Palladium-catalyzed C-N and C-O coupling - A practical guide from an industrial vantage point

The palladium-catalyzed coupling of amines with aryl halides or aryl alcohol derivatives, commonly dubbed Buchwald-Hartwig amination, has matured from a synthetic laboratory procedure to a technique that is widely used in natural product synthesis as well as in other fields of academic interest. Furthermore, due to the versatility and reliability of this reaction, researchers in industrial environments have included this methodology in their toolbox as a standard procedure for the synthesis of amine derivatives. Therefore, it is not surprising that first industrial processes up to ton-scale have been performed using this cross-coupling reaction. The authors who are involved in the application of this reaction to industrial processes on this scale give an overview of the recent developments in this field of chemistry, also including fundamental principles, with a special focus on the industrial approach and issues to be considered relevant in scaling-up this transition metal-catalyzed chemistry. This review differs from the already existing excellent academic reviews by focusing on the practical problems arising during implementing the methodology in an industrial environment as well as giving practical hints to this end. 1 Introduction 2 Components of the Catalytic System 2.1 Ligands 2.2 Palladium Precursors 2.3 Bases 2.4 Solvents/Temperature 3 C-N Coupling of Amines 3.1 Motivation 3.2 Description of Table 2 3.3 General Statements 3.4 Aryl Bromides 3.5 Aryl Chlorides 3.6 Aryl Iodides 3.7 Arenesulfonic Acid Esters 3.8 Pyridyl Halides 3.9 Other Heteroaromatic Halides 3.10 Catalyst Activity 3.11 Weak Bases 3.12 Low Temperatures 3.13 New Bases 3.14 Amine Nucleophiles 4 Coupling Reactions with Non-Amine Nucleophiles 4.1 Coupling of Amides, Sulfonamides, Carbamates and Ureas 4.2 Coupling with Sulfoximines, Hydrazines and Guanidines 4.3 Ammonia Surrogates 5 Applications of Buchwald-Hartwig Amination 5.1 Synthesis of Natural Products and Analogues as Active Agents 5.2 Applications in Ligand Synthesis 5.3 Applications in Material Science 6 C-O Coupling 7 Contributions Elucidating the Mechanism 7.1 C-N Coupling 7.2 C-Amide Coupling 7.3 C-O Coupling 8 Overview of Current Review Articles 9 Conclusions.