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

Forberg Forberg,Kallmeier Kallmeier,Kempe Kempe

doi:10.3390/inorganics7080097

Forberg Forberg, Kallmeier Kallmeier + Show 1 more

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https://doi.org/10.3390/inorganics7080097

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Journal: Inorganics	Publication Date: Aug 6, 2019
Citations: 7	License type: CC BY 4.0

Affiliation: University of Bayreuth

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.

Highlights

The conservation of natural resources is a key element in ensuring a sustainable future for mankind
Reactions that use alcohols as starting materials have seen a sharp rise in popularity in recent years [3] because they permit the synthesis of nitrogen containing heteroarenes, like pyrroles and indoles [4,5]
A synthesis concept for tetrahydro-1H-indoles from alcohols and aminoalcohols seems appealing. It was shown by the groups of Milstein [13], Shimizu [14], and us [15,16] that when cyclohexanol was used in the pyrrole synthesis we developed [17] (Figure 1, top), tetrahydroindoles can be obtained [18,19,20,21,22]

Summary

Introduction

The conservation of natural resources is a key element in ensuring a sustainable future for mankind. Common methods for the synthesis of indoles require harsh reaction conditions or the use of highly reactive or worrisome chemicals [9,10,11,12]. With this background, a synthesis concept for tetrahydro-1H-indoles from alcohols and aminoalcohols seems appealing. A synthesis concept for tetrahydro-1H-indoles from alcohols and aminoalcohols seems appealing It was shown by the groups of Milstein [13], Shimizu [14], and us [15,16] that when cyclohexanol was used in the pyrrole synthesis we developed [17] (Figure 1, top), tetrahydroindoles can be obtained [18,19,20,21,22].

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