Reversed Allylation of 3-Alkenyl Indoles Using Allyl Boronic Acids: Access to Tryptamine Based Alkaloids

All-carbon quaternary and tertiary stereocenters connected at the C2-position of functionalizable C3-alkylated indole nucleus are commonly occurring frameworks found in many indole alkaloids of medicinal importance. Their direct access is scarcely reported, a long-standing problem, and developing a unique yet simple method can pave the pathway to an entirely different retrosynthetic route for the total synthesis of these alkaloids. Herein, this problem is addressed by developing an unprecedented branch-selective allylation strategy employing a broad range of structurally and electronically different 3-alkenyl-indoles and allylboronic acids. The use of readily accessible starting precursors renders this method attractive for the total synthesis of indole alkaloids. The present strategy shows excellent functional group tolerance, atom economic, redox-neutral, scalable and easy to operate. The DFT calculation on the possible transition states indicated that allylboronic acid acts as a nucleophile rather than a more reactive boroxine. Mechanistically, this strategy is designed by exploiting the loss as well as regaining the indole's aromaticity. The utility of this method is demonstrated in the total syntheses of seven prenylated tryptamine alkaloids and the first total syntheses of dimeric indole alkaloids, fluevirine E and mucronatin B.