Ketoximes. reaction with alkynes

A rhodium-catalyzed one-pot synthesis of substituted pyridine derivatives from a,(3-unsaturated ketoximes and alkynes was developed in 2008 by Cheng and coworkers [99], Good yields of the desired pyri-dines can be obtained (Scheme 3.48). The reaction was proposed to proceed via rhodium-catalyzed chelation-assisted activation of the (3—C—H bond of a,(3-unsaturated ketoximes and subsequent reaction with alkynes followed by reductive elimination, intramolecular electro-cyclization, and aromatization to give highly substituted pyridine derivatives finally [100]. Later on, in their further studies, substituted isoquinolines and tetrahydroquinoline derivatives can be prepared by this catalyst system as well [101]. Their reaction mechanism was supported by isolation of the ort/jo-alkenylation products. Here, only asymmetric internal alkynes can be applied. 

Benzofuranyl)pyrroles, 2-(2-thienyl)pyrroles , 2,2 -dipyrroles, 3-(2-pyr-rolyl)indoles , 2-(2-benzimidazolyl)pyrroles and2-(2-, 3- and4-pyridyl)pyrroles were prepared using this method. Reaction of alkynes (for example, propyne) or allene with ketoximes in a superbase system (MOH/DMSO) leads to 2,5-di- or 2,3,5-trisubstituted pyrroles Pyrroles and dipyrroles were synthesized also from corresponding dioximes and acetylene in a KOH/DMSO system It has also been shown that 1,2-dichloroeth-ane can serve as a source of acetylene in pyrrole synthesis. Oxime 52 in the system acetylene/RbOH/DMSO at 70 °C afforded a mixture of three pyrroles 53-55 in low yields (equation 23). The formation of product 53 occurred through recyclization of pyrrolopy-ridine intermediate. ... 

The importance of the results obtained with dibromopropane lies in not only that a new simple procedure of introducing the methyl substituent into the position 2(5) of the pyrrole ring has been found, but also that an opportunity of utilizing alkynes and allenes in the reaction with ketoximes to prepare pyrroles is being outlined. 

An efficient access to substituted isoquinolines via the oxidative cyclization of aromatic and heteroaromatic ketoximes with alkynes has been developed by Jeganmohan and coworkers (Eq. (7.32)) [40]. In the presence of 2.5mol% of [RuCl2(/ -cymene)]2 and 25mol% of NaOAc, the reaction occurred with high regioselectivity. A variety of unsymmetrical alkynes even including terminal alkynes are compatible for this transformation. Under the reaction conditions, the five-membered ruthenacycle key intermediate 9 was isolated from the stoichiometric reaction. 

Recently, Guan et al. developed a novel Cu(OAc)2-promoted oxidative coupling of enamides with electron-deficient alkynes for the synthesis of multisubstituted NH pyrroles. This reaction tolerates a wide range of functional groups and is a reliable procedure for the rapid elaboration of readily available enamides into a variety of diester-substituted NH pyrroles. The reaction proceeded through C-H and N-H bond functionalization of enamides CU/O2 system [22]. They also developed an efficient CuBr-catalyzed homocoupling of ketoxime carboxylates for the synthesis of symmetrical pyrroles [23] (Scheme 8.10). 

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