Combined Iminium-Enamine Catalyzed Approaches

It has been shown in this chapter that combined iminium-enamine catalyzed approaches offer the potential to achieve complex (multistep) transformations in a single operational step, thus giving access to high structural complexity combined with excellent effectivity. In addition, it was pointed out also that organocatalysis can be used successfully when combined with metal catalysis e.g. metathesis). Although these complex approaches have been pursued only for the last few years, the results obtained so far are very promising and thus this methodology should be applied more widely in the future (Table 3). 

The examples depicted so far have made use primarily of single organocatalytic transformations conducted typically quite early in the multi-step sequences applied towards the syntheses of complex natural products. In contrast, more and more reports describing organocatalytic cascade reactions or combined approaches using different organocatalytic key transformations to achieve a complex synthesis have been reported over the last several years (30, 32, 176-178). In this chapter, the application of combined enamine-catalyzed approaches for the syntheses of natural products will be described. Examples using different activation modes (e.g. enamine and iminium activation) will be discussed later. 

Our theoretical investigation regarding the understanding of the conversion of iminium into enamine in the framework of a proline-catalyzed aldol reaction emphasizes that the reactive force field (FF), ReaxFF, used in combination with molecular dynamics (MD) simulations is a relevant method to investigate the mechanism of proton transfers in iminium-enamine conversions. This approach should be extended to model other steps of proline-catalyzed... 

---