Development of Sustainable Biocatalytic Reduction Processes for Organic Chemists

Among the different factors contributing to a good chemical manufacturing process, the process efficiency and specifically volume–time output in terms of reactor capacity and cycle time, respectively, have been given the largest weight – among the conversion costs, with material cost being the second [1]. Raw materials or intermediates with a higher oxidation state than the target products are often preferred to oxidations on an industrial scale due to process safety and toxicity concerns [2] and therefore have to be transformed in one or more reduction processes to the desired oxidation state; the importance to use as few redox steps as possible in a multistep synthesis has been outlined in the concept of redox economy [3–5]. Nonselective reductions often require additional protection–deprotection steps influencing process economy and leading to waste that scales stoichiometrically with increasing production. Therefore, the reduction of the number of synthetic steps by highly selective and sustainable reduction processes in organic synthesis is of key importance and has influenced the development of reduction processes, reagents, and tools (see Figure 1.1 for route selection in reductions). The variety of reducing agents, from simple molecular hydrogen with chiral or nonchiral catalysts in catalytic hydrogenations to reducing equivalents from inorganic or organic reagents with the required reducing power for the specific reduction, has enabled a large number of selective reduction reactions. The scope of reducing agents has been greatly expanded from the use of hydrogen gas in catalytic hydrogenation, the preparation of nongaseous reducing agents like lithium aluminum hydride and sodium borohydride, to the development of highly selective boranes by HC Brown, representing a milestone of organic synthesis and optically active organoboranes and providing versatile synthetic methodologies for asymmetric reductions of prochiral ketones, whereby the chiral auxiliary is recovered in an easily recyclable form [6–8]. With the growing importance of safety, health, and environment aspects, the nature of the reducing agents, the transition from stoichiometric to catalytic reductions, and the development of sustainable chemistry