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