Iridium Catalysed Asymmetric Allylic Substitution Reaction of Indolizine Derivatives

Abstract

A highly efficient direct asymmetric allylic substitution (AAS) reaction of indolizine derivatives with allylic alcohols for accessing enantioenriched indolizine derivatives was realized by combining a chiral iridium complex catalyst with Lewis acid under mild reaction conditions, delivering various chiral allylation products in remarkably high yields and excellent enantioselectivities. This protocol distinguishes itself by availability of the starting materials, mild reaction conditions, broad substrate scope, high yields, excellent selectivity and easy scale-up in a stereoselective manner, which provides a highly efficient protocol for chiral indolizines.

Indolizine: A Promising Framework for Developing a Diverse Array of C−H Functionalized Hybrids

“…Lu et al [42] . reported the asymmetric allylic substitution of indolizines (1) with allylic alcohols (68) in the presence of iridium complex and Lewis acid as catalyst.…”

“…Now a days, C−H functionalization is a very simple and a momentous technique for the synthesis of wide range of organic compounds. Reactions like alkylation, arylation, [33] alkenylation, [34] vinylation, [35] sulphenylation, [36] phosphonylation, [37] cycloaddition, [38] sulphonylation, [22] N ‐sulphonyl alkenylation, [39] dithiocarbomation, [40] olefination, [35] propargylation [41] and allylation [42] could be successfully achieved by C−H functionalization of indolizines (Figure 2). The present review deals with the pioneering work in the field of C−H functionalization of indolizines since 2016.…”

Recent advances in iridium-catalyzed enantioselective allylic substitution using phosphoramidite-alkene ligands

“…Zeng and coworkers reported the enantioselective allylation of indolizines. 64,65 The reaction of alcohol 1 with indolizine 38…”

“…Zeng and co-workers reported the enantioselective allylation of indolizines. 64,65 The reaction of alcohol 1 with indolizine 38 gave 3-allylated indolizine 39 with high enantioselectivity (Scheme 21). Notably, the reaction of aliphatic allylic alcohol gave the corresponding product with >99% ee.…”

Chiral Phosphoric Acid-Catalyzed Asymmetric Arylation of Indolizines: Atroposelective Access to Axially Chiral 3-Arylindolizines

“…Accordingly, much interest has been paid to the functionalization of indolizine, including transition-metal-catalyzed cross-couplings, electrochemical coupling, organocatalytic alkylation, and others . Among these advances, several excellent asymmetric C3-functionalizations of indolizine scaffolds were established due to the electron-rich property of the aromatic ring . However, to the best of our knowledge, the atroposelective synthesis of arylindolizines has been very limited thus far (Scheme b).…”