University of Illinois at Chicago

New Chemistry of Multiynes: Development of Novel Aryne-Based Transformations and Click Reactions

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posted on 2020-08-01, 00:00 authored by Sourav Ghorai
This thesis consists of two main parts, Part I and Part II. The six chapters in Part I cover various multicomponent coupling reactions of arynes generated via the hexadehydro Diels-Alder (HDDA) reactions of multiynes, whereas Part II is devoted to describe an unprecedented click reaction of terminal 1,3-diynes. Below is the brief outline of each chapter. Chapter 1 provides a brief overview of the origins, developments and synthetic applications of HDDA reactions. Aryne-based transformations developed under thermal and metal-catalyzed conditions to generate highly functionalized aromatic systems constitute the major portion of this chapter. In addition, herein are summarized recently developed multicomponent reactions of arynes derived from multiynes. In Chapter 2, Ritter-type transformations of arynes with nitriles are discussed. Nitriles, usually unreactive towards aryne, could be used as nucleophilic component upon activating arynes with a silver catalyst. Trapping of the initially formed aryne-nitrile adduct, a nitrilium species, with water contained in wet solvent provided amides. When nitrilium intermediate was trapped by carboxylic acid, arylimide was generated. In Chapter 3, an unprecedented [2+2+2] annulation reaction of arynes with nitriles has been highlighted. It was found that, in the absence of water or carboxylic acid, the nitrilium species generated from an aryne and a nitrile molecule could react further with another nitrile molecule to generate quinazoline derivatives. The generality of this transformation has been studied with a broad array of multiyne systems and with different sets of aliphatic and aromatic nitriles. Chapter 4 describes a novel and efficient [2+1+1] annulation reaction of arynes with isonitriles. In the presence of silver catalyst, arynes react with two molecules of isonitrile to generate benzocyclobutene-1,2-diimines. However, this reaction is limited to aromatic isonitriles. The mechanisms of these annulation reactions are investigated by DFT calculations. Synthetic utilities of benzocyclobutene-1,2-diimines are demonstrated in the latter part. Continued with silver catalyzed transformations of arynes with nitriles or isonitriles, a cross condensation involving arynes, nitriles, and isonitriles has been presented in Chapter 5. Initial screenings showed the impact of the stoichiometry of nitrile and isonitrile on the formation of aryne-nitrile-isonitrile adduct. A sequential addition of nitrile and isonitrile to aryne was observed to deliver 3-iminoindolin-2-ol and 3H-indol-3-imine. Because of the higher reactivity of isonitrile as a nucleophile, the incorporation of less reactive nitrile was feasible only with its significantly higher concentration compared to that of isonitrile and activated aryne with a silver catalyst. In Chapter 6, a variety of aryne-based multicomponent coupling reactions for the formation of functionalized aromatic compounds are presented. Arynes readily reacted with isonitriles to generate a nitrilium intermediate, which was intercepted with various weak nucleophiles including carboxylic acids, alcohols, sulfonamides, and water to generate the corresponding imides, imidates, amidines, and amides. An unprecedented click reaction of terminal 1,3 diynes is presented in Chapter 7. Cu( catalyzed [3+2] cycloaddition between terminal alkynes and tosyl azide generated N sulfonyl triazolyl copper species, which subsequently released N2 to generate ketenimide intermediates, which could be trapped with amines or alcohols to generate 3 alkynyl or allenyl imidamides and imidates. The selectivity for the formation of these products critically depended on the substituents of the diynes and the nucleophiles that reacted with the ketenimide intermediate. Depending on the type of nucleophiles, base additives, and the substituents patterns of the 1,3 diynes, this click reaction could promote the formation of alternative products such as heterocycles, [3]cumulenes and triple bond migrated products.



Lee, Daesung


Lee, Daesung



Degree Grantor

University of Illinois at Chicago

Degree Level

  • Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

Mohr, Justin Wardrop, Duncan Aldrich, Leslie Chong, Hyun-soon

Submitted date

August 2020

Thesis type



  • en

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