Trimethylsilyl‐Protected Alkynes as Selective Cross‐Coupling Partners in Titanium‐Catalyzed [2+2+1] Pyrrole Synthesis

Abstract

Trimethylsilyl (TMS)-protected alkynes served as selective alkyne cross-coupling partners in titanium-catalyzed [2+ +2+ +1] pyrrole synthesis.R eactions of TMS-protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido complexes yielded pentasubstituted 2-TMS-pyrroles with greater than 90 %s electivity over the other nine possible pyrrole products.The steric and electronic effects of the TMS group were both identified to playkey roles in this highly selective pyrrole synthesis.This strategy provides aconvenient method to synthesize multisubstituted pyrroles as well as an entry point for further pyrrole diversification through facile modification of the resulting 2-silyl pyrrole products,asdemonstrated through ashort formal synthesis of the marine natural product lamellarin R.

Synthesis of pentasubstituted 2-aryl pyrroles from boryl and stannyl alkynes via one-pot sequential Ti-catalyzed [2+2+1] pyrrole synthesis/cross coupling reactions

“…Although nitro groups and esters are commonly tolerated in Suzuki reactions, 11 B NMR spectroscopic evidence indicates that deleterious chemistry with the 9-BBN group may be taking place ( Figure S150). Finally, given that 9-BBN and Sn alkynes undergo coupling with similar chemo-and regioselectivity to TMS-protected alkynes, 33 intramolecular competition experiments were conducted to determine the relative directing ability of the two functional groups compared to TMS ( Figure 5). There are few points of comparison for the regioselectivity of insertion into these types of doubly-functionalized alkynes.…”

Acid-Catalyzed Multicomponent Rearrangements via 2-((Quinoxalin-3(4H)-on-2-yl)(aryl)methylene)malononitriles, Generated In Situ, for Divergent Synthesis of Pyrroles with Different Substitution Patterns

“…To date, many skillful strategies have been developed to construct highly substituted pyrroles, , such as ring contraction, multicomponent reactions, C–H bond activation, 1,3-dipolar cycloaddition, oxidative cross-coupling/cyclization, and rearrangement cascades . Among them, [4 + 1] annulation (Paal–Knorr synthesis, Clauson−Kaas synthesis) and [2 + 2 + 1] annulation (Hantzsch synthesis, Piloty–Robinson synthesis) are the most common methods to obtain pyrroles. Along with the procedures listed, in the literature, various modifications of these methods are presented .…”