Synthesis of Pyrrolo[2,1,5-cd]indolizines through Dehydrogenative Heck Annelation of Indolizines with Diaryl Acetylenes Using Dioxygen as an Oxidant

Abstract

A dehydrogenative Heck annelation reaction of indolizine with diaryl acetylene via dual C-H bond cleavage was developed. Oxygen gas was employed as a clean oxidant in this catalysis under base-free conditions. Diarylpyrrolo[2,1,5-cd]indolizines were synthesized with high atom economy. In addition, kinetic isotope experiments provided evidence for C-H bond metalation of the 5-position of the indolizine as the rate-limiting step.

Synthesis of heterocycles via aerobic oxidation

“…Hu and co-workers reported an interesting synthesis of pyrrolo [2,1,5-cd]indolizines 150 via cyclization between indolizines 149 and diarylalkynes under Pd catalysis ( Scheme 20B). 110 The substrate scope for this reaction is limited to electron-poor indolizines (EWG in position 2 or 3) and to diarylalkynes (unsymmetrical alkynes give regioisomeric mixtures).…”

Synthesis of Pyrrolo[2,1,5-cd]indolizine Rings via Visible-Light-Induced Intermolecular [3+2] Cycloaddition of Indolizines and Alkynes

“…In light of this, the development of more efficient and straightforward synthetic methods for the construction of fused indolizines is highly desirable. To date, considerable attentions have been devoted to the synthesis of such compounds. , Among these methods, the [3+2]-cycloaddition of indolizines with unsaturated hydrocarbons was undoubtedly the most concise strategy. , In 2015, Hu’s group have reported a highly regioselective palladium-catalyzed dehydrogenative Heck annulation of indolizine with diaryl acetylene, affording a wide range of diarylpyrrolo­[2,1,5- cd ]­indolizines with high atom economy (Scheme a). Recently, photocatalytic transformations have been considered to be a green alternative in synthetic chemistry. , Therefore, our group has developed a metal-free, visible-light-induced intermolecular [3+2] cycloaddition strategy in 2019.…”

“…A broad range of pyrrolo­[2,1,5- cd ]­indolizine derivatives were conveniently synthesized under simple conditions, thus providing a novel green synthetic route (Scheme b). However, this method is unable to synthesize 2-substituted pyrrolo­[2,1,5- cd ]­indolizine, which limits the diversity of these compounds to some degree.…”

Design and Synthesis of Novel Indolizine Analogues as COX-2 Inhibitors: Computational Perspective and in vitro Screening

“…[8][9][10][11][12][13][14][15][16][17][18] Accordingly, synthesis and derivatization of indolizines have attracted considerable attention of medicinal chemist over the decades. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Particularly the 3-benzoylindolizines are attractive since their derivatives have been used as pharmacologically interesting compounds and their vital role as the synthetic intermediates for 3-substituted indolizines is also apparent. 34 Indolizine system is isoelectronic with indole nucleus and signifies a group of heterocyclic compounds structurally associated to purines.…”