P-Stereogenic Ir-MaxPHOX: A Step toward Privileged Catalysts for Asymmetric Hydrogenation of Nonchelating Olefins DOI Creative Commons
Maria Biosca, Pol de la Cruz‐Sánchez, Jorge Faiges

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(5), P. 3020 - 3035

Published: Feb. 14, 2023

The Ir-MaxPHOX-type catalysts demonstrated high catalytic performance in the hydrogenation of a wide range nonchelating olefins with different geometries, substitution patterns, and degrees functionalization. These air-stable readily available have been successfully applied asymmetric di-, tri-, tetrasubstituted (ee′s up to 99%). combination theoretical calculations deuterium labeling experiments led uncovering factors responsible for enantioselectivity observed reaction, allowing rationalization most suitable substrates these Ir-catalysts.

Language: Английский

Molybdenum-Catalyzed Asymmetric Hydrogenation of Fused Arenes and Heteroarenes DOI
Peter Viereck, Gabriele Hierlmeier,

Paolo Tosatti

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(25), P. 11203 - 11214

Published: June 17, 2022

The synthesis of enantioenriched molybdenum precatalysts for the asymmetric hydrogenation substituted quinolines and naphthalenes is described. Three classes pincer ligands with chiral substituents were evaluated as supporting in molybdenum-catalyzed reactions, where oxazoline imino(pyridine) chelates identified optimal. A series 2,6-disubstituted was hydrogenated to decahydroquinolines high diastereo- enantioselectivities. For quinoline derivatives, selective both carbocycle heterocycle observed depending on ring substitution. Spectroscopic mechanistic studies established η6-arene complexes catalyst resting state that partial arises from dissociation substrate coordination sphere prior complete reduction. stereochemical model proposed based relative energies respective prochiral faces arene determined by steric interactions between ligand, rather than through precoordination a heteroatom.

Language: Английский

Citations

44
Translating Planar Heterocycles into Three‐Dimensional Analogs by Photoinduced Hydrocarboxylation** DOI Creative Commons
Myriam Mikhael, Sara N. Alektiar, Charles S. Yeung

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(30)

Published: May 18, 2023

The rapid preparation of complex three-dimensional (3D) heterocyclic scaffolds is a key challenge in modern medicinal chemistry. Despite the increased probability clinical success for small molecule therapeutic candidates with 3D complexity, new drug targets remain dominated by flat molecules due to abundance coupling reactions available their construction. In principle, heteroarene hydrofunctionalization offer an opportunity transform readily accessible planar into more three-dimensionally analogs through introduction single molecular vector. Unfortunately, dearomative limited. Herein, we report strategy enable hydrocarboxylation indoles and related heterocycles. This reaction represents rare example that meets numerous requirements broad implementation discovery. transformation highly chemoselective, scope, operationally simple, amenable high-throughput experimentation (HTE). Accordingly, this process will allow existing libraries heteroaromatic compounds be translated diverse exploration classes medicinally relevant molecules.

Language: Английский

Citations

35
Stereodivergent asymmetric hydrogenation of quinoxalines DOI Creative Commons
Chenguang Liu,

Xufang Liu,

Qiang Liu

et al.

Chem, Journal Year: 2023, Volume and Issue: 9(9), P. 2585 - 2600

Published: May 31, 2023

Language: Английский

Citations

24
Oxidative Dearomatization of Pyridines DOI

Zohaib Siddiqi,

Tanner W. Bingham, Tsukasa Shimakawa

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2358 - 2363

Published: Jan. 17, 2024

Dearomatization of pyridines is a well-established synthetic approach to access piperidines. Although remarkably powerful, existing dearomatization processes have been limited the hydrogenation or addition carbon-based nucleophiles activated pyridiniums. Here, we show that arenophile-mediated dearomatizations can be applied directly introduce heteroatom functionalities without prior substrate activation. The arenophile platform in combination with olefin oxidation chemistry provides dihydropyridine cis-diols and epoxides. These previously elusive compounds are now readily accessible used for downstream preparation diversely functionalized

Language: Английский

Citations

14
Organometallic Mn(I) Complexes in Asymmetric Catalytic (Transfer) Hydrogenation and Related Transformations DOI Creative Commons
Dexin Fu, Zheng Wang, Qingbin Liu

et al.

ChemCatChem, Journal Year: 2024, Volume and Issue: 16(14)

Published: March 7, 2024

Abstract Direct asymmetric hydrogenation (AH) and transfer (ATH) are among the most efficient approaches to produce chiral building blocks. Recently, these types of transformations have witnessed a shift towards use molecular catalysts based on earth‐abundant transition metals due their ready availability, economic advantage, novel properties. With particular regard manganese, catalyst development has seen both efficiency substrate scope in AH ATH greatly improved, with emergence large number well‐defined Mn‐complexes employed this field. The reaction includes C=O bonds, reduction C=N bonds reductive C=C bonds. Herein, our survey area focuses catalytic activity such complexes, versatility routes convert substrates target molecules. We consider collected findings article will be helpful reader by providing an insight into ligand design, thereby aiding future development. Moreover, review is aimed at highlighting remarkable progress made last seven years manganese complexes for enantioselective reduction.

Language: Английский

Citations

11
Rhodium‐Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of 1,3‐Dipolar Nitrones DOI

Liren Xu,

Tilong Yang, Hao Sun

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(14)

Published: Feb. 17, 2024

Abstract Owing to their distinctive 1,3‐dipolar structure, the catalytic asymmetric hydrogenation of nitrones hydroxylamines has been a formidable and longstanding challenge, characterized by intricate enantiocontrol susceptibility N−O bond cleavage. In this study, transfer were accomplished with tethered TsDPEN‐derived cyclopentadienyl rhodium(III) catalyst (TsDPEN: p ‐toluenesulfonyl‐1,2‐diphenylethylene‐1,2‐diamine), reaction proceeds via novel 7‐membered cyclic transition state, producing chiral up 99 % yield >99 ee. The practical viability methodology was underscored gram‐scale reactions subsequent transformations. Furthermore, mechanistic investigations DFT calculations also conducted elucidate origin enantioselectivity.

Language: Английский

Citations

9
Asymmetric Hydrogenation of Racemic 2-Substituted Indoles via Dynamic Kinetic Resolution: An Easy Access to Chiral Indolines Bearing Vicinal Stereogenic Centers DOI
Nianxin Rong,

Ao Zhou,

Mingrong Liang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5081 - 5087

Published: Feb. 15, 2024

The asymmetric hydrogenation (AH) of N-unprotected indoles is a straightforward, yet challenging method to access biologically interesting NH chiral indolines. This has for years been limited 2/3-monosubstituted or 2,3-disubstituted indoles, which produce indolines bearing endocyclic centers. Herein, we have reported an innovative Pd-catalyzed AH racemic α-alkyl aryl-substituted indole-2-acetates using acid-assisted dynamic kinetic resolution (DKR) process, affording range structurally fascinating that contain exocyclic stereocenters with excellent yields, diastereoselectivities, and enantioselectivities. Mechanistic studies support the DKR process relies on rapid interconversion each enantiomer substrates, leveraged by acid-promoted isomerization between aromatic indole nonaromatic enamine intermediate. reaction can be performed gram scale, products derivatized into non-natural β-amino acids via facile debenzylation amino alcohol upon reduction.

Language: Английский

Citations

8
Dynamic Kinetic Resolution-Based Asymmetric Transfer Hydrogenation of Racemic 2-Substituted Quinolines DOI
Liang Meng,

Xian Du,

Jian Jun Lin

et al.

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

Published: Jan. 22, 2025

The synthesis of chiral tetrahydroquinolines (THQs) has garnered significant interest from medicinal chemists due to their frequent presence as pharmacophores in bioactive compounds. While existing synthetic methods have primarily focused on THQs with single or multiple endocyclic centers, the selective construction both endo- and exo-cyclic centers remains a challenge that requires further development. This study introduces dynamic kinetic resolution (DKR)-based transfer hydrogenation racemic 2-substituted quinolines, which yields structurally novel consecutive excellent stereoselectivities (59 examples, generally >20:1 dr >90% ee, up three stereocenters). Our approach offers mechanistically method for asymmetric transformation electron-deficient aromatic N-heterocycles presents an innovative way expand N-heterocycle chemical space chemistry.

Language: Английский

Citations

1
Rhodium-Catalyzed Homogeneous Asymmetric Hydrogenation of Naphthol Derivatives DOI
Shuxin Zhang, Linhong Long, Zeyu Li

et al.

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

Published: Jan. 29, 2025

Due to their strong aromaticity and difficulties in chemo-, regio-, enantioselectivity control, asymmetric hydrogenation of naphthol derivatives 1,2,3,4-tetrahydronaphthols has remained a long-standing challenge. Herein, we report the first example homogeneous catalyzed by tethered rhodium-diamine catalysts, affording wide array optically pure high yields with excellent enantioselectivities (up 98% yield >99% ee). Mechanistic studies experimental computational approaches reveal that fluorinated solvent 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) plays vital roles control reactivity selectivity, 1-naphthol is reduced via cascade reaction pathway, including dearomative tautomerization, 1,4-hydride addition, 1,2-hydride addition sequence. A novel synergistic activation mode was proposed which HFIP assists both hydrogen molecule presence base, situ-generated fleeting keto tautomer immediately trapped Rh(III)-H species before it escapes from cage. This protocol provides straightforward practical pathway for synthesis key intermediates several chiral drugs. Particularly, Nadolol, drug treatment hypertension, angina pectoris, congestive heart failure, certain arrhythmias, enantioselectively synthesized time.

Language: Английский

Citations

1
Enantio‐ and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis DOI Creative Commons

Daniel Moock,

Tobias Wagener,

Tianjiao Hu

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(24), P. 13677 - 13681

Published: April 12, 2021

We report an enantio- and diastereoselective, complete hydrogenation of multiply substituted benzofurans in a one-pot cascade catalysis. The developed protocol facilitates the controlled installation up to six new defined stereocenters produces architecturally complex octahydrobenzofurans, prevalent many bioactive molecules. A unique match chiral homogeneous ruthenium-N-heterocyclic carbene situ activated rhodium catalyst from precursor act sequence enable presented process.

Language: Английский

Citations

54