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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Palladium‐Catalyzed Inward Isomerization Hydroaminocarbonylation of Alkenes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)

Published: April 15, 2024

In contrast to the kinetically favored outward isomerization-hydrocarbonylation of alkenes, disfavored inward alkenes remains an important challenge. Herein, we have developed a novel and effective palladium-catalyzed isomerization-hydroaminocarbonylation unactivated aniline hydrochlorides for formation synthetically valuable α-aryl carboxylic amides in high yields site-selectivities. The efficiency reaction is attributed relay catalysis strategy, which Markovnikov-favored [PdH]-P

Language: Английский

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Photocatalytic Anti-Markovnikov Hydroamination of Alkenes with Primary Heteroaryl Amines

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(40), P. 21738 - 21744

Published: Oct. 3, 2023

We report a light-driven method for the intermolecular anti-Markovnikov hydroamination of alkenes with primary heteroaryl amines. In this protocol, electron transfer between an amine substrate and excited-state iridium photocatalyst affords aminium radical cation (ARC) intermediate that undergoes C–N bond formation nucleophilic alkene. Integral to reaction success is electronic character amine, wherein increasingly electron-deficient amines generate reactive ARCs. Counteranion-dependent reactivity observed, triflate photocatalysts are employed in place conventional hexafluorophosphate complexes. This exhibits broad functional group tolerance across 55 examples N-alkylated products derived from pharmaceutically relevant

Language: Английский

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Regio- and Enantioselective Nickel-Catalyzed Ipso- and Remote Hydroamination Utilizing Organic Azides as Amino Sources for the Synthesis of Primary Amines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Primary amines serve as key synthetic precursors to most other

Language: Английский

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Iridium‐Catalyzed Remote Site‐Switchable Hydroarylation of Alkenes Controlled by Ligands

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(41)

Published: Aug. 23, 2023

An iridium-catalyzed remote site-switchable hydroarylation of alkenes was reported, delivering the products functionalized at subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields with to excellent site-selectivities. The catalytic system showed functional group tolerance a broad substrate scope, including unactivated activated alkenes. More importantly, regioconvergent transformations mixtures isomeric were also successfully realized. results mechanistic studies demonstrate that reaction undergoes chain-walking process give [Ar-Ir-H] complex alkene. subsequent processes proceed through modified Chalk-Harrod-type mechanism via migratory insertion alkene into Ir-C bond followed C-H reductive elimination afford hydrofunctionalization site-selectively.

Language: Английский

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Iridium-Catalyzed Migratory Terminal C(sp³)–H Amidation of Heteroatom-Substituted Internal Alkenes via Olefin Chain Walking

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 31, 2023

Hydroamination facilitated by metal hydride catalysis is an appealing synthetic approach to access valuable nitrogen-containing compounds from readily available unsaturated hydrocarbons. While high regioselectivity can be achieved usually for substrates bearing polar chelation groups, the reaction involving simple alkenes frequently provides nonselective outcomes. Herein, we report iridium-catalyzed highly regioselective terminal C(sp3)-H amidation of internal utilizing dioxazolones as amino source via olefin chain walking. Most notably, this mechanistic motif double bond migration position operates not only with dialkyl-substituted including styrenes but also heteroatom-substituted olefins such enol ethers, vinyl silanes, and borons, thus representing first example methyl latter type through a nondissociative walking process.

Language: Английский

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Rhodium(III)-Catalyzed Remote Hydroamidation of Internal Alkenes Via Chain Walking

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(24), P. 16337 - 16343

Published: Dec. 6, 2023

Hydroamination of terminal alkenes represents a powerful and well-established way to introduce nitrogenous functionality feedstock chemicals. Remote hydroamination reactions are far less known represent functionalize unactivated C(sp3) centers distal the site alkene. These transformations commonly take place via metal-hydride-mediated chain walking, as such, regioselectivity can be challenging. The remote introduction amides is particular interest due their prevalence in pharmaceuticals. Herein we report Rh(III)-catalyzed hydroamidation procedure position internal alkenes, using dioxazolones amidation reagents i-PrOH hydride source. reaction proceeds with high yield tolerates variety functionality. Regioconvergent synthesis single linear amide from mixture isomeric demonstrated. Key development this was determining that inorganic bases poison catalyst identifying suitable trialkylamine replacement.

Language: Английский

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Photoredox and Cobalt-Catalyzed Markovnikov-Selective Radical Hydroamination of Unactivated Alkenes with Anilines

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

The intermolecular hydroamination of unactivated alkenes with simple amines continues to be an attractive and challenging undertaking in organic synthesis. current state-of-the-art strategies for photocatalyzed usually commence the formation a C–N bond, thereby delivering exclusively anti-Markovnikov products. We herein reported facile mild Markovnikov anilines through photoredox cobalt-catalyzed hydrogen atom transfer followed by radical-polar crossover nucleophilic amination process. reaction features wide substrate scope, good functional group tolerance, excellent yields. Application this late-stage functionalization relatively complex natural products bioactive molecules further increases utility developed methodology.

Language: Английский

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Palladium-catalyzed cascade of aza-Wacker and Povarov reactions of aryl amines and 1,6-dienes for hexahydro-cyclopenta[b]quinoline framework

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 8, 2024

Palladium catalyzed tandem reaction represents a one-pot synthetic approach to efficiently synthesize complex functionalized molecules while reducing steps, aligning with the principles of green chemistry. However, achieving direct cascade aza-Wacker and Povarov reactions in synthesis presents challenge due substrate compatibility issues between two reactions. In this work, we describe an aza-Wacker/Povarov employing highly electrophilic palladium catalyst, which effectively converts anilines 1,6-dienes into hexahydro-cyclopenta[b]quinolines. The optimized conditions yield up 79%, diastereoselectivity > 20:1. Substrate range testing reveals various sensitive functional groups, successful late-stage modifications are performed on several natural products drug molecules, demonstrating versatility practicality method. Additionally, preliminary investigation mechanism suggests process followed by process.

Language: Английский

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Remote Catalytic C(sp³)–H Alkylation via Relayed Carbenoid Transfer upon Olefin Chain Walking

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(45), P. 31114 - 31123

Published: Oct. 30, 2024

Transition metal carbenes have emerged as versatile intermediates for various types of alkylations. While reactions carbene species with alkenes been extensively studied, most examples focus on cyclopropanation and allylic C-H insertion. Herein, we present the first example a catalytic strategy carbene-involved regioselective remote alkylation internal olefins by synergistically combining two iridium-mediated reactivities olefin chain walking carbenoid migratory The method, utilizing sulfoxonium ylides bench-stable robust precursor, was found to be effective series tethered alkyl chains, heteroatom substituents, complex biorelevant moieties. Combined experimental computational studies revealed that reversible iridium hydride-mediated proceeds lead terminal alkyl-Ir intermediate, which then forms final insertion, resulting in terminal-alkylated products.

Language: Английский

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