Rare‐Earth‐Metal‐Catalyzed Synthesis of Azaindolines and Naphthyridines via C−H Cyclization of Functionalized Pyridines

Abstract

We report herein a rare‐earth‐metal‐catalyzed insertion of a 2‐pyridine C(sp2)−H bond into an intramolecular unactivated vinyl bond. This reaction provides streamlined access to a range of azaindolines in moderate to excellent yields. The salient features of this reaction include simple and mild reaction conditions, 100% atom efficiency, and wide substrate scope. This methodology is also used to construct other nitrogen‐containing compounds such as naphthyridine derivatives. A plausible mechanism for the formation of azaindolines involving initial C−H bond activation by the lanthanide complex followed by C=C insertion into a Ln−C bond to form an alkyl lanthanide species that subsequently undergoes cyclization is proposed.

Recent Advances in Rare‐Earth Metal‐Catalyzed C−H Functionalization Reactions

“…This reaction provides streamlined access to a range of azaindolines 9 in moderate to excellent yields (Scheme 3). [14] Notably, when catalytic amount of dibenzylamine (Bn 2 NH) was added, the yield increased significantly. Mechanism studies have shown the reaction ChemCatChem undergoes an initial C(sp 2 )À H bond activation which followed by C=C insertion to form the final cyclization products.…”

“…For instance, Chen and coworkers established a highly regio‐ and diastereoselective cyclization reaction of 1,5‐ and 1,6‐dienes ( 36 and 37 ) with anisoles by using a 2‐picoline‐tethered‐half‐sandwich scandium alkyl complex 38 (Scheme 11). [27] The scope of aromatic substrate was also expanded to include tertiary anilines 35 .…”

Homoleptic Lanthanide Amide Catalysts for Organic Synthesis: Experiment and Theory

“…More recently, Chen and co-workers reported the Ln­[N­(TMS) 2 ] 3 -catalyzed C–H activation/cyclization of functionalized pyridines (Scheme ). Activation of the ortho -pyridyl C–H bond followed by intramolecular coordination and insertion into an unactivated vinylic bond provides facile access to a variety of azaindolines in 23–92% yields.…”

“…Regarding C–C bond-forming processes, recent reports , of catalytic heteroarene C–H activation using commercially available homoleptic lanthanide amide catalysts are exciting. The commercial availability of these catalysts and their functional group tolerance, paired with the simple and mild reaction conditions, warrant further investigations of scope in organic synthetic methodology.…”

“…More recently, Chen and co-workers 26 reported the Ln[N(TMS) 2 ] 3 -catalyzed C−H activation/cyclization of functionalized pyridines (Scheme 3). Activation of the orthopyridyl C−H bond followed by intramolecular coordination Scheme 1.…”