Chiral Secondary Amine Catalyzed Asymmetric Synthesis Of Indole Derivatives

Indole scaffolds are present in many natural products and therapeutic agents.Great efforts have been devoted to asymmetric synthesis of optically pure indolederivatives, leading to the appearance of many elegant catalytic methods. In this thesis,a series of chiral organocatalysts were synthesized. A chiral secondary amine catalystwas employed for the asymmetric Michael additions of aliphatic aldehydes toindolylnitroalkenes and hetero-Diels–Alder reaction of trans-α-cyano-α,β-unsaturatedketone with crotonaldehyde, which provide tryptamine precursors and3,4-dihydro-2H-pyran respectively, two kind of indole derivatives.Asymmetric organocatalysis has become a powerful tool for the synthesis ofoptically active compounds. Organocatalysts have a great deal of advantages. Forexample, they are inexpensive and readily available, as well as inert in air. Herein wesynthesized some organocatalysts according to the literatures such as proline derivedsecondary amine, cyclohexanediamine or quinine derived tertiary amine thiourea andbinaphthol derived phenol.Chiral secondary amine catalyzed asymmetric Michael addition of aliphaticaldehydes to indolylnitroalkenes is mainly discussed in this thesis. The Michaeladdition furnished tryptamine precursors in high yield with excellent diastereo-andenantioselectivity. Considering the versatile transformation of nitro-and formyl-groups, optically active1,4-nitro alcohol,1,4-amino alcohols,3,4-disubstitutedpyrrolidine and tryptamine derivative were readily synthesized by stepwise systematictransformations as synthetic usefulness of this methodology.The asymmetric hetero-Diels–Alder reaction of trans-α-cyano-α,β-unsaturatedketone and crotonaldehyde using the same amine catalyst was probed as well. Thedesired indolyl3,4-dihydro-2H-Pyran was obtained in moderate yield with moderate stereoselectivity. Many acids as additives were screened to improve the reactivity andstereochemistry control. Investigation is still ongoing to find appropriate substrates orcatalysts for this asymmetric reaction.