Enantioselective Synthesis of Indoloquinolizidines via Asymmetric Catalytic Hydrogenation/Lactamization of Imino Diesters

We have developed a highly efficient cascade sequence for asymmetric synthesis of indoloquinolizidines with absolute control of cis-H2/H12b relative geometry in good to excellent yields and excellent enantioselectivities. This cascade was triggered by the Ru(II)-TsDPEN-catalyzed asymmetric transfer hydrogenation of imino diesters, with subsequent spontaneous lactamization with discrimination between the two cliastereotopic 2-alkoxy-2-oxoethyl groups. The synthetic utility of this strategy was demonstrated by the asymmetric preparation of dihydrocorynantheol, geissoschizol, and isogeissoschizol.