Hydrodealkenylative C(sp³)–C(sp²) Bond Fragmentation Using Isayama–Mukaiyama Peroxidation

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Advancements in radical capture strategies have expanded the range of products accessible from alkenes through dealkenylative synthesis. These methods, however, are still limited, as they rely on ozonolysis to generate key peroxide intermediates alkenes. Ozonolysis has several limitations. It is not compatible with containing electron-rich aromatics. also inapplicable certain alkene substitution patterns context Additionally, it struggles sterically hindered alkenes, internal nucleophiles and electrophiles, allylic alcohols. In this paper, using Isayama-Mukaiyama peroxidation (IMP), we address limitations rescue previously inaccessible substrates broaden applicability functionalization. particular, apply IMP hydrodealkenylation describe a novel hydrogenation condition─employing catalytic [FeIII], benzenethiol, γ-terpinene refluxing methanol─to resolve β-scission issues associated IMP-generated alkyl silylperoxides.

Language: Английский

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C(sp3)–heteroatom bond formation by iron-catalyzed soft couplings

Communications Chemistry, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 8, 2025

Carbon–heteroatom bonds are of great importance due to their prevalence in pharmaceuticals, agrochemicals, materials, and natural products. Despite the effective use metal-catalyzed cross-coupling reactions between sp2-hybridized organohalides soft heteroatomic nucleophiles for carbon–heteroatom bond formation, sp3-hybridized remain limited coupling with thiols remains elusive. Here, we report benzyl or tertiary halides thiol catalyzed by iron extend utility alcohol amine nucleophiles. The reaction is broad substrate scope both partners applicable construction congested tri- tetrasubstituted carbon centers as well β-quaternary synthetic further emphasized gram-scale synthesis rapid herbicide library synthesis. Overall, provide an efficient method prepare pharmaceutically materially relevant expanding iron-catalyzed organic chemistry, however, approaches access substrates limited. authors thiol,

Language: Английский

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Enantioselective Hydrodifluoroalkylation of Alkenes with Conformationally Tuned Peptidyl Hydrogen Atom Transfer Catalysts

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

We report the enantioselective hydrodifluoroalkylation of alkenes proceeding via an asymmetric hydrogen atom transfer (HAT) event catalyzed by thiol-containing tetrapeptides. Photocatalytic generation a difluoroacetyl radical followed carbon–carbon bond formation results in prochiral carbon-centered that engages with chiral catalyst. A trialkylamine reductant is proposed to turn over catalyst this net-reductive transformation. Notably, incorporating (S)-β-methyl-substituted cysteine as N-terminal residue improved selectivity relative native (Cys) residue, and X-ray crystallographic analysis supports conformational underpinning effect. range enantioenriched γ-substituted amides were synthesized up 96:4 enantiomeric ratio, demonstrating broad functional group tolerance method. Models accounting for induction are supporting DFT calculations.

Language: Английский

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Synthesis through C(sp³)–C(sp²) Bond Scission in Alkenes and Ketones

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

ConspectusThe homolytic cleavage of C-C bonds adjacent to functional groups has recently become a popular strategy for restructuring the skeletons complex organic molecules. In contrast traditional reactivity profiles polar bond disconnections, scission furnishes carbon-centered free radicals primed controlled termination with diverse range radicophiles. Beyond standard radical capture, transition-metal catalysis facilitates sophisticated and C-heteroatom bond-forming reactions. Intensive efforts have been focused over many years into neighboring carboxylic acids alcohols. Despite ubiquity alkenes ketones in natural products, feedstock chemicals, common synthetic intermediates, much less attention paid exploiting their potential diversifying chiral pool materials, such as terpenes terpenoids. Defunctionalization this manner is powerful approach synthesizing high-value chemicals advanced intermediates because possibility reconstruct further decorate chirality-bearing carbon skeletons. Motivated by necessity, since 2018 our group on developing ozonolysis-based dealkenylative molecular diversification, we expanded deacylation 2025. Account, chronicle initial motivation, describe historical background, summarize research deacylative synthesis. Our capitalizes ozonolysis MeOH generate α-methoxyhydroperoxides reaction reducing agents. Their reduction through single electron transfer, mediated transition metal, leads formation an alkoxyl that undergoes rapid β-scission, furnishing both ester derived from acetal atom. The produced can be strategically terminated radicophiles, thereby delivering remodeled Using concept, developed hydrodealkenylation (through hydrogen atom transfer benzenethiol), thiylation thiyl diaryl disulfides), alkenylation addition/elimination nitrostyrenes), oxodealkenylation treatment TEMPO followed oxidation). Furthermore, kinetic analysis enabled development catalytic FeII/vitamin C system alkynylation halodealkenylation. Synergizing copper aminodealkenylation net-redox-neutral C-N formation. Although high oxidation ozone relative compounds makes alkene-to-peroxide conversion possible, it also limits applicability techniques substrates featuring ozone-sensitive groups. We overcame constraint first applying Isayama-Mukayiama peroxidation olefins then using novel system─catalytic FeIII PhSH stoichiometric γ-terpinene─for ozone-free hydrodealkenylation. alkenes, straightforward methodology well, including cycloalkanones. This process applicable total syntheses late-stage modifications ketone-containing products.

Language: Английский

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Nickel‐Catalyzed Hydrogenation of Enamides and Quinolines via Photoinduced Hydrogen Atom Transfer

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Comprehensive Summary Radical hydrogenation facilitated by metal (Fe, Co, Mn, etc .) hydride‐mediated hydrogen atom transfer ( m HAT) has emerged as a powerful technique in organic synthesis. However, nickel‐hydride (NiH) catalyzed radical remained largely unexplored. Herein, we develop NiH catalytic system that achieves the of enamides high efficiency. This strategy stands out for its ability to hydrogenate challenging quinolines at room temperature, avoiding catalyst poisoning and deactivation their products. Furthermore, deuteration alkenes was achieved with rates (up > 99%), underscoring potential synthesis deuterium‐containing molecules.

Language: Английский

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Directed Hydrogen Atom Transfer for Selective Reactions of Polyenols

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18224 - 18229

Published: June 25, 2024

Directed hydrogen atom transfer to alkenes is described. The process catalyzed by iron complexes and allows for the site-selective hydrofunctionalization of polyenols. Experimental data suggest that coordination hydroxy group hydride intermediate plays an important role in preferential engagement allylic alcohol motif provides a new basis selectivity radical events. As proof concept, β- γ-amino alcohols are prepared from corresponding polyenols selective manner.

Language: Английский

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C(sp3) Cross-Couplings of Benzyl and Tertiary Halides with Thiols or Alcohols Catalyzed by Iron

Published: June 19, 2024

Various metal catalysts have proven effective in carbon–heteroatom bond formation with softer heteroatomic nucleophiles, but examples remain largely limited to sp2 hybridized carbon electrophiles. Here, we report the coupling of sp3 benzyl or tertiary halides soft thiol nucleophiles catalyzed by iron. The reaction is broad substrate scope for both partners and applicable construction congested tri- tetrasubstituted carbon-centers as well beta-quaternary thioethers. synthetic utility further emphasized alcohol gram-scale synthesis, bioconjugation, rapid herbicide library synthesis. Results from mechanistic experiments are consistent a stereoablative pathway that likely involves radical intermediate. Overall, provide an efficient method prepare pharmaceutically materially relevant carbon–sulfur carbon–oxygen bonds expanding iron-catalyzed cross-coupling reactions electrophiles nucleophiles.

Language: Английский

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Building Catalytic Reactions One Electron at a Time

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

ConspectusClassical education in organic chemistry and catalysis, not the least my own, has centered on two-electron transformations, from nucleophilic attack to oxidative addition. The focus is well-founded, as this brand of enabled incredible feats synthesis, development life-saving pharmaceuticals production ubiquitous commodity chemicals. With that said, approach many ways complementary nature, where enzymes frequently make use single-electron "radical" steps achieve challenging reactions with exceptional selectivity, including light detection C-H hydroxylation. While power radical elementary undeniable, fundamental understanding of─and ability apply─these catalysis remains underdeveloped, constraining palette which chemists can new reactions.Motivation remedy traditional underemphasis been intensified by runaway success outer-sphere photoredox only confirming versatility radicals anthropogenic but also teaching value robust well-understood catalytic cycles for reaction design. Indeed, I would argue fueled strong its underlying steps, consideration transfer (SET) energetics allowing be designed

Language: Английский

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