Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enecarbamates

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(4), P. 1959 - 1967

Published: Jan. 22, 2021

Chiral alkyl amines are omnipresent as bioactive molecules and synthetic intermediates. The catalytic enantioselective synthesis of from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble wide range chiral enecarbamates (N-Cbz-protected enamines) halides with high regio- enantioselectivity. works for both nonactivated activated able produce enantiomerically enriched two minimally differentiated α-alkyl substituents. mild conditions lead functional group tolerance, which demonstrated in the postproduct functionalization many natural products drug molecules, well building blocks key intermediates compounds.

Language: Английский

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NiH-Catalyzed Functionalization of Remote and Proximal Olefins: New Reactions and Innovative Strategies

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(23), P. 3519 - 3536

Published: Nov. 9, 2022

Transition metal hydride catalyzed functionalization of remote and proximal olefins has many advantages over conventional cross-coupling reactions. It avoids the separate, prior generation stoichiometric amounts organometallic reagents use preformed reagents, which are sometimes hard to access may compromise functional group compatibility. The migratory insertion complexes generated in situ into readily available alkene starting materials, hydrometalation process, provides an attractive straightforward route alkyl intermediates, can undergo a variety sequential In particular, with synergistic combination chain-walking chemistry nickel, NiH-catalyzed undergone particularly intense development past few years. This Account aims chronicle progress made this arena terms activation modes, diverse functionalizations, chemo-, regio-, enantioselectivity.We first provide brief introduction general reaction mechanisms. Taking hydroarylation as example, four oxidation states Ni have allowed us develop two different strategies form final product: Ni(I)-H/X-Ni(II)-H platform that relies on reductants Ni(I/II/III) cycle redox-neutral or FG-Ni(II)-H reacts substrate forms products via Ni(0/II) pathway. We also demonstrate functionalization, including C-C bond-forming reactions more challenging C-N/C-S could be realized. Moreover, employment appropriate chiral ligands successfully realize corresponding asymmetric hydrofunctionalization olefins, hydroalkylation, hydroarylation, hydroalkenylation, hydroalkynylation, hydroamination. Interestingly, enantio-determining step enantioselective hydronickelation, selective oxidative addition, reductive elimination. To hydrofunctionalization, we developed ligand relay catalytic strategy simple ligands, for second coupling. novel design single, possibly structurally complex promote both steps success multicomponent convenient approach gain molecules. Finally, halides used olefin precursors cross-electrophile coupling Applications these discussed. hope will inspire future field overcome key challenges, conceptually new strategies, high-performance systems enhanced reactivity selectivity, cutting-edge catalyst design, further mechanistic studies.

Language: Английский

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Hydroamination, Aminoboration, and Carboamination with Electrophilic Amination Reagents: Umpolung-Enabled Regio- and Stereoselective Synthesis of N-Containing Molecules from Alkenes and Alkynes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(2), P. 648 - 661

Published: Jan. 6, 2022

Nitrogen (N) is ubiquitously found in bioactive molecules, pharmaceutical agents, and organic functional materials. Accordingly, development of new C–N bond-forming catalysis has been one the long-standing research subjects synthetic chemistry. In this Perspective, recent advances highly selective amination reactions with electrophilic reagents are described: by taking advantage concept nitrogen umpolung, otherwise challenging aminofunctionalizations, such as hydroamination, aminoboration, carboamination, readily available feedstock-like alkenes alkynes possible, giving densely functionalized complex often chiral alkylamines high selectivity. The scope, limitations, reaction mechanism briefly summarized.

Language: Английский

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Nickel-Catalyzed Multicomponent Coupling: Synthesis of α-Chiral Ketones by Reductive Hydrocarbonylation of Alkenes

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(35), P. 14089 - 14096

Published: Aug. 26, 2021

A nickel-catalyzed, multicomponent regio- and enantioselective coupling via sequential hydroformylation carbonylation from readily available starting materials has been developed. This modular hydrofunctionalization strategy enables the straightforward reductive hydrocarbonylation of a broad range unactivated alkenes to produce wide variety unsymmetrical dialkyl ketones bearing functionalized α-stereocenter, including enantioenriched chiral α-aryl α-amino ketones. It uses bisoxazoline as ligand, silane reductant, chloroformate safe CO source, racemic secondary benzyl chloride or an N-hydroxyphthalimide (NHP) ester protected acid alkylation reagent. The benign nature this process renders method suitable for late-stage functionalization complex molecules.

Language: Английский

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Enantioselective NiH‐Catalyzed Reductive Hydrofunctionalization of Alkenes

Chinese Journal of Chemistry, Journal Year: 2021, Volume and Issue: 40(5), P. 651 - 661

Published: Dec. 3, 2021

Comprehensive Summary Enantioselective NiH‐catalyzed reductive hydrofunctionalization of olefins has attracted much attention in recent years. Using simple chiral ligands, a wide array functionalized and electrophiles can undergo diverse transformations to afford hydrofunctionalized products, regio‐ enantioselectively. These processes avoid the prior preparation organometallic reagents, construct stereogenic center at carbon originating either from olefin or electrophile. This review discusses background, major progress mechanistic investigations this reaction.

Language: Английский

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Nickel-Catalyzed 1,2-Carboamination of Alkenyl Alcohols

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(34), P. 13962 - 13970

Published: Aug. 20, 2021

An alcohol-directed, nickel-catalyzed three-component umpolung carboamination of unactivated alkenes with aryl/alkenylboronic esters and electrophilic aminating reagents is reported. This transformation enabled by specifically tailored O-(2,6-dimethoxybenzoyl)hydroxylamine electrophiles that suppress competitive processes, including undesired β-hydride elimination transesterification between the alcohol substrate electrophile. The reaction delivers desired 1,2-carboaminated products generally high regio- syn-diastereoselectivity exhibits a broad scope coupling partners alkenes, complex natural products. Various mechanistic experiments analysis stereochemical outcome cyclic alkene substrate, as confirmed X-ray crystallographic analysis, support alcohol-directed syn-insertion an organonickel(I) species.

Language: Английский

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Thioether-Directed NiH-Catalyzed Remote γ-C(sp³)–H Hydroamidation of Alkenes by 1,4,2-Dioxazol-5-ones

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(37), P. 14962 - 14968

Published: Sept. 8, 2021

A NiH-catalyzed thioether-directed cyclometalation strategy is developed to enable remote methylene C–H bond amidation of unactivated alkenes. Due the preference for five-membered nickelacycle formation, chain-walking isomerization initiated by NiH insertion an alkene can be terminated at γ-methylene site from moiety. By employing 2,9-dibutyl-1,10-phenanthroline (L4) as ligand and dioxazolones reagent, occurs γ-C(sp3)–H bonds afford amide products in up 90% yield (>40 examples) with remarkable regioselectivity (up 24:1 rr).

Language: Английский

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A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

Chem, Journal Year: 2021, Volume and Issue: 7(11), P. 3171 - 3188

Published: Nov. 1, 2021

Language: Английский

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Facile Synthesis of Chiral Arylamines, Alkylamines and Amides by Enantioselective NiH‐Catalyzed Hydroamination

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(44), P. 23584 - 23589

Published: Aug. 27, 2021

Regio- and enantioselective hydroarylamination, hydroalkylamination hydroamidation of styrenes have been developed by NiH catalysis with a simple bioxazoline ligand under mild conditions. A wide range enantioenriched benzylic arylamines, alkylamines amides can be easily accessed nitroarenes, hydroxylamines dioxazolones, respectively as amination reagents. The chiral induction in these reactions is proposed to proceed through an enantiodifferentiating syn-hydronickellation step.

Language: Английский

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γ-Selective C(sp3)–H amination via controlled migratory hydroamination

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 27, 2021

Abstract Remote functionalization of alkenes via chain walking has generally been limited to C(sp 3 )–H bonds α and β polar-functional units, while γ -C(sp through controlled alkene transposition is a longstanding challenge. Herein, we describe NiH-catalyzed migratory formal hydroamination alkenyl amides achieved chelation-assisted control, whereby various amino groups are installed at the -position aliphatic chains. By tuning olefin isomerization ligand directing group optimization, -selective amination can be stabilization 6-membered nickellacycle by an 8-aminoquinoline subsequent interception aminating reagent. A range amines bond unactivated with varying alkyl lengths, enabling late-stage access value-added -aminated products. Moreover, employing picolinamide-coupled substrates, this approach further extended δ amination. The chain-walking mechanism pathway selectivity investigated experimental computational methods.

Language: Английский

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