Expanding the Scope of Intramolecular Silver-catalyzed Nitrene Transfer

Expanding the Scope of Intramolecular Silver-catalyzed Nitrene Transfer
Author: Emily Zerull Schroeder
Publisher:
Total Pages: 0
Release: 2024
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ISBN:
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Nitrene transfer (NT) is a convenient strategy to directly transform C-H bonds into more valuable C-N bonds. Intramolecular NT reactions offer access to various N-heterocycles which are common in drugs and natural products. Many of these heterocycles can also be transformed into useful building blocks such as amino alcohols or diamines. However, the high reactivity of nitrenes often results in reactions that are primarily controlled by substrate identity, rendering these reactions less useful. This work will describe our attempts to use silver catalysts to control reactions with challenging selectivity problems such as asymmetric reactions and dearomatization reactions. Chapter 1 features a broad look at the history of transition metal catalyzed NT, followed by a more in-depth discussion of intramolecular asymmetric NT variants. Chapter 2 describes the use of silver salts ligated to an unusual, quaternary-centered bis(oxazoline) (BOX) ligand, readily accessible through a modular synthetic approach, which enables site- and enantioselective nitrene transfers into benzylic, allylic and unactivated C-H bonds of carbamate esters. The resulting 1,3-aminoalcohol building blocks are delivered in good yields and moderate-to-excellent enantioselectivities. Computational models were employed to rationalize the observed stereochemical outcomes and set the stage for the predictive design of second-generation Ag-BOX catalysts. Chapter 3 presents a combination of silver-catalysts that are able to preferentially undergo either a dearomatization event to form bicyclic azepine structures or an insertion event into the benzylic C(sp3)-H bond. This chemoselective reaction requires the use of carbamimidate precursors featuring a large sulfamate protecting group, which allows the reaction to be controlled by a combination of ligand sterics and electronics.

Development of Silver-catalyzed Chemo-, Regio- and Enantioselective Nitrene Transfer Reactions Through Rational Catalyst Design

Development of Silver-catalyzed Chemo-, Regio- and Enantioselective Nitrene Transfer Reactions Through Rational Catalyst Design
Author: Minsoo Ju
Publisher:
Total Pages: 0
Release: 2020
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ISBN:
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The development of selective C-N bond forming reactions represents an important research area because amines are prevalent in biologically active natural products, pharmaceuticals, agrochemicals, and ligands. Traditionally, the reactivity and selectivity of amine-forming reactions had a strong dependence on pre-functionalized starting materials which resulted in costly chemical steps. More direct C-H amination or C=C bond aziridination reactions via transition metal-catalyzed nitrene transfer have been brought to the synthetic community's attention recently for their potential to efficiently form valuable C-N bonds. Unfortunately, the development of efficient NT methods has been met with several challenges including substrate-dependent selectivity and the need for costly transition metal catalysts. The work described herein represents a new approach to these reactions in which rationally designed silver catalysts are utilized to achieve high chemo-, regio- and ultimately, enantioselectivity in a catalyst-controlled manner. Chapter 1 serves as an introduction by providing a selected review of literature on recent asymmetric metal-catalyzed nitrene transfer reactions emphasizing the common catalyst design strategies to solve problems associated with selectivity and reactivity. Chapter 2 describes a method for chemo- and enantioselective silver-catalyzed nitrene transfer in which homoallylic carbamates are transformed into [4.1.0]-carbamate-tethered aziridines in good yields and enantiomeric excess (ee) via intramolecular aziridination. The aziridine products undergo nucleophilic ring-opening to yield enantioenriched amines with no erosion in stereochemical integrity. Chapter 3 presents two complementary silver catalysts that are capable of selecting between [Beta] or [gamma] C(sp3)-H bonds residing in similar steric/electronic environments, overriding reaction at a weaker C-H bond in favor of a stronger one, and activating primary C-H bonds. Further experimental and computational studies revealed some mechanistic insights into this system and what seems to be causing this interesting catalyst-controlled regioselectivity. Finally, Chapter 4 offers an extension of the regioselective silver-catalyzed NT, where [gamma]-propargylic-[gamma]-amino alcohol motifs are synthesized with high site- and enantioselectivity. The protocol was enabled by a new optically active bis(oxazoline) ligand designed via a rapid structure-activity relationship analysis.

Tunable, Selective C(sp3)-h Aminations Via Silver-catalyzed Nitrene Transfer Reactions

Tunable, Selective C(sp3)-h Aminations Via Silver-catalyzed Nitrene Transfer Reactions
Author: Minxue Huang
Publisher:
Total Pages: 0
Release: 2020
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ISBN:
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Abstract The ubiquitousness of amines in pharmaceuticals, agrochemicals, ligands for transition metals, biologically active natural compounds and functional materials is the strong motivation of organic chemists to develop highly efficient yet mild reactions to install valuable C-N bonds. Transition metal-catalyzed nitrene transfer is a convenient strategy to directly functionalize a hydrocarbon substrate with amine functionality. For all means of C(sp3)−H amination, one of the core issues hampering their developments is the difficulty to differentiate multiple C-H bonds that have nearly identical electronic properties and bond strengths. As described in this work, this problem is addressed through utilizing Ag catalysts based on deliberately designed ligands, which is inspired by mechanism study, to achieve tunable site-, regio-, and stereoselectivity. Chapter 1 gives a brief introduction by providing a selected review of literature on transition metal-catalyzed C(sp3)−H aminations reactions via nitrene transfer, emphasizing the common problems associated with reactivity and selectivity. Chapter 2 demonstrates both the solid and solution-state behavior of diverse Ag(I) catalysts competent for nitrene transfor through X-ray characterization and NMR studies, and discusses our understanding of how the ligand identity manipulate those behavior of corresponding Ag(I) complexes. Chapter 3 describes both computational models and experimental probes revealing possible roles of noncovalent interactions in directing the site-selectivity of silver-catalyzed C−H aminations. Chapter 4 addresses the fluxional behavior of Ag(tpa)OTf in solution potentially hampering its site-selectivity in nitrene insertion by a rigid ligand. Finally, chapter 5 provide a novel silver catalytic system which is able to tune the selectivity between [beta] or [gamma] C-H bond amindation of an easily prepared carbamate, overriding substrate control, and amidate traditionally difficult primary aliphatic C-H bonds. Further experimental and computational studies revealed some mechanistic insights into this system. Additional, synthetic utility of this methodology was proven by the late-stage functionalization of natural products and drug-like molecules, even in gram-scale.

Heterocycles from Carbenes and Nitrenes

Heterocycles from Carbenes and Nitrenes
Author: Michael P. Doyle
Publisher: Springer Nature
Total Pages: 381
Release: 2023-08-09
Genre: Science
ISBN: 3031367359
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This book provides researchers in the fields of organic chemistry, organometallic chemistry and homogeneous catalysis with an overview of recent developments in the applications of reactions involving carbene and nitrene intermediates directed to the synthesis of heterocyclic compounds. Multiple pathways through which diverse heterocyclic compounds are accessed occur from a variety of carbene and nitrene precursors through C-H/X-H insertions, cycloadditions, ylide transformations, rearrangements, and cascade reactions. Catalytic processes that form metallo-carbenes and nitrenes offer unparalleled chemo-, regio-, and stereo-selectivities. Insights are provided into the scope of these methodologies and the inherent control of catalyst ligands on reaction selectivities.

Recent Advances in Synthesizing and Utilizing Nitrogen-containing Heterocycles

Recent Advances in Synthesizing and Utilizing Nitrogen-containing Heterocycles
Author: Hyun-Joon Ha
Publisher: Frontiers Media SA
Total Pages: 101
Release: 2024-05-31
Genre: Science
ISBN: 2832549187
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Nitrogen-containing heterocycles, so-called aza-heterocycles, are widely found in natural products, pharmaceuticals, agrochemicals, and functional materials, and thus their synthesis has long been studied intensively. In addition, their preparation and utilization as synthons or intermediates from one to another are also developed to build higher and more complex aza-heterocycles. Some of them are also used as ligands for metal catalysts and organocatalysts. Despite many studies of the synthesis and utilization of nitrogen-containing heterocycles, a more efficient and general preparation is still required to diversify the structural backbones and improve their biological activities. Their usage as ligands and catalysts is also under expansion in various reactions.

Progress in Inorganic Chemistry, Volume 50

Progress in Inorganic Chemistry, Volume 50
Author: Kenneth D. Karlin
Publisher: John Wiley & Sons
Total Pages: 641
Release: 2004-03-24
Genre: Science
ISBN: 047146077X
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This series provides inorganic chemists and materials scientists with a forum for critical, authoritative evaluations of advances in every area of the discipline. Volume 50 continues to report recent advances with a significant, up-to-date selection of contributions on topics such as the following: Structural and mechanistic investigations in asymmetric copper; Catalyzed reactions; Phenoxyl radical complexes; Synthesis of large pore zeolites and molecular sieves; Inorganic nanoclusters with fullerene-like structure and nanotubes

Enhancing Selectivity and Tunability of Nitrene Transfer Reactions Through the Coordinative Malleability of Silver Complexes

Enhancing Selectivity and Tunability of Nitrene Transfer Reactions Through the Coordinative Malleability of Silver Complexes
Author: Ryan Joseph Scamp
Publisher:
Total Pages: 0
Release: 2017
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Carbon-nitrogen bonds are common to many classes of natural products and bioactive compounds. As such, efficient methods to construct nitrogenated organic scaffolds are in constant demand. Catalytic nitrene insertions are powerful methods to introduce these functionalities to hydrocarbon groups, but they presently are limited to substrate control owing to the inherent electrophilicity of nitrene intermediates, the use of catalysts with inflexible coordination environments, and a lack of understanding as to how electronic properties of metallonitrenes influence selectivity in the reaction. Chapter 1 summarizes and explores efforts by various research groups to address these issues. Our group seeks to address this problem through the use of silver, a metal displaying an array of accessible coordination geometries, to tune for chemo-, regio-, and stereoselectivity in these reactions and thus provide opportunities to divergently functionalize complex molecules. Explorations into catalyst tunability for regioselective C-H amination reactions are detailed in Chapter 2. Immediately following, Chapter 3 will expand upon this concept and illustrate how our initial conclusions informed subsequent catalyst design. Chapter 4 describes our advances in the regioselective differentiation of adjacent methylene units and the underlying mechanistic principles governing the product distribution. Finally, Chapter 5 discusses intermolecular functionalization of alkene feedstocks and the mechanistic principles fundamental to tuning for nitrene insertion into either C=C or C-H bonds.

Silver Catalysis in Organic Synthesis

Silver Catalysis in Organic Synthesis
Author: Chao-Jun Li
Publisher: John Wiley & Sons
Total Pages: 400
Release: 2018-12-07
Genre: Science
ISBN: 3527807691
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Covers all the aspects of the recent achievements in silver catalyzed reactions Silver catalysis has emerged as a powerful tool in the field of organic synthesis. This comprehensive book systematically explores the unique performance of silver catalysis, introducing all the recent progress of silver catalysis in organic synthesis. It clearly emphasizes the unique features of silver catalysis and provides the reaction mechanism involved. This two-volume book also provides vivid schematics and tables throughout to enhance the accessibility to the relevant theory and mechanisms. Silver Catalysis in Organic Synthesis begins with an introduction to Silver Chemistry before moving on to chapters covering: Silver-Catalyzed Cycloaddition Reactions; Silver-Catalyzed Cyclizations; Silver-Mediated Radical Reactions; Silver-Mediated Fluorination, Perfluoroalkylation and Trifluoromethylthiolation Reactions; Coupling Reactions and C-H Functionalization; Silver-Catalyzed CO2 Incorporation; Silver-Catalyzed Carbene, Nitrene, and Silylene Transfer Reactions; Asymmetric Silver-Catalyzed Reactions; Silver-Catalyzed Reduction and Oxidation of Aldehydes and Their Derivatives; Silver Complexes in Organic Transformations; and Silver Nanoparticles in Organic Transformations. -Covers recently developed organic reactions catalyzed by silver, along with their reaction mechanism -Introduces many new reactions and mechanisms related to silver catalysis -Offers professionals and newcomers in the related fields a survey of new advances in silver catalysis in organic synthesis Silver Catalysis in Organic Synthesis will appeal to a wide readership including chemists, biochemists, pharmaceutical scientists, biomedical researchers, agriculture scientists, and graduate students in the related fields.

Application of Nitrene Transfer Reactions for Streamlining Amine Synthesis

Application of Nitrene Transfer Reactions for Streamlining Amine Synthesis
Author: Joshua Robert Corbin
Publisher:
Total Pages: 479
Release: 2020
Genre:
ISBN:
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Metal-catalyzed nitrene transfer is a versatile strategy for the direct incorporation of C-N bonds into organic compounds through direct C-H insertion to form amines or C=C insertion to form aziridines. The identity of the metal catalyst plays a crucial role in controlling the fate of the hyperelectrophilic nitrene when multiple reaction outcomes are possible. Part One of this thesis details the development of a catalytic system based on Ag(I) supported by diverse pyridyl N-donor ligands to achieve unprecedented and tunable site-selectivity in the amination of sterically and electronically similar tertiary C(sp3)-H bonds. When ligand-control in Ag(I) catalysis failed, exchanging the metal/ligand identity to Rh2Ln frequently provided selectivity for the orthogonal site. Further work demonstrated water could be employed as the solvent in these C-H amination reactions using Ag(I) or Rh2(II,II) catalysts and sulfamate nitrene precursors. Intramolecular chemo- and regioselective aziridination of allenes using Rh2(II,II)-catalyzed nitrene transfer provides access to bicyclic methyleneaziridine intermediates that can be rapidly diversified into complex amine-containing products by forming up to four new bonds across the cumulated pi-bonds. An underexploited strategy for accessing amidoallyl cations is treating these methyleneaziridines with a mild Lewis acid to heterolytically open the strained ring. This strategy is applied in Part Two to overcome the challenges that are associated with 3-amidopentadienyl cation imino-Nazarov electrocyclizations and the method provides access to densely functionalized aminocyclopentanes with flexible substitution patterns and control over the stereochemical outcome. This thesis in its entirety demonstrates the utility of metal-nitrenes as useful oxidants in the context of the diversity-oriented synthesis of both simple and complex amines.