Fine Chemical Synthesis – Homogeneous

Abstract

Use of homogeneous catalysis for fine chemical production is rapidly expanding. Advantages of its use are high chemo‐, regio‐, and enantioselectivity, which can be tuned by ligand design. Use of catalysis also leads to cleaner production processes. A third adavantage are the mild conditions that are often possible, which allows the application of homogeneous catalysis as a late step in a total synthesis. Often protective groups are unnecessary. While in the past homogeneous catalysis was mainly used for second‐generation processes of rather large products, it is now increasingly used in the first production processes. This is related to an increased availability of catalysts with sufficient rate and stability. In addition, high throughput experimentation allows rapid screening of these catalysts. While several hundred reactions are known that are catalyzed by homogeneous transition metal catalysts, only a limited number of these are applied for fine chemical production. They can be subdivided into four main classes: hydrogenation, carbon–carbon bond formation, carbon–heteroatom bond formation, and isomerization reactions. Important requirements are rate of the reaction, expressed as turnover frequency (TOF) and catalyst stability, expressed as turnover number (TON). Examples are given of many processes on scales varying from 1 to 10,000 ton/year. Recycle of catalysts is rarely practiced in fine chemical production, as the extra unit operations involved does not outweigh the gains of a reuse of the catalyst. Immobilization of homogeneous transition metal catalysts often leads to loss of activity and selectivity. In addition catalyst deactivation makes this an unattractive option. Emphasis is on the development of very fast catalysts. The metal is usually sent to the producer for reclaiming and refining. Two‐phase catalysis might be a viable option for catalyst recycle. Double digit growth is expected in the coming years for the application of homogeneous catalysis in the production of fine chemicals.