Access to Diverse Organoborons by α-Deprotonation and Functionalization of Benzylboronates

Jin, Hao; Han, Jinhui; Liu, Xirong; Feng, Chao; Zhan, Miao

doi:10.1021/acs.orglett.3c01465

“…Suzuki-Miyaura coupling product (6) was obtained using the secondary alkyl boronate 2a generated in situ, without encountering undesirable interferences from residual catalyst species. Based on the base-mediated dehydrogenative alkylation of secondary boronates, 39 the highly valuable α-boryl functionalized alkane (7) was obtained in good yield (79%). The isolated 2a was treated with lithiated methoxyamine delivering primary amine (8) with 67% yield.…”

Section: Resultsmentioning

confidence: 99%

Markovnikov Selective Hydroboration of Aryl Alkenes Catalyzed by Quaternary Ammonium Salts

Huninik,

Im,

Szyling

et al. 2024

Preprint

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Despite recent advancements in the development of catalytic Markovnikov-selective hydroboration of alkenes, the metal-free procedure has long remained an unsolved challenge. Here, we report an organocatalytic Markovnikov-selective hy-droboration of aryl alkenes using a commercially available quaternary ammonium catalyst. The method is operationally simple, scalable, and compatible with a wide variety of substrates and it can be successfully applied in the synthesis of active pharmaceutical ingredients (API) such as Chlorphenoxamine. Through in-depth experimental and DFT studies, we elucidate a nuanced understanding of the mechanism and regioselectivity of this reaction.

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Enantioconvergent Cross‐Nucleophile Coupling: Copper‐Catalyzed Deborylative Cyanation

Vu,

Haug,

Li

et al. 2024

Angewandte Chemie

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Organoboron compounds are widely utilized in organic synthesis for their diverse reactivity, modular preparation, and stability compared to other classes of organometallic reagents. While organoboron species are commonly employed as nucleophiles in cross‐coupling reactions, their potential as racemic building blocks in enantioconvergent transformations remains largely untapped. Herein, we demonstrate the direct utilization of alkylboronic pinacol esters in intermolecular enantioconvergent transformations. Specifically, this work describes the development and mechanistic study of an enantioconvergent deborylative cyanation enabled by Cu catalysis. This method imparts a high degree of enantioselectivity and tolerates a wide range of common functional groups and heterocycles. The reaction is proposed to proceed through a radical‐relay mechanism. Aniline‐assisted homolysis of the carbon–boron bond results in prochiral alkyl radicals that are functionalized by in situ generated Cu(II)(CN)2 species in an enantioselective fashion. The Cu(II)(CN)2 intermediate was characterized by electron paramagnetic resonance (EPR) spectroscopy, and its electronic structure was probed using density functional theory (DFT) calculations. Computational studies were carried out to corroborate the proposed radical‐relay mechanism.

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Enantioconvergent Cross‐Nucleophile Coupling: Copper‐Catalyzed Deborylative Cyanation

Vu,

Haug,

Li

et al. 2024

Angew Chem Int Ed

0

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Organoboron compounds are widely utilized in organic synthesis for their diverse reactivity, modular preparation, and stability compared to other classes of organometallic reagents. While organoboron species are commonly employed as nucleophiles in cross‐coupling reactions, their potential as racemic building blocks in enantioconvergent transformations remains largely untapped. Herein, we demonstrate the direct utilization of alkylboronic pinacol esters in intermolecular enantioconvergent transformations. Specifically, this work describes the development and mechanistic study of an enantioconvergent deborylative cyanation enabled by Cu catalysis. This method imparts a high degree of enantioselectivity and tolerates a wide range of common functional groups and heterocycles. The reaction is proposed to proceed through a radical‐relay mechanism. Aniline‐assisted homolysis of the carbon–boron bond results in prochiral alkyl radicals that are functionalized by in situ generated Cu(II)(CN)2 species in an enantioselective fashion. The Cu(II)(CN)2 intermediate was characterized by electron paramagnetic resonance (EPR) spectroscopy, and its electronic structure was probed using density functional theory (DFT) calculations. Computational studies were carried out to corroborate the proposed radical‐relay mechanism.

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Access to Diverse Organoborons by α-Deprotonation and Functionalization of Benzylboronates

Cited by 8 publications

References 85 publications

Markovnikov Selective Hydroboration of Aryl Alkenes Catalyzed by Quaternary Ammonium Salts

Markovnikov Selective Hydroboration of Aryl Alkenes Catalyzed by Quaternary Ammonium Salts

Enantioconvergent Cross‐Nucleophile Coupling: Copper‐Catalyzed Deborylative Cyanation

Enantioconvergent Cross‐Nucleophile Coupling: Copper‐Catalyzed Deborylative Cyanation

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