Enantioselective Synthesis of Chiral 1,4-Dihydroquinolines via Iridium-Catalyzed Asymmetric Partial Hydrogenation of Quinolines

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

Published: Feb. 5, 2025

Chiral 1,4-dihydroquinolines are frequently found in natural products and pharmaceuticals, yet a generally useful route for their synthesis remains elusive. Here, we present an asymmetric partial hydrogenation strategy to access enantioenriched from quinolines. Our involves incorporating ester group at position 3 of the quinoline ring, thereby enhancing electronic deficiency polarity C3–C4 double bond. Employing chiral Ir-SpiroPAP catalyst facilitated wide variety 4-substituted 3-ethoxycarbonylquinolines, yielding high yields (up 95%) with exceptional enantioselectivity efficiency 99% ee 1840 TONs). Noteworthy its scalability practicality, method provides robust avenue valuable compounds such as 9-aryl aza-podophyllotoxins melatonin MT2 receptor modulators. Density functional theory calculations were performed gain insights into reaction mechanism origins enantioselectivity.

Language: Английский

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Asymmetric catalysis with FLPs

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(24), P. 8580 - 8598

Published: Jan. 1, 2023

This review provides an overview of the important progress in FLP-catalyzed asymmetric reactions made over past 15 years, and both merits limitations FLP-catalysis have been highlighted.

Language: Английский

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Incorporation of Chiral Frustrated Lewis Pair into Metal–Organic Framework with Tailored Microenvironment for Heterogeneous Enantio- and Chemoselective Hydrogenation

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(8), P. 1692 - 1701

Published: July 27, 2023

The development of efficient heterogeneous catalysts with multiselectivity (e.g., enantio- and chemoselectivity) has long been sought after but limited progress being made so far. To achieve chemoselectivity in a system, as inspired by enzymes, we illustrate herein an approach creating enzyme-mimic region (EMR) within the nanospace metal–organic framework (MOF) exemplified context incorporating chiral frustrated Lewis pair (CFLP) into MOF tailored pore environment. Due to high density EMR featuring active site CFLP auxiliary sites hydroxyl group/open metal vicinity CFLP, resultant EMR@MOF demonstrated excellent catalysis performance hydrogenation α,β-unsaturated imines afford β-unsaturated amines yields chemoselectivity. role regulating was proved observation catalyst–substrate interaction experimentally, which also rationalized computational results. This work not only contributes new platform for multiselective opens promising avenue develop challenging yet important transformations.

Language: Английский

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Unlocking the Phosphoric Acid Catalyzed Asymmetric Transfer Hydrogenation of 2-Alkenyl Quinolines for Efficient Flow Synthesis of Hancock Alkaloids

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Chiral tetrahydroquinolines are present in several bioactive molecules, such as the Hancock alkaloids. Although organocatalytic asymmetric transfer hydrogenation of 2-aryl quinolines has emerged a safer alternative to using hydrogen gas, analogous reactions with 2-alkenyl remain unexplored. Here we protocol synthesize key enantioenriched intermediates alkaloids, providing constant outcome for, at least, 24 h continuous flow operation.

Language: Английский

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Enantioselective Synthesis of 2-Aryl-3,3-Disubstituted Indolines from 3H-Indoles via Deracemization

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

An enantioselective synthesis of 2-aryl 3,3-disubstituted 3H-indoles has been successfully developed via a deracemization process involving borane-catalyzed hydrogenation and chiral phosphoric-acid-catalyzed asymmetric transfer hydrogenation. A variety were effective substrates to afford the desired indolines in 86-95% yields with 45-92% ee's.

Language: Английский

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Molecular and Descriptor Spaces for Predicting Initial Rate of Catalytic Homogeneous Quinoline Hydrogenation with Ru, Rh, Os, and Ir Catalysts

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Developing highly active catalysts for quinoline hydrogenation is crucial efficient hydrogen carrier technologies and clean fossil fuel hydrodenitrogenation. In this work, we employed Tensor Algebra-based 3D-Geometrical Molecular Descriptors (QuBiLS-MIDAS) to develop Quantitative Structure-Property Relationship (QSPR) models predicting the initial rate of homogeneous catalyzed by transition metal complexes Ru, Rh, Os, Ir. A data set 32 catalytic precursors was used: 25 model training (training set) 7 external validation (testing set). Multiple linear regression analysis yielded a with good predictive ability (R 2 = 0.90) satisfactory testing (QEXT 0.86). The model's descriptors highlighted importance hardness, softness, electrophilicity, mass in activity. virtual screening revealed that Rh Ir π-acidic ligands (e.g., olefins, diolefins, η5-Cp) nitrile exhibited highest predicted activity, suggesting potential further improvement through ligand structural modification. Notably, iridium complexes, particularly those tri(cyclopropyl)phosphine ligands, demonstrated significant storage, transport, production, underscoring their relevance sustainable energy systems. These findings demonstrate QuBiLS-MIDAS approach silico design processes.

Language: Английский

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Biomimetic Asymmetric Reduction Based on the Regenerable Coenzyme NAD(P)H Models

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(15), P. 2096 - 2109

Published: July 13, 2023

ConspectusIn nature, the coenzyme NAD(P)H is utilized for transfer of hydrogen and electrons in biocatalytic reduction, which involves process recycling, usage, reduction. Inspired by biological system, a series nonregenerable achiral chiral models were synthesized employed. However, this approach faced intractable limitations, such as need an equivalent amount mimics, accompanied production byproducts, resulted poor atom economy difficult separation products. Therefore, development new efficient methodologies synthesis, regeneration, application organic synthesis greatly desired.To tackle these challenges, regenerable designed based on principles reduction applied them biomimetic asymmetric (BMAR) reactions. This Account summarizes our endeavors rational design, models. First, we will introduce design (dihydrophenanthridine dihydropyrroloquinoxaline), successfully to BMAR imines heteroaromatics using homogeneous ruthenium complex regeneration catalyst, phosphoric acid terminal reductant. Regenerable require addition catalysts or ligands stereoselective control during process. screening tedious. Narrow substrate scope further limited their synthesis. (CYNAM FENAM) with planar chirality, commercially available Brønsted acids, Lewis organocatalysts catalyst. Notably, original factor enantioselective from In addition, strategy could also realize myriad electron-deficient tetrasubstituted alkenes, are challenging substrates transition metal catalyzed hydrogenation. methodology provides building blocks bioactive molecules. Finally, detailed mechanism BMAR, models, was elaborated through combination experiments density functional theory calculations. summary, believe that results presented hold significant implications beyond work have potential applications field catalysis synthetic methodology.

Language: Английский

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A Metal‐Free KO^tBu‐Mediated Protocol towards the Synthesis of Quinolines, Indenoquinolines and Acridines

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(4)

Published: Jan. 23, 2024

Abstract An expeditious strategy has been developed for the synthesis of diverse quinolines, indenoquinolines and acridines using KO t Bu‐mediated reaction conditions. The designed process utilizes 2‐aminoaryl carbaldehydes/2‐aminoaryl ketones methyl/methylene group containing as readily available feedstock. chemical transformation was affected at room temperature within a short duration time to obtain N ‐heterocycles yields up 92 %. established also exhibits considerable functional tolerance with an operational simplicity.

Language: Английский

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Asymmetric Transfer Hydrogenation of 2-Substituted Quinoxalines with Regenerable Dihydrophenanthridine

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(5), P. 3666 - 3671

Published: Feb. 15, 2024

The asymmetric hydrogenation of quinoxalines represents one the most efficient approaches for synthesis optically active tetrahyroquinoxalines. In this paper, we demonstrate a metal-free transfer 2-substituted with regenerable dihydrophenanthridine under H2 using combination chiral phosphoric acid and achiral borane as catalysts. A wide range tetrahydroquinoxalines were produced in high yields ≤98% ee.

Language: Английский

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An Overview of Hydrogen Production from Renewable Sources and Its Main Applications

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(35)

Published: Sept. 12, 2024

Abstract There is a misconception that sustainability only related to greenhouse gas emissions into the atmosphere, and this risk which planet exposed. Sustainability multidimensional concept must advance simoutaneously on several fronts, such as urgent need increase energy, clean water, air, food, mobility, health, poverty reduction. All problems of these multi‐dimensions are aggravated by continuous growth world population, mainly in economic socio‐environmental issues. However, biggest challenge supply energy from renewable sources, all other dimensions depend policy decisions. The consumption fossil fuels has supplied current demand approximately 87 %. Still, there predictions depletion, effects caused environment production gases bring significant losses. In review, we will address most common methods for hydrogen production, well its main technological applications organic synthesis generation.

Language: Английский

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