Low Temperature Organocopper-Mediated Two-Component Cross Coupling/Cycloisomerization Approach Toward N-Fused Heterocycles

Abstract

Organocopper reagents smoothly react with heterocyclic propargyl mesylates at low temperature to produce N-fused heterocycles. The copper reagent plays a "double duty" in this novel cascade transformation, which proceeds via an SN2' substitution followed by a subsequent cycloisomerization step.

Heterocycles Containing a Ring‐Junction Nitrogen

“…In this approach propargyl mesylates 148, when treated with an organocopper reagent, undergo a cascade involving addition and cyclization to give the indolizine 150 [87] via the allenic intermediate 149 (Scheme 22.26). …”

Transition Metal‐Catalyzed Synthesis of Fused Five‐Membered Aromatic Heterocycles

“…This route features generation of the reactive allenylpyridines via a propargylic substitution in conjugated pyridyl-substituted propargylic mesylates 326 with various organocopper reagents 327. A subsequent facile cycloisomerization of these allenes in the presence of stoichiometric amounts of the in situ generated Cu(I) salt by-product gives the expected indolizines 328 (Scheme 9.113) [290]. The authors suggested two mechanisms for this cascade transformation which are illustrated in Scheme 9.114.…”

“…The only precedent of this transformation was documented by Gevorgyan and coworkers. Thus, 1,3-disubstituted alkyl-and aryl-indolizines 316 were synthesized via the Cu(I)-catalyzed 5-endo-trig cyclization of the corresponding disubstituted allenylpyridines 315, whereas the cycloisomerization of gemdisubstituted allene failed to produce the expected monosubstituted indolizine (Scheme 9.109)[290].…”

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.…”