Nickel‐Catalyzed Synthesis of Dialkyl Ketones from the Coupling of N‐Alkyl Pyridinium Salts with Activated Carboxylic Acids

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(32), P. 13484 - 13489

Published: May 6, 2020

Abstract While ketones are among the most versatile functional groups, their synthesis remains reliant upon reactive and low‐abundance starting materials. In contrast, amide formation is most‐used bond‐construction method in medicinal chemistry because reliable draws large diverse substrate pools. A new for of presented here that from same substrates used bond synthesis: amines carboxylic acids. nickel terpyridine catalyst couples N‐alkyl pyridinium salts with situ formed acid fluorides or 2‐pyridyl esters under reducing conditions (Mn metal). The reaction has a broad scope, as demonstrated by 35 different bearing wide variety groups an average yield 60±16 %. This approach capable coupling substrates, including pharmaceutical intermediates, to rapidly form complex ketones.

Language: Английский

---

Enantio‐ and Regioselective NiH‐Catalyzed Reductive Hydroarylation of Vinylarenes with Aryl Iodides

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(48), P. 21530 - 21534

Published: Aug. 28, 2020

Abstract A highly enantio‐ and regioselective hydroarylation process of vinylarenes with aryl halides has been developed using a NiH catalyst new chiral bis imidazoline ligand. broad range structurally diverse, enantioenriched 1,1‐diarylalkanes, structure found in number biologically active molecules, have obtained excellent yields enantioselectivities under extremely mild conditions.

Language: Английский

---

Electrochemical Arylation of Aldehydes, Ketones, and Alcohols: from Cathodic Reduction to Convergent Paired Electrolysis

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(13), P. 7275 - 7282

Published: Dec. 30, 2020

Abstract Arylation of carbonyls, one the most common approaches toward alcohols, has received tremendous attention, as alcohols are important feedstocks and building blocks in organic synthesis. Despite great progress, there is still a gap to develop an ideal arylation method featuring mild conditions, good functional group tolerance, readily available starting materials. We now show that electrochemical can fill gap. By taking advantage synthetic electrochemistry, commercially aldehydes (ketones) benzylic be arylated provide general scalable access structurally diverse (97 examples, >10 gram‐scale). More importantly, convergent paired electrolysis, but challenging technology, was employed transform low‐value into more useful alcohols. Detailed mechanism study suggests two plausible pathways involved redox neutral α‐arylation

Language: Английский

---

Nickel catalysis enables convergent paired electrolysis for direct arylation of benzylic C–H bonds

Chemical Science, Journal Year: 2020, Volume and Issue: 11(39), P. 10786 - 10791

Published: Jan. 1, 2020

A direct arylation of benzylic C–H bonds is achieved by integrating Ni-catalyzed benzyl–aryl coupling into convergent paired electrolysis.

Language: Английский

---

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

---