Asymmetric organocatalysis: an enabling technology for medicinal chemistry

Chemical Society Reviews, Год журнала: 2021, Номер 50(3), С. 1522 - 1586

Опубликована: Янв. 1, 2021

This review provides a comprehensive overview of the recent applications organocatalytic strategies in pharmaceutical synthesis, with focus on preparation antiviral, anticancer, neuroprotective, cardiovascular, antibacterial and antiparasitic agents.

Язык: Английский

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Bifunctional N-Heterocyclic Carbenes Derived from l-Pyroglutamic Acid and Their Applications in Enantioselective Organocatalysis

Accounts of Chemical Research, Год журнала: 2020, Номер 53(3), С. 690 - 702

Опубликована: Март 6, 2020

In nature, enzymes are a powerful medium for the construction of enantiomerically pure chemicals, which always inspires synthetic chemists to explore new catalysts imitate enzyme machinery asymmetric transformations. Vitamin B1, bifunctional thiazolium N-heterocyclic carbene (NHC) precursor, is coenzyme transketolase. past two decades, series chiral NHCs, including monocyclic, bicyclic, tetracyclic, and even bridged ones, have been synthesized successfully utilized as efficient organocatalysts wide variety organic reactions. The utility can enhance catalytic activity improve stereochemical control through their synchronous activation both reaction partners. However, NHCs possessing multiple sites far less developed.This Account gives an overview our research on design, development, applications in organocatalysis. We l-pyroglutamic acid-derived bearing free hydroxyl group interact with carbonyl or imino groups via hydrogen-bonding. Further studies revealed that these worked well developed NHC-catalyzed aza-benzoin reactions, [2 + 2], 3], 4] cycloadditions ketenes, [3 2] annulations enals, aza-MBH Rauhut-Currier reactions Michael acceptors. addition nucleophilic Breslow intermediates, enolates, homoenolates, zwitterionic azolium 3] annulation 1,3-biselectrophilic α,β-unsaturated acyl intermediates was also developed.In showed amazing effects compared normal nonbifunctional NHCs. some cases, facilitated did not work under NHC catalysis, possibly due additional H-bonding. More interestingly, could only but switch enantioselectivity get products opposite stereochemistry H-bond controlled directing. Furthermore, mode be totally changed from give kinetically favored when were employed. future, other challenging such carbon-carbon unsaturated bonds, involving alkyl heteroatom radicals will major focus group.

Язык: Английский

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Recent advances in N-heterocyclic carbene-catalyzed radical reactions

Chinese Chemical Letters, Год журнала: 2020, Номер 32(2), С. 660 - 667

Опубликована: Авг. 19, 2020

Язык: Английский

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Diastereo- and Atroposelective Synthesis of Bridged Biaryls Bearing an Eight-Membered Lactone through an Organocatalytic Cascade

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(43), С. 17062 - 17067

Опубликована: Окт. 11, 2019

We present herein an unprecedented stereoselective synthesis of bridged biaryls with defined axial and central chirality from readily available starting materials. This N-heterocyclic carbene-catalyzed method proceeds through propargylic substitution azolium enolates followed by two-directional cyclization, as supported DFT calculation. A range benzofuran/indole-derived bearing eight-membered lactone are accessed uniformly high stereoselectivity (>98:2 dr, mostly >98% ee).

Язык: Английский

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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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Tale of the Breslow intermediate, a central player in N-heterocyclic carbene organocatalysis: then and now

Chemical Science, Год журнала: 2021, Номер 12(23), С. 7973 - 7992

Опубликована: Янв. 1, 2021

Molecular insights on the formation, detection, and even isolation of Breslow intermediate, which is most important species in N-heterocyclic carbene (NHC) catalysis, as obtained from experimental computational studies, are presented.

Язык: Английский

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Carbene and photocatalyst-catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles to form ketones

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Май 23, 2022

The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile a precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized precursors two-component coupling. Herein, an N-heterocyclic catalyzed decarboxylative carboxylic acids imidazoles disclosed, in which the are directly used precursors. could also be generated situ by reaction acid with CDI thus furnishing formally two acids. In addition, successfully extended three-component using alkene third partner via relay process. mild conditions, operational simplicity, use reacting partners make our powerful strategy construction complex ketones from readily available starting materials, late-stage modification natural products medicines.

Язык: Английский

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NHC and visible light-mediated photoredox co-catalyzed 1,4-sulfonylacylation of 1,3-enynes for tetrasubstituted allenyl ketones

Chemical Science, Год журнала: 2022, Номер 13(11), С. 3169 - 3175

Опубликована: Янв. 1, 2022

The modulation of selectivity highly reactive carbon radical cross-coupling for the construction C-C bonds represents a challenging task in organic chemistry. N-Heterocyclic carbene (NHC) catalyzed transformations have opened new avenue acyl With this method, selective an with alkyl efficient was successfully realized. However, reaction radicals vinyl has been much less investigated. We herein describe NHC and visible light-mediated photoredox co-catalyzed 1,4-sulfonylacylation 1,3-enynes, providing structurally diversified valuable tetrasubstituted allenyl ketones. Mechanistic studies indicated that ketyl are formed from aroyl fluorides via oxidative quenching photocatalyst excited state, generated chemo-specific sulfonyl addition to finally, key provides

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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Radical Reactions with N-Heterocyclic Carbene (NHC)-Derived Acyl Azoliums for Access to Multifunctionalized Ketones

ACS Catalysis, Год журнала: 2024, Номер 14(11), С. 8270 - 8293

Опубликована: Май 13, 2024

As one of the most important key intermediates, NHC-bound acylazolium-based ionic transformations have been intensively explored in past two decades. With expeditious development NHC-catalyzed radical recent years, acylazolium chemistry has reached another level, with number relevant publications increasing significantly. However, a summary focused on acylations NHC-derived acyl azoliums classified according to mechanistic difference not reported. Such detailed classification and deep analysis provide opportunities for better understanding history trend this field. In review, reactions N-heterocyclic carbene (NHC)-derived are systematically introduced. The achievements challenges within area also summarized discussed at end.

Язык: Английский

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