Non-C2-Symmetric Chiral-at-Ruthenium Catalyst for Highly Efficient Enantioselective Intramolecular C(sp3)-H Amidation

• Published in: Journal of the American Chemical Society Vol. 141; no. 48; pp. 19048 - 19057
• Main Authors: Zhou, Zijun, Chen, Shuming, Hong, Yubiao, Winterling, Erik, Tan, Yuqi, Hemming, Marcel, Harms, Klaus, Houk, K. N., Meggers, Eric
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 04.12.2019
• Subjects: carbenes; carbon-hydrogen bond activation; catalysts; catalytic activity; Chemistry; Chemistry, Multidisciplinary; diastereomers; enantioselectivity; heterocyclic nitrogen compounds; ligands; optical isomerism; Physical Sciences; ruthenium; Science & Technology; stereochemistry; AMINATION; ASYMMETRIC-SYNTHESIS; IRIDIUM; C-H AMIDATION; COMPLEXES; GAMMA-LACTAMS; NITRENE TRANSFER-REACTIONS
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.9b09301

A new class of chiral ruthenium catalysts is introduced in which ruthenium is cyclometalated by two 7-methyl-1,7-phenanthrolinium heterocycles, resulting in chelating pyridylidene remote N-heterocyclic carbene ligands (rNHCs). The overall chirality results from a stereogenic metal center featuring either a Lambda or Delta absolute configuration. This work features the importance of the relative metal-centered stereochemistry. Only the non-C-2-symmetric chiral-at-ruthenium complexes display unprecedented catalytic activity for the intramolecular C(sp(3))-H amidation of 1,4,2-dioxazol-5-ones to provide chiral gamma-lactams with up to 99:1 er and catalyst loadings down to 0.005 mol % (up to 11 200 TON), while the C-2-symmetric diastereomer favors an undesired Curtius-type rearrangement. DFT calculations elucidate the origins of the superior C-H amidation reactivity displayed by the non-C-2-symmetric catalysts compared to related C-2-symmetric counterparts.