Ruthenium-catalyzed cascade C-H functionalization of phenylacetophenones

Abstract

Three orthogonal cascade CH functionalization processes are described, based on ruthenium-catalyzed CH alkenylation. 1-Indanones, indeno indenes, and indeno furanones were accessed through cascade pathways by using arylacetophenones as substrates under conditions of catalytic [{Ru(p-cymene)Cl2 }2 ] and stoichiometric Cu(OAc)2 . Each transformation uses CH functionalization methods to form CC bonds sequentially, with the indeno furanone synthesis featuring a CO bond formation as the terminating step. This work demonstrates the power of ruthenium-catalyzed alkenylation as a platform reaction to develop more complex transformations, with multiple CH functionalization steps taking place in a single operation to access novel carbocyclic structures.

Keywords: C-H activation; cascade chemistry; homogeneous catalysis; oxidative coupling; ruthenium.

Scheme 1

Cascade C—H functionalization. DG=directing group, EWG=electron-withdrawing group.

Scheme 2

a) 1-Indanone substrate scope. Indanones 6 a–6 x were isolated as the trans isomers, d.r.≥10:1 in all cases. b) Further reaction of compounds 6u and 6t. TsOH=p-toluenesulfonic acid.

Scheme 3

Indeno indene synthesis

Scheme 4

Substrate scope for alkenylation–cyclization–lactonization.

Scheme 5

Mechanistic investigations and possible reaction pathway.