Cu-Catalyzed Diastereo- and Enantioselective Synthesis of Borylated Cyclopropanes with Three Contiguous Stereocenters

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

Опубликована: Янв. 17, 2025

Direct synthesis of enantioenriched scaffolds with multiple adjacent stereocenters remains an important yet challenging task. Herein, we describe a highly diastereo- and enantioselective Cu-catalyzed alkylboration cyclopropenes, less reactive alkyl iodides as electrophiles, for the efficient tetra-substituted borylated cyclopropanes bearing three consecutive stereocenters. This protocol features mild conditions, broad substrate scope, good functional group tolerance, affording array chiral in to high yields excellent enantioselectivities. Detailed mechanistic experiments kinetic studies were conducted elucidate reaction pathway rate-determining step reaction. DFT calculations revealed that π···π stacking interaction between phenyl groups on phosphorus ligand, along smaller distortion CuL-Bpin part, contributed The synthetic utility was showcased by facile some valuable centers.

Язык: Английский

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Asymmetric Radical Cyclopropanation of α,β-Unsaturated Amides with α-Boryl and α-Silyl Dibromomethanes via Cr(II)-Based Metalloradical Catalysis

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(9), С. 7282 - 7292

Опубликована: Фев. 20, 2025

Transition-metal-catalyzed asymmetric carbene-transfer reactions represent a powerful strategy for synthesizing chiral cyclopropanes. However, current methods predominantly rely on stabilized carbene-bearing α-π-conjugated groups, restricting access to less carbenes, such as α-silyl and α-boryl carbenes. Herein, we present an unprecedented Cr(II)-based metalloradical system the cyclopropanation of α,β-unsaturated amides with dibromomethanes in presence Mn reducing agent. Employing chromium complex, reaction proceeds under mild conditions, yielding cyclopropanes three contiguous stereocenters high diastereo- enantioselectivities. This method features Cr-catalyzed radical-based stepwise mechanism. The broad substrate scope, encompassing various amides, demonstrates protocol's versatility robustness. Mechanistic insights, supported by experimental computational studies, suggest formation α-Cr(III)-alkyl radical intermediates, delineating pathway distinct from that classical concerted cyclopropanations. approach provides tool highly functionalized cyclopropanes, offering potential applications drug discovery development.

Язык: Английский

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Facile Access to Cyclopropylboronates via Stereospecific Deborylative Cyclization: A Leaving Group‐Assisted Activation of Geminal Diborons

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

Опубликована: Март 24, 2023

Herein we reported a transition metal-free deborylative cyclization strategy, based on which two routes have been developed, generating racemic and enantioenriched cyclopropylboronates. The of geminal-bis(boronates) bearing leaving group was highly diastereoselective, tolerating few functional groups applicable to heterocycles. When optically active epoxides were used as the starting materials, cyclopropylboronates could be efficiently prepared with >99 % stereospecificity. Mechanistic studies showed that at γ-position played crucial role significantly promoted activation gem-diboron moiety.

Язык: Английский

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Catalytic Enantioselective Primary C–H Borylation for Acyclic All-Carbon Quaternary Stereocenters

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(2), С. 1635 - 1643

Опубликована: Янв. 5, 2024

Creating a perfect catalyst to operate enzyme-like chiral recognition has been long-sought aim. A challenging example in this context is constructing acyclic all-carbon quaternary stereogenic centers by transition metal-catalyzed enantioselective C–H activation. We now report highly iridium-catalyzed primary borylation of α-all-carbon substituted 2,2-dimethyl amides enabled tailor-made bidentate boryl ligand (CBL). The success the current transformation attributed CBL/iridium catalyst, which confined pocket. This protocol provides diverse array stereocenters with excellent enantiocontrol and distinct structural features. Computational study reveals that steric hindrance CBL could regulate type dominant orbital interaction between substrate, crucial conferring high induction.

Язык: Английский

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2-Aminophenanthroline Ligands Enable Mild, Undirected, Iridium-Catalyzed Borylation of Alkyl C–H Bonds

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(11), С. 7124 - 7129

Опубликована: Март 8, 2024

The catalytic, undirected borylation of alkyl C–H bonds typically occurs at high reaction temperatures or with excess substrate, both, because the low reactivity bonds. Here we report a new iridium system comprising 2-anilino-1,10-phenanthroline as ligand that catalyzes little to no induction period and rates. This superior activation profile 2-aminophenanthroline-ligated catalysts leads broader scope, including reactions sensitive substrates, such epoxides glycosidic acetals, enhanced diastereoselectivity, higher yields borylated products. These also enable alkanes, amines, ethers room temperature for first time. Mechanistic studies imply facile N-borylation under conditions complexes containing N-boryl aminophenanthrolines are competent precatalysts reaction.

Язык: Английский

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Enantioselective Ni-Catalyzed 1,2-Borylalkynylation of Unactivated Alkenes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(25), С. 17140 - 17149

Опубликована: Июнь 12, 2024

Enantioselective three-component difunctionalization of alkenes with boron reagents represents an attractive strategy for assembling three-dimensional chiral organoboron compounds. However, regio- and enantiocontrol comprise the pivot challenges in these transformations, which predominantly require use activated conjugated alkenes. Herein, by utilizing various carbonyl directing groups, including amides, sulfinamides, ketones, esters, we succeed realizing a nickel-catalyzed 1,2-borylalkynylation unactivated to enable simultaneous incorporation entity sp-fragment across double bond. The products contain boryl, alkynyl, functional groups orthogonal synthetic reactivities, offering three handles further derivatization access valuable intermediates. utility this ligand-enabled asymmetric protocol has been highlighted through late-stage decoration drug-relevant molecules.

Язык: Английский

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Synthesis of α-Substituted Cyclic Boronates via Titanium-Catalyzed Cyclization of Vinyl Boronates with Dihaloalkanes

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

A titanium-catalyzed reductive cyclization of vinyl boronates with gem -dihaloalkanes is developed. α-Substituted cyclic that are otherwise difficult to access, such as those heteroatom-containing rings, readily obtained.

Язык: Английский

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Metal‐Free Stereoconvergent C−H Borylation of Enamides

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(44)

Опубликована: Сен. 18, 2023

Enamides, functional derivatives of enamines, play a significant role as synthetic targets. However, the stereoselective synthesis these molecules has posed longstanding challenge in organic chemistry, particularly for acyclic enamides that are less thermodynamically stable. In this study, we present general strategy constructing β-borylenamides by C-H borylation, which provides versatile platform generating stereodefined enamides. Our approach involves utilization metalloid borenium cation, generated through reaction BBr3 and presence two different additives, avoiding any exogenous catalyst. Importantly, stereoconvergent nature methodology allows use starting materials with mixed E/Z configurations, thus highlighting unique advantage chemistry. Mechanistic investigations have shed light on pivotal roles played reactive boron species, phenomenon stereoconvergence.

Язык: Английский

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Biocatalytic Enantioselective Reduction of Cyclopropenyl Esters and Ketones Using Ene-Reductases

ACS Catalysis, Год журнала: 2024, Номер 14(8), С. 6188 - 6193

Опубликована: Апрель 8, 2024

Enantioselective reduction of cyclopropenyl esters and ketones to optically active cyclopropanes has been achieved by using whole-cell-overexpressing ene-reductases (EREDs). By these enzymes, trans-cyclopropanes were isolated in good yield high enantiomeric excess. A wide range cyclopropane obtained, a variety substituent patterns on the cyclopropenes tolerated.

Язык: Английский

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C–H Borylation of Benzophenones Using Hydrazone as the Traceless Directing Group

Organic Letters, Год журнала: 2023, Номер 25(31), С. 5875 - 5879

Опубликована: Июль 27, 2023

C–H borylation is one of the powerful bond functionalization reactions. In this context, a metal-free benzophenones using hydrazone as traceless directing group has been reported. The dibromoboron intermediates can be obtained in excellent yields, and corresponding arylboronic esters are generated moderate to yields. Furthermore, borylated compounds transformed one-pot method, avoiding loss overall yield caused by separation esters.

Язык: Английский

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