Multiplicative enhancement of stereoenrichment by a single catalyst for deracemization of alcohols

Science, Journal Year: 2023, Volume and Issue: 382(6669), P. 458 - 464

Published: Oct. 26, 2023

Stereochemical enrichment of a racemic mixture by deracemization must overcome unfavorable entropic effects as well the principle microscopic reversibility; recently, photochemical reaction pathways unveiled energetic input light have led to innovations toward this end, most often ablation stereogenic C(sp3)-H bond. We report photochemically driven protocol in which single chiral catalyst two mechanistically different steps, C-C bond cleavage and formation, achieve multiplicative enhancement stereoinduction, leads high levels stereoselectivity. Ligand-to-metal charge transfer excitation titanium coordinated phosphoric acid or bisoxazoline efficiently enriches alcohols that feature adjacent fully substituted centers enantiomeric ratios up 99:1. Mechanistic investigations support pathway sequential radical-mediated scission formation through common prochiral intermediate reveal that, although overall stereoenrichment is high, selectivity each individual step moderate.

Language: Английский

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Catalytic asymmetric photocycloaddition reactions mediated by enantioselective radical approaches

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The use of olefins in the construction cyclic compounds represents a powerful strategy for advancing pharmaceutical industry.

Language: Английский

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A General Approach for the Synthesis of Cyanoisopropyl Bicyclo[1.1.1]pentane (BCP) Motifs by Energy Transfer Process

Organic Letters, Journal Year: 2024, Volume and Issue: 26(33), P. 7060 - 7065

Published: Aug. 13, 2024

Bicyclo[1.1.1]pentane (BCP) heteroaryls make up an important class of BCP derivatives in drug discovery. Herein, we report the visible-light-mediated synthesis cyanoisopropyl BCP-heteroaryls motifs from

Language: Английский

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Photoexcited Palladium-Catalyzed Deracemization of Allenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 21137 - 21146

Published: July 18, 2024

The different enantiomers of specific chiral molecules frequently exhibit disparate biological, physiological, or pharmacological properties. Therefore, the efficient synthesis single is particular importance not only to pharmaceutical sector but also other industrial sectors, such as agrochemical and fine chemical industries. Deracemization, a process during which racemic mixture converted into nonracemic product with 100% atom economy theoretical yield, most straightforward method access enantioenriched challenging task due decrease in entropy microscopic reversibility. Axially allenes bear distinctive structure two orthogonal cumulative π-systems are acknowledged synthetically versatile synthons organic synthesis. selective creation axially high optical purity under mild reaction conditions has always been very popular hot topic remains challenging. Herein, photoexcited palladium-catalyzed deracemization nonprefunctionalized disubstituted disclosed. This provides an economical strategy accommodate broad scope good enantioselectivities yields (53 examples, up 96% yield 95% ee). use suitable palladium complex visible light irradiation essential factor achieving this transformation. A metal-to-ligand charge transfer mechanism was proposed based on control experiments density functional theory calculations. Quantum mechanical studies implicate dual modes asymmetric induction behind our new protocol: (1) sterically controlled stereoselective binding one allene enantiomer ground-state (2) facile, noncovalent interaction-driven excited-state isomerization toward opposite enantiomer. success newly established photochemical should provide inspiration for expansion multisubstituted will open mode enantioselective catalysis.

Language: Английский

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Enantioselective [2 + 2] Photocycloreversion Enables De Novo Deracemization Synthesis of Cyclobutanes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(32), P. 22840 - 22849

Published: Aug. 2, 2024

While photochemical deracemization significantly enhances atom economy by eliminating the necessity for additional oxidants or reductants, laborious presynthesis of substrates from feedstock chemicals is often required, thereby compromising practicality this method. In study, we propose a novel approach known as de novo synthesis, which involves direct utilization simple undergoing both transformation and reversible transformation. The efficient enantiocontrol chiral catalysts in latter process establishes an effective platform deracemization. This alternative practical to address challenges asymmetric photocatalysis has been successfully demonstrated photosensitized synthesis azaarene-functionalized cyclobutanes featuring three stereocenters, including all-carbon quaternary center. By exclusively employing suitable catalyst enable kinetically controlled [2 + 2] photocycloreversion, pave creative path toward achieving more cost-effective

Language: Английский

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Photoinduced copper-catalysed deracemization of alkyl halides

Nature, Journal Year: 2025, Volume and Issue: 640(8057), P. 107 - 113

Published: April 2, 2025

Language: Английский

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Mechanochemical Deracemization: A Sustainable Approach to Enantiopurity

Chemistry - A European Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract We introduce mechanochemical deracemization (MCDR) as a novel strategy for obtaining enantiopure compounds. This study demonstrates the successful transposition of six archetypical reactions from solvent‐based to solvent‐minimized ball milling environment. The scope includes ketone, isoindolinones, imines, an ester, and inorganic compound, all which deracemized successfully. Key parameters such material, number size, use bulk material liquid‐assisted grinding (LAG) were systematically investigated, revealing their crucial role. Quantitative enantiomeric excesses (ee) achieved, while reaction times reduced by up 97 % solvent consumption much 100 %. work establishes MCDR versatile, sustainable pathway By highlighting generalizability this approach its huge potential minimizing waste, provides foundation future advancements in deracemization.

Language: Английский

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Light-Driven Deracemization by a Designed Photoenzyme

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

Published: April 12, 2025

The creation of enzymes with abiological abilities offers exciting opportunities to access new-to-nature biocatalysis beyond that found in nature. Here, we repurpose a novel protein scaffold, CTB10, as an artificial photoenzyme through genetic code expansion. It enables catalytic deracemization cyclopropane, process remains inaccessible traditional due its thermodynamically unfavorable Following structural optimization directed evolution, broad substrate scope high enantioselectivities is achieved. Furthermore, the crystal structure CTB10-based photoenzyme-substrate complex well demonstrates how chiral cavity sculpted promote efficient and selective light-enabled deracemization. Therefore, this study unlocks potential for achieving challenging biocatalysis.

Language: Английский

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Enantioselective organocatalytic strategies to access noncanonical α-amino acids

Chemical Science, Journal Year: 2024, Volume and Issue: 15(16), P. 5832 - 5868

Published: Jan. 1, 2024

Organocatalytic asymmetric synthesis has evolved over the years and continues to attract interest of many researchers worldwide. Enantiopure noncanonical amino acids (ncAAs) are valuable building blocks in organic synthesis, medicinal chemistry, chemical biology. They employed elaboration peptides proteins with enhanced activities and/or improved properties compared their natural counterparts, as chiral catalysts, ligand design, for syntheses complex molecules, including products. The linkage ncAA enantioselective organocatalysis, subject this perspective, tries imitate biosynthetic process. Herein, we present contemporary earlier developments field organocatalytic activation simple feedstock materials, providing potential ncAAs diverse side chains, unique three-dimensional structures, a high degree functionality. These strategies, useful forging wide range C-C, C-H, C-N bonds combinations thereof, vary from classical name reactions, such Ugi, Strecker, Mannich most advanced concepts deracemisation, transamination, carbene N-H insertion. Concurrently, some interesting mechanistic studies/models, information on chirality transfer Finally, perspective highlights, through diversity (AAs) not selected by nature protein incorporation, generic modes activation, induction, reactivity commonly used, enamine, hydrogen bonding, Brønsted acids/bases, phase-transfer reflecting increasingly important role applied chemistry.

Language: Английский

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Organic Synthesis Away from Equilibrium: Contrathermodynamic Transformations Enabled by Excited-State Electron Transfer

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(13), P. 1827 - 1838

Published: June 21, 2024

ConspectusChemists have long been inspired by biological photosynthesis, wherein a series of excited-state electron transfer (ET) events facilitate the conversion low energy starting materials such as H

Language: Английский

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