Silver-catalyzed cyclization of 2-pyridyl alkynyl carbinols with isocyanides: divergent synthesis of indolizines and pyrroles

Abstract

Divergent syntheses of indolizines and 2,4-disubstituted pyrroles by the silver-catalyzed cyclization of 2-pyridyl alkynyl carbinols with isocyanides are reported.

Isocyanide-based multicomponent reactions in the synthesis of heterocycles

“…Furthermore, their compatibility with domino and cascade reactions, paved the way for developing novel atom and bond economy synthetic strategies [70][71][72] .…”

Recent advances in the synthesis of indolizines and their π-expanded analogues

“…51 This reaction occurred smoothly in most cases, although propargyl alcohol bearing i-Pr group cyclized less efficiently, giving corresponding indolizine in 30% yield. 51 This reaction occurred smoothly in most cases, although propargyl alcohol bearing i-Pr group cyclized less efficiently, giving corresponding indolizine in 30% yield.…”

Silver‐Catalyzed Sequential Cascade Reaction of Isocyanides with 1‐(2‐Ethynyl‐phenyl)‐prop‐2‐yn‐1‐ol: Access to Benzo[b]fluorenes and Benzofuran‐Pyrroles

“…Subsequently, the effect of solvent was also investigated (entries 9-12), with 1,4-dioxane proving as the most suitable; 1,2-dichloroethane (DCE) and toluene also enabled the formation of 3 a in acceptable yield, whereas ethanol only allowed the formation of trace amount of the product. Encouraged by these findings, we tested the impact of additives such as bases [12] and ligands [13] (entries [14][15][16][17], to improve the efficiency of this reaction. Gratifyingly, the addition of a substochiometric amount of 1,8-diazabicyclo[5.4.0]undec-7ene (DBU) increased the yield of the desired product 3 a to 82% (entry 14).…”

“…[14] This unexpected outcome can be rationalized in light of recent reports by the Likhar's group and by us on the [3 + 2] cycloaddition reaction of isocyanides with alkynes, also to give 2,4-disubstituted pyrroles. [15] A series of control experiments were conducted to investigate the reaction mechanism (Scheme 4). We found that when quenched the reaction mixture of 1 a and 2 f, 5 a and 2 a in half of standard reaction time, 4 e', F, G, were obtained in acceptable yields, respec-Scheme 2.…”

“…Based on experiments and related precedents, [15,16] a plausible reaction mechanism for the synthesis of benzo [b]fluorene and benzofuran-pyrrole is proposed (Scheme 5). In the case of benzo [b]fluorene synthesis, the reaction of 1 with the catalyst gives the silver acetylide intermediate A, which is converted into the acetylenic imido complex B by 1,1-insertion with the isocyanide 2 a.…”