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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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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Merging NiH Catalysis and Inner-Sphere Metal-Nitrenoid Transfer for Hydroamidation of Alkynes

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(15), P. 5867 - 5877

Published: April 9, 2021

The formal hydroamination/hydroamidation utilizing metal hydride is an appealing synthetic tool for the construction of valuable nitrogen-containing compounds from unsaturated hydrocarbons. While significant advances have been made functionalizations alkenes in this realm, direct hydroamidation alkynes remains rather limited due to high feasibility key metal-alkenyl intermediate choose other reaction pathways. Herein, we report a NiH-catalyzed strategy with dioxazolones, which allows convenient access synthetically useful secondary enamides (E)-anti-Markovnikov or Markovnikov selectivity. viable both terminal and internal also tolerant range subtle functional groups. With H2O found as essential component catalyst turnovers, involvement inner-sphere nitrenoid transfer proposed that outcompetes undesired semireduction process, thus representing first example show competence Ni catalysis metal-nitrenoid formation dioxazolones.

Language: Английский

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Ligand-Controlled Cobalt-Catalyzed Regiodivergent Alkyne Hydroalkylation

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(30), P. 13961 - 13972

Published: July 22, 2022

Regiodivergent alkyne hydroalkylation to generate different isomers of an alkene from the same starting material would be beneficial; however, it remains a challenge. Herein, we report ligand-controlled cobalt-catalyzed regiodivergent hydroalkylation. The sensible selection bisoxazoline (L1) and pyridine-oxazoline (L8) ligands led reliable predictable protocols that provided (E)-1,2-disubstituted 1,1-disubstituted alkenes with high E/Z stereoselectivity regioisomeric ratio identical terminal alkyl halide substrates produced trisubstituted in case internal alkynes. This method exhibits broad scope for alkynes wide range activated unactivated halides shows excellent functional group compatibility.

Language: Английский

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Enantioselective Hydrothiolation: Diverging Cyclopropenes through Ligand Control

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(16), P. 6176 - 6184

Published: April 15, 2021

In this article, we advance Rh-catalyzed hydrothiolation through the divergent reactivity of cyclopropenes. Cyclopropenes undergo to provide cyclopropyl sulfides or allylic sulfides. The choice bisphosphine ligand dictates whether pathway involves ring-retention ring-opening. Mechanistic studies reveal origin for switchable selectivity. Our results suggest two pathways share a common cyclopropyl-Rh(III) intermediate. Electron-rich Josiphos ligands promote direct reductive elimination from intermediate afford in high enantio- and diastereoselectivities. Alternatively, atropisomeric (such as DTBM-BINAP) enable ring-opening generate with regiocontrol.

Language: Английский

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Orthogonal Regulation of Nucleophilic and Electrophilic Sites in Pd‐Catalyzed Regiodivergent Couplings between Indazoles and Isoprene

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(15), P. 8321 - 8328

Published: Jan. 19, 2021

Abstract Depending on the reactant property and reaction mechanism, one major regioisomer can be favored in a that involves multiple active sites. Herein, an orthogonal regulation of nucleophilic electrophilic sites regiodivergent hydroamination isoprene with indazoles is demonstrated. Under Pd‐hydride catalysis, 1,2‐ or 4,3‐insertion pathway respect to could controlled by choice ligands. In terms indazoles, occurs at either N 1 ‐ 2 ‐position governed acid co‐catalysts. Preliminary experimental studies have been performed rationalize mechanism regioselectivity. This study not only contributes practical tool for selective functionalization isoprene, but also provides guide manipulate regioselectivity ‐functionalization indazoles.

Language: Английский

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Switchable 1,2-Rearrangement Enables Expedient Synthesis of Structurally Diverse Fluorine-Containing Scaffolds

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(26), P. 11626 - 11637

Published: May 23, 2022

Skeletal rearrangement that changes the connectivity of molecule via cleavage and reorganization carbon–carbon bonds is a fundamental powerful strategy in complex molecular assembly. Because lack effective methods to control migratory tendency different groups, achieving switchable selectivity skeletal has been long-standing quest. Metal-based dyotropic provides unique opportunity address this challenge. However, remains unexplored. Herein, we show such problem could be solved by modifying ligands on metal catalyst changing oxidation states aptitude thereby providing ligand-controlled, strategy. Experimental density functional theory calculation studies prove rational design. The occurs only when nickel(II) intermediate reduced more nucleophilic nickel(I) species, sterically hindered iPrPDI ligand facilitates 1,2-aryl/Ni rearrangement, while terpyridine promotes 1,2-acyl/Ni rearrangement. This method allows site-selective activation C–C applied for divergent synthesis four medicinally relevant fluorine-containing scaffolds from same starting material.

Language: Английский

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Catalytic Asymmetric Hydroalkylation of α,β-Unsaturated Amides Enabled by Regio-Reversed and Enantiodifferentiating syn-Hydronickellation

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(14), P. 8766 - 8773

Published: July 2, 2021

Here, we report an enantioselective nickel-hydride catalyzed hydroalkylation of readily accessible β-alkyl-α,β-unsaturated amides to form structurally diverse β-chiral amides. This process was proposed proceed through enantiodifferentiating syn-hydrometalation nickel hydride, forming chiral alkylnickel at the β-position in which regioselectivity is different from that with copper hydride. regio-reversed hydronickellation provides a complementary approach access enantioenriched β-functionalization stereocenter β-position.

Language: Английский

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NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes and the ligand effects on regioselectivity

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

Published: April 7, 2022

Abstract Alkene hydrocarbonation reactions have been developed to supplement traditional electrophile-nucleophile cross-coupling reactions. The branch-selective hydroalkylation method applied a broad range of unactivated alkenes remains challenging. Herein, we report NiH-catalysed proximal-selective access β- or γ-branched alkyl carboxylic acids and β-, γ- δ-branched amines. A iodides bromides with different functional groups can be installed excellent regiocontrol availability for site-selective late-stage functionalization biorelevant molecules. Under modified reaction conditions NiCl 2 (PPh 3 ) as the catalyst, migratory takes place provide (rather than γ-) branched products. keys success are use aminoquinoline picolinamide suitable directing combined experimental computational studies ligand effects on regioselectivity detailed mechanisms.

Language: Английский

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Regiodivergent Alkylation of Pyridines: Alkyllithium Clusters Direct Chemical Reactivity

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Regiodivergent C-C bond-forming reactions are a powerful tool for constructing diverse molecular architectures from common precursors. While transition metal catalysis has dominated regioselective transformations, achieving similar precision with transition-metal-free methods remains an unmet challenge, particularly when using identical starting materials. In this work, we report transition-metal-free, regiodivergent direct alkylation of electronically unbiased pyridines 1,1-diborylalkanes as the sole alkylating agent. The key to controlling regioselectivity lies in choice alkyllithium activator 1,1-diborylalkanes: methyllithium directs predominantly C4 position, while sec-butyllithium promotes C2-alkylation. Mechanistic studies reveal that structural dynamics clusters dictate regioselectivity, tetrameric favoring C4-alkylation and dimeric preferring This method demonstrates broad substrate scope, enables late-stage functionalization complex molecules, allows sequential installation two distinct alkyl groups onto pyridine scaffold. Our approach provides versatile site-selective functionalization, offering new possibilities synthesizing alkylated pharmaceutical materials research.

Language: Английский

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