Interrogation of Enantioselectivity in the Photomediated Ring Contractions of Saturated Heterocycles

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

Published: Jan. 2, 2025

We recently reported a chiral phosphoric acid (CPA) catalyzed enantioselective photomediated ring contraction of piperidines and other saturated heterocycles. By extruding single heteroatom from ring, this transformation builds desirable C(sp3)–C(sp3) bonds in the contracted products; however, origins enantioselectivity remain poorly understood. In work, has been explored across an expanded structurally diverse substrate scope, revealing wide range enantioselectivities (0–99%) using two distinct CPA catalysts. Mechanistic investigations support rate-determining excitation that generates short-lived achiral intermediates are intercepted by enantiodetermining closure. The effects competitive uncatalyzed reactivity light-driven reversibility closure on have elucidated. Statistical models were built regressing scope against key structural features products for both resultant suggested factors influence response each catalyst enabled rational modification pharmaceutically relevant target molecule to improve enantioselectivity. Finally, density functional theory (DFT)-based transition state analysis identified noncovalent interactions with correlated unique selectivity-relevant uncovered through statistical modeling. Our findings not only offer comprehensive insight into system but should also aid future development related CPA-catalyzed reactions.

Language: Английский

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Controlling Stereoselectivity with Noncovalent Interactions in Chiral Phosphoric Acid Organocatalysis

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

Published: March 18, 2025

Chiral phosphoric acids (CPAs) have emerged as highly effective Brønsted acid catalysts in an expanding range of asymmetric transformations, often through novel multifunctional substrate activation modes. Versatile and broadly appealing, these benefit from modular tunable structures, compatibility with additives. Given the unique types noncovalent interactions (NCIs) that can be established between CPAs various reactants─such hydrogen bonding, aromatic interactions, van der Waals forces─it is unsurprising catalyst systems become a promising approach for accessing diverse chiral product outcomes. This review aims to provide in-depth exploration mechanisms by which impart stereoselectivity, positioning NCIs central feature connects broad spectrum catalytic reactions. Spanning literature 2004 2024, it covers nucleophilic additions, radical atroposelective bond formations, highlighting applicability CPA organocatalysis. Special emphasis placed on structural mechanistic features govern CPA-substrate well tools techniques developed enhance our understanding their behavior. In addition emphasizing details stereocontrolling elements individual reactions, we carefully structured this natural progression specifics broader, class-level perspective. Overall, findings underscore critical role catalysis significant contributions advancing synthesis.

Language: Английский

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Controlled generation of ortho-quinone methides and (4+3) cyclization with 2-indolylalcohols by dual photoredox/Brønsted acid relay catalysis

Green Synthesis and Catalysis, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Given the significance of oxacyclic frameworks in molecular scaffolds and drug discovery, it is intriguing to precisely construct manipulate such ring systems chemical research. In this area, intermolecular, multicomponent cyclization for synthesis diversely substituted seven-membered oxacycles under simple conditions still a challenge. Here, we report dual photoredox/Brønsted acid relay catalytic strategy situ generation ortho-quinone methides subsequent (4+3) with 2-indolylalcohols. one-pot reaction, two C-C one C-O bonds are formed, providing de novo access various biologically important indole-fused, oxygen-containing heterocycles. By virtue chiral phosphoric acid, an asymmetric version can also be achieved good excellent levels enantioselectivity (up 96:4 er).

Language: Английский

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Enantioselective Desymmetrization of Biaryls via Cooperative Photoredox/Brønsted Acid Catalysis and Its Application to the Total Synthesis of Ancistrobrevolines

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

Published: April 5, 2025

Photoredox catalysis has emerged as a powerful tool for forming and breaking chemical bonds, further taking hold with its integration asymmetric catalysis. While the dual-catalytic approach led to successful examples of control stereogenic centers, axes remained underexplored. In this study, an acylimine intermediate was generated through photoredox catalysis, symmetric substrate, 2-arylresorcinol, desymmetrized aid chiral phosphoric acid Using approach, center axis were successfully controlled provide natural-product-driven compound. The origins enantioselectivity diastereoselectivity investigated density functional theory study four possible enantiodetermining transition states. Consequently, first total syntheses ring-contracted naphthylisoquinoline alkaloid ancistrobrevolines A B accomplished concisely. This provides not only novel methodology strategy synthesize alkaloids but also direction advance catalytic research synthesis studies.

Language: Английский

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Aporphinol-Derived Chiral Phosphoric Acids: Synthesis and Catalytic Performance

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

Published: April 18, 2025

A novel series of chiral phosphoric acid (CPA) catalysts based on a bioinspired aporphinol scaffold has been developed. The efficacy these CPAs is demonstrated through enantioselective transfer hydrogenation C2-substituted quinolines, achieving excellent enantioselectivities (93-99% enantiomeric excess). They also exhibit catalytic efficiency comparable to that classic acids in the asymmetric Friedel-Crafts reaction and reduction ketone. This work highlights potential aporphinol-based for diverse transformations.

Language: Английский

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Asymmetric Three-Component Radical Cascade Reactions Enabled by Synergistic Photoredox/Brønsted Acid Catalysis: Access to α-Amino Acid Derivatives

ACS Central Science, Journal Year: 2024, Volume and Issue: 11(1), P. 36 - 45

Published: Aug. 16, 2024

Multicomponent reactions (MCRs), highly sought-after methods to produce atom-, step-, and energy-economic organic syntheses, have been developed extensively. However, catalytic asymmetric MCRs, especially those involving radical species, remain largely unexplored owing the difficulty in stereoselectively regulating extraordinarily high reactivity of open-shell species. Herein, we report a conceptually novel three-component cascade reaction readily accessible glycine esters, α-bromo carbonyl compounds 2-vinylcyclopropyl ketones via synergistic photoredox/Brønsted acid catalysis, which three sequential C–C (σ/π/σ) bond-forming events occurred through addition/ring-opening/radical–radical coupling protocol, affording an array valuable enantioenriched unnatural α-amino derivatives bearing two contiguous stereogenic centers alkene moiety moderate good yield with diastereoselectivity, excellent enantioselectivity E-dominated geometry under mild conditions. The relay process, unique proton-coupled electron transfer (PCET)-promoted radical–radical coupling, is supported by mechanistic investigations quantum mechanics calculations should garner broad interest further inspire development multicomponent reactions.

Language: Английский

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Enantioselective synthesis of 3-(N-indolyl)quinolines containing axial and central chiralities

Chemical Communications, Journal Year: 2023, Volume and Issue: 60(5), P. 582 - 585

Published: Dec. 7, 2023

Quinoline and indole are important core structures in biologically active compounds materials. Atropisomeric biaryls consisting of quinoline a unique class axially chiral molecules. We report herein enantioselective synthesis 3-(

Language: Английский

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Controlled Generation of Ortho-Quinone Methides and (4+3) Cyclization with 2-Indolylalcohols by Dual Photoredox/Brønsted Acid Relay Catalysis

Published: Jan. 1, 2024

Given the significance of oxacyclic frameworks in molecular scaffolds and drug discovery, it is intriguing to precisely construct manipulate such ring systems chemical research. In this area, intermolecular, multicomponent cyclization for synthesis diversely substituted seven-membered oxacycles under simple conditions still a challenge. Here, we report dual photoredox/Brønsted acid relay catalytic strategy situ generation ortho-quinone methides subsequent (4+3) with 2-indolylalcohols. one-pot reaction, two C-C one C-O bonds are formed, providing de novo access various biologically important indole-fused, oxygen-containing heterocycles. By virtue chiral phosphoric acid, an asymmetric version can also be achieved good excellent level enantioselectivity (up 96:4 er).

Language: Английский

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