Annulation of Hydrazones and Alkynes via Rhodium(III)-Catalyzed Dual C–H Activation: Synthesis of Pyrrolopyridazines and Azolopyridazines

• Published in: Organic letters Vol. 22; no. 3; pp. 1217 - 1221
• Main Authors: Streit, Andrew D, Zoll, Adam J, Hoang, Gia L, Ellman, Jonathan A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07-02-2020
• Subjects: Alkynes - chemistry; Azoles - chemical synthesis; Azoles - chemistry; Catalysis; Hydrazones - chemistry; Molecular Structure; Organometallic Compounds - chemistry; Pyridazines - chemical synthesis; Pyridazines - chemistry; Pyrroles - chemical synthesis; Pyrroles - chemistry; Rhodium - chemistry; Stereoisomerism
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.0c00186

Hydrazones readily synthesized from N-aminopyrroles or N-aminoazoles and aldehydes undergo Rh­(III)-catalyzed dual C–H activation and coupling with aryl- and alkyl-substituted alkynes to give pyrrolopyridazines or azolopyridazines, respectively. This transformation represents a rare example of hydrazoyl C–H activation and proceeds without heteroatom functionality to direct C–H activation. Hydrazones derived from aromatic, alkenyl, and aliphatic aldehydes were effective inputs, and tethering the alkyne to the hydrazone enabled annulations to more complex, tricyclic products.