Synthesis of Poly‐Functionalized Indolizines via [5+1] Annulative Access to Pyridines

Abstract

Multi-functionalization of the pyridine motif of indolizine was achieved through [5 + 1] annulative construction of pyridine from 2-hydroxyacetophenone and pyrrole derivative in the presence of Cs 2 CO 3 . The reaction is proposed to take place via domino aldol-oxa Michael-Michael-elimination-oxidation procedure, leading to installation of three different functional groups at the C5, C6, and C7 positions of indolizines. Solvent (2-MeTHF) and the hydroxyl of 2-hydroxyacetophenones seemed to play crucial roles for this successful cyclization event. Further elaboration of the resulting scaffold and expansion of this protocol using other methyl ketones were demonstrated as well.

AgOTf/Et3N Cooperative Catalysis Enabled One‐Pot Access to α‐(Indolizinylethyl)‐Substituted N‐Sulfonyl Ketimines via an Imino‐Alkyne Cyclization

“…The synthetic applicability of our prepared molecule was successfully established by a desulfonamidation of 3 ac using 20 mol % of DABCO in water at 80 °C, affording 87% yield of indolizine 10 . Next, o ‐hydroxybenzoyl group of 10 was converted to vital classes [29,30] of coumarinyl‐ and benzofuranyl‐substituted indolizines 11 and 12 in 92% and 84% yields by using Ph 3 P=CHCO 2 Et and 2‐bromoacetophenone/K 2 CO 3 [14d] in toluene under refluxing conditions, respectively.…”

Catalyst-free assembly of a polyfunctionalized 1,2,4-triazole-fused N-heterocycle, 6-acylated pyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine

“…, annulative functionalization. 4 Using this concept, recently, we were able to construct a novel 1,2,4-triazole-fused ring system 5 ( 2 ) bearing two substituents at the C2 and C5 sites (Scheme 1c). 6 During our efforts to extend this work, we discovered a synthetic route to 3 having two different functional groups at the C2 and C6 positions under catalyst-free conditions (Scheme 1d).…”

C3 Functionalization of Indolizines via HFIP-Promoted Friedel–Crafts Reactions with (Hetero)arylglyoxals

“…Unique reactivity of reagents or catalysts employed in chemical reactions, sometimes, leads to unexpected and/or unprecedented results. In the course of our continuing efforts to expand N-fused heterocyclic chemical space, we were able to find new outcomes from the reaction of 5 with (hetero)­glyoxals in the presence of hexafluoroisopropanol (HFIP), which recently finds its use in a number of chemical transformations. , Previously, Friedel–Crafts reactions of N-fused heterocycle 1 with arylglyoxals under catalyst-free and catalytic FeCl 3 conditions have been reported to furnish the adduct 2 bearing a 1,2-dicarbonyl group, respectively (Scheme a). More recently, Cao and co-workers described visible-light-mediated conversion of indolizine 3 – 4 via a radical mechanism .…”