Palladium-Catalyzed Multicomponent Coupling of Alkynes, Imines, and Acid Chlorides:  A Direct and Modular Approach to Pyrrole Synthesis

Abstract

A new palladium-catalyzed method to prepare pyrroles directly from three basic building blocks-imines, alkynes, and acid chlorides-is described. This approach provides a straightforward method both to prepare pyrroles in one step and to diversify their structure by simple variation of any of the three starting materials. Mechanistic studies suggest that this process occurs via a complex series of eight individual steps, and this is discussed.

Recent Progresses in the Chemistry of Münchnones

“…此后, 他们利用这种方法成功合成并分离出了慕尼 黑酮, 并通过醇解得到酰基氨基酸酯 5 [17] . 接着, 他们 在后续的研究工作中, 合成了一系列慕尼黑酮环加成反 应衍生物, 包括与炔类反应生成吡咯 6 [18] 、与亚胺反应 生成 β-内酰胺 7 [19] 、与 N-对甲苯磺酰基亚胺反应生成吡 唑 8 [20] (Scheme 3). 这个方法也是最近广受关注的多组 915 2011 年, Arndtsen [22] …”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…The use of N-acylm€ unchnones provides access to N-acylpyrroles as mixtures of isomers [174], whereas 2-arylthio-or alkylthio-substituted 5-amino-1,3-thiazolium salts give 2-arylthio-or 2-alkylthiopyrrole derivatives, respectively, upon reaction with dimethyl acetylenedicarboxylate (DMAD) via extrusion of isothiocyanates [175]. Modern, multi-component variants that presumably involve m€ unchnones feature generation of the dipoles from imines, acid chlorides, and carbon monoxide via palladium catalysis [176], or by annulation of products derived from Ugi four-component reactions involving carboxylic acids, primary amines, aldehydes and 1-isocyanocyclohexene [177]. A solid phase version using polymer bound m€ unchnones has also been described.…”

“…Multi-component processes, which are carried out in a one pot operation, have become increasingly popular tools for pyrrole synthesis in recent years. Some of these approaches employ well-known principles for pyrrole ring formation, for example the Paal-Knorr reaction [88], or dipolar cycloaddition of alkynes to m€ unchnones [176,177] (see above). Samarium-catalyzed three-component coupling of amines, aldehydes and nitroalkanes has been demonstrated to furnish modest to moderate yields of the pyrroles 131 (Scheme 4.39).…”

Metal-mediated synthesis of furans and pyrroles

“…38 The approach is based upon the ability of alkynes to undergo 1,3-dipolar addition to 1,3-oxazolium-5-oxides (Munchnones) to form pyrroles. Munchnones 129 are generated from palladium-catalyzed coupling of imines …”