Enantioselective Formal [4+2] Cycloadditions to 3-Nitroindoles by Trienamine Catalysis: Synthesis of Chiral Dihydrocarbazoles

Yang Li; Fernando Tur; Rune Pagh Nielsen; Hao Jiang; Frank Jensen; Karl Anker Jørgensen

doi:10.1002/anie.201509693

Enantioselective Formal [4+2] Cycloadditions to 3-Nitroindoles by Trienamine Catalysis: Synthesis of Chiral Dihydrocarbazoles

Angew Chem Int Ed Engl. 2016 Jan 18;55(3):1020-4. doi: 10.1002/anie.201509693. Epub 2015 Dec 4.

Authors

Yang Li¹, Fernando Tur¹, Rune Pagh Nielsen¹, Hao Jiang¹, Frank Jensen¹, Karl Anker Jørgensen²

Affiliations

¹ Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark.
² Department of Chemistry, Aarhus University, 8000, Aarhus C, Denmark. kaj@chem.au.dk.

PMID: 26636665
DOI: 10.1002/anie.201509693

Abstract

The first enantioselective formal [4+2] cycloadditions of 3-nitroindoles are presented. By using 3-nitroindoles in combination with an organocatalyst, chiral dihydrocarbazole scaffolds are formed in moderate to good yields (up to 87%) and enantioselectivities (up to 97% ee). The reaction was extended to include enantioselective [4+2] cycloadditions of 3-nitrobenzothiophene. The reaction proceeds through a [4+2] cycloaddition/elimination cascade under mild reaction conditions. Furthermore, a diastereoselective reduction of an enantioenriched cycloadduct is presented. The mechanism of the reaction is discussed based on experimental and computational studies.

Keywords: asymmetric catalysis; cycloaddition; heterocycles; organocatalysis; synthetic methods.

Publication types

Research Support, Non-U.S. Gov't