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Chemical Structure| 85698-56-2

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Michelle E. Akana ; Sergei Tcyrulnikov ; Brett D. Akana-Schneider ; Giselle P. Reyes ; Sebastien Monfette ; Matthew S. Sigman , et al.

Abstract: Cross-electrophile has emerged as an attractive and efficient method for the synthesis of C(sp2)–C(sp3) bonds. These reactions are most often catalyzed by complexes of nitrogenous ligands, especially 2,2′-bipyridines. Precise prediction, selection, and design of optimal ligands remains challenging, despite significant increases in reaction scope and mechanistic understanding. Molecular parameterization and statistical modeling provide a path to the development of improved ligands that will enhance the selectivity of existing reactions and broaden the scope of electrophiles that can be coupled. Herein, we describe the generation of a computational ligand library, correlation of observed reaction outcomes with features of the ligands, and the in silico design of improved ligands for Ni-catalyzed cross-electrophile . The new nitrogen-substituted ligands display a 5-fold increase in selectivity for product formation versus homodimerization when compared to the current state of the art. This increase in selectivity and yield was general for several cross-electrophile couplings, including the challenging of an aryl chloride with an N-alkylpyridinium salt.

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Michelle Elizabeth Akana ;

Abstract: This dissertation will discuss advancements made toward understanding the intrinsic reactivity of nitrogenous ligands in nickel-catalyzed cross-electrophile coupling, as well as their impacts on reaction selectivities. Chapter 1 will introduce cross-electrophile coupling, highlight the importance of ligands in promoting diverse elementary steps, and discuss strategies to search for, understand, and improve ligand architecture. Chapter 2 describes our initial investigation utilizing descriptors from a diverse set of ligands and ligand-like molecules to predict reaction yield and selectivity. This investigation provided critical insight into experimental design, construction of a training set, and determining project outcomes. The results of these efforts informed our studies that are detailed in successive chapters. Chapter 3 summarizes the application of statistical methods to develop a model for selectivity in bipyridine-nickel-catalyzed cross-electrophile coupling. The resulting model was used to rationalize experimental outcomes, develop mechanistic insight, and design improved ligands in silico. Chapter 4 summarizes initial insights into the relationships between the structure of other classes of heterocycle-based L2 dinitrogen ligands and their corresponding experimental outcomes. These investigations provide a basis for understanding the performance of these ligands and expands on the insights described in Chapter 3. A plan for ongoing research informed by these results is proposed. Chapter 5 describes additional computationally informed projects that were undertaken by the author. These projects utilize computed catalyst structures and energies to rationalize the impact of ligand binding on the reactivity of novel 2,2’-bipyridine-6-carbonitrile ligands, as well as the relationship of ligand structure to selectivity in decarbonylative cross-electrophile coupling.

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Product Details of [ 85698-56-2 ]

CAS No. :85698-56-2
Formula : C14H18N4
M.W : 242.32
SMILES Code : CN(C1=CC(C2=NC=CC(N(C)C)=C2)=NC=C1)C
MDL No. :MFCD00233881
InChI Key :IHULFFMBCBEJPL-UHFFFAOYSA-N
Pubchem ID :145093

Safety of [ 85698-56-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319
Precautionary Statements:P501-P261-P270-P271-P264-P280-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330-P302+P352+P312-P304+P340+P312
 

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