Atroposelective Synthesis of Axially Chiral N‐Arylpyrroles by Chiral‐at‐Rhodium Catalysis
Chen‐Xi Ye, Shuming Chen, Feng Han, Xiulan Xie, Sergei I. Ivlev, K. N. Houk, Eric Meggers
Abstract
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‐1 H ‐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.
Topics & Concepts
RhodiumElectrophileChemistryLewis acids and basesCatalysisElectrophilic substitutionYield (engineering)AlkylationEnantioselective synthesisCombinatorial chemistryStereochemistryMedicinal chemistryOrganic chemistryMaterials scienceMetallurgyAxial and Atropisomeric Chirality SynthesisMolecular spectroscopy and chiralitySphingolipid Metabolism and Signaling