Recent Progress toward the Construction of Axially Chiral Molecules Catalyzed by an N-heterocyclic Carbene

ACS Catalysis, Год журнала: 2021, Номер 11(20), С. 12520 - 12531

Опубликована: Сен. 28, 2021

Axial chirality widely exists in natural products, pharmaceutical compounds, and other functional molecules; these axially chiral compounds also find wide utility as catalysts or ligands organic synthetic chemistry. Nevertheless, whereas significant progress has been made toward the synthesis of enantioenriched molecules over past two decades, strategies involving organocatalysis have only started to emerge recently. N-heterocyclic carbene (NHC) organocatalysts recognized be powerful tools for rapid construction complex molecular architectures. However, previous works mainly focused on assembly point recently it realized that asymmetric axial could achieved by using NHCs organocatalysts. This Perspective highlights developments advances scaffolds catalyzed NHCs. The aim this is provide an overview area serve a stepping stone future investigations.

Язык: Английский

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Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 15, 2024

Abstract The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and ligands. One efficient method the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis atropisomers with simultaneous creation contiguous axial central chirality by oxidative NHC ( N -heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able synthesize structurally diverse pyrroles indoles vicinal or bearing 2,3-dihydropyrimidin-4-one moiety moderate good yields excellent enantioselectivities. Further synthetic transformations obtained derivative products demonstrated. reaction mechanism origin enantioselectivity understood through DFT calculations.

Язык: Английский

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Amide C–N bonds activation by A new variant of bifunctional N-heterocyclic carbene

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 12, 2024

Abstract We report an organocatalyst that combines a triazolium N-heterocyclic carbene (NHC) with squaramide as hydrogen-bonding donor (HBD), which can effectively catalyze the atroposelective ring-opening of biaryl lactams via unique amide C–N bond cleavage mode. The free species attacks carbonyl, forming axially chiral acyl-azolium intermediate. Various amines be accessed by this methodology up to 99% ee and yield. By using mercaptan catalyst turnover agent, resulting thioester synthon transformed into several interesting atropisomers. Both control experiments theoretical calculations reveal crucial role hybrid NHC-HBD skeleton, activates H-bonding brings it spatially close centre. This discovery illustrates potential chimera demonstrates complementary strategy for activation manipulation.

Язык: Английский

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Organophotoredox-Driven Three-Component Synthesis of β-Trifluoromethyl β-Amino Ketones

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

In this work, we present a photoredox three-component reaction that enables the synthesis of medicinally relevant β-trifluoromethyl β-amino ketones from N-trifluoroethylhydroxylamine derivative, styrenes and DMSO. Remarkably, fluoromethyl, difluoromethyl pentafluoroethyl analogues are also accessed using same conditions. The mechanistic investigations, including radical trapping experiments, cyclic voltammetry, Stern-Volmer quenching studies isotope labelling experiments support photoinduced radical/polar crossover Kornblum-type oxidation mechanisms. Finally, applicability organic skeletons is showcased by notable derivatization reactions.

Язык: Английский

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Enantioselective Seleno‐Michael Addition Reactions Catalyzed by a Chiral Bifunctional N‐Heterocyclic Carbene with Noncovalent Activation

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(23)

Опубликована: Март 24, 2022

Abstract The Michael reaction is a conjugate addition and one of the most powerful methods with which to prepare functional molecules β‐stereogenic center. Despite its success in formation various asymmetric carbon–carbon carbon–heteroatom bonds, enantioselective seleno‐Michael remains essentially unexplored. We report here highly alkyl selenols enones. This method conveniently introduces Se atom an electron‐deficient double bond asymmetrically. A chiral bifunctional N‐heterocyclic carbene (NHC)/thiourea catalyst was developed as key ingredient that delivers β‐seleno ketones remarkable selectivity. new mode action support broad applications catalytic activation nucleophilic reactions.

Язык: Английский

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SuFEx Reactions of Sulfonyl Fluorides, Fluorosulfates, and Sulfamoyl Fluorides Catalyzed by N-Heterocyclic Carbenes

ACS Catalysis, Год журнала: 2023, Номер 13(22), С. 14503 - 14512

Опубликована: Окт. 27, 2023

Sulfur(VI) fluoride exchange (SuFEx) click chemistry provides a powerful tool for the rapid assembly of modular connections. Herein, we report an organocatalytic SuFEx reaction sulfonyl fluorides, fluorosulfates, and sulfamoyl fluorides. Under catalysis 10 mol % N-heterocyclic carbene (NHC), or under relay NHC HOBt, different SuFExable hubs efficiently undergo reactions with alcohols amines to afford sulfonates, sulfonamides, sulfates, sulfamates, sulfamides in 49–99% yields. More than 190 sulfonylated products, including 25 natural product derivatives, have been prepared through this method. Mechanism study showed that NHCs might act as carbon-centered Broønsted base activate formation hydrogen bonding.

Язык: Английский

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Asymmetric Aminative Dearomatization of 2-Naphthols via Non-covalent N-Heterocyclic Carbene Catalysis

Organic Letters, Год журнала: 2023, Номер 25(13), С. 2323 - 2327

Опубликована: Март 30, 2023

Herein, successful utilization of non-covalent N-heterocyclic carbene (NHC) catalysis toward asymmetric aminative dearomatization naphthols is presented. The NHC-catalyzed process offers enantioselective synthesis cyclic enones possessing a nitrogen-containing α-quaternary stereocenter. reaction applies to various functionalized substrates including acid-labile groups and shown be scalable. Substrate activation via an O-H···NHC hydrogen-bonding interaction suggested based on the results obtained in mechanistic studies.

Язык: Английский

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Weak Nucleophiles in the Aza‐Michael Reaction

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(12), С. 1908 - 1925

Опубликована: Май 15, 2023

Abstract The 1,4‐conjugated addition of nitrogen centered nucleophiles to electron‐deficient alkenes is one the most significant and widely used reactions in modern synthetic organic chemistry. To date, various protocols for aza‐Michael reaction have been developed. However, these reports mainly focus on use strong Michael donors. In recent years, conjugate weak acceptors gained increasing popularity. Impressive progress this area has achieved by more efficient catalyst systems. This review aims provide a critical analysis results obtained (azoles, pyrroles, indoles, carbamates, purines, amides, hydrazides, uraciles etc ) with which were reported over past twelve years.

Язык: Английский

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N-Heterocyclic Carbene-Catalyzed Asymmetric S_N2 Alkylation via Noncovalent Activation

Organic Letters, Год журнала: 2024, Номер 26(36), С. 7479 - 7483

Опубликована: Авг. 2, 2024

The field of asymmetric catalysis has been developed by exploring noncovalent interactions, particularly within N-heterocyclic carbene-mediated processes. Despite challenges due to the limited number compatible electrophiles (predominantly π-acceptors), this study introduces first α-alkylation 3-aryl oxindoles using C

Язык: Английский

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Bifunctional NHC-Catalyzed Asymmetric Intramolecular Conjugate Addition via Noncovalent Interaction

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Herein, we report a novel squaramide containing chiral bifunctional N-heterocyclic carbene (NHC) and its utilization in developing asymmetric intramolecular conjugate addition involving noncovalent interaction. Via concomitant activation of both electrophilic nucleophilic centers substrates, the reaction proceeds through well-organized transition state, thereby affording products with up to 94% ee broad scope. The process is found be scalable. initial mechanistic study supports nature newly designed NHC.

Язык: Английский

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