Atroposelective Synthesis of Axially Chiral N-Arylpyrroles by Chiral-at-Rhodium Catalysis

Chen-Xi Ye; Shuming Chen; Feng Han; Xiulan Xie; Sergei Ivlev; K N Houk; Eric Meggers

doi:10.1002/anie.202004799

Atroposelective Synthesis of Axially Chiral N-Arylpyrroles by Chiral-at-Rhodium Catalysis

Angew Chem Int Ed Engl. 2020 Aug 3;59(32):13552-13556. doi: 10.1002/anie.202004799. Epub 2020 Jun 3.

Authors

Chen-Xi Ye¹, Shuming Chen², Feng Han¹, Xiulan Xie¹, Sergei Ivlev¹, K N Houk², Eric Meggers¹

Affiliations

¹ Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße 4, 35043, Marburg, Germany.
² University of California, Los Angeles, Department of Chemistry and Biochemistry, Los Angeles, CA, 90095-1569, USA.

Abstract

A transformation of fluxional into configurationally stable axially chiral N-arylpyrroles was achieved with a highly atroposelective electrophilic aromatic substitution catalyzed by a chiral-at-metal rhodium Lewis acid. Specifically, N-arylpyrroles were alkylated with N-acryloyl-1H-pyrazole electrophiles in up to 93 % yield and with up to >99.5 % ee, and follow-up conversions reveal the synthetic utility of this new method. DFT calculations elucidate the origins of the observed excellent atroposelectivity.

Keywords: N-arylpyrroles; atroposelective reactions; chiral biaryls; chiral-at-metal complexes; homogeneous catalysis.

Grants and funding

ME1805/17-1/Deutsche Forschungsgemeinschaft