{"product_id":"enabling-tools-and-techniques-for-organic-synthesis-9781119855637","title":"Enabling Tools and Techniques for Organic","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003e\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003eList of Contributors xv\u003c\/p\u003e \u003cp\u003ePreface xix\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 Biocatalysis 101 – A Chemist’s Guide to Starting Biocatalysis 1\u003cbr\u003e \u003c\/b\u003e\u003ci\u003ePablo Díaz- Kruik, David Lim, and Francesca Paradisi\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 1\u003c\/p\u003e \u003cp\u003e1.1 Introduction 1\u003c\/p\u003e \u003cp\u003e1.1.1 Enzymes – the Green and Sustainable Way of the Future 1\u003c\/p\u003e \u003cp\u003e1.1.2 Enzymatic and Organic Catalysis Are Not too Different from Each Other 3\u003c\/p\u003e \u003cp\u003e1.1.3 Enzymes 101 4\u003c\/p\u003e \u003cp\u003e1.2 When Should I Choose an Enzyme over a Chemical Catalyst? 4\u003c\/p\u003e \u003cp\u003e1.3 Key Considerations for Running Biocatalytic Reactions 6\u003c\/p\u003e \u003cp\u003e1.3.1 Dispelling Myths 6\u003c\/p\u003e \u003cp\u003e1.3.1.1 Enzymes Are Not Safe to Use 7\u003c\/p\u003e \u003cp\u003e1.3.1.2 Enzymes Are Not as Readily Available as Chemical Catalysts 7\u003c\/p\u003e \u003cp\u003e1.3.1.3 Enzymes Are Seldom Useful Due to Their Limited Substrate Scope 7\u003c\/p\u003e \u003cp\u003e1.3.1.4 The Cost of Enzyme Production Is Very High 8\u003c\/p\u003e \u003cp\u003e1.3.1.5 Enzymes Are Functionally Unstable Under Organic Conditions 9\u003c\/p\u003e \u003cp\u003e1.3.1.6 Sustainability 9\u003c\/p\u003e \u003cp\u003e1.3.2 Challenges of Using Enzymes: the Need for Strict Reaction Conditions 9\u003c\/p\u003e \u003cp\u003e1.3.2.1 Enzymes from Extremophiles 10\u003c\/p\u003e \u003cp\u003e1.3.2.2 Solvents (and Co- solvents) 10\u003c\/p\u003e \u003cp\u003e1.3.2.3 Concentration and Ionic Strength of the Buffer 10\u003c\/p\u003e \u003cp\u003e1.3.2.4 pH Dependence 11\u003c\/p\u003e \u003cp\u003e1.3.2.5 Concentration of Reactants 11\u003c\/p\u003e \u003cp\u003e1.3.2.6 Enzyme Concentration 12\u003c\/p\u003e \u003cp\u003e1.3.2.7 Enzyme Forms 12\u003c\/p\u003e \u003cp\u003e1.3.2.8 Toxicity 13\u003c\/p\u003e \u003cp\u003e1.3.3 What Do I Need to Start Biocatalytic Experiments in My Lab? 13\u003c\/p\u003e \u003cp\u003e1.3.4 Additional Considerations 14\u003c\/p\u003e \u003cp\u003e1.4 Transformations Catalyzed by Enzymes 15\u003c\/p\u003e \u003cp\u003e1.4.1 EC – The Enzyme Commission Number 15\u003c\/p\u003e \u003cp\u003e1.4.1.1 EC 1 – Oxoreductases 15\u003c\/p\u003e \u003cp\u003e1.4.1.2 EC 2 – Transferases 16\u003c\/p\u003e \u003cp\u003e1.4.1.3 EC 3 – Hydrolases 16\u003c\/p\u003e \u003cp\u003e1.4.1.4 EC 4 – Lyases 17\u003c\/p\u003e \u003cp\u003e1.4.1.5 EC 5 – Isomerases 18\u003c\/p\u003e \u003cp\u003e1.4.1.6 EC 6 – Ligases 18\u003c\/p\u003e \u003cp\u003e1.4.1.7 EC 7 – Translocases 18\u003c\/p\u003e \u003cp\u003e1.4.2 Some Applications of Selected Commercially Available Enzymes 19\u003c\/p\u003e \u003cp\u003e1.4.2.1 Horseradish Peroxidase 19\u003c\/p\u003e \u003cp\u003e1.4.2.2 Lysozyme 19\u003c\/p\u003e \u003cp\u003e1.4.2.3 Trypsin 20\u003c\/p\u003e \u003cp\u003e1.4.2.4 Candida Lipase B 20\u003c\/p\u003e \u003cp\u003e1.4.2.5 Amino Acid Dehydrogenase 20\u003c\/p\u003e \u003cp\u003e1.4.2.6 Glycosidases 21\u003c\/p\u003e \u003cp\u003e1.4.3 Engineered (Unnatural) Reactions 21\u003c\/p\u003e \u003cp\u003e1.5 New Trends and Technologies in Biocatalysis 21\u003c\/p\u003e \u003cp\u003e1.5.1 Flow Biocatalysis and New Technologies 21\u003c\/p\u003e \u003cp\u003e1.5.1.1 What Is Flow Biocatalysis? 21\u003c\/p\u003e \u003cp\u003e1.5.1.2 How Does Flow Biocatalysis Work? 21\u003c\/p\u003e \u003cp\u003e1.5.1.3 When Is a Flow Process More Beneficial for a Specific Transformation? 23\u003c\/p\u003e \u003cp\u003e1.5.1.4 Should One Implement Every Enzymatic Reaction in Flow? 23\u003c\/p\u003e \u003cp\u003e1.5.2 Enzyme Engineering 24\u003c\/p\u003e \u003cp\u003e1.5.3 Photobiocatalysis 25\u003c\/p\u003e \u003cp\u003e1.6 Flow Chart to Biocatalysis 25\u003c\/p\u003e \u003cp\u003e1.7 Case Study: Setting up a Biotransformation 27\u003c\/p\u003e \u003cp\u003e1.8 Concluding Remarks 31\u003c\/p\u003e \u003cp\u003eAdditional Resources 31\u003c\/p\u003e \u003cp\u003eReferences 31\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Introduction to Photochemistry for the Synthetic Chemist 37\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eStefano Protti, Davide Ravelli, and Maurizio Fagnoni\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 37\u003c\/p\u003e \u003cp\u003e2.1 Introduction 38\u003c\/p\u003e \u003cp\u003e2.1.1 Light to Make Your Synthesis Greener 38\u003c\/p\u003e \u003cp\u003e2.1.2 A Way to Overcome HOMO\/LUMO Interactions 39\u003c\/p\u003e \u003cp\u003e2.2 How to Plan a Photochemical Synthesis 45\u003c\/p\u003e \u003cp\u003e2.2.1 The Choice of the Solvent 45\u003c\/p\u003e \u003cp\u003e2.2.2 Concentration of the Absorbing Species 47\u003c\/p\u003e \u003cp\u003e2.2.3 The Reaction Vessel 48\u003c\/p\u003e \u003cp\u003e2.2.4 Light Sources 48\u003c\/p\u003e \u003cp\u003e2.2.4.1 Low- Pressure Mercury Arcs 49\u003c\/p\u003e \u003cp\u003e2.2.4.2 Medium- and High- Pressure Mercury Arcs 50\u003c\/p\u003e \u003cp\u003e2.2.4.3 Other Light Sources 50\u003c\/p\u003e \u003cp\u003e2.2.5 From Batch to Flow Conditions 52\u003c\/p\u003e \u003cp\u003e2.2.6 Preparation of the Sample 54\u003c\/p\u003e \u003cp\u003e2.2.7 Safety Equipment 54\u003c\/p\u003e \u003cp\u003e2.3 Selected Applications of Photochemical\/Photocatalyzed Reactions 55\u003c\/p\u003e \u003cp\u003e2.3.1 Reactions Involving the C═C Double Bond 55\u003c\/p\u003e \u003cp\u003e2.3.2 Reactions Involving the C═O Double Bond 58\u003c\/p\u003e \u003cp\u003e2.3.3 Reactions Involving a Photoinduced Homolysis 60\u003c\/p\u003e \u003cp\u003e2.3.4 Reactions Involving Singlet Oxygen 62\u003c\/p\u003e \u003cp\u003e2.3.5 Reactions Involving a Photocatalytic Step 62\u003c\/p\u003e \u003cp\u003e2.4 Conclusions 67\u003c\/p\u003e \u003cp\u003eAcknowledgment 67\u003c\/p\u003e \u003cp\u003eReferences 67\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 How to Confidently Become an Electrosynthetic Practitioner 73\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eSylvain Charvet, Taline Kerackian, Camille Z. Rubel, and Julien C. Vantourout\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 73\u003c\/p\u003e \u003cp\u003eAbbreviations 76\u003c\/p\u003e \u003cp\u003e3.1 Introduction 77\u003c\/p\u003e \u003cp\u003e3.2 General Definition of Organic Electrosynthesis 78\u003c\/p\u003e \u003cp\u003e3.3 Why is Organic Electrosynthesis Used? 78\u003c\/p\u003e \u003cp\u003e3.4 How is Organic Electrosynthesis Performed? 78\u003c\/p\u003e \u003cp\u003e3.5 Where to Start with Electrosynthesis? 79\u003c\/p\u003e \u003cp\u003eSelected General Reviews 79\u003c\/p\u003e \u003cp\u003eSelected General Guides 79\u003c\/p\u003e \u003cp\u003e3.6 Electrasyn 2.0 80\u003c\/p\u003e \u003cp\u003e3.6.1 Machine and Consumables 80\u003c\/p\u003e \u003cp\u003e3.6.1.1 Opening the IKA ElectraSyn 2.0 Box 80\u003c\/p\u003e \u003cp\u003e3.6.1.2 Cell (Vial and Cap) 81\u003c\/p\u003e \u003cp\u003e3.6.1.3 Electrodes 82\u003c\/p\u003e \u003cp\u003e3.6.2 Interface 83\u003c\/p\u003e \u003cp\u003e3.6.2.1 Hardware 83\u003c\/p\u003e \u003cp\u003e3.6.2.2 Menus 84\u003c\/p\u003e \u003cp\u003e3.6.3 How to Set Up the Cell 84\u003c\/p\u003e \u003cp\u003e3.6.4 How to Start an Experiment 85\u003c\/p\u003e \u003cp\u003e3.6.5 During the Reaction 88\u003c\/p\u003e \u003cp\u003e3.6.6 After the Reaction 89\u003c\/p\u003e \u003cp\u003e3.7 Case Study 90\u003c\/p\u003e \u003cp\u003e3.7.1 Project Overview 90\u003c\/p\u003e \u003cp\u003e3.7.2 Optimization of Parameters 92\u003c\/p\u003e \u003cp\u003e3.7.2.1 Designing an Electrochemical Experiment 92\u003c\/p\u003e \u003cp\u003e3.7.3 Proof of Concept 94\u003c\/p\u003e \u003cp\u003e3.7.3.1 Optimization 94\u003c\/p\u003e \u003cp\u003e3.7.3.2 Substrate Scope 102\u003c\/p\u003e \u003cp\u003e3.8 Conclusion 103\u003c\/p\u003e \u003cp\u003eReferences 103\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Flow Chemistry 107\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eYosuke Ashikari and Aiichiro Nagaki\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 107\u003c\/p\u003e \u003cp\u003e4.1 Introduction 109\u003c\/p\u003e \u003cp\u003e4.1.1 What is Flow Microchemistry 109\u003c\/p\u003e \u003cp\u003e4.1.1.1 Reaction Time Controllability 110\u003c\/p\u003e \u003cp\u003e4.1.1.2 Fast Mixing 111\u003c\/p\u003e \u003cp\u003e4.1.1.3 Temperature Controllability 112\u003c\/p\u003e \u003cp\u003e4.1.2 Reactions Enabled by Flow Microreactors 112\u003c\/p\u003e \u003cp\u003e4.1.2.1 Competitive Sequential Reactions 112\u003c\/p\u003e \u003cp\u003e4.1.2.2 Reactions Mediated by Unstable Intermediates 114\u003c\/p\u003e \u003cp\u003e4.1.2.3 Reactions Occurring at the Surface: Two- Phase Reactions, Electrochemical Reactions, and Photoreactions 117\u003c\/p\u003e \u003cp\u003e4.1.3 Further Applicability of Flow Microsynthesis 118\u003c\/p\u003e \u003cp\u003e4.1.3.1 Scalability 118\u003c\/p\u003e \u003cp\u003e4.1.3.2 Safety Operation 118\u003c\/p\u003e \u003cp\u003e4.2 General Information for Flow Microreactors 118\u003c\/p\u003e \u003cp\u003e4.2.1 Tools and Equipment for Flow Chemistry 119\u003c\/p\u003e \u003cp\u003e4.2.1.1 Micromixer 119\u003c\/p\u003e \u003cp\u003e4.2.1.2 Tube Reactor 120\u003c\/p\u003e \u003cp\u003e4.2.1.3 Pump 120\u003c\/p\u003e \u003cp\u003e4.2.1.4 Pre- Cooling Tubes 121\u003c\/p\u003e \u003cp\u003e4.2.1.5 PTFE Tubes 121\u003c\/p\u003e \u003cp\u003e4.2.2 How to Perform Experiments 122\u003c\/p\u003e \u003cp\u003e4.2.2.1 Selection of Reaction Conditions 122\u003c\/p\u003e \u003cp\u003e4.2.2.2 Preparation of Reagent Solution 125\u003c\/p\u003e \u003cp\u003e4.2.2.3 Preparation for Reactions 126\u003c\/p\u003e \u003cp\u003e4.2.2.4 Preparation for Reaction Evaluation 128\u003c\/p\u003e \u003cp\u003e4.2.2.5 Cleaning Up 129\u003c\/p\u003e \u003cp\u003e4.3 Case Studies 129\u003c\/p\u003e \u003cp\u003e4.3.1 Competitive Sequential Reaction (General Procedure) 129\u003c\/p\u003e \u003cp\u003e4.3.1.1 Preparation 130\u003c\/p\u003e \u003cp\u003e4.3.1.2 Experiment 132\u003c\/p\u003e \u003cp\u003e4.3.1.3 Screening of Reaction Conditions 133\u003c\/p\u003e \u003cp\u003e4.3.1.4 Analysis 134\u003c\/p\u003e \u003cp\u003e4.3.1.5 Clean Up 136\u003c\/p\u003e \u003cp\u003e4.3.2 Reactions Mediated by Short- Lived Intermediates 136\u003c\/p\u003e \u003cp\u003e4.3.3 Reaction Integration 139\u003c\/p\u003e \u003cp\u003e4.4 Further Expertise 142\u003c\/p\u003e \u003cp\u003e4.4.1 Reaction Integration 142\u003c\/p\u003e \u003cp\u003e4.4.2 Chemoselective Reactions 143\u003c\/p\u003e \u003cp\u003e4.4.3 Heterogeneous Catalytic Reactions 143\u003c\/p\u003e \u003cp\u003e4.5 Summary and Outlook 144\u003c\/p\u003e \u003cp\u003eReferences 144\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Reaction Optimization Using Design of Experiments 149\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eLaura Forfar and Paul Murray\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 149\u003c\/p\u003e \u003cp\u003e5.1 Introduction 151\u003c\/p\u003e \u003cp\u003e5.1.1 How Do We Experiment and DoE Terminology 151\u003c\/p\u003e \u003cp\u003e5.1.2 OVAT vs. DoE 153\u003c\/p\u003e \u003cp\u003e5.1.2.1 A Simple Chemical Example 153\u003c\/p\u003e \u003cp\u003e5.1.3 A Note on Error, Accuracy, and Precision 156\u003c\/p\u003e \u003cp\u003e5.2 When and How Can DoE Be Used? 157\u003c\/p\u003e \u003cp\u003e5.3 What Information Can I Get from a DoE and How Is It Obtained? 158\u003c\/p\u003e \u003cp\u003e5.3.1 Which Factors Are Important? 159\u003c\/p\u003e \u003cp\u003e5.3.2 How Are the Models Generated? 161\u003c\/p\u003e \u003cp\u003e5.4 What Types of Design Are Available? 164\u003c\/p\u003e \u003cp\u003e5.4.1 Screening Designs 164\u003c\/p\u003e \u003cp\u003e5.4.1.1 Fractional Factorial Designs 165\u003c\/p\u003e \u003cp\u003e5.4.1.2 Definitive Screening Designs 166\u003c\/p\u003e \u003cp\u003e5.4.2 Designs for Optimizing Reactions 167\u003c\/p\u003e \u003cp\u003e5.4.3 Response Surface Designs 167\u003c\/p\u003e \u003cp\u003e5.5 The DoE Process 169\u003c\/p\u003e \u003cp\u003e5.5.1 Aim and Objective 170\u003c\/p\u003e \u003cp\u003e5.5.2 Selecting Factors and Ranges 171\u003c\/p\u003e \u003cp\u003e5.5.2.1 Factors 171\u003c\/p\u003e \u003cp\u003e5.5.2.2 Ranges 173\u003c\/p\u003e \u003cp\u003e5.5.3 Selecting Responses 175\u003c\/p\u003e \u003cp\u003e5.5.4 Select a Design to Answer the Objective 176\u003c\/p\u003e \u003cp\u003e5.5.5 Carry Out Design and Analyze Samples 177\u003c\/p\u003e \u003cp\u003e5.5.6 Check Results 178\u003c\/p\u003e \u003cp\u003e5.5.7 Model Data 179\u003c\/p\u003e \u003cp\u003e5.5.7.1 General Steps for Developing a Model 180\u003c\/p\u003e \u003cp\u003e5.5.7.2 Wittig Reaction 181\u003c\/p\u003e \u003cp\u003e5.5.7.3 Complementing the Design 187\u003c\/p\u003e \u003cp\u003e5.5.8 Validate Predictions 189\u003c\/p\u003e \u003cp\u003e5.6 Combining DoE with Other Screening and Optimization Techniques 191\u003c\/p\u003e \u003cp\u003e5.7 Software 192\u003c\/p\u003e \u003cp\u003e5.8 “I Tried Experimental Design But It Did Not Work” 193\u003c\/p\u003e \u003cp\u003e5.9 Conclusion 194\u003c\/p\u003e \u003cp\u003eReferences 195\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Introduction to High- Throughput Experimentation (HTE) for the Synthetic Chemist 197\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eStephanie Felten, Michael Shevlin, and Marion H. Emmert\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 197\u003c\/p\u003e \u003cp\u003e6.1 What Is HTE? 199\u003c\/p\u003e \u003cp\u003e6.2 Why HTE and What Can It Achieve? 199\u003c\/p\u003e \u003cp\u003e6.2.1 Commonly Perceived Barriers to Employing HTE in Synthetic Chemistry 200\u003c\/p\u003e \u003cp\u003e6.2.1.1 Cost 200\u003c\/p\u003e \u003cp\u003e6.2.1.2 Availability of Dedicated HTE Facilities 200\u003c\/p\u003e \u003cp\u003e6.2.1.3 Access to Knowledge and Training 201\u003c\/p\u003e \u003cp\u003e6.2.1.4 Perception of HTE as Antithesis of Hypothesis- driven Research 201\u003c\/p\u003e \u003cp\u003e6.2.2 Advantages of HTE Workflows vs. Traditional Reaction Setup 203\u003c\/p\u003e \u003cp\u003e6.2.2.1 Setup Time per Reaction 203\u003c\/p\u003e \u003cp\u003e6.2.2.2 Miniaturization and Efficient Reagent Use 203\u003c\/p\u003e \u003cp\u003e6.2.2.3 Multivariable vs. Sequential Optimization 203\u003c\/p\u003e \u003cp\u003e6.2.2.4 Visualizing Reactivity Patterns 204\u003c\/p\u003e \u003cp\u003e6.2.2.5 Serendipity in Reaction Discovery 204\u003c\/p\u003e \u003cp\u003e6.2.2.6 Avoiding Cross- contamination 206\u003c\/p\u003e \u003cp\u003e6.3 Practical Considerations and Tools for HTE 206\u003c\/p\u003e \u003cp\u003e6.3.1 Outline of a Typical HTE Workflow 207\u003c\/p\u003e \u003cp\u003e6.3.2 Types of HTE Designs 209\u003c\/p\u003e \u003cp\u003e6.3.2.1 HTE for Reaction Discovery 209\u003c\/p\u003e \u003cp\u003e6.3.2.2 HTE for Reaction Optimization 210\u003c\/p\u003e \u003cp\u003e6.3.3 HTE Design Software: Tools for Building Arrays 211\u003c\/p\u003e \u003cp\u003e6.3.4 HTE Reactors and Consumables 214\u003c\/p\u003e \u003cp\u003e6.3.4.1 Reaction Blocks 214\u003c\/p\u003e \u003cp\u003e6.3.4.2 HTE Vials 214\u003c\/p\u003e \u003cp\u003e6.3.4.3 Reaction Blocks with Sealing Top Plate 215\u003c\/p\u003e \u003cp\u003e6.3.4.4 Special Reactors for Photochemistry, Electrochemistry, and High- Pressure Reactions 215\u003c\/p\u003e \u003cp\u003e6.3.4.5 Reaction Stirring and Temperature Control 217\u003c\/p\u003e \u003cp\u003e6.3.4.6 Consumables 219\u003c\/p\u003e \u003cp\u003e6.3.5 Considerations for Experimental Setup 220\u003c\/p\u003e \u003cp\u003e6.3.5.1 Reaction Atmosphere 220\u003c\/p\u003e \u003cp\u003e6.3.5.2 Reagent Preparation and Dispensing 221\u003c\/p\u003e \u003cp\u003e6.3.5.3 Storage of Preplated Reagents 223\u003c\/p\u003e \u003cp\u003e6.3.5.4 Pipetting 224\u003c\/p\u003e \u003cp\u003e6.3.5.5 Solvent Evaporation 225\u003c\/p\u003e \u003cp\u003e6.3.6 Analysis of HTE Screens 226\u003c\/p\u003e \u003cp\u003e6.3.6.1 Suitable Instrumentation 226\u003c\/p\u003e \u003cp\u003e6.3.6.2 Autosampler Configurations 226\u003c\/p\u003e \u003cp\u003e6.3.6.3 Analytical Methods 227\u003c\/p\u003e \u003cp\u003e6.3.6.4 Internal Standards and Assay Yields 227\u003c\/p\u003e \u003cp\u003e6.3.6.5 Data Visualization and Analysis 228\u003c\/p\u003e \u003cp\u003e6.3.7 The Role of Automation and Robotics in HTE 229\u003c\/p\u003e \u003cp\u003e6.4 Section Summary and Outlook 232\u003c\/p\u003e \u003cp\u003e6.5 Case Study 1: Development of an HTE Platform for Nickel- Catalyzed Suzuki–Miyaura Reactions 233\u003c\/p\u003e \u003cp\u003e6.5.1 Motivation 233\u003c\/p\u003e \u003cp\u003e6.5.2 Design of Test Reaction and Initial Ligand Screen 233\u003c\/p\u003e \u003cp\u003e6.5.3 Second Round of Ligand\/Base\/Solvent Screens 235\u003c\/p\u003e \u003cp\u003e6.5.4 Final Platform Design 237\u003c\/p\u003e \u003cp\u003e6.5.5 Validation of Platform Design 237\u003c\/p\u003e \u003cp\u003e6.6 Case Study 2: HTE Enabled Reaction Discovery and Optimization of Silyl- Triflate- Mediated C–H Aminoalkylation of Azoles 240\u003c\/p\u003e \u003cp\u003e6.6.1 Motivation 240\u003c\/p\u003e \u003cp\u003e6.6.2 Reaction Discovery Plate Design 240\u003c\/p\u003e \u003cp\u003e6.6.3 Ligand Screen 243\u003c\/p\u003e \u003cp\u003e6.6.4 Parallel Optimization of Three Reagents 244\u003c\/p\u003e \u003cp\u003e6.6.5 Base Screen 244\u003c\/p\u003e \u003cp\u003e6.7 Current Challenges and the Future of HTE 247\u003c\/p\u003e \u003cp\u003e6.7.1 Summary and Conclusions 247\u003c\/p\u003e \u003cp\u003e6.7.2 Remaining Challenges: The Next Frontiers 248\u003c\/p\u003e \u003cp\u003e6.7.2.1 Biphasic Reaction Mixtures 248\u003c\/p\u003e \u003cp\u003e6.7.2.2 Flow Chemistry and HTE 248\u003c\/p\u003e \u003cp\u003e6.7.2.3 Reaction Profiling 249\u003c\/p\u003e \u003cp\u003e6.7.2.4 Building Machine Learning Models to Predict Reactivity 249\u003c\/p\u003e \u003cp\u003e6.7.2.5 Addressing Future Challenges 250\u003c\/p\u003e \u003cp\u003eAcknowledgments 250\u003c\/p\u003e \u003cp\u003eFurther Recommended Reading 250\u003c\/p\u003e \u003cp\u003eReferences 250\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Concepts and Practical Aspects of Computational Chemistry 259\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eMartin Breugst\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 259\u003c\/p\u003e \u003cp\u003e7.1 Introduction 261\u003c\/p\u003e \u003cp\u003e7.2 Hardware and Software Requirements for Computational Investigations 264\u003c\/p\u003e \u003cp\u003e7.3 Typical Methods in Computational Organic Chemistry 265\u003c\/p\u003e \u003cp\u003e7.3.1 General Aspects 265\u003c\/p\u003e \u003cp\u003e7.3.2 Molecular Mechanics and Force Fields 266\u003c\/p\u003e \u003cp\u003e7.3.3 Wave- Function Methods I – Hartree–Fock Theory 267\u003c\/p\u003e \u003cp\u003e7.3.4 Wave- Function Methods II – Post- Hartree–Fock Theory 267\u003c\/p\u003e \u003cp\u003e7.3.5 Semiempirical Methods 269\u003c\/p\u003e \u003cp\u003e7.3.6 Density Functional Theory 269\u003c\/p\u003e \u003cp\u003e7.3.7 Dispersion- Corrected Density Functional Theory 271\u003c\/p\u003e \u003cp\u003e7.3.8 Typical Computational Times 272\u003c\/p\u003e \u003cp\u003e7.4 Basis Sets Used in Computational Organic Chemistry 273\u003c\/p\u003e \u003cp\u003e7.4.1 General Aspects of Basis Sets 273\u003c\/p\u003e \u003cp\u003e7.4.2 Introduction to the Mathematical Formalism in Basis Sets 274\u003c\/p\u003e \u003cp\u003e7.4.3 Polarization and Diffuse Functions 275\u003c\/p\u003e \u003cp\u003e7.4.4 Basis Set Families 276\u003c\/p\u003e \u003cp\u003e7.4.5 Effective Core Potentials (Pseudopotentials) 278\u003c\/p\u003e \u003cp\u003e7.4.6 The Basis Set Superposition Error (BSSE) 279\u003c\/p\u003e \u003cp\u003e7.5 Typical Computational Tasks in Organic Chemistry 279\u003c\/p\u003e \u003cp\u003e7.5.1 Preliminary Remarks 279\u003c\/p\u003e \u003cp\u003e7.5.2 Single- Point Calculations 281\u003c\/p\u003e \u003cp\u003e7.5.3 Geometry Optimizations 281\u003c\/p\u003e \u003cp\u003e7.5.4 Frequency Calculations 282\u003c\/p\u003e \u003cp\u003e7.5.5 Intrinsic Reaction Coordinate (IRC) Calculations 284\u003c\/p\u003e \u003cp\u003e7.5.6 Conformational Analysis 285\u003c\/p\u003e \u003cp\u003e7.6 Notation of the Model Chemistry 286\u003c\/p\u003e \u003cp\u003e7.7 The Diels–Alder Reaction as a Tutorial Case Study 286\u003c\/p\u003e \u003cp\u003e7.7.1 General Aspects and Requirements 286\u003c\/p\u003e \u003cp\u003e7.7.2 Preparing Input Files 288\u003c\/p\u003e \u003cp\u003e7.7.3 Conformational Sampling – Generation of Initial Geometries 290\u003c\/p\u003e \u003cp\u003e7.7.4 Geometry Optimizations of Starting Materials and Products 291\u003c\/p\u003e \u003cp\u003e7.7.5 Locating the Transition States 294\u003c\/p\u003e \u003cp\u003e7.7.6 Verifying the Nature of the Transition State 298\u003c\/p\u003e \u003cp\u003e7.8 More Advanced Aspects 300\u003c\/p\u003e \u003cp\u003e7.8.1 General Comments 300\u003c\/p\u003e \u003cp\u003e7.8.2 Influence of Solvation 300\u003c\/p\u003e \u003cp\u003e7.8.3 Integration Grid 302\u003c\/p\u003e \u003cp\u003e7.8.4 Standard States 302\u003c\/p\u003e \u003cp\u003e7.8.5 Treating Unpaired Electrons 303\u003c\/p\u003e \u003cp\u003e7.9 Important and Frequently Used Keywords 304\u003c\/p\u003e \u003cp\u003e7.10 Practical Considerations 304\u003c\/p\u003e \u003cp\u003e7.11 Conclusions 306\u003c\/p\u003e \u003cp\u003eReferences 306\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 NMR Prediction with Computational Chemistry 313\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eAmy T. Merrill, Wentao Guo, and Dean J. Tantillo\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 313\u003c\/p\u003e \u003cp\u003e8.1 Introduction 314\u003c\/p\u003e \u003cp\u003e8.2 Quantum- Chemistry- Based Computational NMR 315\u003c\/p\u003e \u003cp\u003e8.2.1 Methods 315\u003c\/p\u003e \u003cp\u003e8.2.1.1 Time\/Resources for Calculations 316\u003c\/p\u003e \u003cp\u003e8.2.1.2 Structural Considerations in Modeling 317\u003c\/p\u003e \u003cp\u003e8.2.1.3 Geometry Optimizations 323\u003c\/p\u003e \u003cp\u003e8.2.1.4 Calculating Isotropic Shielding Constants 324\u003c\/p\u003e \u003cp\u003e8.2.1.5 Common Pitfalls and How to Address Them 328\u003c\/p\u003e \u003cp\u003e8.2.1.6 Converting to Chemical Shifts 329\u003c\/p\u003e \u003cp\u003e8.2.1.7 Calculating Coupling Constants 330\u003c\/p\u003e \u003cp\u003e8.2.2 Confidence Analysis 330\u003c\/p\u003e \u003cp\u003e8.2.3 Computer- Aided Automated Approaches 332\u003c\/p\u003e \u003cp\u003e8.2.3.1 Case 332\u003c\/p\u003e \u003cp\u003e8.2.4 A Case Study 336\u003c\/p\u003e \u003cp\u003e8.2.5 Practicing 1 H and 13 C Chemical Shift Prediction 338\u003c\/p\u003e \u003cp\u003e8.3 Summary and Outlook 339\u003c\/p\u003e \u003cp\u003eKey References 339\u003c\/p\u003e \u003cp\u003eReferences 340\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Introduction to Programming for the Organic Chemist 347\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eJason M. Stevens\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 347\u003c\/p\u003e \u003cp\u003e9.2 Better Visualizations: Communicating Structure–Data Relationships 351\u003c\/p\u003e \u003cp\u003e9.3 Text Extraction: Automating Density Functional Theory Calculations 354\u003c\/p\u003e \u003cp\u003e9.4 Statistical Analysis: Deriving Insight from Historical Data 357\u003c\/p\u003e \u003cp\u003e9.5 Machine Learning: A Predictive Model for Deoxyfluorination 359\u003c\/p\u003e \u003cp\u003e9.6 Working with Public Datasets: Identifying Reactivity Cliffs 364\u003c\/p\u003e \u003cp\u003e9.7 Running Simulations: Process Greenness 367\u003c\/p\u003e \u003cp\u003e9.8 Application Development: Process Mass Intensity Predictor 371\u003c\/p\u003e \u003cp\u003e9.9 Machine Learning for Reaction Optimization 374\u003c\/p\u003e \u003cp\u003e9.10 Executing Robotic Tasks 378\u003c\/p\u003e \u003cp\u003e9.11 Autonomous Reaction Optimization 381\u003c\/p\u003e \u003cp\u003e9.12 Conclusion 384\u003c\/p\u003e \u003cp\u003eReferences 385\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Machine Learning for the Optimization of Chemical Reaction Conditions 393\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eA. Filipa de Almeida and Tiago Rodrigues\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 393\u003c\/p\u003e \u003cp\u003e10.1 Introduction 394\u003c\/p\u003e \u003cp\u003e10.2 Prior Art and Alternative Methods for Rational Reaction Optimization 396\u003c\/p\u003e \u003cp\u003e10.3 Reaction Optimization Using LabMate.ML 400\u003c\/p\u003e \u003cp\u003e10.3.1 Step One: Accessing the LabMate.ML Code and Installation 401\u003c\/p\u003e \u003cp\u003e10.3.2 Step Two: Initializing the Optimization Routine in LabMate.ML 402\u003c\/p\u003e \u003cp\u003e10.3.3 Step Three: Iterative Optimization Routine 404\u003c\/p\u003e \u003cp\u003e10.3.4 Examples 406\u003c\/p\u003e \u003cp\u003e10.4 Primer on Evaluation Guidelines 408\u003c\/p\u003e \u003cp\u003e10.4.1 Code and Dataset Availability 408\u003c\/p\u003e \u003cp\u003e10.4.2 Retrospective Evaluation 409\u003c\/p\u003e \u003cp\u003e10.4.3 Baselines and Comparing Tools 410\u003c\/p\u003e \u003cp\u003e10.4.4 Prospective Evaluation 412\u003c\/p\u003e \u003cp\u003e10.5 Outlook 414\u003c\/p\u003e \u003cp\u003eReferences 416\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Computer- Assisted Synthesis Planning 423\u003cbr\u003e \u003c\/b\u003e\u003ci\u003eZhengkai Tu, Itai Levin, and Connor W. Coley\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary 423\u003c\/p\u003e \u003cp\u003e11.1 Introduction to Computer- Aided Synthesis Planning 424\u003c\/p\u003e \u003cp\u003e11.1.1 Defining the Tasks and Use Cases 424\u003c\/p\u003e \u003cp\u003e11.1.2 Historical Approaches to Computer- Aided Synthesis Planning 425\u003c\/p\u003e \u003cp\u003e11.1.3 The Inflection Point of CASP Methods 425\u003c\/p\u003e \u003cp\u003e11.1.4 Preliminaries on Molecular Representation and Cheminformatics 426\u003c\/p\u003e \u003cp\u003e11.1.5 Outline of the Rest of the Chapter 428\u003c\/p\u003e \u003cp\u003e11.2 Approaches and Algorithms for Retrosynthesis 428\u003c\/p\u003e \u003cp\u003e11.2.1 Data- driven v. Expert- Driven Programs 428\u003c\/p\u003e \u003cp\u003e11.2.2 Template- Based Approaches 429\u003c\/p\u003e \u003cp\u003e11.2.3 Template- free Approaches with Graphs and Sequences 431\u003c\/p\u003e \u003cp\u003e11.2.4 Multistep Planning Algorithms 433\u003c\/p\u003e \u003cp\u003e11.3 Approaches and Algorithms for Condition Recommendation and Forward Synthesis 436\u003c\/p\u003e \u003cp\u003e11.3.1 Condition Recommendation Approaches 436\u003c\/p\u003e \u003cp\u003e11.3.2 Forward Synthesis Approaches 437\u003c\/p\u003e \u003cp\u003e11.4 Select Examples of Software Tools for CASP 439\u003c\/p\u003e \u003cp\u003e11.4.1 Open- Source Tools 439\u003c\/p\u003e \u003cp\u003e11.4.1.1 Askcos 439\u003c\/p\u003e \u003cp\u003e11.4.1.2 AiZynthFinder 440\u003c\/p\u003e \u003cp\u003e11.4.1.3 Retro* 442\u003c\/p\u003e \u003cp\u003e11.4.2 Closed- Source Tools 443\u003c\/p\u003e \u003cp\u003e11.4.3 CASP Tools for Enzymatic Catalysis 446\u003c\/p\u003e \u003cp\u003e11.4.4 Practical Considerations for CASP Programs 446\u003c\/p\u003e \u003cp\u003e11.4.4.1 Traceability to Literature Precedent 447\u003c\/p\u003e \u003cp\u003e11.4.4.2 How to Use CASP: Command Line Versus Graphical User Interface 447\u003c\/p\u003e \u003cp\u003e11.4.4.3 Data Privacy 448\u003c\/p\u003e \u003cp\u003e11.4.4.4 Customization Ability 448\u003c\/p\u003e \u003cp\u003e11.5 Case Studies 448\u003c\/p\u003e \u003cp\u003e11.5.1 Segler et al.’s Data- driven Program and A\/B Testing Success 449\u003c\/p\u003e \u003cp\u003e11.5.2 MIT’s ASKCOS Program and Robotic Synthesis Demonstration 449\u003c\/p\u003e \u003cp\u003e11.5.3 Grzybowski’s Chematica\/Synthia Program’s Experimental Validations and Acquisition 450\u003c\/p\u003e \u003cp\u003e11.6 Conclusion 451\u003c\/p\u003e \u003cp\u003eKey References 453\u003c\/p\u003e \u003cp\u003eReferences 453\u003c\/p\u003e \u003cp\u003eIndex 461\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49989881332055,"sku":"9781119855637","price":133.2,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781119855637.jpg?v=1739542148","url":"https:\/\/bookcurl.com\/products\/enabling-tools-and-techniques-for-organic-synthesis-9781119855637","provider":"Book Curl","version":"1.0","type":"link"}