SUSTAINABLE CATALYSIS: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries -- Contents -- Foreword -- Preface -- Contributors -- Abbreviations -- 1 Catalytic Reduction of Amides Avoiding LiAlH4 or B2H6 -- 1.1 INTRODUCTION -- 1.2 AMIDES -- 1.3 IMPORTANCE OF AMIDE REDUCTIONS IN PHARMACEUTICAL SYNTHESIS -- 1.4 HETEROGENEOUS AMIDE HYDROGENATION -- 1.5 HOMOGENEOUS AMIDE HYDROGENATION -- 1.5.1 Hydrogenation of Primary Amides -- 1.5.2 Hydrogenation of Secondary Amides -- 1.5.3 Tertiary Amides -- 1.5.4 Scope of Ru/Triphos Amide Hydrogenation -- 1.5.5 Hydrogenation of Diacids in the Presence of Amines -- 1.5.6 Homogeneous Amide Hydrogenation Mechanism -- 1.5.7 Amide C - N Cleavage by Hydrogenation -- 1.6 HYDROSILATION -- 1.6.1 Rhodium-Catalyzed Reduction of Amides Using Silanes -- 1.6.2 Ruthenium-Catalyzed Reduction of Amides Using Silanes -- 1.6.3 Platinum-Catalyzed Reduction of Amides Using Silanes -- 1.6.4 Molybdenum-Catalyzed Reduction of Amides Using Silanes -- 1.6.5 Indium Bromide-Catalyzed Reduction of Amides Using Silanes -- 1.6.6 Iron-Catalyzed Reduction of Amides Using Silanes -- 1.6.7 Zinc-Catalyzed Reduction of Amides Using Silanes -- 1.7 CONCLUSIONS AND FUTURE PERSPECTIVES -- REFERENCES -- 2 Hydrogenation of Esters -- 2.1 INTRODUCTION -- 2.2 HYDROGENATION OF ALIPHATIC ESTERS -- 2.3 HYDROGENATION OF LACTONES -- 2.4 HYDROGENATION OF AROMATIC ESTERS -- 2.5 HYDROGENATION OF FURANOIC ESTERS -- 2.6 HYDROGENATION OF CHIRAL ESTERS (BASE-FREE CONDITIONS) -- 2.7 CONCLUSIONS -- REFERENCES -- 3 Synthesis of Chiral Amines Using Transaminases -- 3.1 IMPORTANCE OF CHIRAL AMINES -- 3.1.1 Challenges with Chemocatalytic Synthesis of Chiral Amines -- 3.2 TRANSAMINASES -- 3.2.1 Transaminase Mechanism -- 3.2.2 Transaminase Selectivity -- 3.3 TRANSAMINASE-CATALYZED RESOLUTION OF RACEMIC AMINES.

3.4 TRANSAMINASE-CATALYZED ASYMMETRIC SYNTHESIS OF AMINES -- 3.5 CONCLUSIONS -- REFERENCES -- 4 Development of a Sitagliptin Transaminase -- 4.1 INTRODUCTION -- 4.2 CREATING ACTIVITY -- 4.3 TRANSAMINASE EVOLUTION -- 4.4 PROCESS OPTIMIZATION -- 4.5 A GENERAL AMINATION METHODOLOGY -- 4.6 CONCLUSION AND OUTLOOK -- 4.7 PROCEDURES -- 4.7.1 Transaminase Reaction at 1 kg Reaction Scale -- 4.7.2 FiltrationWorkup -- 4.7.3 Direct Extraction Workup -- REFERENCES -- 5 Direct Amide Formation Avoiding Poor Atom Economy Reagents -- 5.1 INTRODUCTION -- 5.2 MECHANISM FOR BORONIC AND BORIC ACID CATALYSIS -- 5.3 BORIC ACID-BASED CATALYSIS -- 5.4 BORONIC ACID-BASED CATALYSIS -- 5.5 TRIAZINE-BASED REAGENTS -- 5.6 TITANIUM(IV)-BASED REAGENTS -- 5.7 ANTIMONY-BASED REAGENTS -- 5.8 HETEROGENEOUS CATALYSTS AND MICROWAVE-ASSISTED AMIDE SYNTHESIS -- 5.9 SUMMARY AND FUTURE DIRECTIONS -- REFERENCES -- 6 Industrial Applications of Boric Acid and Boronic Acid-Catalyzed Direct Amidation Reactions -- 6.1 INTRODUCTION -- 6.2 THE SYNTHESIS OF EFAPROXIRAL UTILIZING A DIRECT AMIDATION REACTION -- 6.3 DIRECT AMIDATION EXAMPLES FROM DR. REDDY'S LABORATORIES -- 6.4 DIRECT AMIDATION EXAMPLES FROM PFIZER -- 6.5 POTENTIAL TOXICITY OF BORIC ACID -- 6.6 CONCLUSIONS -- ACKNOWLEDGMENT -- REFERENCES -- 7 OH Activation for Nucleophilic Substitution -- 7.1 INTRODUCTION -- 7.2 FORMATION OF C - C BONDS FROM ALCOHOLS -- 7.3 FORMATION OF C - N BONDS FROM ALCOHOLS -- REFERENCES -- 8 Application of a Redox-Neutral Alcohol Amination in the Kilogram-Scale Synthesis of a GlyT1 Inhibitor -- 8.1 INTRODUCTION -- 8.2 BACKGROUND AND INITIAL SYNTHETIC WORK -- 8.3 FIRST-GENERATION SYNTHESIS OF 10 -- 8.4 FIRST APPLICATION OF IR CHEMISTRY AND INITIAL PROCESS DEVELOPMENT EFFORTS -- 8.5 PROCESS OPTIMIZATION OF THE AMINATION REACTION -- 8.5.1 Reliability Optimization -- 8.5.2 Catalyst Loading Optimization.

8.5.3 Solvent Optimization and Additional Parameters -- 8.5.4 Kilogram-Scale Runs under Optimized Conditions -- 8.6 MECHANISTIC DISCUSSION -- 8.7 IRIDIUM CONTROL -- 8.8 FINAL COMMENTS -- ACKNOWLEDGMENTS -- REFERENCES -- 9 Olefin Metathesis: From Academic Concepts to Commercial Catalysts -- 9.1 INTRODUCTION -- 9.2 RECOVERY AND REUSE OF RU-BASED METATHESIS CATALYSTS: THE ACADEMICS' VIEW -- 9.3 APPLICATION OF RUTHENIUM METATHESIS CATALYSTS IN WATER -- 9.4 SUMMARY AND OUTLOOK -- ACKNOWLEDGMENTS -- REFERENCES -- 10 Challenge and Opportunity in Scaling-up Metathesis Reaction: Synthesis of Ciluprevir (BILN 2061) -- 10.1 INTRODUCTION -- 10.2 SYNTHESIS OF CILUPREVIR (BILN 2061) AND CRITICAL CHALLENGES -- 10.3 PREPARATIONS OF BUILDING BLOCKS -- 10.4 THE FIRST GENERATION CILUPREVIR (BILN 2061) PROCESS -- 10.5 CHALLENGES IN SCALING UP THE RCM REACTION -- 10.6 DEVELOPMENT OF A PRACTICAL AND SCALABLE RCM PROCESS -- 10.7 THE SECOND GENERATION CILUPREVIR (BILN 2061) PROCESS -- 10.8 CONCLUSION -- REFERENCES -- 11 C-H Activation of Heteroaromatics -- 11.1 INTRODUCTION -- 11.2 DIRECT ARYLATION -- 11.2.1 C - H/ C - X Coupling -- 11.2.2 C - H /C - M Coupling -- 11.2.3 C - H/C - H Coupling -- 11.3 DIRECT ALKENYLATION -- 11.3.1 Coupling with Alkenyl Halides -- 11.3.2 Coupling with Alkenes (Fujiwara - Moritani Reaction) -- 11.3.3 Coupling with Alkynes (Hydroarylation) -- 11.4 DIRECT ALKYNYLATION -- 11.4.1 Coupling with Alkynyl Halides or Pseudohalides -- 11.4.2 Coupling with Terminal Alkynes -- 11.5 DIRECT ALKYLATION -- 11.5.1 Benzylation and Allylation -- 11.5.2 Alkylation with Unactivated Systems -- 11.6 CONCLUSION -- REFERENCES -- 12 The Discovery of a New Pd/Cu Catalytic System for C-H Arylation and Its Applications in a Pharmaceutical Process -- 12.1 INTRODUCTION -- 12.2 DEVELOPMENT OF INITIAL PROCESS FOR THE AGONIST OF S1P1.

12.3 DEVELOPMENT OF C - H ARYLATION FOR THE SYNTHESIS OF AMG 369 -- 12.3.1 Initial Results -- 12.3.2 Discovery of a New Cocatalyst -- 12.3.3 Applications to the Synthesis of AMG 369 -- 12.3.4 Latest Developments and Future Perspective -- 12.4 CONCLUSION -- REFERENCES -- 13 Diarylprolinol Silyl Ethers: Development and Application as Organocatalysts -- 13.1 INTRODUCTION AND BACKGROUND -- 13.2 ENAMINE INTERMEDIATE -- 13.2.1 Michael Reaction -- 13.2.2 Acetaldehyde as Nucleophile -- 13.2.3 a-Oxidation Using Benzoyl Peroxide -- 13.2.4 Tandem Reaction Between Nitro-olefin and Pentane-1,5-dial -- 13.2.5 Multicomponent Reactions -- 13.2.6 [6+2] Cycloaddition -- 13.3 IMINIUM ION INTERMEDIATE -- 13.3.1 Diels-Alder and Ene-Type Reactions of Cyclopentadiene -- 13.3.2 Nitroalkane as a Nucleophile -- 13.3.3 Nitroethanol as Nucleophile -- 13.3.4 Formal Aza- and Carbo-[3+3] Cycloaddition -- 13.4 FORMAL C - H INSERTION -- 13.5 REACTIONS IN THE PRESENCE OFWATER -- 13.6 SYNTHESIS OF BIOLOGICALLY ACTIVE MOLECULES -- 13.6.1 Synthesis of ( - )-b-Santalol -- 13.6.2 Synthesis of Oseltamivir -- 13.6.3 Synthesis of ABT-341 (127) -- 13.7 CONCLUSION -- REFERENCES -- 14 Organocatalysis for Asymmetric Synthesis: From Lab to Factory -- 14.1 INTRODUCTION -- 14.2 PREPARATION OF TELCAGEPANT, AN APPLICATION OF IMINIUM ORGANOCATALYSIS -- 14.2.1 Background and Synthetic Strategy -- 14.2.2 Preliminary Results, Identification of By-products, and Reaction Pathway Consideration -- 14.2.3 "Cocktail" Cocatalysts in Non-alcohol Solvents -- 14.2.4 The Use of Crude Jørgensen - Hayashi Catalyst -- 14.2.5 Evolution to a Streamlined Through-process -- 14.2.6 Completion of Telcagepant Synthesis -- 14.3 PREPARATION OF MK-8613, APPLICATION OF ASYMMETRIC MICHAEL ADDITION CATALYZED BY DESMETHYL QUINIDINE -- 14.3.1 Synthetic Target and Strategy Analysis.

14.3.2 A Practical Process to Prepare Catalyst DMQ -- 14.3.3 Substrate-Specific Process Evolution -- 14.3.4 Completion of MK-8613 Synthesis -- 14.4 CONCLUSIONS -- ACKNOWLEDGMENTS -- REFERENCES -- 15 Catalytic Variants of Phosphine Oxide-Mediated Organic Transformations -- 15.1 GENERAL INTRODUCTION -- 15.2 WITTIG CHEMISTRY -- 15.3 AZA-WITTIG CHEMISTRY -- 15.4 MITSUNOBU CHEMISTRY -- 15.5 APPEL HALOGENATIONS -- 15.6 CONCLUSIONS -- REFERENCES -- 16 Formation of C-C Bonds Via Catalytic Hydrogenation and Transfer Hydrogenation -- 16.1 INTRODUCTION: MINIMIZING PREACTIVATION FOR SYNTHETIC EFFICIENCY -- 16.2 CARBONYL AND IMINE VINYLATION -- 16.3 CARBONYL ALLYLATION AND PROPARGYLATION -- 16.4 ALDOL, MANNICH, AND RELATED PROCESSES -- 16.5 FUTURE DIRECTIONS -- ACKNOWLEDGMENTS -- REFERENCES -- Index.