Iridium Catalyzed Synthesis of Tetrahydro-1H-Indoles by Dehydrogenative Condensation

Abstract

Novel synthetic routes to the commonly encountered indole motif are highly sought after. Tetrahydro-1H-indoles were synthesized for the first time from secondary alcohols and 2aminocyclohexanol in the presence of a well-established iridium catalyst using a modified synthetic procedure recently developed for the synthesis of hydrocarbazoles. The catalyst is stabilized by an inexpensive and easy-to-synthesize triazine based PN5P pincer ligand. The reaction proceeds through acceptorless dehydrogenative condensation (ADC) and yields the title compound, dihydrogen, and water and can thus be classified as sustainable synthesis. Overall, five examples, three of which were previously unknown compounds, were prepared. The propitious isolated yields and the mild reaction conditions show the synthetic value of this approach. These tetrahydroindoles can be quantitatively dehydrogenated over a heterogeneous Pd catalyst to yield the corresponding indoles.

Recent Advances in the Synthesis of Indoles with Partially Hydrogenated Benzene Ring (Tetrahydroindoles)

“…Kallmeier and Kempe 74a synthesized for the first time 4,5,6,7-tetrahydroindoles 125 from 2-aminocyclohexanol ( 123 ) and secondary alcohols 124 in the presence of a well-proven iridium catalyst using a recently developed modified method for the synthesis of hydrocarbazoles 74b (Scheme 35 ). An inexpensive and easily synthesized triazine based PN 5 P pincer ligand is used for stabilizing of catalyst (Scheme 35 ).…”

“…4,5,6,7-Tetrahydroindoles 125 can be quantitatively dehydrogenated over a heterogeneous Pd catalyst to yield the corresponding indoles 126 . 74a…”