Distal meta-alkenylation of formal amines enabled by catalytic use of hydrogen-bonding anionic ligands

Goswami, Nupur; Sinha, Sucharita; Mondal, Partha; Adhya, S.; Datta, Ayan

doi:10.1016/j.chempr.2022.12.018

Cited by 23 publications

(6 citation statements)

References 44 publications

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“…These catalysts enabled a highly meta selective C−H olefination of protected benzylamines through charge-induced H-bonding interactions. 54 To uncover the origins of meta selectivity, we conducted extensive experimental mechanistic investigations and DFT studies. We found that L1 indeed fulfills dual roles and identified TS3 as the preferred pathway for the C−H activation.…”

Section: Meta-selective C−h Olefination Enabled By Non-covalent Inter...mentioning

confidence: 99%

“…Notably, in a study contemporaneous to our own work, Maiti developed a dual-ligand-enabled catalyst system that combined our general dual-ligand design with a sulfonate group on the ligand. These catalysts enabled a highly meta selective C–H olefination of protected benzylamines through charge-induced H-bonding interactions …”

Section: Meta-selective C–h Olefination Enabled By Non-covalent Inter...mentioning

confidence: 99%

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Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Kaltenberger,

van Gemmeren

2023

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Aromatic structures are widespread motifs throughout organic chemistry, and C−H activation has been recognized as a major tool for enabling their sustainable and efficient functionalization. Through C−H activation, arenes can be modified without the need for prefunctionalization, leading to inherent atom-and step-economic advantages over traditional methods. However, for the development of synthetically useful methods, several hurdles have to be overcome. The strength of C−H bonds necessitates the development of sufficiently reactive catalysts, while the presence of multiple C−H bonds within a substrate poses challenges in terms of site-selectivity. Traditionally these challenges have been addressed by substrate control. By attaching different directing groups (DGs), the reactivity of the respective arene was significantly enhanced and the DG guided the metal in close proximity to specific C−H bonds, resulting in high site-selectivity. However, the introduction and removal of the DG add additional steps to the synthetic sequence, and the scope of the reaction is limited to a specific substrate class. The development of complementary nondirected methods that can be applied to a broad range of arenes without the necessity to carry a specific functional group that coordinates to Pd (referred to as simple arenes) is therefore highly desirable. However, the intrinsically lower reactivity of such substrates and the absence of a selectivity-determining DG pose significant challenges that can be solved only by the development of highly efficient catalysts. Consequently, the field of nondirected C−H activation, especially with respect to Pd-catalyzed methods, remained comparatively underdeveloped when we initiated our research program in 2017. At that time, stateof-the-art methods required the arene to be used in large excess, precluding its use in late-stage functionalization. Since organopalladium species are among the most versatile synthetic intermediates, we realized that developing a system, which can effectively and selectively activate C−H bonds in simple arenes with the arene as the limiting reagent, would be a powerful tool in synthetic organic chemistry. This account summarizes our groups' research toward the development and application of catalytic systems offering this desired reactivity and focuses explicitly on Pd-catalyzed nondirected C−H functionalization reactions of arenes, where the arene is employed as a limiting reagent. After an introduction that summarizes the state of Pd-catalyzed C−H activation of arenes before 2017 and the associated challenges, experimental and mechanistic details about the development of the first arenelimited, nondirected C−H functionalization of simple arenes with palladium will be discussed. This reactivity was enabled by the identification and combination of two complementary ligands, an N-heterocycle and an amino acid-derived ligand. Afterward we will discuss the expansion of this dual-ligand approach to further arene-limi...

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Section: Meta-selective C−h Olefination Enabled By Non-covalent Inter...mentioning

confidence: 99%

Section: Meta-selective C–h Olefination Enabled By Non-covalent Inter...mentioning

confidence: 99%

Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Kaltenberger,

van Gemmeren

2023

Acc. Chem. Res.

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“…We have recently disclosed an ionic catalyst-enabled desymmetrizing Suzuki–Miyaura reaction to establish remote cyclic quaternary stereocenters within fluorene and xanthene skeletons. , Within a given substrate, the enantiotopic reaction sites are distant from the ionic catalyst-binding group . This key feature differs from previous catalyst systems that employ ligands containing chiral ionic groups, where enantiocontrol is invariably exerted directly at the counterionic sites of reaction intermediates .…”

Section: Introductionmentioning

confidence: 99%

Amino Acid-Derived Ionic Chiral Catalysts Enable Desymmetrizing Cross-Coupling to Remote Acyclic Quaternary Stereocenters

2023

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Synthetic application of asymmetric catalysis relies on strategic alignment of bond construction to creation of chirality of a target molecule. Remote desymmetrization offers distinctive advantages of spatial decoupling of catalytic transformation and generation of a stereogenic element. However, such spatial separation presents substantial difficulties for the chiral catalyst to discriminate distant enantiotopic sites through a reaction three or more bonds away from a prochirality center. Here, we report a strategy that establishes acyclic quaternary carbon stereocenters through cross-coupling reactions at distal positions of aryl substituents. The new class of amino acid-derived ionic chiral catalysts enables desymmetrizing (enantiotopic-group-selective) Suzuki–Miyaura reaction, Sonogashira reaction, and Buchwald–Hartwig amination between diverse diarylmethane scaffolds and aryl, alkynyl, and amino coupling partners, providing rapid access to enantioenriched molecules that project substituents to widely spaced positions in the three-dimensional space. Experimental and computational investigations reveal electrostatic steering of substrates by the C-terminus of chiral ligands through ionic interactions. Cooperative ion-dipole interactions between the catalyst’s amide group and potassium cation aid in the preorganization that transmits asymmetry to the product. This study demonstrates that it is practical to achieve precise long-range stereocontrol through engineering the spatial arrangements of the ionic catalysts’ substrate-recognizing groups and metal centers.

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“…This traditional method incorporates at least two extra steps with the directing template: pre- and postfunctionalization. To overcome these difficulties, transient directing groups (TDG) have been developed that react via weak covalent interactions and do not upsurge the debt in atom economy …”

Section: Introductionmentioning

confidence: 99%

Deciphering the Mechanistic Insights of Temporary Directing-Group-Assisted meta-Alkenylation of Complex Biaryl Systems

et al. 2023

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The recently developed palladium-catalyzed C-(sp 2 )−H olefination of 2-arylbenzaldehyde with the aid of a temporary directing group (TDG) via reversible imine formation delivers selective meta-C−H functionalization and possesses significant advantages over the well-established covalently attached directing group (DG) approach. In this report, a combined computational and experimental investigation has been performed to elucidate the detailed reaction mechanism and the origins of such remote meta-selectivity. The reaction proceeds in three major steps: C−H activation, 1,2-migratory insertion, and β-hydride elimination. While 1,2-migratory insertion of olefin is found to be the turnover-determining step, the selectivity is predetermined by the preceding C−H activation step. The computational observations have been corroborated along with experimentally conducted order determination studies, primary kinetic isotope effect (PKIE) study, and free energy correlation with Hammett plots. A temporary DG-bound Pd complex has been shown to be competent to promote meta-alkenylation. All the possible Pd-catalyzed template-directed C−H (ortho′, ortho, meta, para) olefinations of the 2-aryl benzaldehyde/aniline have been computationally investigated. The density functional theory (DFT)-based computations indicated that the other olefination reactions necessitate higher activation energy barriers compared with metaolefination. Distortion-interaction analysis (DIA), noncovalent interaction (NCI) analysis, and isodesmic studies were executed to unravel the mystery behind the origin of meta-regioselectivity.

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Distal meta-alkenylation of formal amines enabled by catalytic use of hydrogen-bonding anionic ligands

Cited by 23 publications

References 44 publications

Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Amino Acid-Derived Ionic Chiral Catalysts Enable Desymmetrizing Cross-Coupling to Remote Acyclic Quaternary Stereocenters

Deciphering the Mechanistic Insights of Temporary Directing-Group-Assisted meta-Alkenylation of Complex Biaryl Systems

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