Ligand-Based Control of Nickel Catalysts: Switching Chemoselectivity from One-Electron to Two-Electron Pathways in Competing Reactions of 4-Halotetrahydropyrans

Thane, Taylor A.; Jarvo, Elizabeth R.

doi:10.1021/acs.orglett.2c01335

Cited by 5 publications

(11 citation statements)

References 74 publications

(35 reference statements)

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“…Despite this, intramolecular variants of XEC reactions have and continue to be significantly underrepresented as compared to intermolecular XEC. 23 We developed a series of stereospecific C(sp 3 )−C(sp 3 ) coupling reactions that generate cyclopropanes (Scheme 5B) and C(sp 3 )−C(sp 2 ) coupling reactions that generate indanes and tetralins (Scheme 5C). Reactions were also expanded to include intermolecular arylation of benzylic esters.…”

Section: Part I: Stereospecific Reactions Of Alcohol Derivativesmentioning

confidence: 99%

“…Introduction and control of C(sp 3 ) stereogenic centers is a key challenge in synthetic and medicinal chemistry. Strategies for late-stage functionalization will have the highest impact if they engage common functional groups.…”

Section: ■ Introductionmentioning

confidence: 99%

“…This wide availability of complex alkyl alcohols makes them attractive as potential alkyl coupling partners in cross-coupling and crosselectrophile coupling reactions. One obvious challenge of engaging alkyl alcohols as electrophilic coupling partners is the activation of the strong C(sp 3 )−O bond for oxidative addition. Our group is focused on developing nickel-catalyzed reactions with suitable electrophiles that can be accessed through simple synthetic manipulations to weaken the C−O bond.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Our group is focused on developing nickel-catalyzed reactions with suitable electrophiles that can be accessed through simple synthetic manipulations to weaken the C−O bond. To this end, we have developed nickelcatalyzed transformations of ethers, esters, carbamates, lactones, and sulfonates to C(sp 3 )−C(sp 2 ) and C(sp 3 )−C(sp 3 ) coupled products, through traditional cross-coupling (XC), crosselectrophile coupling (XEC), and cascade reactions. In contrast to palladium catalysts more commonly employed in aryl coupling reactions, nickel catalysts are generally more reactive toward sluggish oxidative addition and less prone to deleterious β-hydride elimination.…”

Section: ■ Introductionmentioning

confidence: 99%

“…In this Account, we present the developments our group has made in stereospecific and stereoselective reactions using nickel catalysts. Our work demonstrates stereoselective couplings of C(sp 3 )−C(sp 3 ) and C(sp 3 )−C(sp 2 ) centers in the context of cross-coupling, cross-electrophile coupling, and cascade reactions. We also discuss our progress toward defining catalyst features that control the mechanism of oxidative addition.…”

Section: ■ Introductionmentioning

confidence: 99%

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Nickel-Catalyzed Stereoselective Coupling Reactions of Benzylic and Alkyl Alcohol Derivatives

Herbert,

Jarvo

2023

Acc. Chem. Res.

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Conspectus Nickel-catalyzed reactions of alkyl alcohol derivatives leverage the high prevalence of hydroxyl groups in natural products, medicinal agents, and synthetic intermediates to provide access to C(sp3)-rich frameworks. This Account describes our laboratory’s development of stereospecific and stereoconvergent C–C bond forming reactions employing C(sp3)–O and C(sp3)–N electrophiles. In the context of development of new transformations, we also define fundamental characteristics of the nickel catalysts. Part I details the nickel-catalyzed cross-coupling reactions developed by our group which hinges on stereospecific formation of stable π-benzyl intermediates. Acyclic and cyclic ethers, esters, carbamates, lactones, and sulfonamides undergo Kumada-, Suzuki-, and Negishi-type coupling reactions to produce enantioenriched products with high fidelity of stereochemical information. We describe extension to include ring-opening reactions of saturated heterocycles to afford acyclic 1,3-fragments in high diastereomeric ratios. We also describe our advances in stereospecific nickel-catalyzed cross-electrophile coupling reactions. Tethered C–O and C–X electrophiles proved fruitful for construction of a variety of carbocyclic frameworks. We report an intramolecular cross-electrophile coupling of benzylic pivalates with aryl bromides for the synthesis of indanes and tetralins. We found that 4-halotetrahydropyrans and 4-halopiperidines readily undergo stereospecific ring contraction to afford substituted cyclopropanes. Mechanistic investigations are consistent with closed-shell intermediates, a Ni(0)/Ni(II) cycle, and an intramolecular SN2-type reaction of a key organonickel intermediate to form the cyclopropane. Building toward more complex cascade reactions, we have demonstrated that 2-alkynyl piperidines incorporate MeMgI in a dicarbofunctionalization of the alkyne to afford highly substituted vinyl cyclopropanes. In Part II we present our development of stereoconvergent reactions of alkyl alcohol derivatives. In order to expand the utility of the intramolecular XEC reaction, we sought to employ unactivated alkyl electrophiles. Specifically, alkyl dimesylates engage in intramolecular XEC reactions to form alkyl cyclopropanes. In contrast to our previous work, these reactions proceed through open-shell intermediates and favor stereoconvergent formation of the trans-cyclopropane. Enantioselective aldol reactions can be employed in syntheses of 1,3-diols which furnish enantioenriched cyclopropanes in high ee. Experimental and computational evidence reveals that MeMgI mediates formation of alkyl iodides in situ. The coupling reaction initiates with halogen atom abstraction at the secondary alkyl iodide. The alkyl Ni(II) complex then proceeds through a stereospecific SN2-type ring closure to form cyclopropane. In an effort to increase functional group compatibility in the synthesis of cyclopropanes from alkyl dimesylates we developed a zinc-mediated reaction of 1,3-dimesylates prepared from medicinal analogues. In cha...

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Section: Part I: Stereospecific Reactions Of Alcohol Derivativesmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nickel-Catalyzed Stereoselective Coupling Reactions of Benzylic and Alkyl Alcohol Derivatives

Herbert,

Jarvo

2023

Acc. Chem. Res.

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Picolinamide Ligands: Nickel‐Catalyzed Reductive Cross‐Coupling of Aryl Bromides with Bromocyclopropane and Beyond

Han

Sun

Jin

2022

Chemistry An Asian Journal

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The arylcyclopropane motif as the combination of aryl and cyclopropyl ring systems can be found in an increasing amount of approved and investigational drugs. Herein, we have developed a mild, efficient nickel-catalyzed reductive cross-coupling protocol, featuring a simple Ni(II) precatalyst and a novel picolinamide NN 2 pincer ligand. A variety of (hetero)aryl bromides could successfully couple with cyclopropyl bromide to furnish the valued arylcyclopropanes in good to excellent yields. This method is applicable to other alkyl bromides as well. Notably, the reaction is tolerant of a broad range of functionalities including free amines. Furthermore, the synthesis of several significant intermediates of bioactive molecules was achieved in grams, proving the practicability of this method.

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Ni-catalyzed ligand-controlled divergent and selective synthesis

Yang

Liu

et al. 2023

Sci. China Chem.

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Ligand-Based Control of Nickel Catalysts: Switching Chemoselectivity from One-Electron to Two-Electron Pathways in Competing Reactions of 4-Halotetrahydropyrans

Cited by 5 publications

References 74 publications

Nickel-Catalyzed Stereoselective Coupling Reactions of Benzylic and Alkyl Alcohol Derivatives

Nickel-Catalyzed Stereoselective Coupling Reactions of Benzylic and Alkyl Alcohol Derivatives

Picolinamide Ligands: Nickel‐Catalyzed Reductive Cross‐Coupling of Aryl Bromides with Bromocyclopropane and Beyond

Ni-catalyzed ligand-controlled divergent and selective synthesis

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