The Development and Mechanistic Studies of Group(IX)Cp*-Catalyzed Allylic C–H Functionalization Reactions Proceeding via a π-allyl Intermediate Open Access

Abstract

Allylic C–H functionalization has proven to be a simple method to form complex allylic products from their olefin counterparts. However, the traditional palladium-catalyzed allylic C–H functionalization reactions are largely limited to terminal olefins with stabilized nucleophiles. In order to fully realize the potential of allylic C–H functionalization to include a wider olefin and nucleophile scope, a novel catalyst system was deemed necessary. Herein is reported the development and mechanistic studies of novel group(IX)Cp*-catalyzed allylic C–H functionalization reactions that aim to address this problem. First, an intermolecular allylic C–H oxygenation reaction was developed utilizing internal olefins and alcohols or carboxylates as the oxygen nucleophile. Following this study, a full mechanistic investigation of a corresponding allylic C–H amination was performed revealing a novel Rh(III)/(IV)/(II) catalytic cycle followed by a Lewis-acid catalyzed allylic substitution to form the corresponding C–N bond. The mechanism described above precludes the use of an asymmetric metal-catalyst to induce enantioselectivity from direct reductive elimination. For this reason, a second-generation allylic C–H sulfamidation reaction was developed proceeding through an Ir(V) nitrenoid complex providing branched products selectively. In order to develop a regiodivergent protocol based on reagent choice, optimization of the first-generation linear-selective allylic C–H amination was also performed. Following this investigation, we sought to develop novel C–C bond forming methods. Therefore, we set out to determine the mechanism of a previously disclosed allylic C–H arylation reaction. Stoichiometric synthesis and reactivity of putative group(IX)Cp*-π-allyl intermediates afforded a more complete picture confirming a novel Rh(III)/(IV)/(II) catalytic cycle refuting the development of a corresponding allylic C–H alkylation reaction. Development of an enantioselective C–H arylation is currently ongoing.

Table of Contents

Table of Contents

 

Chapter 1:  Introduction and Background: Allylic C–H Functionalization via π-allyl Intermediates Prior to 2018

     I.        Palladium-Catalyzed Reactions...................................................................... 1

I.1.         Introduction and Seminal Work...................................................................... 1                                                

I.2.         C–O bond forming reactions...........................................................................4

I.3.         C–N Bond forming reactions...........................................................................8

I.4.         C–C bond forming reactions........................................................................... 9

I.5.         Conclusions and Outlook...............................................................................10

   II.        Group(IX) catalyzed systems..........................................................................11

II.1.       Intramolecular Allylic C–H Aminations.......................................................... 12

II.2.       Allylic C–H Electrocyclization to form Heterocycles......................................... 15

II.3.       Stoichiometric RhCpE-π-allyl Complex Studies................................................16

II.4.       Intermolecular Allylic C–H Amination.............................................................18

II.5.       Conclusions and Outlook................................................................................19

 III.        References.....................................................................................................20

 

Chapter 2:  Rhodium-Catalyzed C–O Bond Formation via Allylic C–H Functionalization of Internal Olefins

     I.        Introduction: Allylic Ethers............................................................................28

I.1.         Synthesis.......................................................................................................28

I.2.         Allylic C–H Functionalization......................................................................... 30

   II.        Optimization Studies......................................................................................33

 III.        Scope Studies of Allylic C–H Etherification.......................................................35

III.1.     Alcohol Coupling Partner................................................................................ 35

III.2.     Olefin Coupling Partner.................................................................................. 39

III.3.     Terminal Olefins..............................................................................................41

 IV.        Mechanistic Investigations...............................................................................43

   V.        Conclusion......................................................................................................44

 VI.        Experimental Procedures..................................................................................45

VI.1.     General Information.........................................................................................45

VI.2.     General Procedure A for Reaction Optimization..................................................46

VI.3.     General Procedure B for Allylic Etherification.....................................................47

VI.4.     General Procedure C for Suzuki Cross-Coupling..................................................47

VI.5.     Procedures and Characterization.......................................................................48

VI.6.     Deuterium Exchange Experiment......................................................................83

VI.7.     Kinetic Isotope Effect........................................................................................83

VI.8.     Starting Material Synthesis...............................................................................84

VII.        Characterization Data......................................................................................89

VIII.        References....................................................................................................163

 

 

Chapter 3:  The Mechanism of Rhodium-Catalyzed Allylic C–H Amination Proceeding via a Rh(IV)-π-allyl Intermediate

     I.        Introduction: Mechanisms in C–H Functionalization........................................168

I.1.         Rh(III)/Rh(I) Catalytic Cycles...........................................................................168

I.2.         Rh(III)/Rh(V) Catalytic Cycles..........................................................................169

I.3.         Ir(III)/Ir(IV)/Ir(II) Catalytic Cycles....................................................................171

I.4.         Stoichiometric π-allyl Complex Reactivity........................................................173

   II.        Results and Discussion................................................................................... 174

II.1.       Kinetic Analysis and Determination of the Rate-determining Step......................175

II.2.       Stoichiometric π-allyl Complex Formation and Reactivity..................................178

II.3.       Lewis-acid Catalyst Investigations...................................................................182

II.4.       Computational Investigation of the Key Steps in the Catalytic Cycle...................184

II.5.       Electrochemical Characterization of 3-32.........................................................185

 III.        Conclusion.....................................................................................................190

 IV.        Experimental Procedures: ...............................................................................191

IV.1.     General Information........................................................................................191

IV.2.     Detailed Catalytic Cycle...................................................................................193

IV.3.     Experimental Rate Law Determination..............................................................193

IV.3.1.   Representative Procedure for Initial Rate Kinetic Experiments...........................193

IV.3.2.   Determination of KIE......................................................................................200

IV.4.     Synthesis and Reactivity of Rhodium Complex...................................................201

IV.5.     Reactions of Complexes with a halide abstractor, silver oxidant, and base............206

IV.6.     Reactivity of Allylic Acetate..............................................................................213

IV.7.   General Procedure for Silver (AgSbF6) or Rhodium (RhCp*(MeCN)3(SbF6)2) as the Lewis-Acid

.................................................................................................................................214

IV.8.   General procedure for Cyclic Voltammetry Experiments.......................................216

IV.9.   General Procedure for Allylic Amination Time Course..........................................219

IV.10. Computational details.......................................................................................220

IV.11. X-ray Crystal Structure Reports..........................................................................223

IV.11.1. RhCp*-π-allyl-acetate (3-32) ..........................................................................223

IV.11.2. RhCp*-π-allyl-Cl (3-27) .................................................................................243

IV.11.3. Rhodium Cp*-π-allyl-NHTs (3-30) ..................................................................264

IV.12. DFT Optimized Geometries and Computed Vibrational Frequencies.....................283

IV.12.1. XYZ coordinates............................................................................................283

IV.12.2. Frequencies...................................................................................................294

   V.        References.....................................................................................................301

 VI.        Characterization of Compounds.......................................................................305

 

Chapter 4:  Regiodivergent Allylic C–H Sulfamidation of Allylbenzene Derivatives via a Ir(V)Cp*-π-allyl Nitrenoid Intermediate

     I.        Introduction..................................................................................................313

I.1.         MCp*-catalyzed Allylic C–N Bond Formation...................................................313

I.2.         A Novel Allylic C–H Amination Protocol..........................................................316

   II.        Results and Discussion...................................................................................317

II.1.       Branched-selective Optimization.....................................................................317

II.2.       Linear-selective Optimization.........................................................................319

II.3.       Scope of Linear Selective Sulfamidation...........................................................321

II.4.       Scope of Branched-selective Sulfamidation......................................................322

II.5.       Proposed Catalytic Cycle of Branched Selective Allylic C–H Amination..............324

II.6.     Diversification of Branched Products to form Heterocycles.................................326

 III.        Conclusion....................................................................................................327

 IV.        Experimental Procedures: ..............................................................................327

IV.1.     General Information...................................................................................... 327

IV.2.     Preparation of Olefin Coupling Partners..........................................................329

IV.3.     General Procedure for Linear-Selective Reaction Optimization..........................330

IV.4.     General Procedure A: Optimization of Allylic C–H Sulfamidation Reaction.........331

IV.5.     General procedure B: Allylic C–H Sulfamidation of Allylbenzene Derivatives......332

IV.6.     General Procedure C: Linear Selective Amination of Allylbenzene Derivatives....333

IV.7.     Characterization of Allylic C–H Sulfamidation Products...................................333

IV.8.     Spectra of Compounds...................................................................................348

   V.        Reference: ...................................................................................................383

 

 

Chapter 5:  Reactivity of Group (IX)Cp*-π-allyl Complexes as Putative Intermediates in Allylic C–H Arylation and Alkylation Reactions

     I.        Introduction................................................................................................387

I.1.         Allylic C–H Arylation Reactions.....................................................................387

I.2.         Previous disclosed Allylic C–H Arylation Mechanistic Investigations................390

   II.        Results and Discussion: ................................................................................392

II.1.       Formation of MCp*-π-allyl Complexes with a Chloro Ligand............................392

II.2.       Formation of RhCp*-π-allyl Complexes with a Me or Ph Ligand........................393

II.3.       Formation of IrCp*-π-allyl Complexes with a Me or Ph Ligand.........................394

II.4.       Characterization of MCp*-π-allyl Complexes..................................................396

II.5.       Single-crystal X-Ray Diffractometry of MCp*-π-allyl Complexes......................397

II.6.       Stoichiometric Reactivity of MCp*-π-allyl Complexes.....................................399

II.7.       Cyclic Voltammetry Studies...........................................................................404

II.8.       New Proposed Catalytic Cycle........................................................................405

     III.        Conclusion................................................................................................407

     IV.        Experimental Procedures: ..........................................................................408

IV.1.     General Information: .................................................................................... 408

IV.2.     Synthesis of Complexes: ............................................................................... 409

IV.3.     Subjection of Complexes to Heat:....................................................................416

IV.4.     Reaction of Complexes with AgSbF6.................................................................418

IV.5.     Cyclic Voltammetry General Procedure:...........................................................424

IV.6.     Crystallography: ........................................................................................... 434

IV.7.     Spectra of Complexes......................................................................................517

References............................................................................................................... 530

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School	Laney Graduate School
Department	Chemistry
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Chemistry, Organic Chemistry, General Chemistry, Inorganic
Keyword	Sulfamidation Complexes Organometallic RhCp* C–H Activation Arylation Allylic Chemistry C–H Functionalization IrCp* π-allyl Etherification Amination
Committee Chair / Thesis Advisor	Nathan Jui, Emory University Simon Blakey, Emory University William Wuest, Emory University

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