C-H Functionalization Reactions of Unprotected N-Heterocycles by Gold Catalyzed Carbene Transfer

ChemRxiv

Abstract

The C-H functionalization reaction of N-heterocycles with unprotected N-H group is one of the most step-economic strategies to introduce functional groups without the need of installation and removal of protecting groups. Despite recent significant advances in C-H functionalization chemistry, this strategy remains unsatisfactorily developed. In this report, we disclose a simple and straightforward protocol to allow for the selective C-H functionalization of unprotected double benzannellated N-heterocycles via gold catalyzed carbene transfer reactions (29 examples, up to 86% yield). The scope of the reaction can also be expanded to the corresponding protected heterocycles (37 examples, up to 98% yield), further demonstrating the generality of this method. Mechanistic studies by DFT calculations underpin the importance of the gold catalyst and reveal that the selectivity of this reaction is driven by trace amounts of water present in the reaction mixture.

Authors 6

1. Sripati Jana Aachen

   RWTH Aachen University · UNSW Sydney

   Affiliation as printed

   RWTH Aachen University Institute of Organic Chemistry Landoltweg 1, D-52074 Aachen, Germany

   School of Chemistry, UNSW Sydney, Australia

2. Claire Empel Aachen

   RWTH Aachen University · UNSW Sydney

   Affiliation as printed

   RWTH Aachen University Institute of Organic Chemistry Landoltweg 1, D-52074 Aachen, Germany

   School of Chemistry, UNSW Sydney, Australia

3. Pei Chao Aachen

   RWTH Aachen University · UNSW Sydney

   Affiliation as printed

   RWTH Aachen University Institute of Organic Chemistry Landoltweg 1, D-52074 Aachen, Germany

   School of Chemistry, UNSW Sydney, Australia

4. Polina Aseeva Aachen

   RWTH Aachen University · UNSW Sydney

   Affiliation as printed

   RWTH Aachen University Institute of Organic Chemistry Landoltweg 1, D-52074 Aachen, Germany

   School of Chemistry, UNSW Sydney, Australia

5. Thành Vinh Nguyễn Aachen

   RWTH Aachen University · UNSW Sydney

   Affiliation as printed

   RWTH Aachen University Institute of Organic Chemistry Landoltweg 1, D-52074 Aachen, Germany

   School of Chemistry, UNSW Sydney, Australia

6. René M. Koenigs Aachen

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University