During the last decades along with the development of asymmetric organocatalysis, tremendous achievements have been made in asymmetric organocatalytic domino or cascade reactions. Herein, the examples of domino or cascade reactions based on asymmetric organocatalyzed Michael addition are described. More specifically, this review aims to cover and discuss the hemi-aminoacetalyzation/acylimminium-cyclization initiated by Michael addition, and the application of this type of reactions in the synthesis of alkaloids.

A s y m m e t r i c O r g a n o c a t a l y t i c S y n t h e s i s o f I n d o l o q u i n o l i z i d i n e sAbstract: An organocatalyzed one-pot Michael addition and Pictet-Spengler sequence utilizing b-keto amide and aliphatic a,bunsaturated aldehydes was developed, which provided access to highly substituted indolo[2,3-a]quinolizidines as a mixture of keto and enol tautomers. Such tautomeric pairs were transformed into stable compounds with an E-ethylidenyl group in telescoped steps. This method was successfully applied in the synthesis of epi-geissoschizol.During our continuous development of stereoselective synthetic methods for highly substituted quinolizidines, 1 we have recently discovered a cascade reaction 2 between aromatic nucleophile-tethered activated methylene compound 1 and a,b-unsaturated aldehydes 2 catalyzed by prolinol TMS ether 3 (Scheme 1). When an aromatic aldehyde was used, the conjugate addition of 1 to 2 and subsequent acid-catalyzed Pictet-Spengler (PS) cyclization provided polycyclic enol 3 as a sole diastereomer. Moderate to good yields and good to excellent enantioselectivities were achieved. 2 However, when an aliphatic aldehyde was employed, this cascade sequence resulted in a pair of inseparable keto-enol tautomers.Scheme 1 Cascade reactions between indole-tethered activated methylene compounds 1 and a,b-unsaturated aldehydes 2