High-throughput and parallel screening methods are being used more and more extensively in various areas of chemistry, including enantioselective synthesis.1 This due to the extremely small energy differences determining such critical factors as enantioselectivity. Yue and Nugent2 (Scheme 1) and Boulton et al.3 (Scheme 2) recently described two examples, which illustrate this quite well. In both cases, completely unexpected solutions were identified for the problems studied. A conformationally flexible ligand, 2,4-bis(diphenylphosphino)pentane 3, was found to be optimal in the enantioselective hydrogenation of 3-alkylidenlactams.2 Phanephos 10 was found to be optimal in the hydrogenation of an (E)-4,4-diaryl-3-butenoate ammonium salt 8. This ligand had shown lower enantioselectivities in comparison to phospholane-type ligands in earlier hydrogenation studies within this group.3 In recent years, industrial applications of asymmetric hydrogenation4 have increased considerably and many examples have been summarized in the literature.5 Information, however, on catalyst identification procedures, route selection, and scale-up is usually scattered and sometimes not easily available. We have been especially interested in understanding which strategies are used for route selection and which for optimization and scale-up and why (availability of equipment, sensitivities, reproducibility, size of parameter space that can be tested, etc). We will focus this review on these issues. We will also primarily focus on work done in the last 2-3 years, because this has been a particularly fruitful time in this area of research. Due to the historical development of this field, many descriptions of this type of work can be found using keywords such as “combinatorial chemistry” or “highthroughput screening”. A more detailed analysis, however, shows that work done in such areas as enantioselective hydrogenation, an area of particular interest in industrial as well as academic laboratories, does not actually fit well in the original definitions of these terms. For example, due to the nature of the chemistry involved in this area, highthroughput often involves relatively modest numbers of reactions, in comparison to some of the biological screening methods described in the literature. A large amount of work has been done, as shown in the examples above, using only a relatively limited number of parallel reactors. In this review, we wish to discuss such strategies using the example of enantioselective hydrogenation. We wish to order them according to the stages of process development, which have been discussed in more general terms for fine chemical synthesis a number of times in the literature,6 and to analyze their strengths and weaknesses based on the needs of the different stages. The methodologies of interest to us focus on route selection and the first stages of scale-up. Constraints to be considered included raw material costs, time pressure, and the necessity for using existing equipment. Raw material costs, such as ligand costs in enantioselective synthesis, can be a significant factor in the decision to commercialize or not. The time available for identifying and developing a route for chiral intermediates has become considerably shorter in the last years, as pharmaceutical companies attempt to reduce their own development times. The fact that many optically * To whom correspondence should be addressed. Tel: +49 621 60-78181. Fax: +49 621 66-78181. E-mail: rocco.paciello@basf.com.