Tandem One-Pot Synthesis of Polysubstituted NH-Pyrroles Involving the Palladium-Catalyzed Intramolecular Oxidative Amination of the Zinc Bromide Complex of β-Enamino Esters

Abstract

The Pd-catalyzed oxidative olefin amination of the zinc bromide complex intermediate, formed by the sequential reaction of nitriles with a Reformatsky reagent and 1-alkynes, affords pyrrole derivatives in good to excellent yields. This tandem protocol provides a simple, efficient, and atom- and pot-economical way to quickly build polysubstituted NH-pyrroles starting from readily available reagents in a regiocontrolled manner with a broad substrate scope and high functional group tolerance. In contrast, the Pd-catalyzed oxidative olefin amination of an isolated α-vinyl-β-enamino ester did not proceed effectively, but the reaction efficiency can be restored by addition of n-BuZnBr or Zn(OAc)2, indicating the crucial role of the zinc complex in this transformation. The synthetic utility of this protocol is exemplified by the rapid synthesis of pyrrolophenanthrenes and pyranopyrrolones through selective Pd- and Cu-catalyzed C-C and C-O bond-forming reactions.

Copper‐Catalyzed Tandem Reaction of Enamino Esters with ortho‐Halogenated Aromatic Carbonyls: One‐Pot Approach to Functionalized Quinolines

“…On the basis of the above experimental results and previous reports, a plausible mechanism for the tandem reaction is depicted in Scheme . Initially, enamino ester 1 and ortho ‐halogenated aromatic carbonyl compound 2 undergo a C–C bond formation reaction to give intermediate I , which then undergoes an oxidative addition process to lead to intermediate II .…”

“…Enamino esters are useful synthons that have broad applications in organic synthesis and have widespread use in the construction of N‐containing heterocyclic compounds, such as pyrroles, pyridines, pyrazoles, and oxazoles . Our continuous work towards the synthesis of nitrogenous heterocyclic compounds by using enamino esters has led to the design of a copper‐catalyzed tandem reaction for the synthesis of quinolines that proceeds through the cascade formation of C–C and C–N bonds (Scheme d).…”

Condensation of chloromethyl propargyl ether with nitriles

“…One of important methods of building up a С-С bond is Blaise reaction [1] that up till now is widely used in the synthesis of various organic compounds [2][3][4][5][6][7][8][9]. The reaction consists in the interaction of nitriles with esters of haloorganic acids in the presence of zinc to obtain the corresponding β-ketoesters.…”

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Reactions of aromatic and aliphatic nitriles with chloromethyl propargyl ether in the presence of activated zinc followed by treatment with water in the presence of H 3 PMo 12 O 40 afforded β-oxoethers.

SHORT COMMUNICATIONSOne of important methods of building up a С-С bond is Blaise reaction [1] that up till now is widely used in the synthesis of various organic compounds [2][3][4][5][6][7][8][9]. The reaction consists in the interaction of nitriles with esters of haloorganic acids in the presence of zinc to obtain the corresponding β-ketoesters.

…”

“…This complex is surrounded with a dense solvate shell thus impeding the formation of side products [2,4]. In the course of the reaction chloromethyl propargyl ether adds to the cyano group forming an intermediate organozinc compound [6][7][8][9]. Both aliphatic and aromatic nitriles enter this reaction.…”