Modular Synthesis of Fused Indole Derivatives

Significance

Complementary routes to strained doubly cycloalkyl-fused indole derivatives using modern cross-coupling methodology are reported. Stille coupling of 7-stannylated indoline with 2-iodo cyclic enones leads to the key intermediate A which, by reduction and LiHMDS-mediated triflation using Comins’ excellent reagent, gives isomeric triflates. The latter compounds are deprotected and transformed to the tetracyclic indole derivative B by the Buchwald-Hartwig C-N coupling tactic or, directly, by acid-catalyzed cyclization. The overall yields are reasonable but the scope in terms of benzene-moiety substitution and variable cycloalkyl ring size remains to be explored.