Gold(i)/Zn(ii) catalyzed tandem hydroamination/annulation reaction of 4-yne-nitriles

Abstract

The tandem hydroamination-annulation reaction of 4-pentynenitriles in the presence of amine nucleophiles and a cooperatively operating catalyst system, consisting of Ph 3 PAuCl and Zn(ClO 4 ) 2 , provides an efficient route to 2-aminopyrroles. Two regioisomeric 2-aminopyrroles were formed in moderate to good yields.Over the past six years, gold catalysis has shown to be a powerful tool in organic synthesis. Cationic gold(I) and gold(III) complexes show unique behavior towards unactivated alkenes, alkynes, allenes, 1,3-dienes, and enynes promoting the nucleophilic addition of a variety of functional groups both inter-and intramolecularly.1 In that respect, a great number of gold catalyzed tandem reactions of various systems with external nucleophiles that enable the formation of cyclic systems are present in the literature.2 Especially those transformations including the catalytic addition of N-H bonds across C-C multiple bonds (hydroamination) that are catalyzed by both gold(I) and gold(III) complexes have found wide application for the generation of new C-N bonds 3,4 affording nitrogen containing heterocycles, such as pyrroles and pyridines.Among the various synthetic strategies, catalytic transformations that use transition-metal catalysts are one of the modern approaches for forming pyrroles. 5 Relatively few examples of the gold-catalyzed synthesis of highly substituted pyrroles have been reported, however. 4e,6 In the course of our research to develop new methodologies for the synthesis of nitrogen containing heterocycles that are promoted by transition metal catalysts, we recently demonstrated Zn(II) salts to be effective catalysts for the activation of the CQO bond and CN triple bond.7 These principles led us to the discovery of a novel catalytic one-pot synthesis of 2-aminopyrroles starting from a-cyanomethyl-b-ketoesters. Zinc perchlorate smoothly catalyzes the amination of nitriles, and the subsequent cyclocondensation affords five-membered rings (pyrroles) in good yield, as exemplified in the conversion of 1 to 2 and 3 (Scheme 1). 7a

The roles of Lewis acidic additives in organotransition metal catalysis

“…Spiroketals 65 and fused tricyclic compounds 67 are also accessible from similar alkyne hydrofunctionalisation/cycloaddition sequences, where the Lewis acid also acts to generate ortho-quinonemethides from 2-(hydromethyl)phenol derivatives. Au and Lewis acid-catalysed alkyne hydroamination has also been applied to the synthesis of N-heterocycles such as a pyrroles 68 and indoles. 69 Lewis acids can also affect Au-mediated steps of the catalytic reaction.…”

A minireview of hydroamination catalysis: alkene and alkyne substrate selective, metal complex design

“…In 2010, Demir et al [50] successfully developed a 4-amine 24 (Scheme 30) cyclochemistry catalyzed by Au(I)/Zn(II) in series as well. An effective, versatile and widely available synthetic pyrrole with multiple substituents is provided.…”

Homogeneous Gold‐Catalyzed Cyclization Reactions of Alkynes with N‐ and S‐Nucleophiles

“…The authors suggested that the Zn catalyst was responsible for the hydroamination of the nitrile, while the Au catalyst activated the alkyne for pyrrole formation. Mixtures of 2‐amino‐ and 2‐alkylaminopyrroles 156/157 were obtained in 13–81% yield 110…”