are the most affected by inflammation storm. These results could provide guidance in improvement of clinical treatments for cardiovascular diseases associated with COVID-19.
An aerobic coupling of benzhydryl phosphonium salts with simple alkenes for accessing trisubstituted olefins is developed under metal‐free, catalyst‐free, and additive‐free conditions. New ...C(sp3)−C(sp2) bond is constructed via the C−P and C−H bond functionalization by synergistically using O2 as a “green” oxidant and DMSO as a promoter. The method also distinguishes itself by its broad substrate scope and synthetic potential. Particularly, the use of 1,3,5‐trimethoxybenzene fragment in the resulting products as a carbon‐based leaving group for further transformations is proved to be feasible.
A H2O-promoted and (NH4)2CO3-enabled deiodoamination and defluoroiminization reaction of fluoroalkyl alkenes has been developed under transition-metal-free conditions. Structurally important ...fluoroalkylated 1,5-diazapentadienes were obtained in excellent Z-selectivity with good functional group tolerance. The versatility of the method was illustrated in the synthesis of valuable organofluorides from the obtained products. Compared to traditional synthetic methods, several apparent limitations, including distillation for purification, multistep manipulation, harsh reaction conditions, moisture exclusion, and the use of toxic/sensitive reagents, could be avoided. The key to the success of the reaction is the use of (NH4)2CO3 as a commercially available, inexpensive, low-toxic, and efficient NH2/NH source and water as a C(sp3)–F bond cleavage promoter. Moreover, the distinctive fluorine effects of perfluoroalkyl substituents on substrates are also vital for enhancing the reaction efficiency.
The unique advantages conferred by incorporation of all‐substituted carbon stereocenters in organic molecules have gained widespread recognition. In this work, we describe a three‐component ...cyclization to access C‐2 fluoroalkylated oxazolidines by fragments assembly of readily available silyl enol ether, fluoroalkyl halide, and chiral amino alcohol in a single reaction vessel, which provides an efficient strategy for expanding the pool of pharmaceutically important heterocycles featuring an all‐substituted carbon stereocenter. This process proceeds efficiently in a chemo‐, regio‐, and stereoselective fashion under mild reaction conditions at room temperature and exhibits broad functional group tolerance. The successful realization of this controlled heteroannulation sequence relies on distinctive perfluoroalkylation, regio‐ and stereoselective radical cyclization through visible‐light photoredox catalysis. Moreover, a one‐pot procedure directly employing ketone as substrate has also been achieved.
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