Rhodium(III)-Catalyzed Anti-Markovnikov Hydroamidation of Unactivated Alkenes Using Dioxazolones as Amidating Reagents

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(49), P. 22426 - 22432

Published: Dec. 1, 2022

The amide is one of the most prevalent functional groups in all pharmaceuticals, and for this reason, reactions that introduce moiety are particular value. Intermolecular hydroamidation alkenes remains an underexplored method synthesis amide-containing compounds. majority procedures exhibit Markovnikov regioselectivity, while current methods anti-Markovnikov somewhat limited to activated alkene substrates or radical processes. Herein, we report a general intermolecular unactivated under mild conditions, utilizing Rh(III) catalysis conjunction with dioxazolone amidating reagents isopropanol as environmentally friendly hydride source. reaction tolerates wide range efficiently converts electron-deficient alkenes, styrenes, 1,1-disubstituted addition their corresponding linear amides. Mechanistic studies reveal reversible rhodium migratory insertion step, leading exquisite selectivity product.

Language: Английский

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Enantioselective synthesis of α-aminoboronates by NiH-catalysed asymmetric hydroamidation of alkenyl boronates

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 26, 2022

Abstract Chiral α-aminoboronic acids and their derivatives are generally useful as bioactive compounds some have been approved therapeutic agents. Here we report a NiH-catalysed asymmetric hydroamidation process that with simple amino alcohol ligand can easily produce wide range of highly enantioenriched α-aminoboronates from alkenyl boronates dioxazolones under mild conditions. The reaction is proposed to proceed by an enantioselective hydrometallation followed inner-sphere nitrenoid transfer C–N bond forming sequence. synthetic utility this transformation was demonstrated the efficient synthesis current pharmaceutical agent, Vaborbactam.

Language: Английский

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Remote Site‐Selective Asymmetric Protoboration of Unactivated Alkenes Enabled by Bimetallic Relay Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(23)

Published: March 17, 2022

Abstract A remote C(sp 3 )−H bond asymmetric borylation of unactivated alkenes was achieved by bimetallic relay catalysis. The reaction proceeded through reversible and consecutive β‐H elimination/olefin insertion promoted CoH species generated in situ, followed copper‐catalyzed protoboration. use this synergistic Co/Cu catalysis protocol allowed the enantioselective protoboration various terminal internal alkenes, as well an unrefined mixture olefin isomers, at distal less‐reactive β‐position to a functional group, leading chiral organoboronates.

Language: Английский

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Chain Walking as a Strategy for Iridium-Catalyzed Migratory Amidation of Alkenyl Alcohols to Access α-Amino Ketones

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(9), P. 4277 - 4285

Published: Feb. 24, 2022

Catalytic carbon–nitrogen bond formation in hydrocarbons is an appealing synthetic tool to access valuable nitrogen-containing compounds. Although a number of approaches have been developed construct bifunctional α-amino carbonyl scaffold this realm, installation amino functionality at the remote and unfunctionalized aliphatic sites remains underdeveloped. Here we present tandem iridium catalysis that enables redox-relay amidation alkenyl alcohols via chain walking metal-nitrenoid transfer, which eventually offers new route various ketones with excellent regioselectivity. The virtue transformation unrefined isomeric mixture can be utilized as readily available starting materials lead regioconvergent amidation. Mechanistic investigations revealed reaction proceeds process involving two key components intermolecular nitrenoid transfer assistance hydrogen bonding, thus representing competence Ir for olefin migratory C–N coupling high efficiency exquisite selectivity.

Language: Английский

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Nickel-Catalyzed Remote C(sp³)–N/O Bond Formation of Alkenes with Unactivated Amines and Alcohols

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(7), P. 4409 - 4420

Published: March 17, 2023

Transition metal-catalyzed remote hydrofunctionalization of alkenes is an efficient method to realize C(sp3)–H functionalization. However, with unactivated amines and alcohols has not been successfully developed date. Herein, we report nickel-catalyzed hydroamination hydroetherification alcohols, accessing a series gem-diamine N,O-acetal derivatives in good high yields (up 93%) exclusive regioselectivities. The mechanistic investigations DFT computations indicated that the use 2-iodo-2-methylpropane (tBuI) as both mild hydride source radical precursor was essential afford functionalized products. This research work provides install amino or alkoxyl group at position far from double bond alkenes.

Language: Английский

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Intramolecular hydroamidation of alkenes enabling asymmetric synthesis of β-lactams via transposed NiH catalysis

Nature Catalysis, Journal Year: 2023, Volume and Issue: 6(9), P. 784 - 795

Published: Aug. 24, 2023

Language: Английский

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Ligand-Controlled NiH-Catalyzed Regiodivergent and Enantioselective Hydroamination of Alkenyl Amides

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(15), P. 10041 - 10047

Published: July 18, 2023

Transition-metal-catalyzed remote hydrofunctionalization of alkenes remains an efficient but challenging protocol in chemical synthesis. Herein, we reported a ligand-controlled, directing-group-assisted strategy to promote NiH-catalyzed site-selective (α, β, or γ) hydroamination unactivated with weakly coordinating amide groups. The key success lies the employment proper yet commercially available bidentate nitrogen-containing ligands, which enables delivery 1,1-, 1,2-, and 1,3-diamines good-to-excellent regioselectivity starting from same substrates. A broad range O-benzoylhydroxylamine electrophiles different functional groups can be installed via Ni migration nonmigration. Moreover, these predicable positionally selective protocols provide method for enantioselective synthesis highly valued 1,2-diamines (via aliphatic C–H amination) 1,3-diamines.

Language: Английский

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Remote Hydroamination of Disubstituted Alkenes by a Combination of Isomerization and Regioselective N–H Addition

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 3875 - 3881

Published: Feb. 13, 2023

Remote hydrofunctionalizations of alkenes incorporate functional groups distal to existing carbon–carbon double bonds. While remote carbonylations are well-known, most common for addition relatively nonpolar B–H, Si–H, and C–H bonds with alkenes. We report a system the hydroamination disubstituted functionalize an alkyl chain selectively at subterminal, unactivated, methylene position. Critical high regioselectivity reaction rates electronic properties substituent on amine development ligand DIP-Ad-SEGPHOS by evaluating steric effects modules reactivity selectivity. The is compatible broad scope aminopyridines enables regioconvergent synthesis amines from isomeric mixture products can be derivatized nucleophilic aromatic substitution amino variety nucleophiles.

Language: Английский

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Regiodivergent sp³ C–H Functionalization via Ni-Catalyzed Chain-Walking Reactions

JACS Au, Journal Year: 2023, Volume and Issue: 3(12), P. 3270 - 3282

Published: Nov. 28, 2023

The catalytic translocation of a metal catalyst along saturated hydrocarbon side chain constitutes powerful strategy for enabling bond-forming reactions at remote, yet previously unfunctionalized, sp3 C–H sites. In recent years, Ni-catalyzed chain-walking have offered counterintuitive strategies forging architectures that would be difficult to accomplish otherwise. Although these evolved into mature tools advanced organic synthesis, it was only recently chemists showed the ability control motion which "walks" throughout alkyl chain. Specialized ligand backbones, additives and judicious choice noninnocent functional groups on allowed design "a la carte" protocols enable regiodivergent scenarios different sites with distinct topological surface areas. Given inherent interest in increasing fraction hybridized carbons medicinal chemistry, might expedite access target leads drug discovery campaigns.

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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