Recent advances in visible light-induced C(sp3)–N bond formation

Nature Reviews Chemistry, Год журнала: 2022, Номер 6(8), С. 544 - 561

Опубликована: Июль 11, 2022

Язык: Английский

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Catalytic Enantioselective Intramolecular Oxa-Michael Reaction to α,β-Unsaturated Esters and Amides

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(23), С. 12771 - 12782

Опубликована: Май 30, 2023

A bifunctional iminophosphorane (BIMP)-catalyzed, enantioselective intramolecular oxa-Michael reaction of alcohols to tethered, low electrophilicity Michael acceptors is described. Improved reactivity over previous reports (1 day vs 7 days), excellent yields (up 99%), and enantiomeric ratios 99.5:0.5 er) are demonstrated. The broad scope, enabled by catalyst modularity tunability, includes substituted tetrahydrofurans (THFs) tetrahydropyrans (THPs), oxaspirocycles, sugar natural product derivatives, dihydro-(iso)-benzofurans, iso-chromans. state-of-the-art computational study revealed that the enantioselectivity originates from presence several favorable intermolecular hydrogen bonds between BIMP substrate induce stabilizing electrostatic orbital interactions. newly developed catalytic approach was carried out on multigram scale, multiple adducts were further derivatized an array useful building blocks, providing access enantioenriched biologically active molecules products.

Язык: Английский

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Enantiocontrolled Cyclization to Form Chiral 7- and 8-Membered Rings Unified by the Same Catalyst Operating with Different Mechanisms

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Chiral medium-sized rings, albeit displaying attractive properties for drug development, suffer from numerous synthetic challenges due to difficult cyclization steps that must take place form these unusually strained, atropisomeric rings sterically crowded precursors. In fact, catalytic enantioselective methods the formation of chiral seven-membered are unknown, and corresponding eight-membered variants also sparse. this work, we present a substrate preorganization-based, enantioselective, organocatalytic strategy construct seven- featuring chirality is intrinsic ring in absence singular stereogenic atoms or single bond axes chirality. The reactions proceed under mild conditions with high levels stereocontrol. Notably, same bifunctional iminophosphorane catalyst orchestrates substrates two different sizes, mechanistic paradigms. We envision size versatility method could guide further applications asymmetric catalysis other challenging reactions.

Язык: Английский

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Bifunctional Iminophosphorane-Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α,β-Unsaturated Amides

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(2), С. 1006 - 1015

Опубликована: Янв. 6, 2022

The first metal-free catalytic intermolecular enantioselective Michael addition to unactivated α,β-unsaturated amides is described. Consistently high enantiomeric excesses and yields were obtained over a wide range of alkyl thiol pronucleophiles electrophiles under mild reaction conditions, enabled by novel squaramide-based bifunctional iminophosphorane catalyst. Low catalyst loadings (2.0 mol %) achieved on decagram scale, demonstrating the scalability reaction. Computational analysis revealed origin enantiofacial selectivity via relevant transition structures provided substantial support for specific noncovalent activation carbonyl group amide

Язык: Английский

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Bifunctional Iminophosphorane‐Catalyzed Enantioselective Nitroalkane Addition to Unactivated α,β‐Unsaturated Esters**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(21)

Опубликована: Март 16, 2023

Abstract Herein we describe the enantioselective intermolecular conjugate addition of nitroalkanes to unactivated α,β‐unsaturated esters, catalyzed by a bifunctional iminophosphorane (BIMP) superbase. The transformation provides most direct access pharmaceutically relevant enantioenriched γ‐nitroesters, utilizing feedstock chemicals, with unprecedented selectivity. methodology exhibits broad substrate scope, including β‐(fluoro)alkyl, aryl and heteroaryl substituted electrophiles, was successfully applied on gram scale reduced catalyst loading, and, additionally, recovery carried out. formal synthesis range drug molecules, an ( S )‐rolipram were achieved. Additionally, computational studies revealed key reaction intermediates transition state structures, provided rationale for high enantioselectivities, in good agreement experimental results.

Язык: Английский

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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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Two Decades of Progress in the Asymmetric Intramolecular aza‐Michael Reaction

The Chemical Record, Год журнала: 2021, Номер 22(1)

Опубликована: Авг. 20, 2021

Abstract The asymmetric intramolecular aza‐Michael reaction (IMAMR) is a very convenient strategy for the generation of heterocycles bearing nitrogen‐substituted stereocenters. Due to ubiquitous presence these skeletons in natural products, IMAMR has found widespread applications total synthesis alkaloids and biologically relevant compounds. development versions are quite recent, most them reported this century. fundamental advances field involve use organocatalysts. Chiral imidazolidinones, diaryl prolinol derivatives, Cinchone ‐derived primary amines quaternary ammonium salts, BINOL‐derived phosphoric acids account success those methodologies. Moreover, N ‐sulfinyl imines with dual role, as nitrogen nucleophiles chiral auxiliaries, appeared versatile mode performing IMAMR.

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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Computational Identification of Potential Organocatalysts (CIPOC) Reveals a 2-aminoDMAP/Urea Catalyst Superior to Its Thiourea Analogue

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Asymmetric organocatalysis by bifunctional acid- and base-type small organic molecules has emerged as a promising way to enhance stereoselective transformations since the beginning of this millennium. Takemoto's tert-amine/thiourea catalyst, an archetype in these endeavors, encouraged many design new multifunctional alternatives. However, discovery efficient catalysts library thousands candidates containing desired functionalities their structures remains great challenge both synthetically computationally. We, toward ends, developed computational protocol (CIPOC─Computational Identification POtential (Organo)Catalysts), which discovered chiral 2-aminoDMAP/urea catalyst among 1600 enabling conjugate addition malonates trans-β-nitroalkenes rapidly (in few hours) with exquisite selectivities yields, producing superior results than that Takemoto's. The unique activity is attributed dual function 2-aminoDMAP unit (double H-bonding π-stacking interactions) exceptional performance urea compared thiourea, result lower energetic penalty required distort its active conformation provide optimal catalytic interactions.

Язык: Английский

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Asymmetric Synthesis of Hydroquinazolines Bearing C4-Tetrasubstituted Stereocenters via Kinetic Resolution of α-Tertiary Amines

Organic Letters, Год журнала: 2022, Номер 24(2), С. 625 - 630

Опубликована: Янв. 3, 2022

A novel protocol for asymmetric synthesis of hydroquinazolines bearing C4-tetrasubstituted stereocenters has been achieved through kinetic resolution 2-amido α-tertiary benzylamines via chiral phosphoric acid catalyzed intramolecular dehydrative cyclizations. This method gave access to both and with broad scope high enantioselectivities. An intriguing restricted rotation the C-N bond was observed hydroquinazoline products stereocenters.

Язык: Английский

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