Total synthesis industrial type

To date, only a few iridium catalysts have been applied to industrially relevant targets, especially on the larger scale. It is likely that several types of Ir catalyst are, in principle, feasible for technical applications in the pharmaceutical and agrochemical industries. At present, the most important problems are the relatively low catalytic activities of many highly selective systems and the fact, that relatively few catalysts have been applied to multifunctional substrates. For this reason, the scope and limitations of most catalysts known today have not yet been explored. For those in academic research, the lesson might be to employ new catalysts not only with monofunctional model compounds but also to test functional group tolerance and-as has already been done in some cases-to apply the catalysts to the total synthesis of relevant target molecules. 

Salinomycin (3), isolated from Streptomyces albus by Miyazaki et al. in 1972 [18], is very important as an anticoccidial agent in the poultry industry, and the first total synthesis was achieved by Kishi et al. in 1981 [19]. Quite recently, the second and stereoselective synthesis of 3 was completed [20]. Coupling of 63 and 64 into the C10-C30 fragment (65) followed by its aldol condensation with 62 was good way to complete a new total synthesis of 3, in which the benzyl-type protecting groups acted a crucial role (Scheme 19). 

An advantage of this total synthesis is the use of optically pure ketone S-S, commercially available and produced on an industrial scale by a biocatalytic process with L-proline as a cheap organocatalyst (see Chap. 8). Scheme 14.2 indicates only the reagents and conditions required for step i, the Heck-type ring closure of 13-14. 

We have already met many examples of catalyzed reactions, using acids, bases, solid metals, or metal complexes. There are many types—indeed it s now difficult to find a total synthesis where a catalyzed reaction was not used at some stage. The advantages of catalyzed reactions over stoichiometric ones are many. Firstly, the reaction will proceed more rapidly, and this may be translated into an ability to perform the transformation under much milder than usual conditions. For example, acetonitrile, MeCN, is hydrolyzed only slowly by base at 100 °C, but in the complex [Co(NH3)5(MeCN)] +, the acetonitrile is hydrolyzed instantaneously at room temperature. Milder reaction conditions, in industrial processes, translate into lower cost, greener processes, and improved safety. 

Ethylene oxide was first manufactured industrially by this route in 1938 by Union Carbide, which acquired the patents published by Lefort in 1931 concerning the synthesis of ethylene oxide by direct oxidation. Two years later, in 1940. this type of process accounted for 10 percent of total installed capacity at the time in the United States, and, since 1973, the process is employed by nearly all plants in operation or planned throughout the world. 

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