Indole Synthesis via Allenyl Ester; Enantioselective Total Synthesis of Geissoschizoline

Abstract

Methyl indole-2-acetate is a key structural motif in plant-derived indole alkaloids. In this study, a mild and efficient protocol is presented for its preparation using readily available aniline derivatives, which are synthesized from malonic esters. The reaction proceeds via an allenyl ester intermediate, with NaCN-mediated indole formation occurring at ambient temperature, affording high yields and broad substrate scope. The synthetic utility of this approach is demonstrated through the asymmetric total synthesis of geissoschizoline, a Strychnos-type monoterpenoid indole alkaloid. This synthesis not only establishes a novel route to monoterpenoid indole alkaloids but also achieves complete stereochemical control in constructing the six chiral centers of the natural product.