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Development and Mechanistic Investigation of the Palladium- Catalyzed Α-Arylation of Aldehydes and N-Arylation of Ammonia by Gi

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Development and Mechanistic Investigation of the Palladium- Catalyzed Α-Arylation of Aldehydes and N-Arylation of Ammonia by Gi DEVELOPMENT AND MECHANISTIC INVESTIGATION OF THE PALLADIUM- CATALYZED -ARYLATION OF ALDEHYDES AND N-ARYLATION OF AMMONIA BY GIANG DONG VO DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry in the Graduate College of the University of Illinois at Urbana-Champaign, 2010 Urbana, Illinois Doctoral Committee: Professor John F. Hartwig, Chair Professor Scott E. Denmark Professor M. Christina White Professor Gregory S. Girolami ABSTRACT A general method for the palladium-catalyzed -arylation of aldehydes was developed to couple linear and branched aldehydes with electron-poor and electron-rich bromo- and chloroarenes in high yields. Catalysts generated from allylpalladium chloride (APC) and 1,1’- diphenylphosphinoferrocene (DPPF) coupled linear aldehydes with aryl bromides, and catalysts generated from APC and Q-phos coupled branched aldehydes with aryl bromides and chlorides. Arylpalladium enolate complexes of aldehydes were proposed as intermediates in this process, and these complexes were isolated and characterized. The effects of steric and electronic properties of the aryl groups on the rates of reductive elimination and yields of coupled products were evaluated. The reactivity of these complexes and an arylpalladium enolate complex of acetone was compared. A general method for the palladium-catalyzed coupling of ammonia with aryl halides and sulfonates was also developed. The catalyst generated from Pd[P(o-tol)3]2 and the alkylbisphophine CyPF-t-Bu is a highly active and selective catalyst for the coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates. The couplings of ammonia with this catalyst conducted with a solution of ammonia in dioxane formed primary arylamines from a variety of aryl electrophiles in high yields. Catalyst loadings as low as 0.1 mol % were sufficient for reactions of many aryl chlorides and bromides. In the presence of this catalyst, aryl sulfonates also coupled with ammonia for the first time in high yields. The utility of this method to generate amides, imides, and carbamates is illustrated by a one-pot synthesis of a small library of these carbonyl compounds from aryl bromides and chlorides, ammonia, and acid chlorides or anhydrides. Mechanistic studies showed that reactions conducted with the combination of CyPF- ii t-Bu and Pd[P(o-tol)3]2 as catalyst occur with faster rates and higher yields than those conducted with CyPF-t-Bu and palladiun(II) as catalyst precursors. iii To my parents iv “The fear of the Lord is the beginning of knowledge; fools despise wisdom and instruction.” Proverbs 1:7 v ACKNOWLEDGMENTS During the past five years, I have had the privilege of being mentored and working with many talented individuals. I am indebted to my advisor Professor John Hartwig for teaching me scientific writing and presentation. I thank him for giving me the opportunity to work in his labs, encouraging me, teaching me organometallic chemistry, and being so patient. I thank my thesis committee members, Prof. Scott Denmark, Prof. M. Christina White and Prof. Gregory Girolami, for their support and encouragement. It was a pleasure to work with such a talented group of scientists in the Hartwig group. I thank the “ammonia-team” members, Prof. Qilong Shen and Jessica Klinkenberg for many hours of engaging philosophical and scientific discussions. I am especially grateful to Qilong for his help when I started research in the group, many thanks to him for sharing his vast knowledge of the literature. I thank Jessica for proofreading my research summaries and a part of my thesis. The entire Hartwig group was instrumental in my development as a scientist. They spent many hours helping me rehearse presentations, write prelim paper and learn new lab techniques. I thank Nam Holda for organizing many fun group activities. I thank the three administrative assistants, Becky, Stacy and Susan, for their down-to- earth personalities and for feeding this hungry graduate student with Butterfingers, Starbursts, cashews and delicious chicken salads. We had so many good memories. They made me smile every time I walked into their office after an exhaustive experiment or meeting. I don’t think I will ever again find administrative assistants like them. This work would not be accomplished had my family not been so supportive and loving. I thank my brother, Kha Vo, for being a true big brother who always encourages and helps me. I vi dedicate this work to my parents. I thank them for making the decision to go to America so my brother and I could get an education. They have taught me strong family values and personal integrity. They are the best parents I could ever have. I thank my mom for her wisdom and insight. She taught me how to write and how to be content in life. I thank my Dad for teaching me integrity and hard work in all areas of life. In a way, I hope to have fulfilled my parents’ dream of going to America. Mom and Dad, you are the best. Above all, I want to thank my heavenly Father who has made everything possible. This work was only possible through His unfailing love and sovereign grace. He surrounded me with a wonderful family, supportive friends and knowledgeable colleagues. Without His teaching through the Bible, I could never have looked at research as an exciting search for the truth. I thank my Lord and Savior Jesus Christ for freeing me from bondage to the pursuit of fame, money and pleasure by His blood. The joy of working in lab comes from serving others because He has served me with boundless love and sacrifice: “…even as the Son of Man came not to be served but to serve, and to give his life as a ransom for many.” Matthew 20:28 vii TABLE OF CONTENTS Chapter 1. Overview of the Palladium-Catalyzed -Arylation of Carbonyl Compounds and N- Arylation of Amines with Aryl Halides and Sulfonates ................................................................. 1 1.1. Introduction ..................................................................................................................... 1 1.2. Overview of -Arylation of Carbonyl Compounds ........................................................ 3 1.2.1. Noncatalytic Methods ............................................................................................... 3 1.2.2. Palladium-Catalyzed Methods .................................................................................. 6 1.2.3. Other Transition-Metal Catalyzed -Arylation ...................................................... 27 1.2.4. Summary ................................................................................................................. 30 1.3. Overview of Amination of Aryl Halides and Sulfonates .............................................. 31 1.3.1. Noncatalytic Methods ............................................................................................. 31 1.3.2. Palladium-Catalyzed Methods ................................................................................ 32 1.3.3. Other Transition-metal Catalysts ............................................................................ 48 1.3.4. Summary ................................................................................................................. 49 References ..................................................................................................................................... 50 Chapter 2. -Arylation of Aldehydes with Bromo- and Chloroarenes Catalyzed by Allylpalladium Chloride and DPPF or Q-phos ............................................................................. 57 2.1. Introduction ................................................................................................................... 57 2.2. Background ................................................................................................................... 58 2.3. Results and Discussion ................................................................................................. 60 viii 2.3.1. Identification of Catalysts and Optimization of Reaction Conditions for the Coupling of Octanal with 1-Bromo-4-tert-butylbenzene ........................................ 60 2.3.2. Evaluation of the Substrate Scope of Reactions Catalyzed by Cinnamylpalladium Chloride and DPPF. ................................................................................................ 64 2.3.3. Identification of Catalysts for the -Arylation of Branched Aldehydes ................ 66 2.3.4. Identification of APC as the Catalyst Precursor and Optimization of Reaction Conditions ............................................................................................................... 68 2.3.5. Scope of the -Arylation of Linear Aldehydes ...................................................... 70 2.3.6. Scope of the -Arylation of - and -branched Aldehydes ................................... 72 3 2.3.7. Comparison of Two Catalyst Systems: Pd(OAc)2 and rac-BINAP versus Pd( - allyl)Cl]2 and DPPF ................................................................................................ 73 2.4. Conclusion and Outlook ............................................................................................... 76 2.5. Experimental Information ............................................................................................. 77 References ................................................................................................................................... 101 Chapter 3. Synthesis, Characterization
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