B₂pin₂-Mediated Cascade Cyclization/Aromatization Reaction: Facial Access to Functionalized Indolizines

Abstract

Herein, a B 2 pin 2 -mediated radical cascade cyclization/aromatization reaction of enaminone with pyridine is described. This strategy provides a practical way for the construction of valuable functionalized indolizines under metal-, external oxidant-, and base-free conditions, which could be compatible with various kinds of functional groups, such as halogen, π-system, heterocycle, ferrocenyl, etc. A preliminary mechanism investigation indicated that the pyridine-boryl radical formed in situ triggered the reaction to occur.

Study on Pyridine-Boryl Radical-Promoted, Ketyl Radical-Mediated Carbon–Carbon Bond-Forming Reactions

“…However, the typical basic hydrolysis with aq. Na 2 CO 3 was ineffective, and only partial deborylation was observed upon treatment with tetra- n -butylammonium fluoride (TBAF). Eventually, aq.…”

Cu(II)‐Catalyzed [3+2]‐Annulation of 2‐Pyridinyl‐substituted p‐Quinone Methides with Enaminones: Access to Functionalized Indolizine Derivatives

“…In recent years, enaminones and analogous stable enamines have been widely used in the construction of diverse heterocyclic scaffolds, especially, N ‐heterocycles [15] . Very recently Huang's group reported a B 2 pin 2 ‐mediated radical cascade cyclization/aromatization of enaminones with cyano‐substituted pyridines to access indolizine derivatives [16] . However, the [3+2] annulation reaction of 2‐pyridinyl‐substituted p‐ QMs with enaminones to access 2‐acyl substituted indolizines has not been reported so far, which triggered us to investigate this transformation.…”

Synthesis of Indolizines via Tf2O-Mediated Cascade Reaction of Pyridyl-enaminones with Thiophenols/Thioalcohols

“…In addition, compound 4 is used as a dye for organic light emitting devices (OLEDS) or dye sensitized solar cells (DSSCs) owing to its obvious photophysical properties. With the broad application of indolizines, diversified effective synthetic methods have been exploited to realize the construction of indolizine derivatives, mainly including the Chichibabin indolizine synthesis and cycloaddition reactions of pyridinium ylides or pyridine derivatives . However, these methods generally suffered from the need for prefunctionalized starting materials, excess oxidants, transition metals, or high temperature, − which are slightly uneconomical or unfavorable for large-scale preparation.…”

“…With the broad application of indolizines, diversified effective synthetic methods have been exploited to realize the construction of indolizine derivatives, mainly including the Chichibabin indolizine synthesis and cycloaddition reactions of pyridinium ylides or pyridine derivatives . However, these methods generally suffered from the need for prefunctionalized starting materials, excess oxidants, transition metals, or high temperature, − which are slightly uneconomical or unfavorable for large-scale preparation. Accordingly, exploring a cost-effective and useful approach to prepare indolizine compounds from easy to get raw materials would be of great importance.…”