Highly Enantioselective Tandem Michael Addition of Tryptamine‐Derived Oxindoles to Alkynones: Concise Synthesis of Strychnos Alkaloids

Abstract

Ah ighly enantioselective tandem Michael addition of tryptamine-derived oxindoles to alkynonesw as developed by taking advantage of achiral N,N'-dioxide Sc(OTf) 3 catalyst. The reaction enables the facile preparation of enantioenriched spiro[pyrrolidine-3,3'-oxindole] compounds,w hich provides an ovel strategy for the synthesis of monoterpenoid indole alkaloids.A sademonstration, the asymmetric synthesis of strychnos alkaloids [(À)-tubifoline,( À)-tubifolidine,( À)dehydrotubifoline] was achieved in 10-11 steps.Scheme 2. Substrate scope with respect to alkynones. [a] The reaction was performed with CH 2 Cl 2 as solvent. Cy = cyclohexanyl; Ph = phenyl.Scheme 3. Asymmetric synthesis of strychnos alkaloids.

Novel Pathway for the Synthesis of 20-Deethyltubifolidine

“…The existence of the 1,5-methanoazocino [4,3-b]indole structure in another type of alkaloids has also led further progress of paths to this frame, which could be an advantageous exemplary for the access to key infrastructure and analogues of Strychnos alkaloids (Figure 1) [9,10]. These alkaloids constitute a key subgroup of the Strychnos alkaloids [11][12][13][14][15][16][17][18][19][20] and belong to moneterpenoid indole alkaloids, which are represented by the existence of the 1,5-methanoazocino [4,3-b] indole, including the tetracyclic ring system. Our aim to synthesize deethyltubifolidine is predicated on the structure of a 1,5-methanoazocino [4,3-b] indole skeleton, the basic component of deethyltubifolidine and other type alkaloids, by recognizing tetrahydrocarbazole analogues transporting a monoalkyl nitrile side chain (1) with tetrachloro-1,4benzoquinone (TCB) [21][22][23][24][25][26].…”