Asymmetric Cycloaddition and Cyclization Reactions Catalyzed by Chiral N,N′-Dioxide–Metal Complexes

Accounts of Chemical Research, Journal Year: 2017, Volume and Issue: 50(10), P. 2621 - 2631

Published: Oct. 2, 2017

ConspectusCatalytic asymmetric cycloadditions and cascade cyclizations are a major focus for the enantioselective construction of chiral carbo- heterocycles. A number Lewis acids organocatalysts have been designed such reactions. The development broadly applicable catalysts bearing novel backbones to meet demands various applications is an ongoing challenge. Approximately 10 years ago, we introduced group conformationally flexible C2-symmetric N,N′-dioxide amide compounds, which represent new class privileged ligands. coordination four oxygens around central metal generates octahedral tricyclometalated acid catalyst that can carry out In this Account, summarize our recent studies on between dienophiles dienes, dipoles dipolarophiles, catalyzed by N,N′-dioxide–metal complexes. principle, these unique lower LUMO energy electron-deficient 2π components or heterodienes with functional groups via binding modes.With N-Boc-3-alkenyloxindole alkylidene malonate as components, complexes provided excellent catalytic activities inductions variety transformations, including [2 + 1], [3 2], [4 [8 2] cycloadditions. Mechanistically, substrates could be efficiently activated through bidentate coordination. strategy was also useful form polycyclic adducts. Monodentate other α,β-unsubstituted carbonyl compounds centers enabled both normal Diels–Alder reactions inverse-electron-demand hetero-Diels–Alder well additions. Furthermore, aldehydes, ketones, imines well-tolerated afford This includes allowing concise synthesis antimalarial compound KAE609. Asymmetric Michael/cyclization α,β-unsaturated pyrazolamides gave efficient access drugs (−)-paroxetine (R)-thiazesim. formal donor–acceptor epoxides aziridines enantioselectively series five-membered oxo- aza-heterocycles. reaction cyclopropane diketones showed unprecedented reactivities route dihydropyrrole benzimidazole derivatives.General models emerged from knowledge absolute configurations products several X-ray crystal structures catalysts. field chirality created center, bonding one two reactants establishes perfect template generation target Representative examples used demonstrate how substructures ligands affect stereoselectivity salts impact reactivity. These results reveal importance tunability compatibility precursors achieving high stereoinduction activity.

Language: Английский

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Lewis Acid Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic N-Sulfonylaziridines

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 140(49), P. 17211 - 17217

Published: Nov. 13, 2018

The first Lewis acid catalyzed stereoconvergent transformation of racemic 2-(hetero)aryl-N-sulfonylaziridines via C–N bond cleavage with nucleophiles is presented. This includes the [3 + 2] annulations (hetero)aromatic aldehydes and 1,3-disubstituted indoles, asymmetric Friedel–Crafts type reaction electron-rich (hetero)arenes, aminolysis amines, providing facile access to chiral 1,3-isoxazolidines, pyrroloindolines, 2-(hetero)arylphenethylamines, vicinal diamines. method features a simple cheaply available complex Cu(I)–chiral BINAP catalyst, excellent yield high diastereo- enantioselectivities, mild conditions. A mechanism involving I dynamic kinetic transformations (DyKATs) aziridines proposed based on results control experiments.

Language: Английский

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Ring-Opening Cyclization (ROC) of Aziridines with Propargyl Alcohols: Synthesis of 3,4-Dihydro-2H-1,4-oxazines

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(7), P. 4504 - 4518

Published: March 27, 2023

Activated aziridines react with propargyl alcohols in the presence of Zn(OTf)2 as Lewis acid catalyst following an SN2-type ring-opening mechanism to furnish corresponding amino ether derivatives. Those ethers further undergo intramolecular hydroamination via 6-exo-dig cyclization and tetrabutylammonium triflate salt additive under one-pot two-step reaction conditions. However, for nonracemic examples, steps were conducted two-pot The works well without any additional solvents. final 3,4-dihydro-2H-1,4-oxazine products obtained 13 84% yield 78 98% enantiomeric excess (for examples).

Language: Английский

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Efficient synthesis of dihydronaphthalenes via cerium-catalyzed annulation of 1-alkoxy substituted 1H-isochromenes with cinnamic acids

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A novel and highly efficient synthetic strategy toward dihydronaphthalenes via a cerium-catalyzed cycloaddition reaction has been developed.

Language: Английский

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Catalytic Asymmetric Chemodivergent C2 Alkylation and [3 + 2]-Cycloaddition of 3-Methylindoles with Aziridines

ACS Catalysis, Journal Year: 2018, Volume and Issue: 8(11), P. 10261 - 10266

Published: Oct. 3, 2018

Highly enantioselective C2 alkylation and inverse-electron-demand [3 + 2]-cycloaddition of 3-methylindoles with 2,2′-diester aziridine were accomplished. The chemodivergent synthesis provided an access to two kinds chiral indole derivatives in good yields stereoselectivities the presence N,N′-dioxide/Tm(OTf)3 or N,N′-dioxide/Ho(OTf)3 complexes. An eight-coordinated mode complex was confirmed by X-ray crystal diffraction interpret roles additives H2O 1,4-dioxane. In addition, control experiments indicated that substituent nitrogen atom determined conversion patterns divergent reactions.

Language: Английский

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Enantioselective Synthesis of Azetidines through [3 + 1]-Cycloaddition of Donor–Acceptor Aziridines with Isocyanides

Organic Letters, Journal Year: 2022, Volume and Issue: 24(7), P. 1513 - 1517

Published: Feb. 11, 2022

The enantioselective [3 + 1]-cycloaddition of racemic donor-acceptor (D-A) aziridines with isocyanides was first realized under mild reaction conditions using a chiral N,N'-dioxide/MgII complex as catalyst, providing facile route to enantioenriched exo-imido azetidines good excellent yield (up 99%) and enantioselectivity 94% ee). An obvious amplification effect observed in this system, an explanation elucidated based on the experimental investigation X-ray crystal structure enantiomerically pure catalyst.

Language: Английский

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Aziridine used as a vinylidene unit in palladium-catalyzed [2 + 2 + 1] domino annulation

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(13), P. 3413 - 3420

Published: Jan. 1, 2021

A series of chromone fused methylenecyclopentanes are efficiently constructed in moderate to good yields by Pd-catalyzed [2 + 2 1] annulation, which aziridine is used as a vinylidene unit cleavage two C–N bonds for the first time.

Language: Английский

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Enantioselective Synthesis of 2,3,3a,8a-Tetrahydrofuro[2,3-b]benzofuran Scaffolds Enabled by Cu(II)/SPDO-Catalyzed [3+2] Cycloaddition of 2,3-Dihydrofuran and Quinone Esters

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(20), P. 14670 - 14675

Published: Oct. 10, 2023

An asymmetric [3+2] cycloaddition of quinone esters with 2,3-dihydrofuran has been realized via a newly developed Cu(II)/SPDO complex. It provides straightforward access to 2,3,3a,8a-tetrahydrofuro[2,3-b]benzofurans (TFB) high enantioselectivity (up 97.5:2.5 er) and diastereoselectivity (all >20:1 dr). The resulting adducts contain two adjacent stereocenters continuously functionalized benzene ring. Additionally, this transformation could be easily performed on gram scale, allowing for expedient synthesis natural dihydroaflatoxin D2 aflatoxin B2.

Language: Английский

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Chiral Magnesium(II) Complex‐Catalyzed Enantioselective Desymmetrization of meso‐Aziridines with Pyrazoles

Advanced Synthesis & Catalysis, Journal Year: 2017, Volume and Issue: 359(20), P. 3532 - 3537

Published: Aug. 8, 2017

Abstract A highly enantioselective catalytic protocol for the desymmetrization of meso ‐aziridines via ring‐opening with pyrazoles is reported using an N,N ′‐dioxide‐Mg(OTf) 2 complex as catalyst. The corresponding trans ‐α‐pyrazole‐substituted amines were obtained in good yields and enantioselectivities (up to 99% yield 94% ee ) under mild reaction conditions. Moreover, a remarkably high asymmetric amplification was observed system. magnified image

Language: Английский

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Lewis Acid‐Catalyzed Intramolecular [3+2] Cross‐Cycloaddition of Aziridine 2,2‐Diesters with Conjugated Dienes for Construction of Aza‐[n.2.1] Skeletons

Chemistry - A European Journal, Journal Year: 2017, Volume and Issue: 23(71), P. 17862 - 17866

Published: Oct. 25, 2017

A novel Lewis acid-catalyzed [3+2] intramolecular cross-cycloaddition (IMCC) between aziridine 2,2-diesters and conjugated dienes has been developed. This is the first regiospecific IMCC of 1,3-dipolar cycloadditions azomethine ylides with carbon=carbon double bonds, supplies a general efficient strategy for construction structurally complex diverse aza-[n.2.1] skeletons. The [3+2]IMCC could be carried out under mild conditions in gram scale. More importantly, 3-alkyl-substituted aziridines were also successful. excellent structural diversity, facile operation versatile post-modifications will support applications natural products synthesis drugs discovery.

Language: Английский

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