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Cobalt catalyzed arylation of aliphatic amides with aryl halides in water
Author
Tan, Edwin Yi Heng
Supervisor
Teo, Yong Chua
Abstract
N-arylated amides are an important class of compounds commonly found in natural products and bio-active compounds. There are many methods to synthesise these functional groups, with the use of aryl halides to arylate aliphatic amides being the strategy of choice due to its simplicity. With the aid of transition metals, this strategy has found widespread applications in the synthesis of natural products as well as pharmaceuticals. These cross-coupling reactions are typically facilitated by copper-based Ullmann-type reactions and palladium-based Buchwald-Hartwig-type reactions. While these protocols are robust and well-established with reported yield as high as 98% in some cases, there remains a need to develop cheaper and more sustainable protocols that are able to perform under more environmentally friendly conditions.
Cobalt salts have proved to be a sustainable alternative in a field dominated by copper and palladium catalysts. Cobalt-mediated C⸺C cross-coupling reactions has advanced greatly, with much attention remaining in C⸺C bond formation. Cobalt salts are attractive due to it being cheap and readily available compared to palladium catalysts. However, C⸺N cross coupling reactions catalysed by cobalt remains unexplored with limited reports in this field. As the first research group to report the first successful application of the N-arylation of nitrogen heterocycles using aryl iodides while bypassing the need for electrochemical and chemical reductive methods to regenerate the catalyst, we are investigating the feasibility of this methodology on other N-nucleophiles, thereby expanding the scope of the methodology.
In this project, we have demonstrated a simple strategy for the N-arylation of aliphatic amides with substituted aryl iodides in water catalysed by cobalt (II) chloride hexahydrate with N,N’-dimethylethylenediamine (DMEDA) as the assisting ligand. The protocol produced a wide range of N-arylated products in moderate to good yields (up to 82%) using relatively mild conditions and is easy to perform.
Cobalt salts have proved to be a sustainable alternative in a field dominated by copper and palladium catalysts. Cobalt-mediated C⸺C cross-coupling reactions has advanced greatly, with much attention remaining in C⸺C bond formation. Cobalt salts are attractive due to it being cheap and readily available compared to palladium catalysts. However, C⸺N cross coupling reactions catalysed by cobalt remains unexplored with limited reports in this field. As the first research group to report the first successful application of the N-arylation of nitrogen heterocycles using aryl iodides while bypassing the need for electrochemical and chemical reductive methods to regenerate the catalyst, we are investigating the feasibility of this methodology on other N-nucleophiles, thereby expanding the scope of the methodology.
In this project, we have demonstrated a simple strategy for the N-arylation of aliphatic amides with substituted aryl iodides in water catalysed by cobalt (II) chloride hexahydrate with N,N’-dimethylethylenediamine (DMEDA) as the assisting ligand. The protocol produced a wide range of N-arylated products in moderate to good yields (up to 82%) using relatively mild conditions and is easy to perform.
Date Issued
2017
Call Number
QD505 Tan
Date Submitted
2017