Electrocatalytic Access to Azetidines via Intramolecular Allylic Hydroamination: Scrutinizing Key Oxidation Steps through Electrochemical Kinetic Analysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(28), P. 15360 - 15369

Published: July 10, 2023

Azetidines are prominent structural scaffolds in bioactive molecules, medicinal chemistry, and ligand design for transition metals. However, state-of-the-art methods cannot be applied to intramolecular hydroamination of allylic amine derivatives despite their underlying potential as one the most prevalent synthetic precursors azetidines. Herein, we report an electrocatalytic method sulfonamides access azetidines first time. The merger cobalt catalysis electricity enables regioselective generation key carbocationic intermediates, which could directly undergo C-N bond formation. mechanistic investigations including electrochemical kinetic analysis suggest that either catalyst regeneration by nucleophilic cyclization or second oxidation intermediate is involved rate-determining step (RDS) our protocol highlight ability electrochemistry providing ideal means mediate oxidation.

Language: Английский

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Nickel-Catalyzed Remote Asymmetric Hydroalkylation of Alkenyl Ethers to Access Ethers of Chiral Dialkyl Carbinols

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 10411 - 10421

Published: April 26, 2023

Site- and enantio-selective alkyl-alkyl bond formation is privileged in the retrosynthetic analysis due to universality of sp3-hybridized carbon atoms organic molecules. Herein, we report a nickel-catalyzed remote asymmetric hydroalkylation alkenyl ethers via synchronous implementation alkene isomerization enantioselective C(sp3)-C(sp3) formation. Regression catalyst structure-activity relationships accelerates rational ligand modification through modular regulation. This reaction has several advantages for synthesizing chiral dialkyl carbinols their ether derivatives, including broad substrate scope, good functional group tolerance, excellent regioselectivity (>20:1 regioisomeric ratio), high enantioselectivity (up 95% enantiomeric excess).

Language: Английский

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Progression of Hydroamination Catalyzed by Late Transition-Metal Complexes from Activated to Unactivated Alkenes

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(12), P. 1565 - 1577

Published: June 5, 2023

ConspectusCatalytic intermolecular hydroamination of alkenes is an atom- and step-economical method for the synthesis amines, which have important applications as pharmaceuticals, agrochemicals, catalysts, materials. However, hydroaminations in high yield with selectivity are challenging to achieve because these reactions often lack a thermodynamic driving force accompanied by side reactions, such alkene isomerization, telomerization, oxidative amination. Consequently, early examples were generally limited additions N-H bonds conjugated or strained alkenes, catalytic unactivated late transition metals has only been disclosed recently. Many classes including metals, rare-earth acids, photocatalysts, reported hydroamination. Among them, transition-metal complexes possess several advantages, their relative ease handling compatibility substrates containing polar sensitive functional groups.This Account describes progression our laboratory catalyzed from initial activated more recent alkenes. Our developments include Markovnikov anti-Markovnikov vinylarenes palladium, rhodium, ruthenium, dienes trienes nickel hydroanimation bicyclic neutral iridium, terminal internal cationic iridium ruthenium. Enantioselective form enantioenriched, chiral amines also developed.Mechanistic studies elucidated elementary steps turnover-limiting reactions. The nickel, ruthenium occurs nucleophilic attack amine on coordinated benzyl, allyl, alkene, arene ligand. On other hand, unconjugated migratory insertion into metal-nitrogen bond. In addition, pathways formation products, isomeric enamines, identified during studies. During enantioselective hydroamination, reversibility shown erode enantiopurity products. Based mechanistic understandings, new generations catalysts that promote higher rates, chemoselectivity, enantioselectivity developed. We hope discoveries insights will facilitate further development selective, practical, efficient

Language: Английский

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Recent advances in nickel-catalyzed asymmetric hydrofunctionalization of alkenes

Chem Catalysis, Journal Year: 2022, Volume and Issue: 2(11), P. 3140 - 3162

Published: Nov. 1, 2022

Language: Английский

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Remote and Proximal Hydroaminoalkylation of Alkenes Enabled by Photoredox/Nickel Dual Catalysis

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(39), P. 17776 - 17782

Published: Sept. 22, 2022

A mild and site-selective hydroaminoalkylation of activated unactivated alkenes via dual photoredox/Ni catalysis is developed. This catalytic strategy enables exclusive access to α-selective products, which complementary previously reported photocatalytic that provides the β-selective products. The chain-walking a Ni–H intermediate toward carbonyl allows for at remote sp3 C–H sites. method tolerates broad substrate scope both amines as well providing streamlined synthesis value-added β-amino acid derivatives from readily available starting materials.

Language: Английский

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Cobalt‐Catalyzed Enantioselective Hydroamination of Arylalkenes with Secondary Amines

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(2)

Published: Nov. 7, 2022

Abstract Catalytic asymmetric hydroamination of alkenes with Lewis basic amines is great interest but remains a challenge in synthetic chemistry. Here, we developed Co‐catalyzed arylalkenes directly using commercially accessible secondary amines. This process enables the efficient access to valuable α ‐chiral tertiary good excellent yields and enantioselectivities. Mechanistic studies suggest that reaction includes CoH‐mediated hydrogen atom transfer (MHAT) arylalkenes, followed by pivotal catalyst controlled S N 2‐like pathway between situ generated electrophilic cationic alkylcobalt(IV) species free radical‐polar crossover strategy not only provides straightforward alternative approach for synthesis enantioenriched ‐tertiary amines, also underpins substantial opportunities developing radical functionalization various nucleophiles oxidative MHAT catalysis.

Language: Английский

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Catalyst‐Controlled Regiodivergent and Enantioselective Formal Hydroamination of N,N‐Disubstituted Acrylamides to α‐Tertiary‐α‐Aminolactam and β‐Aminoamide Derivatives

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(22)

Published: March 30, 2023

Enantioenriched α-tertiary-α-aminoacid and α-chiral-β-aminoacid derivatives play an important role in biological science pharmaceutical chemistry. Thus, the development of methods for their synthesis is highly valuable yet remains challenging. Herein, unprecedented catalyst-controlled regiodivergent enantioselective formal hydroamination N,N-disubstituted acrylamides with aminating agents has been developed, accessing enantioenriched α-tertiary-α-aminolactam α-chiral-β-aminoamide derivatives. Sterically-disfavored electronically-disfavored electron-deficient alkenes have successfully tuned using different transition metals chiral ligands. Notably, extremely hindered aliphatic were synthesized by Cu-H catalyzed asymmetric C-N bond forming tertiary alkyl species. accessed Ni-H anti-Markovnikov-selective hydroaminations alkenes. This set reactions tolerates a wide range functional groups to deliver diverse good yields high levels enantioselectivity.

Language: Английский

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Recent Advances in Nonprecious Metal Catalysis

Organic Process Research & Development, Journal Year: 2023, Volume and Issue: 27(3), P. 423 - 447

Published: Feb. 17, 2023

Nonprecious-metal-catalyzed alternatives to powerful precious metal transformations are of increasing interest in academia and the pharmaceutical industry due lower cost, better sustainability, toxicity. With continual growth broad field nonprecious catalysis (NPMC), we have chosen highlight selected articles published from March June 2022 which intended examples NPMC that feel may be especially relevant development. We aim inspire academic industrial innovation through discussion herein.

Language: Английский

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Nickel-Catalyzed Hydrofluorination in Unactivated Alkenes: Regio- and Enantioselective C–F Bond Formation

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9375 - 9384

Published: March 21, 2024

Catalytic formation of a regio- and enantioselective C–F bond chiral center from readily available alkenes is crucial goal, yet it continues to pose significant challenges in organic synthesis. Here, we report the regioselective bonds facilitated by NiH catalysis coordination directing strategy that enables precise hydrofluorination both terminal internal alkenes. Notably, have optimized this methodology achieve high enantioselectivity creating aliphatic stereogenic centers especially with β,γ-alkenyl substrates, using tailored Bn-BOx ligand. Another pivotal finding our research identification (+)-nonlinear effect under conditions, allowing for even moderately enantiomerically enriched ligands. Given role fluorine pharmaceuticals synthetic materials, offers essential insights into centers, paving way efficient production valuable fluorinated compounds.

Language: Английский

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Enantioselective Ni-Catalyzed 1,2-Borylalkynylation of Unactivated Alkenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(25), P. 17140 - 17149

Published: June 12, 2024

Enantioselective three-component difunctionalization of alkenes with boron reagents represents an attractive strategy for assembling three-dimensional chiral organoboron compounds. However, regio- and enantiocontrol comprise the pivot challenges in these transformations, which predominantly require use activated conjugated alkenes. Herein, by utilizing various carbonyl directing groups, including amides, sulfinamides, ketones, esters, we succeed realizing a nickel-catalyzed 1,2-borylalkynylation unactivated to enable simultaneous incorporation entity sp-fragment across double bond. The products contain boryl, alkynyl, functional groups orthogonal synthetic reactivities, offering three handles further derivatization access valuable intermediates. utility this ligand-enabled asymmetric protocol has been highlighted through late-stage decoration drug-relevant molecules.

Language: Английский

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