Understanding the Regioselectivity of Ion-Pair-Assisted Meta-Selective C(sp<sup>2</sup>)–H Activation in Conformationally Flexible Arylammonium Salts

Mondal, Partha; Pal, Rapti; Pal, Arun K.; Das, Soumik; Misra, Anirban; Datta, Ayan

doi:10.1021/acs.joc.2c00957

Cited by 5 publications

(4 citation statements)

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“…The remarkable impact that iridium-catalyzed arene borylation has had since its first development two decades ago has meant that mechanistic studies soon followed and that for the most common bipyridine ligand system, mechanism is well established . In addition to experimental mechanistic studies, there have also been several primarily computational studies that explore the postulated mechanism and selectivity using DFT methods . Increasingly, reports of new borylation catalysts or methods include computational elements .…”

Section: Resultsmentioning

confidence: 99%

“… 26 In addition to experimental mechanistic studies, there have also been several primarily computational studies that explore the postulated mechanism and selectivity using DFT methods. 27 Increasingly, reports of new borylation catalysts or methods include computational elements. 28 The catalytic cycle typically commences with a borylated Ir complex, produced from the precatalyst, and when bipyridine ligands are used, it is generally accepted that an Ir(III)/Ir(V) catalytic cycle is in operation.…”

Section: Resultsmentioning

confidence: 99%

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Interrogating the Crucial Interactions at Play in the Chiral Cation-Directed Enantioselective Borylation of Arenes

Ermanis,

Gibson,

Genov

et al. 2023

ACS Catal.

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Rendering a common ligand scaffold anionic and then pairing it with a chiral cation represents an alternative strategy for developing enantioselective versions of challenging transformations, as has been recently demonstrated in the enantioselective borylation of arenes using a quinine-derived chiral cation. A significant barrier to the further generalization of this approach is the lack of understanding of the specific interactions involved between the cation, ligand, and substrate, given the complexity of the system. We have embarked on a detailed computational study probing the mechanism, the key noncovalent interactions involved, and potential origin of selectivity for the desymmetrizing borylation of two distinct classes of substrate. We describe a deconstructive, stepwise approach to tackling this complex challenge, which involves building up a detailed understanding of the pairwise components of the nominally three component system before combining together into the full 263-atom reactive complex. This approach has revealed substantial differences in the noncovalent interactions occurring at the stereodetermining transition state for C–H oxidative addition to iridium for the two substrate classes. Each substrate engages in a unique mixture of diverse interactions, a testament to the rich and privileged structure of the cinchona alkaloid-derived chiral cations. Throughout the study, experimental support is provided, and this culminates in the discovery that prochiral phosphine oxide substrates, lacking hydrogen bond donor functionality, can also give very encouraging levels of enantioselectivity, potentially through direct interactions with the chiral cation. We envisage that the findings in this study will spur further developments in using chiral cations as controllers in asymmetric transition-metal catalysis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Interrogating the Crucial Interactions at Play in the Chiral Cation-Directed Enantioselective Borylation of Arenes

Ermanis,

Gibson,

Genov

et al. 2023

ACS Catal.

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“…Additionally, the distortion-interaction/activation-strain (DI-AS) analysis − is employed using two fragments (Figure ), pivalic acid moieties (Frag1 in blue) and palladium including the substrate (Frag2 in red), to gain a simplistic picture of the stabilization of TSA2 over TSA2′ and TSP2 over TSP2′ . Table shows that although the strain (distortion, D eff ) for TSA2 is 23.0 kcal/mol higher than that for TSA2′ , the overall stabilization of TSA2 results from the interaction between the two fragments in TSA2 , which is 24.7 kcal/mol greater than in TSA2′ .…”

Section: Resultsmentioning

confidence: 99%

Computational Insights into Palladium-Catalyzed Site-Selective Anilide and Benzamide-Type [3+2] Annulation via Double C–H Bond Activation

Mondal,

Mandal,

Pal

et al. 2024

J. Org. Chem.

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The mechanism of palladium-catalyzed annulation reactions of benzamideand anilide-type aromatic systems with maleimides is investigated using density functional theory. Double C−H bond activation is key to forming the desired annulation product. The first C−H bond activation for anilide-and amide-type ligands can occur at the ortho and benzylic C−H bonds, while the second C−H activation occurs at the meta carbon of the aromatic rings. For the anilide-type system, ortho and benzylic C−H bond activations occur via four-and five-membered palladacycles, respectively. In contrast, for the benzamide-type system, ortho and benzylic C−H bond activations occur via five-and six-membered palladacycles, respectively. The energy span model suggests that the initial C−H bond activation step at the benzylic position determines the turnover frequency for both anilideand benzamide-type systems. Energy decomposition analysis and distortion-interaction/ activation-strain analyses are employed to understand the electronic and steric factors controlling the turnover frequency-determining transition state.

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“…41,42 The effect of HFIP was included by implicit SMD 43 S1-S2). 45,46 The AIM analysis reveals that ts-1m is stabilized over ts-1m' by ΔEint…”

Section: Mechanistic Investigations and Computational Studiesmentioning

confidence: 99%

Non-Covalent Interaction within Catalytic Anionic Donor and Neutral Acceptor to Promote Pd-Catalyzed Distal Site- selective Functionalization of Amines

Goswami

Sinha

Mondal

et al. 2022

Preprint

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C‒H activation of simple molecules to provide corresponding functionalized analogues has gained immense prominence. While this is widely applicable to a range of organic motifs, regioselectivity and most importantly site-selectivity of distal C‒H bonds remains a significant challenge. While covalently attached directing groups have been designed to solve the puzzle, their profound impact on the step-economy and substrate biasness cause a significant dent in the applicability of the protocol. To overcome this, weak non-covalent interactions between substrate and ligands have been developed but have been mainly explored with Ir-catalysis. Herein we aim to execute an unprecedented Pd catalyzed meta-selective C‒H functionalization of simple amines harnessing weak non-covalent interactions between anionic H-bond donor and neutral acceptor. Catalytic amount of organic salt acts as an anionic ligand and is suitable for efficient meta-selective C‒H olefination. Experimental and computational studies elucidate the mechanistic understanding and suggest that site-selectivity is governed by the key H-bonding interaction between an anionic donating ligand and a neutral accepting substrate. The protocol can be further extended to amines with variable linker-lengths, outlining the versatility and applicability of our methodology to organic motifs, while utilizing only a catalytic amount of directing ligand for the functionalization.

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Understanding the Regioselectivity of Ion-Pair-Assisted Meta-Selective C(sp²)–H Activation in Conformationally Flexible Arylammonium Salts

Cited by 5 publications

References 85 publications

Interrogating the Crucial Interactions at Play in the Chiral Cation-Directed Enantioselective Borylation of Arenes

Interrogating the Crucial Interactions at Play in the Chiral Cation-Directed Enantioselective Borylation of Arenes

Computational Insights into Palladium-Catalyzed Site-Selective Anilide and Benzamide-Type [3+2] Annulation via Double C–H Bond Activation

Non-Covalent Interaction within Catalytic Anionic Donor and Neutral Acceptor to Promote Pd-Catalyzed Distal Site- selective Functionalization of Amines

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Understanding the Regioselectivity of Ion-Pair-Assisted Meta-Selective C(sp2)–H Activation in Conformationally Flexible Arylammonium Salts

Cited by 5 publications

References 85 publications

Interrogating the Crucial Interactions at Play in the Chiral Cation-Directed Enantioselective Borylation of Arenes

Interrogating the Crucial Interactions at Play in the Chiral Cation-Directed Enantioselective Borylation of Arenes

Computational Insights into Palladium-Catalyzed Site-Selective Anilide and Benzamide-Type [3+2] Annulation via Double C–H Bond Activation

Non-Covalent Interaction within Catalytic Anionic Donor and Neutral Acceptor to Promote Pd-Catalyzed Distal Site- selective Functionalization of Amines

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Understanding the Regioselectivity of Ion-Pair-Assisted Meta-Selective C(sp²)–H Activation in Conformationally Flexible Arylammonium Salts