Correction to "Site-Selective C-H Alkylation of Complex Arenes by a Two-Step Aryl Thianthrenation-Reductive Alkylation Sequence".
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ABSTRACT:
SUBMITTER: Lansbergen B
PROVIDER: S-EPMC8504792 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Herein, we present an undirected para-selective two-step C-H alkylation of complex arenes useful for late-stage functionalization. The combination of a site-selective C-H thianthrenation with palladium-catalyzed reductive electrophile cross-coupling grants access to a diverse range of synthetically useful alkylated arenes which cannot be accessed otherwise with comparable selectivity, diversity, and practicality. The robustness of this transformation is further demonstrated by thianthrenium-based reductive coupling of two complex fragments.
| S-EPMC8297726 | biostudies-literature
Project description:Aryl sulfinates are precursors to a diverse number of sulfonyl-derived arenes, which are common motifs in pharmaceuticals and agrochemicals. Here, we report a site-selective two-step C-H sulfination sequence via aryl sulfonium salts to access aryl sulfonamides. Combined with site-selective aromatic thianthrenation, an operationally simple one-pot palladium-catalyzed protocol introduces the sulfonyl group using sodium hydroxymethylsulfinate (Rongalite) as a source of SO22-. The hydroxymethyl sulfone intermediate generated from the catalytic process can be employed as a synthetic handle to deliver a variety of sulfonyl-containing compounds.
| S-EPMC7309323 | biostudies-literature
Project description:The reductive cleavage of the C-O bonds of aryl ethers has great potential in organic synthesis. Although several catalysts that can promote the reductive cleavage of aryl ethers have been reported, all such systems require the use of an external reductant, e.g., hydrosilane or hydrogen. Here, we report the development of a new nickel-based catalytic system that can cleave the C-O bonds of ethers in the absence of an external reductant. The hydrogen atom required in this new reductive cleavage reaction is provided by the alkoxy group of the substrate, which serves as an internal reductant. The absence of an external reductant enables the unique chemoselectivity, i.e., the selective reduction of an alkoxy group over alkenes and ketones.
| S-EPMC5659071 | biostudies-literature
Project description:A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (-OH, -NHTs, -OAc, -OTs, -OTf, -COMe, -NHBoc, -NHCbz, -CN, -SO(2)Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture. The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki-Miyaura, Stille, and Hiyama-Denmark reactions. Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R-X) and no reaction at the nucleophilic carbon (R-[M]) for organoboron (-Bpin), organotin (-SnMe(3)), and organosilicon (-SiMe(2)OH) containing organic halides (X-R-[M]). A Hammett study showed a linear correlation of σ and σ(-) parameters with the relative rate of reaction of substituted aryl bromides with bromoalkanes. The small ρ values for these correlations (1.2-1.7) indicate that oxidative addition of the bromoarene is not the turnover-frequency determining step. The rate of reaction has a positive dependence on the concentration of alkyl bromide and catalyst, no dependence upon the amount of zinc (reducing agent), and an inverse dependence upon aryl halide concentration. These results and studies with an organic reductant (TDAE) argue against the intermediacy of organozinc reagents.
| S-EPMC3324882 | biostudies-literature
Project description:DNA and RNA nucleobase modifications are biologically relevant and valuable in fundamental biochemical and biophysical investigations of nucleic acids. However, directly introducing site-specific nucleobase modifications into long unprotected oligonucleotides is a substantial challenge. In this study, we used in vitro selection to identify DNAzymes that site-specifically N-alkylate the exocyclic nucleobase amines of particular cytidine, guanosine, and adenosine (C, G and A) nucleotides in DNA substrates, by reductive amination using a 5'-benzaldehyde oligonucleotide as the reaction partner. The new DNAzymes each require one or more of Mg2+, Mn2+, and Zn2+ as metal ion cofactors and have kobs from 0.04 to 0.3 h-1, with rate enhancement as high as ∼104 above the splinted background reaction. Several of the new DNAzymes are catalytically active when an RNA substrate is provided in place of DNA. Similarly, several new DNAzymes function when a small-molecule benzaldehyde compound replaces the 5'-benzaldehyde oligonucleotide. These findings expand the scope of DNAzyme catalysis to include nucleobase N-alkylation by reductive amination. Further development of this new class of DNAzymes is anticipated to facilitate practical covalent modification and labeling of DNA and RNA substrates.
| S-EPMC11347174 | biostudies-literature
Project description:General photoactivation of electron donor-acceptor (EDA) complexes between arylsulfonium salts and 1,4-diazabicyclo[2.2.2]octane with visible light or natural sunlight was discovered. This practical and efficient mode enables the production of aryl radicals under mild conditions, providing an unrealized opportunity for two-step para-selective C-H functionalization of complex arenes. The novel mode for generating aryl radicals via an EDA complex was well supported by UV-vis absorbance measurements, nuclear magnetic resonance titration experiments, and density functional theory (DFT) calculations. The method was applied to the regio- and stereo-selective arylation of various N-heterocycles under mild conditions, yielding an assembly of challengingly linked heteroaryl-(hetero)aryl products. Remarkably, the meaningful couplings of bioactive molecules with structurally complex drugs or agricultural pharmaceuticals were achieved to display favorable in vitro antitumor activities, which will be of great value in academia or industry.
| S-EPMC9116284 | biostudies-literature
Project description:Herein, we first report an electrochemical methodology for the site-selective alkylation of azobenzenes with (thio)xanthenes in the absence of any transition metal catalyst or external oxidant. A variety of groups are compatible with this electrochemical alkylation, which furnishes the products in moderate to good yields.
| S-EPMC9370205 | biostudies-literature
Project description:Rhodium(ii)-catalyzed unusual branch-selective ortho-C-H alkylation of aryl sulfonamides with vinylsilanes was achieved using an 8-aminoquinoline directing group. Notably, the para-substituted aryl sulfonamides gave mono-(branched)alkylated products exclusively without the formation of any double C-H alkylated byproducts. The results of deuterium labeling experiments suggest that both hydrometalation and carbometalation pathways are involved in this conversion.
| S-EPMC7069504 | biostudies-literature
Project description:Substituted arenes are ubiquitous in molecules with medicinal functions, making their synthesis a critical consideration when designing synthetic routes. Regioselective C-H functionalization reactions are attractive for preparing alkylated arenes; however, the selectivity of existing methods is modest and primarily governed by the substrate's electronic properties. Here, we demonstrate a biocatalyst-controlled method for the regioselective alkylation of electron-rich and electron-deficient heteroarenes. Starting from an unselective "ene"-reductase (ERED) (GluER-T36A), we evolved a variant that selectively alkylates the C4 position of indole, an elusive position using prior technologies. Mechanistic studies across the evolutionary series indicate that changes to the protein active site alter the electronic character of the charge transfer (CT) complex responsible for radical formation. This resulted in a variant with a significant degree of ground-state CT in the CT complex. Mechanistic studies on a C2-selective ERED suggest that the evolution of GluER-T36A helps disfavor a competing mechanistic pathway. Additional protein engineering campaigns were carried out for a C8-selective quinoline alkylation. This study highlights the opportunity to use enzymes for regioselective radical reactions, where small molecule catalysts struggle to alter selectivity.
| S-EPMC10859869 | biostudies-literature
Project description:Substituted arenes are ubiquitous in molecules with medicinal functions, making their synthesis a critical consideration when designing synthetic routes. 1,2 Regioselective C-H functionalization reactions are attractive for preparing alkylated arenes, 3-5 however, the selectivity of existing methods is modest and primarily governed by substrate electronic properties. 6,7 Here, we demonstrate a biocatalyst-controlled method for the regioselective alkylation of electron-rich and electron-deficient heteroarenes. Starting from an unselective 'ene'-reductase (ERED) (GluER-T36A), we evolved a variant that selectively alkylates the C4 position of indole, an elusive position using prior technologies. Mechanistic studies across the evolutionary series indicate that changes to the protein active site alter the electronic character of the charge transfer (CT) complex responsible for radical formation. This resulted in a variant with a significant degree of ground state change transfer in the CT complex. Mechanistic studies on a C2 selective ERED suggest that the evolution of GluER-T36A helps disfavor a competing mechanistic pathway. Additional protein engineering campaigns were carried out for a C8 selective quinoline alkylation. This study highlights the opportunity to use enzymes for regioselective reactions where small molecule catalysts struggle to alter selectivity.
| S-EPMC9980219 | biostudies-literature