Enantioselective Hydrogenations with Chiral Titanocenes.docVIP

Molecules 2005, 10, 587-619 molecules ISSN 1420-3049 Review Enantioselective Hydrogenations with Chiral Titanocenes Oleksiy Vassylyev, Anthony Panarello and Johannes G. Khinast* Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854- 8058, USA. Tel.: (+1) 732-445-2970, Fax: (+1) 732-445-2581 * Author to whom correspondence should be addressed; e-mail khinast@ Received: 20 July 2004 / Accepted: 8 October 2004 / Published: 14 July 2005 Abstract: In this review article chiral titanocenes and their application for the enantioselective hydrogenations of different unsaturated compounds are discussed, with a special emphasis on the kinetics and the practicality of the developed systems. The nature of enantioselectivity and the hydrogenation mechanisms are reviewed as well. Catalyst immobilization and the different immobilization techniques are examined. Keywords: Titanocenes, hydrogenation, alkenes, imines, ketones. 1. Introduction Chiral compounds are important products or intermediates in the pharmaceutical, agrochemical and fine chemical industries [1], with the world market for chiral fine chemicals and drugs surpassing $6 billion in 2000 at an annual growth rate significantly larger than 10% [2]. Thus, the continuous increase in the demand for chiral precursors and chemicals requires the development of clean, cost- effective and reliable technology to make these compounds on an industrial scale. Biotechnological processes are used to make many complex chiral molecules, including small-molecule drugs (in contrast to the large-molecule drugs such as proteins and hormones). However, for the synthesis of small-molecule compounds, synthetic chemistry is increasingly accepted as the more effective approach, as it circumvents the drawbacks of biotechnological processes (e.g., low yields, sensitive media, etc.), while build