Enantioselective Flow Synthesis of a Tetrahydroquinoline SERM Enabled by Immobilized Chiral Phosphoric Acid Catalysis and Diboronic Acid Mediated Selective Nitro Reduction

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(4), P. 1024 - 1030

Published: Jan. 13, 2024

Abstract An asymmetric enantioselective flow process is reported for the formal synthesis of a 1,2,3,4‐tetrahydroquinoline selective estrogen receptor modulator. Starting from an easily available 2‐nitrochalcone, first part comprised telescoped nitro reduction/intramolecular cyclocondensation sequence using diboronic acid as simple reductant. Subsequent transfer hydrogenation in presence immobilized phosphoric organocatalyst followed by N ‐alkylation furnished targeted chiral intermediate. The approach ensures flexibility regarding scale synthesis, whilst minimizing need intermediate purifications and ensuring environmentally benign metal‐free conditions.

Language: Английский

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Recent advances in catalytic asymmetric synthesis

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: May 9, 2024

Asymmetric catalysis stands at the forefront of modern chemistry, serving as a cornerstone for efficient creation enantiopure chiral molecules characterized by their high selectivity. In this review, we delve into realm asymmetric catalytic reactions, which spans various methodologies, each contributing to broader landscape enantioselective synthesis molecules. Transition metals play central role catalysts wide range transformations with ligands such phosphines, N -heterocyclic carbenes (NHCs), etc., facilitating formation C-C and C-X bonds, enabling precise control over stereochemistry. Enantioselective photocatalytic reactions leverage power light driving force electrocatalysis has emerged sustainable approach, being both atom-efficient environmentally friendly, while offering versatile toolkit reductions oxidations. Biocatalysis relies on nature’s most catalysts, i.e., enzymes, provide exquisite selectivity, well tolerance diverse functional groups under mild conditions. Thus, enzymatic optical resolution, kinetic resolution dynamic have revolutionized production compounds. organocatalysis uses metal-free organocatalysts, consisting modular phosphorus, sulfur nitrogen components, remarkably transformations. Additionally, unlocking traditionally unreactive C-H bonds through selective functionalization expanded arsenal synthesis, atom-economical construction Incorporating flow chemistry been transformative, continuous systems reaction conditions, enhancing efficiency optimization. Researchers are increasingly adopting hybrid approaches that combine multiple strategies synergistically tackle complex synthetic challenges. This convergence holds great promise, propelling field forward in form. As these methodologies evolve complement one another, they push boundaries what can be accomplished leading discovery novel, highly may lead groundbreaking applications across industries.

Language: Английский

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A robust heterogeneous chiral phosphoric acid enables multi decagram scale production of optically active N,S-ketals

Green Chemistry, Journal Year: 2024, Volume and Issue: 26(8), P. 4593 - 4599

Published: Jan. 1, 2024

A multi-decagram scale synthesis of enantioenriched N,S -ketals was achieved by using a robust heterogeneous organocatalyst. new reactor design crucial to enable the scaling up this reaction while overall catalyst loading below 0.1%.

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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Green Light Promoted Iridium(III)/Copper(I)‐Catalyzed Addition of Alkynes to Aziridinoquinoxalines Through the Intermediacy of Azomethine Ylides

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(12)

Published: Jan. 25, 2024

This manuscript describes the development of alkyne addition to aziridine moiety aziridinoquinoxalines using dual Ir(III)/Cu(I) catalytic system under green light-emitting diode (LED) photolysis (λ

Language: Английский

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Bis(pinacoloto)diboron/4-Phenylpyridine System for One-Pot Photocatalyzed Borylation and Reduction of Aldehyde: Synthesis of Tavaborole in a Flow Reactor

Synthesis, Journal Year: 2023, Volume and Issue: 56(04), P. 573 - 576

Published: Sept. 6, 2023

Abstract A photocatalyzed one-pot borylation of haloarene and reduction aldehyde by cocatalysis bis(pinacoloto)diboron/4-phenylpyridine is reported. The reaction was carried out in a flow reactor irradiating the at 410 nm, with residence time 10 minutes. method successfully applied for synthesis tavaborole single step 81% yield.

Language: Английский

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Enantioselective Parallel Kinetic Resolution of Aziridine-Containing Quinoxalines via Chiral Phosphoric Acid-Catalyzed Transfer Hydrogenation

Organic Letters, Journal Year: 2023, Volume and Issue: 25(42), P. 7721 - 7726

Published: Oct. 18, 2023

This article describes the asymmetric synthesis of chiral aziridinoquinoxalines using (R)-TRIP-catalyzed parallel kinetic resolution under transfer hydrogenation conditions. was successfully accomplished for 16 different substrates and led to highly enantioenriched diastereomers with (R)-configuration newly formed stereocenter (32-61% yield 64-99% ee (R,R,R)-diastereomers 7-46% 97-99% (S,S,R)-diastereomers). process could be coupled ring-opening (S,S,R)-diastereomer thiophenol produce tetrahydroquinoxalines three contiguous stereocenters.

Language: Английский

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A Robust Heterogeneous Chiral Phosphoric Acid Enables Multi Decagram Scale Production Of Optically Active N, S-Ketals

Published: Jan. 22, 2024

Asymmetric organocatalysis has been recognized as one of the Top 10 Emerging Technologies in Chemistry by IUPAC 2019. Its potential to make chemical processes more sustainable is promising, but there are still challenges that need be addressed. Developing new and reliable enantioselective for reproducing batch reactions on a large scale requires combination technical solutions. In this manuscript, we combine robust immobilized chiral phosphoric acid with packed-bed reactor design. This allows scaling up addition thiols imines from few milligrams multi-decagram continuous flow process without physical or degradation catalyst.

Language: Английский

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Enhanced Recyclability of Polymer Brush-Supported Sulfonic Acid with Diblock Architecture

ACS Applied Polymer Materials, Journal Year: 2024, Volume and Issue: 6(17), P. 10977 - 10985

Published: Aug. 27, 2024

Solid polymer brush-supported molecular catalysts generally exhibit activity comparable to catalysts, but they suffer the problems of decreased with increasing recycled times in reactions. This study explores use brushes a diblock architecture design durable silica-based sulfonic acid catalysts. Two brush materials, differing amounts polystyrene (PS) brush, were prepared by first growing PS using copper-catalyzed ARGET SI-ATRP and poly(vinylimidazole) SI-ATRP. The resulting then reacted 1,3-propane sultone trifluoromethanesulfonic obtain two solid For comparison, without layer was also prepared. These acidic applied synthesize acylals from aldehydes acetic anhydride. acids demonstrated superior compared catalyst. Notably, catalyst protection could be 15 (yield ≥95%) decrease activity; contrast, yield 35% 10th run. Thermogravimetric analysis indicated 3% loss materials for 9.5% layer, after specified numbers runs. Polymer probably finds more applications solid-based

Language: Английский

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General and versatile synthesis of highly recyclable chiral phosphoric acid organocatalysts

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(20), P. 5901 - 5907

Published: Jan. 1, 2024

The development of recyclable catalysts has gained more attention in recent years order to minimize the environmental effect and overall cost catalytic processes. Some most broadly used chiral organocatalysts are BINOL-derived phosphoric acids, making it necessary develop efficient recycling strategies. While literature reports require up 13 synthetic steps access here we report a general concise 9-step approach anthracene decorated heterogeneous acids (PS-Anth), which have shown high performance either batch or continuous flow without observing catalyst degradation.

Language: Английский

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