Progress in (Thio)urea‐ and Squaramide‐Based Brønsted Base Catalysts with Multiple H‐Bond Donors

European Journal of Organic Chemistry, Год журнала: 2022, Номер 26(7)

Опубликована: Дек. 15, 2022

Abstract Thiourea‐ and squaramide‐based bifunctional base catalysts represent nowadays a powerful tool in the field of asymmetric catalysis have demonstrated very efficient for promoting wide variety transformations enantioselectively. New versions that incorporate one or various additional H‐bond donor site(s) catalyst structure been developed recently which led to more active (reduced loadings) selective catalysts. This review highlights pioneering ideas most recent contributions area with material organized according nature functionality. The advantages, current limitations perspectives these new multifunctional are discussed.

Язык: Английский

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Development of Chiral Ureates as Chiral Strong Brønsted Base Catalysts

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(8), С. 3724 - 3728

Опубликована: Фев. 11, 2020

Recently, chiral Brønsted bases having high basicity have emerged as a powerful tool in developing new catalytic enantioselective reactions. However, such strong base catalysts are still very scarce. Herein, we report the development of anionic N,N′-dialkyl ureate moiety basic site. Its prominent activity was demonstrated addition reactions α-thioacetamides less acidic pronucleophiles with various electrophiles. Thus, newly developed catalyst accessibility and structural tunability would expand scope viable transformations under catalysis.

Язык: Английский

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Development of Molecular Transformations on the Basis of Catalytic Generation of Anionic Species by Organosuperbase

Bulletin of the Chemical Society of Japan, Год журнала: 2021, Номер 94(1), С. 339 - 356

Опубликована: Янв. 1, 2021

Abstract In this account, we summarized our recent efforts to develop molecular transformations under Brønsted base catalysis on the basis of own guiding principles for designing reaction systems, that include “the generation and application anionic species which are difficult utilize in conventional systems” employment organosuperbases possessing much higher basicities than organic bases as a catalyst”. particular, discussed reactions involving carbanions less acidic compounds through formal umpolung process from carbonyl [3+2] cycloadditions synthetic equivalent 1,3-dipole epoxide opening.

Язык: Английский

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Chiral phosphoric acid-catalyzed asymmetric epoxidation of alkenyl aza-heteroarenes using hydrogen peroxide

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

Опубликована: Июнь 20, 2024

The synthesis of chiral α-azaheteroaryl oxiranes via enantioselective catalysis is a formidable challenge due to the required complex stereoselectivity and diverse N-heterocyclic structures. These compounds play crucial role in developing bioactive molecules, where precise chirality significantly influences biological activity. Here we show that using phosphoric acid as catalyst, our method efficiently addresses these challenges. This technique not only achieves high enantio- diastereoselectivity but also demonstrates superior chemo- stereocontrol during epoxidation alkenyl aza-heteroarenes. Our approach leverages synergistic blend electrostatic hydrogen-bonding interactions, enabling effective activation both substrates hydrogen peroxide. resulting exhibit enhanced diversity functionality, aiding construction azaaryl with contiguous stereocenters. Kinetic density functional theory studies elucidate mechanism, highlighting acid's pivotal this intricate process.

Язык: Английский

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Development of Chiral Organosuperbase Catalysts Consisting of Two Different Organobase Functionalities

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(19), С. 7472 - 7477

Опубликована: Фев. 14, 2020

Abstract In the field of chiral Brønsted base catalysis, a new generation catalysts has been highly anticipated to overcome intrinsic limitation pronucleophiles that are applicable enantioselective reactions. Herein, we reveal conceptually consisting two different organobase functionalities, one which functions as an organosuperbase and other substrate recognition site. Their prominent activity, stems from distinctive cooperative function by organobases in single catalyst molecule, was demonstrated unprecedented direct Mannich‐type reaction α‐phenylthioacetate less acidic pronucleophile. The present achievement would provide guiding principle for design development significantly broaden utility catalysis asymmetric organic synthesis.

Язык: Английский

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A bifunctional iminophosphorane squaramide catalyzed enantioselective synthesis of hydroquinazolinesviaintramolecular aza-Michael reaction to α,β-unsaturated esters

Chemical Science, Год журнала: 2021, Номер 12(17), С. 6064 - 6072

Опубликована: Янв. 1, 2021

The activation of both aromatic and aliphatic ureas as N-centered nucleophiles in intramolecular Michael addition reactions to α,β-unsaturated esters was achieved under bifunctional iminophosphorane squaramide superbase catalysis.

Язык: Английский

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Copper-Catalyzed Asymmetric Conjugate Addition of Alkene-Derived Nucleophiles to Alkenyl-Substituted Heteroarenes

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 9611 - 9620

Опубликована: Июль 22, 2022

We herein report the copper-catalyzed asymmetric conjugate addition of β-substituted alkenyl heteroarenes, one most challenging Michael acceptors, with alkenes as latent nucleophiles. Diverse chiral heteroarenes bearing two vicinal stereocenters were obtained in good to excellent yields, generally enantioselectivity, and a level diastereoselectivity. The products can be readily transformed into other valuable acyclic enantioenriched structures three contiguous via amine catalysis. Mechanistic studies, including an isotope labeling experiment, nonlinear effect study, kinetic experiments, initial-rate kinetics implemented, experimental results indicated that hydrocupration step might turnover-limiting step. Moreover, origin preferential alkene presence Ph-BPE-ligated CuH catalyst was also elucidated some control experiments.

Язык: Английский

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BIMP‐Catalyzed 1,3‐Prototropic Shift for the Highly Enantioselective Synthesis of Conjugated Cyclohexenones

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(40), С. 17417 - 17422

Опубликована: Июнь 19, 2020

A bifunctional iminophosphorane (BIMP)-catalysed enantioselective synthesis of α,β-unsaturated cyclohexenones through a facially selective 1,3-prototropic shift β,γ-unsaturated prochiral isomers, under mild reaction conditions and in short times, on range structurally diverse substrates, is reported. α,β-Unsaturated cyclohexenone products primed for downstream derivatisation were obtained high yields (up to 99 %) consistently enantioselectivity % ee). Computational studies into the mechanism origins enantioselectivity, including multivariate linear regression TS energy, carried out data found be good agreement with experimental findings.

Язык: Английский

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Tunable and Cooperative Catalysis for Enantioselective Pictet‐Spengler Reaction with Varied Nitrogen‐Containing Heterocyclic Carboxaldehydes

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(46), С. 24573 - 24581

Опубликована: Сен. 6, 2021

Herein we report an organocatalytic enantioselective functionalization of heterocyclic carboxaldehydes via the Pictet-Spengler reaction. Through careful pairing novel squaramide and Brønsted acid catalysts, our method tolerates a breadth heterocycles, enabling preparation series heterocycle conjugated β-(tetrahydro)carbolines in good yield enantioselectivity. Careful selection carboxylic co-catalyst is essential for toleration variety regioisomeric heterocycles. Utility demonstrated three-step stereoselective pyridine-containing analogues potent selective estrogen receptor downregulator U.S. FDA approved drug Tadalafil.

Язык: Английский

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Recent Advances in Organocatalyzed Asymmetric Sulfa‐Michael Addition Triggered Cascade Reactions

The Chemical Record, Год журнала: 2023, Номер 23(7)

Опубликована: Янв. 3, 2023

Abstract The sulfa‐Michael addition reaction is a crucial subset of the Michael reaction, and aroused interest numerous synthetic biologists chemists. In particular, triggered cascade has developed quickly in recent years because it offers an efficient method to construct C−S bonds other one approach, which widely applicable for building chiral pharmaceuticals, their intermediates, natural compounds. This review emphasizes advancements addition‐triggered reactions stereoselective synthesis sulfur‐containing compounds, including sulfa‐Michael/aldol, sulfa‐Michael/Henry, sulfa‐Michael/Michael, sulfa‐Michael/Mannich some multi‐step processes. Moreover, mechanisms derivatization experiments are introduced appropriately.

Язык: Английский

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