Palladium Catalyzed Allylic Substitution of Acyloxypyrrolinones

Enantiomerically pure alkoxypyrrolinones have been shown to be facile building blocks for a variety of stereoselective syntheses involving Diels-Alder cycloadditions , 1,3dipolar reactions, conjugate additions, and acyliminium ion intermediates. In particular the application in the asymmetric synthesis of alkaloids based on N-acyliminium ion chemistry is of current interest. For example, (R)-1-acetyl-5-isopropoxy-3-pyrrolin-2-one (compound (–)8.3a (R = i-Pr) in Scheme 8.1) has been used by Hiemstra and Speckamp as an intermediate in the synthesis of gelsemine. However, the stereoselective synthesis from (S)-malic acid is laborious and more practical routes would be desirable. In Chapter 3 and 4, we reported a simple and efficient enzymatic methodology to obtain enantiomerically pure acyloxypyrrolinones 8.2 from hydroxypyrrolinones 8.1. In this process both enantiomers of an acyloxypyrrolinone can be obtained by the same enzyme (Candida antarctica lipase B CAL) using either an esterification (Scheme 8.1) or a transesterification. Although compounds 8.2 have been applied with success in various stereoselective transformations, they are not suitable as acyliminium ion precursors (see Chapter 7). In order to generate an acyliminium ion the acyl group on nitrogen must be removed. This is possible with an alkoxy group at the 5-position, but not with a more sensitive acyloxy group (see Chapter 7). In the previous chapter we already mentioned the discovery of a method to convert acyloxypyrrolinones 8.2 stereospecifically to alkoxypyrrolinones 8.3 by means of a palladium catalyzed allylic substitution. This way the enzymatic method can be combined with a palladium catalyzed allylic substitution to generate optically active alkoxypyrrolinones (Scheme 8.1), which can readily be transformed to acyliminium ion precursors.