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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Metal-Free Photochemical Imino-Alkylation of Alkenes with Bifunctional Oxime Esters

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(34), P. 15871 - 15878

Published: Aug. 19, 2022

The concurrent installation of C-C and C-N bonds across alkene frameworks represents a powerful tool to prepare motifs that are ubiquitous in pharmaceuticals bioactive compounds. To construct such prevalent bonds, most difunctionalization methods demand the use precious metals or activated alkenes. We report metal-free, photochemically mediated imino-alkylation electronically diverse alkenes install both alkyl iminyl groups highly efficient manner. exceptionally mild reaction conditions, broad substrate scope, excellent functional group tolerance, facile one-pot protocol highlight utility this method privileged from readily available acid feedstocks. One key striking feature transformation is an electrophilic trifluoromethyl radical equally with electron-deficient electron-rich Additionally, dispersion-corrected density theory (DFT) empirical investigations provide detailed mechanistic insight into reaction.

Language: Английский

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Photoinduced Copper-Catalyzed Late-Stage Azidoarylation of Alkenes via Arylthianthrenium Salts

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(25), P. 13542 - 13548

Published: June 12, 2023

The arylethylamine pharmacophore is conserved across a range of biologically active natural products and pharmaceuticals, particularly in molecules that act on the central nervous system. Herein, we present photoinduced copper-catalyzed azidoarylation alkenes at late stage with arylthianthrenium salts, allowing access to highly functionalized acyclic (hetero)arylethylamine scaffolds are otherwise difficult access. A mechanistic study consistent rac-BINAP-CuI-azide (2) as photoactive catalytic species. We show utility new method by expedient synthesis racemic melphalan four steps through C-H functionalization.

Language: Английский

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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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Degradation of Polyacrylates by One-Pot Sequential Dehydrodecarboxylation and Ozonolysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(19), P. 10480 - 10485

Published: May 8, 2023

We establish a synthetically convenient method to degrade polyacrylate homopolymers. Carboxylic acids are installed along the polymer backbone by partial hydrolysis of ester side chains, and then, in one-pot sequential procedure, carboxylic converted into alkenes oxidatively cleaved. This process enables robustness properties polyacrylates be maintained during their usable lifetime. The ability tune degree degradation was demonstrated varying acid content polymers. is compatible with wide range polymers prepared from vinyl monomers through copolymerization acrylic different including acrylates, acrylamides, styrenics.

Language: Английский

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Nickel‐Catalyzed Switchable Site‐Selective Alkene Hydroalkylation by Temperature Regulation**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(31)

Published: May 25, 2022

Regiodivergent alkene functionalization that produces either regioisomer starting from the same raw materials is desirable. Herein, we report a nickel-catalyzed switchable site-selective hydroalkylation. The selection of reaction temperatures leads to protocols provide regiodivergent hydroalkylated products single substrate. This protocol allows convenient synthesis α- and β-branched protected amines, both which are important fields pharmaceutical chemistry biochemistry. In addition, enantioenriched alkylamines can be accessed in catalytic asymmetric variant. Preliminary mechanistic studies indicate formation more stable nickelacycle provides driving force migration. thermodynamic kinetic properties different reduction elimination intermediates responsible for site-selectivity.

Language: Английский

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The advent of electrophilic hydroxylamine-derived reagents for the direct preparation of unprotected amines

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(72), P. 9991 - 10003

Published: Jan. 1, 2022

Electrophilic aminating reagents have seen a renaissance in recent years as effective nitrogen sources for the synthesis of unprotected amino functionalities.

Language: Английский

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Endo-Selective Intramolecular Alkyne Hydroamidation Enabled by NiH Catalysis Incorporating Alkenylnickel Isomerization

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(22), P. 10064 - 10074

Published: May 27, 2022

Intramolecular alkyne hydroamidation represents a straightforward approach for the access to synthetically valuable cyclic enamides. Despite some advances made in this realm, ability attain precise regiocontrol still remains challenging, especially endo cyclization that leads six-membered and larger azacyclic rings. Herein, we report NiH-catalyzed intramolecular of alkynyl dioxazolones allows an excellent selectivity, thus affording range six- eight-membered endocyclic enamides with broad scope. Mechanistic investigations revealed Ni(I) catalysis is operative current system, proceeding via regioselective syn-hydronickelation, alkenylnickel E/Z isomerization, Ni-centered inner-sphere nitrenoid transfer. In particular, key isomerization step, which previously lacked mechanistic understandings, was found take place through η2-vinyl transition state. The synthetic value protocol demonstrated by diastereoselective modifications obtained highly functionalized δ-lactam scaffolds.

Language: Английский

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Copper-Catalyzed Stereospecific Transformations of Alkylboronic Esters

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(26), P. 11546 - 11552

Published: June 23, 2022

Copper-catalyzed stereospecific cross-couplings of boronic esters are reported. Boron "ate" complexes derived from pinacol and tert-butyl lithium undergo transmetalation to copper cyanide, followed by coupling with alkynyl bromides, allyl halides, propargylic β-haloenones, hydroxylamine esters, acyl chlorides. Through this simple transformation, commercially available inexpensive compounds can be employed convert primary secondary alkylboronic a wide array synthetically useful compounds.

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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