Synthetic Access to 3,5,7-Trisubstituted Indoles Enabled by Iridium­-Catalyzed C–H Borylation

Abstract

A one-pot conversion of 3-substituted indoles into their 5,7-diboryl derivatives is reported. The simultaneous functionalization of the C5-H and C7-H sites is achieved using an iridium-catalyzed triborylation-protodeborylation sequence. The 5,7-diborylindoles are useful intermediates that can be readily derivatized into a variety of indoles possessing the rare 3,5,7-trisubstitution pattern, including the natural product (+)-plakohypaphorine C.

Synthesis of three Tricholoma-derived indoles via an ortho-quinone methide

“…This desired transformation aligns perfectly with the iridium-catalyzed C-H borylation reaction, 15 the regiochemical outcome of which is reliably dictated by the directing ability of the indole N-H. Subjecting 1 to an iridium-catalyzed C-H borylation using the 3,4,7,8-tetramethylphenanthroline as ligand (Me4Phen) 16,17 gave the 7-borylindole 9 in good yield. A DMAP-assisted 18 Chan-Evans-Lam coupling of 9 with methanol gave the natural product 5,7-dimethoxy-2,4-dimethylindole (3).…”