Catalytic Asymmetric Hydrogen Atom Transfer: Enantioselective Hydroamination of Alkenes

Hejna, Benjamin G.; Ganley, Jacob M.; Shao, Huiling; Tian, He; Ellefsen, Jonathan D.; Fastuca, Nicholas J.; Houk, K. N.; Miller, Scott J.; Knowles, Robert R.

doi:10.1021/jacs.3c04591

Cited by 29 publications

(15 citation statements)

References 105 publications

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“…The non-innocence of steric bulk can usually be traced back to a fine interplay of Pauli repulsion and LD in enantioinduction. [160] A similar effect was recently reported by Knowles et al [161] studying a catalytic asymmetric hydrogen atom transfer reaction. Here, LD as well as hydrogenbonding and π-π stacking were reported to be origin for substrate recognition and enantioinduction.…”

Section: London Dispersion As a Driving Force For Reactivity And Cata...supporting

confidence: 79%

Advances and Prospects in Understanding London Dispersion Interactions in Molecular Chemistry

Rummel,

Schreiner

2024

Angewandte Chemie

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London dispersion (LD) interactions are the main contribution of the attractive part of the van der Waals potential. Even though LD effects are the driving force for molecular aggregation and recognition, the role of these omnipresent interactions in structure and reactivity had been largely underappreciated over decades. However, in the recent years considerable efforts have been made to thoroughly study LD interactions and their potential as a chemical design element for structures and catalysis. This was made possible through a fruitful interplay of theory and experiment. This review highlights recent results and advances in utilizing LD interactions as a structural motif to understand and utilize intra‐ and intermolecularly LD‐stabilized systems. Additionally, we focus on the quantification of LD interactions and their fundamental role in chemical reactions.

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Section: London Dispersion As a Driving Force For Reactivity And Cata...supporting

confidence: 79%

Advances and Prospects in Understanding London Dispersion Interactions in Molecular Chemistry

Rummel,

Schreiner

2024

Angewandte Chemie

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“…In 2023, Knowles and coworkers reported enantioselective radical-based hydroamination of enol esters with sulfonamides, using a triple catalyst system consisting of an Ir photocatalyst, a Brønsted base, and a tetrapeptide thiol catalyst for asymmetric HAT ( Figure 7C ) ( Hejna et al, 2023 ). This reaction provides easy access to a variety of chiral β-amino alcohol derivatives, i.e., α-substituted β-arylsulfonamidoethyl benzoates 7C , in 47–93% yield and 73–94% e. e. In this catalysis, the absolute configuration of the product 7C is determined by enatioselective HAT from the chiral peptide thiol catalyst to a prochiral C - centered radical 7-C4 .…”

Section: Asymmetric Visible-light Photoredox Catalysismentioning

confidence: 99%

Recent advances in catalytic asymmetric synthesis

Garg,

Rendina,

Bendale

et al. 2024

Front. Chem.

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Asymmetric catalysis stands at the forefront of modern chemistry, serving as a cornerstone for the efficient creation of enantiopure chiral molecules characterized by their high selectivity. In this review, we delve into the realm of asymmetric catalytic reactions, which spans various methodologies, each contributing to the broader landscape of the enantioselective synthesis of chiral molecules. Transition metals play a central role as catalysts for a wide range of transformations with chiral ligands such as phosphines, N-heterocyclic carbenes (NHCs), etc., facilitating the formation of chiral C-C and C-X bonds, enabling precise control over stereochemistry. Enantioselective photocatalytic reactions leverage the power of light as a driving force for the synthesis of chiral molecules. Asymmetric electrocatalysis has emerged as a sustainable approach, being both atom-efficient and environmentally friendly, while offering a versatile toolkit for enantioselective reductions and oxidations. Biocatalysis relies on nature’s most efficient catalysts, i.e., enzymes, to provide exquisite selectivity, as well as a high tolerance for diverse functional groups under mild conditions. Thus, enzymatic optical resolution, kinetic resolution and dynamic kinetic resolution have revolutionized the production of enantiopure compounds. Enantioselective organocatalysis uses metal-free organocatalysts, consisting of modular chiral phosphorus, sulfur and nitrogen components, facilitating remarkably efficient and diverse enantioselective transformations. Additionally, unlocking traditionally unreactive C-H bonds through selective functionalization has expanded the arsenal of catalytic asymmetric synthesis, enabling the efficient and atom-economical construction of enantiopure chiral molecules. Incorporating flow chemistry into asymmetric catalysis has been transformative, as continuous flow systems provide precise control over reaction conditions, enhancing the efficiency and facilitating optimization. Researchers are increasingly adopting hybrid approaches that combine multiple strategies synergistically to tackle complex synthetic challenges. This convergence holds great promise, propelling the field of asymmetric catalysis forward and facilitating the efficient construction of complex molecules in enantiopure form. As these methodologies evolve and complement one another, they push the boundaries of what can be accomplished in catalytic asymmetric synthesis, leading to the discovery of novel, highly selective transformations which may lead to groundbreaking applications across various industries.

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“…Two studies published by Hyster and co-workers and by our group explored photoenzymatic catalysis to achieve the asymmetric intermolecular hydroamination using hydroxamic esters and the intermolecular hydroamination using carbamates, respectively. More recently, Knowles and co-workers reported the intramolecular asymmetric hydroamination with sulfonamides using an iridium photocatalyst to generate NCRs and a chiral thiol hydrogen atom transfer catalyst . To date, a wider variety of important amine feedstocks, such as dialkyl amines, have not been explored for the asymmetric radical hydroamination.…”

Section: Introductionmentioning

confidence: 99%

“…More recently, Knowles and coworkers reported the intramolecular asymmetric hydroamination with sulfonamides using an iridium photocatalyst to generate NCRs and a chiral thiol hydrogen atom transfer catalyst. 24 To date, a wider variety of important amine feedstocks, such as dialkyl amines, have not been explored for the asymmetric radical hydroamination. Hence, new strategies that can use photoredox catalysis to generate nitrogen-centered radicals from alkyl amines and harness them for asymmetric hydroamination are needed.…”

Section: ■ Introductionmentioning

confidence: 99%

Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis

Harrison,

Jiang,

Zhang

et al. 2024

J. Am. Chem. Soc.

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Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination. In this reaction, the flavin-dependent ene-reductase photocatalytically generates the aminium radical cation from the corresponding hydroxylamine and catalyzes the asymmetric intermolecular hydroamination to furnish the enantioenriched tertiary amine, whereby enantioinduction occurs through enzyme-mediated hydrogen atom transfer. This work highlights the use of photoenzymatic catalysis to generate and control highly reactive radical intermediates for asymmetric synthesis, addressing a long-standing challenge in chemical synthesis.

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Catalytic Asymmetric Hydrogen Atom Transfer: Enantioselective Hydroamination of Alkenes

Cited by 29 publications

References 105 publications

Advances and Prospects in Understanding London Dispersion Interactions in Molecular Chemistry

Advances and Prospects in Understanding London Dispersion Interactions in Molecular Chemistry

Recent advances in catalytic asymmetric synthesis

Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis

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