Since its first observation in 1907,
ortho
-quinone methide (
o
-QM) has occupied a strategic place within the framework of reactive intermediates in organic synthesis. In recent years,
o
-QM has ...enhanced its importance as a versatile reactive intermediate, and its applications in organic synthesis, material chemistry, fine chemicals, and pharmaceuticals are increasing rapidly. This critical review summarizes the key concepts behind
o
-QMs and provides an overview of current applications in organic synthesis to provide an appropriate background for synthetic, medicinal and combinatorial developments. This review covers the literature from its origin to the mid of 2014 (112 references).
In this critical review, we provide a comprehensive view of the chemistry of
ortho
-quinone methides as versatile reactive intermediates in organic synthesis.
Over the recent decade tremendous interest has been developed on the synthetic modification of natural as well as non‐proteinogenic amino acids and non‐natural linkages due to their immensely ...important applications in proteomics, diagnosis, and drug delivery etc. They are synthetically important also. For example, due to the high natural abundance of enantiopure amino acids, they and their derivatives are regularly employed in the development of several interesting synthetic methods, total syntheses of biologically related structures as well as in ligand elaboration. Thus, the synthetic field possesses a direct impact on several basic and applied sciences. But up to date only limited numbers of reviews are available which either appeared almost half a decade earlier or covered very specific areas of this highly expanding topic. Many achievements have already been realized in this field in the meantime which urgently need to be documented. Therefore, to meet the need this review is intended to cover the emerging versatile synthetic methods on the modification of amino acids and related structures over the recent decade with the relevant details of their respective prospects and problems in the best possible systematic and concise manner. Wherever needed relevant mechanistic details are also described.
Highly convergent and regioselective approach to hitherto unreported and synthetically demanding 6-cycloamino-2-(methyl/benzyl)sulfanyl-3-(aroyl/hetaroyl/alkanoyl)-4-aryl-5,6-dihydro-4H-thiopyrans ...has been developed via one-pot three-component domino coupling of β-oxodithioesters, α,β-unsaturated aldehydes, and cyclic aliphatic secondary amines at room temperature under catalyst-free and solvent-free conditions. The attractive features of this strategy include mild conditions, short reaction time, high atom-economy, excellent yields, and efficacy of forming three new bonds (C–C, C–N and C–S) and one ring in a single stroke.
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A series of novel 4-aminoquinoline analogues bearing a methyl group at 4-aminoquinoline moiety were synthesized via a new and robust synthetic route comprising in situ tert-butoxycarbonyl (Boc) ...deprotection–methylation cascade resulting in the corresponding N-methylated secondary amine using Red-Al and an efficient microwave-assisted strategy for the fusion of N-methylated secondary amine with 4-chloroquinoline nucleus to access the series of novel 4-N-methylaminoquinoline analogues. The new series of compounds were evaluated for their antimalarial activity in in vitro and in vivo models. Among 21 tested compounds, 9a–i have shown a half-maximal inhibitory concentration (IC50) value less than 0.5 μM (i.e., <500 nM) against both chloroquine-sensitive strain 3D7 and chloroquine-resistant strain K1 of Plasmodium falciparum with acceptable cytotoxicity. Based on the in vitro antimalarial activity, selected compounds were screened for their in vivo antimalarial activity against Plasmodium yoelii nigeriensis (a multidrug-resistant) parasite in Swiss mice. Most of the compounds have shown significant inhibition on day 4 post infection at the oral dose of 100 mg/kg. Compound 9a has shown 100% parasite inhibition on day 4, and out of five treated mice, two were cured till the end of the experiment. The present study suggests that 4-methylamino substitution is well tolerated for the antiplasmodial activity with reduced toxicity and therefore will be highly useful for the discovery of a new antimalarial agent against drug-resistant malaria.
An electrocatalytic pathway is disclosed for the hydrogenation and reductive pinacol coupling of aryl ketones. The operationally simple protocol neither requires an external catalyst nor any ...sacrificial anode and proceeds efficiently under the aerobic condition at an ambient temperature and pressure. Under the optimized condition, diaryl ketones transform completely to the corresponding diarylmethanols whereas aryl ketones undergo reductive pinacol coupling leading to the respective 1,2‐diol compounds in good to excellent yields. The protocol showed a high degree of substrate compatibility with moderate to very good diastereoselectivity depending on the substrates. The scope of the developed method was also extended to the different bioactive molecules opening up the possibility for their late‐stage synthetic modification.
An electrocatalytic pathway is disclosed for the hydrogenation and reductive pinacol coupling of aryl ketones. The operationally simple protocol neither requires an external catalyst nor any sacrificial anode and proceeds efficiently under the aerobic condition at an ambient temperature and pressure. Under the optimized condition, diaryl ketones transform completely to the corresponding diarylmethanols whereas aryl ketones undergo reductive pinacol coupling leading to the respective 1,2‐diol compounds in good to excellent yields. The protocol showed a high degree of substrate compatibility with moderate to very good diastereoselectivity depending on the substrates.
Abstract
Functionalization of Csp
3
−H bond meets various challenges owing to their well‐known inertness. The task becomes even more challenging for carbon‐heteroatom coupling e. g., Csp
3
−O ...coupling. Herein we report an electrochemical approach for the direct regioselctive cross‐dehydrogenative hetero‐coupling of benzylic Csp
3
−H bonds of toluidines with alcohols at room temperature under external catalyst, oxidant and base‐free condition. The developed protocol utilizes benzylic substrates as the limiting reagent for the site‐selective coupling and demonstrates wide substrate scope with respect to both the coupling partners synthesizing corresponding benzylic ethers in moderate to excellent yields.
Functionalization of Csp3−H bond meets various challenges owing to their well‐known inertness. The task becomes even more challenging for carbon‐heteroatom coupling e. g., Csp3−O coupling. Herein we ...report an electrochemical approach for the direct regioselctive cross‐dehydrogenative hetero‐coupling of benzylic Csp3−H bonds of toluidines with alcohols at room temperature under external catalyst, oxidant and base‐free condition. The developed protocol utilizes benzylic substrates as the limiting reagent for the site‐selective coupling and demonstrates wide substrate scope with respect to both the coupling partners synthesizing corresponding benzylic ethers in moderate to excellent yields.
External catalyst, base and oxidant‐free site‐selective Csp3−H alkoxylation using alcohol as the alkoxy source has been reported.
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