Enantioselective intramolecular C–H amination of aliphatic azides by dual ruthenium and phosphine catalysis

• Published in: Chemical science (Cambridge) Vol. 10; no. 11; pp. 3202 - 3207
• Main Authors: Qin, Jie, Zhou, Zijun, Cui, Tianjiao, Hemming, Marcel, Meggers, Eric
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 21.03.2019; Royal Society of Chemistry
• Subjects: Aliphatic compounds; Amines; Aromatic compounds; Azides (organic); Catalysis; Chemistry; Chemistry, Multidisciplinary; Coordination compounds; Enantiomers; Physical Sciences; Ruthenium compounds; Science & Technology; PHOSPHORYL AZIDES; FUNCTIONALIZATION; NITRENE TRANSFER; PYRROLIDINE; BOND AMINATION; AZIRIDINATION; COMPLEXES; ARYL AZIDES; C(SP)-H; ALKYL AZIDES
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/C9SC00054B

The catalytic enantioselective intramolecular C(sp 3 )-H amination of aliphatic azides represents an efficient method for constructing chiral saturated cyclic amines which constitute a prominent structural motif in bioactive compounds. We report a dual catalytic system involving a chiral-at-metal bis(pyridyl-NHC) ruthenium complex and tris(4-fluorophenyl)phosphine (both 1 mol%), which facilitates the cyclization of aliphatic azides to chiral α-aryl pyrrolidines with enantioselectivities of up to 99% ee, including a pyrrolidine which can be converted to the anti-tumor alkaloid ( R )-(+)-crispine. Mechanistically, the phosphine activates the organic azide to form an intermediate iminophosphorane and transfers the nitrene unit to the ruthenium providing an imido ruthenium intermediate which engages in the highly stereocontrolled C–H amination. This dual catalysis combines ruthenium catalysis with the Staudinger reaction and provides a novel strategy for catalyzing enantioselective C–H aminations of unactivated aliphatic azides.