Design and Development of Novel Methods for C-H Functionalization for Amination and C-C Bond Formation Open Access

Abstract

Building complex molecules from simple starting materials is the heart of organic chemistry. Recently, the functionalization of generally unreactive C-H bonds has been a common target for such transformations due to their ubiquity and the atom economy associated with the transition. A family of ruthenium(II) 2,6-bis(imido)pyridyl complexes was developed for the intermolecular C-H amination of benzylic C-H bonds using sulfamate esters in a racemic fashion. A chiral derivative of the bisimidopyridyl ligand framework was proposed and progress was made toward its synthesis. Separately, molecular recognition was also explored as a means of inducing enantioselectivity in C-H amination reactions. A pyridinebisoxazoline-derived ligand was proposed and progress was made toward its synthesis. Carbon-carbon bond forming reactions for coupling aryl rings are of interest to the medicinal and materials communities. Methodology for the direct coupling of benzobisthiazoles and aryl halides using a copper/palladium co-catalytic system was developed and optimized, and the substrate scope was explored. This was expanded to the synthesis of cruciform structures and the functionalization of thiazolothiazole. Dehydrogenative carbon-carbon bond forming methodology for the synthesis of thiophene substituted benzothiazole derivatives was developed.

Table of Contents

Table of Contents

1 Ruthenium Bis(imido)pyridyl Complexes as Catalysts for Achiral and Chiral Intramolecular Amination ................................................................................................1 1.1 Introduction .............................................................................................................1 1.2 Proposed Ligand Framework ..................................................................................5 1.3 Results and Discussion. ..........................................................................................7 1.4 Optimization ligand design and reaction conditions for amination ......................11 1.5 Examination of substrate scope in C-H amination using catalyst 25 ...................15 1.6 Bis(imido)pyridyl Complexes as Catalysts for Chiral Intramolecular Amination ....................19 1.7 Chiral Ligand Synthesis ........................................................................................20 1.8 Synthesis of Mixed Ferrocenes in a Model System ..............................................24 1.9 Conclusion ............................................................................................................25 2 Intermolecular Amination via a Molecular Recognition Catalyst ....................27 2.1 Introduction ..........................................................................................................27 2.2 Molecular recognition in enantioselective catalysis ............................................29 2.3 Proposed Molecular Recognition Catalyst...........................................................33 2.4 Ligand Synthesis ..................................................................................................34 2.5 Conclusion ...........................................................................................................41 3 Benzodipyrrolidone via C-H Functionalization ...................................................42 3.1 Introduction .........................................................................................................42 3.2 Proposed C-H Functionalization Synthesis .........................................................49 3.3 Synthesis and Exploration of the Model System .................................................52 3.4 Synthesis of BDP core via C-H Functionalization ..............................................54 3.5 Conclusion ..........................................................................................................58 4 Synthesis of 2,6-Difunctionalized Benzobisthiazoles via C-H Functionalization..................................59 4.1 Introduction .........................................................................................................59 4.2 C-H Functionalization of Benzothiazole ...........................................................62 4.3 Initial Exploration of Difunctionalization of BBT .............................................66 4.4 Optimization of coupling conditions .................................................................68 4.5 Probing the Scope of Aryl halides Amenable to the C-H Functionalization of 14.............................................80 4.6 Synthesis of Cruciform Structures via 2,6-Difunctionalization of Benzobisthiazole 14.............................86 4.7 C-H Functionalization of Thiazolothiazole .......................................................91 4.8 Conclusions .........................................................................................................92 5 Dehydrogenative Cross Coupling of Benzothiazole .............................................94 5.1 Introduction .........................................................................................................94 5.2 Results and Discussion .....................................................................................100 5.3 Optimization of dehydrogenative cross coupling of 1 with 2- methylthiophene ................................................................102 5.4 Conclusion .........................................................................................................117 6 Experimental Procedures and Characterization ...............................................119 6.1 General Information ...........................................................................................119 6.2 Chapter 1 Procedures and Characterization .......................................................121 6.3 Chapter 2 Procedures and Characterization .......................................................149 6.4 Chapter 3 Procedures and Characterization ......................................................158 6.5 Chapter 4 Procedures and Characterization ......................................................166 6.6 Chapter 5 Procedures and Characterization .......................................................187 References .......................................................................................................................192

About this Dissertation

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Laney Graduate School
Department	Chemistry
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Chemistry, Organic Chemistry, General
Keyword	amination oxidative cross-coupling C-H Functionalization
Committee Chair / Thesis Advisor	Blakey, Simon, Emory University
Committee Members	Davies, Huw, Emory University Menger, Fred M, Emory University

Last modified

Primary PDF

Thumbnail	Title	Date Uploaded	Actions
	Design and Development of Novel Methods for C-H Functionalization for Amination and C-C Bond Formation ()	2018-08-28 14:16:39 -0400	Press to Select an action Download

Supplemental Files

Thumbnail	Title	Date Uploaded	Actions