Aminoalkylation of Alkenes Enabled by Triple Radical Sorting

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

Published: Jan. 9, 2025

The direct synthesis of C(sp3)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there strong impetus to develop new methods by which access sp3-rich from commercial feedstocks, such as alkenes. Herein, we report three-component aminoalkylation reaction utilizes the principles triple radical sorting regioselectively add N-centered and C-centered radicals across This process relies upon photoredox catalysis transform alkyl bromides reductively activated precursors into high-energy species redox-neutral fashion. A broad scope coupling partners demonstrated, multiple applications, including facile syntheses pharmacophoric substituted N-heterocycles.

Language: Английский

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General (hetero)polyaryl amine synthesis via multicomponent cycloaromatization of amines

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Language: Английский

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Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10716 - 10722

Published: April 5, 2024

Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system generate aminium cation, suppress deleterious side reactions such as α-deprotonation H atom abstraction, facilitate enantioselective hydrogen transfer formidable task. Herein, we describe application of photoenzymatic catalysis harness cation for intermolecular hydroamination. In reaction, flavin-dependent ene-reductase photocatalytically generates from corresponding hydroxylamine catalyzes hydroamination furnish enantioenriched tertiary amine, whereby enantioinduction occurs through enzyme-mediated transfer. This work highlights use control highly reactive intermediates synthesis, addressing long-standing challenge chemical synthesis.

Language: Английский

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N-Protonated Acridinium Catalyst Enables Anti-Markovnikov Hydration of Unconjugated Tri- and Disubstituted Olefins

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(6), P. 4736 - 4742

Published: Jan. 31, 2025

The preparation of alcohols with anti-Markovnikov selectivity directly from olefins and water is a sought-after reaction due to its atom-economy potential cost-effectiveness. Herein, we present the first general method for direct, catalytic hydration unconjugated tri- disubstituted olefins. key advancement made possible by an oxidative (E*red = 2.15 V) N-H acridinium catalyst, which allowed functionalization alkenes that were previously unreactive in such transformations their high oxidation potential. developed protocol not limited but also enables other hydrofunctionalizations, as hydroetherifications, following same mechanistic pathway.

Language: Английский

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Copper-Catalyzed Selective Amino-alkoxycarbonylation of Unactivated Alkenes with CO

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

Published: Feb. 17, 2025

1,2-Amino-difunctionalization reactions of alkenes allow the efficient introduction different functional groups and rapid construction valuable functionalized amines. In this respect, we report a copper-catalyzed 1,2-amino-alkoxycarbonylation unactivated with CO alkylamine precursors in presence Lewis acid additive. The novel protocol allows direct access to β-amino derivatives from easily available starting materials. presented methods feature high chemo- regioselectivities, good group tolerance, substrate scope including diverse bioactive compounds drug-like molecules. Mechanistic studies indicate that additive is key realizing umpolung addition nucleophilic aminyl radicals electron-rich alkenes, which represents an elegant activation strategy for radicals.

Language: Английский

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Organic Synthesis Away from Equilibrium: Contrathermodynamic Transformations Enabled by Excited-State Electron Transfer

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(13), P. 1827 - 1838

Published: June 21, 2024

ConspectusChemists have long been inspired by biological photosynthesis, wherein a series of excited-state electron transfer (ET) events facilitate the conversion low energy starting materials such as H

Language: Английский

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A Type of Chiral C₂-Symmetric Arylthiol Catalyst for Highly Enantioselective Anti-Markovnikov Hydroamination

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(23), P. 16248 - 16256

Published: May 29, 2024

The development of chiral hydrogen donor catalysts is fundamental in the expansion and innovation asymmetric organocatalyzed reactions via an enantioselective atom transfer (HAT) process. Herein, unprecedented type C2-symmetric arylthiol derived from readily available enantiomeric lactate ester was developed. With these catalysts, anti-Markovnikov alkene hydroamination–cyclization reaction established, affording a variety pharmaceutically interesting 3-substituted piperidines with moderate to high enantioselectivity. Results designed control experiments theoretical computation rationalized origin stereocontrol disclosed spatial effect moiety thiols on We believed facile synthesis, flexible tunability, effective enantioselectivity-controlling capability would shed light versatile HAT related reactions.

Language: Английский

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Counterion Effects in [Ru(bpy)₃](X)₂-Photocatalyzed Energy Transfer Reactions

JACS Au, Journal Year: 2024, Volume and Issue: 4(8), P. 3049 - 3057

Published: July 24, 2024

Photocatalysis that uses the energy of light to promote chemical transformations by exploiting reactivity excited-state molecules is at heart a virtuous dynamic within community. Visible-light metal-based photosensitizers are most prominent in organic synthesis, thanks their versatile ligand structure tunability allowing adjust photocatalytic properties toward specific applications. Nevertheless, large majority these photocatalysts cationic species whose counterion effects remain underestimated and overlooked. In this report, we show modification X counterions constitutive [Ru(bpy)

Language: Английский

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Cooperative Phosphine-Photoredox Catalysis Enables N–H Activation of Azoles for Intermolecular Olefin Hydroamination

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 20349 - 20356

Published: July 10, 2024

Catalytic intermolecular olefin hydroamination is an enabling synthetic strategy that offers direct and atom-economical access to a variety of nitrogen-containing compounds from abundant feedstocks. However, despite numerous advances in catalyst design reaction development, N-H azoles with unactivated olefins remains unsolved problem synthesis. We report dual phosphine photoredox catalytic protocol for the structurally diverse medicinally relevant olefins. Hydroamination proceeds high anti-Markovnikov regioselectivity

Language: Английский

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Visible-Light-Induced photoredox aerobic coupling of sulfonium ylides and amines leading to E-selective formation of 2-amino-2-butene-1,4-diones

Organic Chemistry Frontiers, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A novel visible-light-induced photoredox three-component aerobic coupling reaction of sulfoxonium ylides and amines is reported.

Language: Английский

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