It is often observed that different enantiomers elicit different biological responses. The absolute control of stereochemistry is therefore frequently essential in the synthesis of a number of important pharmaceuticals, food additives and pheromones. Catalytic asymmetric DielsAlder reactions represent an almost uniquely attractive means of achieving such control. The importance of the parent reaction and its various heteroatom varients in organic synthesis cannot be understated. The preparation of pharmacologically important steroids, alkaloids and sesquiterpenes are just a few of the many applications of this reaction. Multifunctional products containing up to four chiral centers may be obtained, thus allowing rapid elaboration of simple starting materials to complex products. The possibility that these reactions can be made enantioselective through the use of a minute amount of optically active catalyst continues to pose a fascinating and formidable challenge to organic chemists. A comprehensive program of development of optically active Lewis acidic catalysts for this purpose is described herein. The key features of proposed research include 1/ the preparation of several new types of catalyst auxiliary, including optically active phenoxy, aryloxy/Noxide and aryloxy/phosphine oxide auxiliaries, 2/ their use in constituting Lewis acidic complexes of A1(III), Sn(IV), Eu(III) and notably, Sc(III) and Y(III), which have been little studied but which offer special advantages of structure and NMR sensitivity, and 3/ detailed physiochemical investigations of the catalytic intermediates. The proposed catalysts are predicted to engender high enantiomeric excesses for a wide variety of DielsAlder reactions. Initial applications will focus on the preparation of optically active bicyclo(2.2.1)heptanes of established synthetic utility.
