Native Amides as Enabling Vehicles for Forging sp³–sp³ Architectures via Interrupted Deaminative Ni-Catalyzed Chain-Walking

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 3869 - 3874

Опубликована: Фев. 8, 2023

Herein, we disclose an interrupted deaminative Ni-catalyzed chain-walking strategy that forges sp3-sp3 architectures at remote, yet previously unfunctionalized, methylene sp3 C-H sites enabled by the presence of native amides. This protocol is characterized its mild conditions and wide scope, including challenging substrate combinations. Site-selectivity can be dictated a judicious choice ligand, thus offering opportunity to enable bond formations are otherwise inaccessible in conventional events.

Язык: Английский

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Nickel-Catalyzed Remote Asymmetric Hydroalkylation of Alkenyl Ethers to Access Ethers of Chiral Dialkyl Carbinols

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(18), С. 10411 - 10421

Опубликована: Апрель 26, 2023

Site- and enantio-selective alkyl-alkyl bond formation is privileged in the retrosynthetic analysis due to universality of sp3-hybridized carbon atoms organic molecules. Herein, we report a nickel-catalyzed remote asymmetric hydroalkylation alkenyl ethers via synchronous implementation alkene isomerization enantioselective C(sp3)-C(sp3) formation. Regression catalyst structure-activity relationships accelerates rational ligand modification through modular regulation. This reaction has several advantages for synthesizing chiral dialkyl carbinols their ether derivatives, including broad substrate scope, good functional group tolerance, excellent regioselectivity (>20:1 regioisomeric ratio), high enantioselectivity (up 95% enantiomeric excess).

Язык: Английский

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Nickel Chain-Walking Catalysis: A Journey to Migratory Carboboration of Alkenes

Accounts of Chemical Research, Год журнала: 2023, Номер 56(22), С. 3246 - 3259

Опубликована: Ноя. 1, 2023

ConspectusChain-walking offers extensive opportunities for innovating synthetic methods that involve constructing chemical bonds at unconventional sites. This approach provides previously inaccessible retrosynthetic disconnections in organic synthesis. Through chain-walking, transition metal-catalyzed alkene difunctionalization reactions can take place a 1,n-addition (n ≠ 2) mode. Unlike classical 1,2-regioselective reactions, there remains scarcity of reports regarding migratory patterns. Moreover, the range olefins utilized these studies is quite limited.About five years ago, our research group embarked on project aimed developing valuable alkenes through chain-walking. Our focus was carboboration utilizing nickel catalysis. The reaction commences with insertion an olefin into Ni-Bpin species. Subsequently, thermodynamically stable alkyl complex generated chain-walking process. then couples carbon-based electrophile, leading to formation alkylboron compound. It worth highlighting success transformations relies significantly utilization bisnitrogen-based ligand and LiOMe as B2pin2 activator. Synthetically, establish robust platform rapid efficient synthesis wide structurally diverse organoboron compounds, which are not facially accessed by conventional methods. incorporation versatile boron introduces wealth possibilities subsequent diversifications, enhancing value resulting products allowing creation broader derivatives applications.This Account comprehensive overview efforts advancements field unactivated using We begin outlining development series 1,1-regioselective terminal alkenes. A significant placed initial integration boronate, only triggers metal species but also exerts control over remote stereochemistry involving substituted methylenecyclohexenes. Continuing exploration, remarkable achieved 1,3-regio- cis-stereoselectivity when dealing cyclic Remarkably, catalysis enables heterocyclic be viable coupling partners within transformations. it grants us ability achieve regioselectivity cyclohexenes unattainable, thus expanding horizons regiochemical reactions. Lastly, we present evolution ligand-modulated regiodivergent allylarenes. By gaining insights underlying mechanisms driving regiodivergence, lay strong foundation tackling challenges related selecting specific sites especially multiple factors. anticipate findings, coupled mechanistic we've gained, will advance realm contribute understanding selectivity this nature. advancement catalyze intricate functional molecules, contributing compounds chemistry.

Язык: Английский

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Ligand-Controlled Cobalt-Catalyzed Regio-, Enantio-, and Diastereoselective Oxyheterocyclic Alkene Hydroalkylation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(5), С. 3405 - 3415

Опубликована: Янв. 29, 2024

Metal-hydride-catalyzed alkene hydroalkylation has been developed as an efficient method for C(sp

Язык: Английский

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Modular access to substituted cyclohexanes with kinetic stereocontrol

Science, Год журнала: 2022, Номер 376(6594), С. 749 - 753

Опубликована: Май 12, 2022

Substituted six-membered cyclic hydrocarbons are common constituents of biologically active compounds. Although methods for the synthesis thermodynamically favored, disubstituted cyclohexanes well established, a reliable and modular protocol their stereoisomers is still elusive. Herein, we report general strategy with excellent kinetic stereocontrol from readily accessible substituted methylenecyclohexanes by implementation chain-walking catalysis. Mechanistically, initial introduction sterically demanding boron ester group adjacent to cyclohexane key guiding stereochemical outcome. The synthetic potential this methodology has been highlighted in late-stage modification complex bioactive molecules comparison current cross-coupling techniques.

Язык: Английский

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Ligand‐Controlled NiH‐Catalyzed Regiodivergent Chain‐Walking Hydroalkylation of Alkenes

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(30)

Опубликована: Май 24, 2022

Abstract A NiH‐catalyzed migratory hydroalkylation of alkenyl amines with predictable and switchable regioselectivity is reported. By utilizing a ligand‐controlled, directing group‐assisted strategy, various alkyl units are site‐selectively installed at inert sp 3 C−H sites far away from the original C=C bonds. range structurally diverse α‐ β‐branched protected conveniently synthesized via stabilization 5‐ 6‐membered nickelacycles respectively. This method exhibits broad scope high functional group tolerance, can be applied to late‐stage modification medicinally relevant molecules.

Язык: Английский

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Catalytic Asymmetric Diarylation of Internal Acyclic Styrenes and Enamides

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(18), С. 8389 - 8398

Опубликована: Апрель 28, 2022

Enantioselective transformations of olefins are among the most important strategies for asymmetric synthesis organic compounds. Chemo-, diastereo-, and stereoselective control reactions with internal acyclic alkenes construction functionalized alkanes still remain a persistent challenge. Here, we report palladium-catalyzed regiodivergent Heck-type diarylation alkenes. The 1,2-diarylation two accessible alkenes, cinnamyl carbamates enamides diazonium salts aromatic boronic acids, furnishes products containing vicinal stereogenic centers via stereospecific formation carbonyl coordination-assisted transient palladacycles. Moreover, migratory enables incontiguous stereocenters by an interrupted diastereoselective 1,3-chain-walking process. This protocol streamlines access to highly multisubstituted enantioenriched amine derivatives which embedded in key biologically active motifs.

Язык: Английский

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Regio- and enantioselective remote hydroarylation using a ligand-relay strategy

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

Опубликована: Май 5, 2022

Abstract The design of a single complicated chiral ligand to well-promote each step an asymmetric cascade reaction is sometimes formidable challenge in transition metal catalysis. In this work, highly regio- and enantioselective Ni-catalysed migratory hydroarylation relay process has been achieved with the combination two simple ligands, one which accomplishes chain-walking other causing arylation. This formal C(sp 3 )−H arylation provides direct access wide range structurally diverse 1,1-diarylalkanes, structural unit found number bioactive molecules. value strategy was further demonstrated by 1,3-arylboration.

Язык: Английский

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Divergent Access to Chiral C2- and C3-Alkylated Pyrrolidines by Catalyst-Tuned Regio- and Enantioselective C(sp³)–C(sp³) Coupling

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(28), С. 15456 - 15464

Опубликована: Июнь 12, 2023

Novel-substituted pyrrolidine derivatives are widely used in drugs and bioactive molecules. The efficient synthesis of these valuable skeletons, especially enantiopure derivatives, is still recognized as a key bottleneck to overcome chemical synthesis. Herein, we report highly catalyst-tuned regio- enantioselective hydroalkylation reaction for the divergent chiral C2- C3-alkylated pyrrolidines through desymmetrization readily available 3-pyrrolines. catalytic system consists CoBr2 with modified bisoxazoline (BOX) ligand, which can achieve asymmetric C(sp3)-C(sp3) coupling via distal stereocontrol, providing series high efficiency. Moreover, nickel allows synthesize C2-alkylated tandem alkene isomerization/hydroalkylation reaction. This method uses catalysts, BOX ligands, reagents, delivering enantioenriched 2-/3-alkyl substituted excellent enantioselectivity (up 97% ee). We also demonstrate compatibility this transformation complex substrates derived from molecules good efficiency, offers distinct entry more functionalized N-heterocycles.

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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