Amidocarbonylation reaction mechanism

The amidocarbonylation reaction was discovered by Wakamatsu [1], who demonstrated the synthesis of a range of A -acyl amino acids through the cobalt carbonyl-catalyzed reactions of various combinations of aldehyde plus amide, with carbon monoxide (eq. (1)). Some aspects of the mechanism of aliphatic aldehyde amidocarbonylation have been examined by both Pino and co-workers [2] and by Getman [3], Magnus and Slater [4] subsequently investigated the scope of this synthesis for variety of A -substituted amide co-reactants and C-sub-stituted aldehydes. Further mechanistic revisions were proposed involving acyl-iminium species. 

Detailed mechanisms for the amidocarbonylation reaction have been proposed by both Pino [2] and Magnus [4], wherein the first step is the formation of a hemi-amidal, followed by the nucleophilic substitution of a hydroxyl group by cobalt tetracarbonyl hydride and carbonyl insertion to an (ct-amidoalkanoyl) cobalt intermediate. This intermediate then provides the desired 7V-acyl-a-amino acid by direct hydrolysis, or via an lactame intermediate, followed by hydrolysis. 

In this chapter, the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions are reviewed and the scope and mechanisms of these reactions are discussed. It is clear that these carbonylation reactions play important roles in synthetic organic chemistry as well as organometallic chemistry. Some of the reactions have already been used in industrial processes and many others have high potential to become commercial processes in the future. The use of microwave irradiation and substitutes of carbon monoxide has made carbonylation processes suitable for combinatorial chemistry and laboratory syntheses without using carbon monoxide gas. The use of non-conventional reaction media such as SCCO2 and ionic liquids makes product separation and catalyst recovery/reuse easier. Thus, these processes can be operated in an environmentally friendly manner. Judging from the innovative developments in various carbonylations in the last decade, it is easy to anticipate that newer and creative advances will be made in the next decade in carbonylation reactions and processes. 

Amidocarbonylation is the only transition metal-catal) ed multi-component reaction, by which the amino acid framework is constructed directly from simple building blocks. [73] In the early 1970s, Hachiro Wakamatsu at Ajinomoto discovered by chance the cobalt-catalysed amidocarbonylation during investigation of the Oxo process with acrylonitrile, where he also found traces of -aminobutyric add. To determine the mechanism of this side-reaction, he... 

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