Fukuyama Indole Synthesis

Abstract The synthesis of 3‐substituted or 2,3‐disubstituted indole derivatives from a tributyltin‐based intramolecular radical cyclization of o ‐alkenylphenylisocyanides (or isonitriles or 2‐isocyanostyrene derivatives) is generally referred to as the Fukuyama indole synthesis. This synthesis reaction has already been upgraded to a second generation. The second generation of the Fukuyama indole synthesis involves the intramolecular radical cyclization of 2‐alkenylthioanilides. The third method has been reported to involve a Sonogashira coupling of 2‐iodoaniline, with terminal alkynes to afford 2‐alkynylanilines. The triethylborane (Et 3 B) has been found to be an effective radical initiator, from which a wide range of both acid‐ and base‐sensitive groups—such as ester, THP ether, and β‐lactam—can be implemented at indole's 2‐ or 3‐position. The Fukuyama indole synthesis has been successfully applied to the total synthesis of several natural alkaloids containing indole moieties.