Amidocarbonylation—An Efficient Route to Amino Acid Derivatives

Abstract

Atom efficient, multicomponent reactions that lead to high-value products from inexpensive starting materials are of both economic and ecological interest for industrial organic synthesis. alpha-Amino acids are amongst the most important compounds in chemistry and biology. As well as their biochemical significance as building blocks of peptides and proteins, alpha-amino acids are also becoming increasingly interesting as fine chemicals. Possibly one of the key reactions in the preparation of these compounds is transition metal catalyzed amidocarbonylation, where the alpha-amino acid framework is constructed in a single step from an aldehyde, an amide, and carbon monoxide. This article gives a current overview of transition metal catalyzed amidocarbonylation reactions used in the synthesis of alpha-amino acids derivatives. A classification and summary of the significant features of this three component reaction is first presented together, with an historical introduction. This section is followed by two sections on cobalt- and palladium-catalyzed amidocarbonylation. A discussion of the mechanism of each of the different amidocarbonylation variants form an introduction. Overviews on further synthetic development of the methodology, such as the domino reaction with an amidocarbonylation step and the expansion of the range of starting materials, form the main topics of both variants. The potential of the method is demonstrated with the help of examples of special synthetic utility (for example, the preparation of arylglycines). Finally, possibilities for future developments in transition metal catalyzed amidocarbonylation reactions are proposed on the basis of the current state of knowledge.

Multicomponent Reactions with Organoboron Compounds

“…While most other methods for amino acid synthesis [35][36][37][38][39] initially generate derivatives of the amino acid moiety, having the amino and or carboxylic acid units protected as amides, esters or other functional groups, this three-component process directly generates the amino acid unit with both a basic and an acidic group. As a result, the amino acid product 51 is typically insoluble in the reaction medium and precipitates out, allowing a simple isolation and purification procedure through filtration and washing.…”

2-[(1-Benzamido-2-methoxy-2-oxoethyl)amino]benzoic Acid

“…Because of the physiological importance of α-amino acids, innumerable studies for their chemistry and synthesis have been published [1].…”

Amidocarbonylation of alkenes at very low pressures with a Co2(CO)8/SbR3 system: two easy routes to reach N-acetyl-α-aminoacids

“…Amidocarbonylation reaction, originally discovered by Wakamatsu et al in 1971 constitutes a good method for the synthesis of aminoacids using olefins [1], aldehydes [2], allylic alcohols [3], oxiranes [4] and acetals [5] as substrates. Cobalt catalysed amidocarbonylation, is generally carried out in several non-protic solvents using synthesis gas pressures of 50-200 bar and 2.5 mol percent of catalyst precursor.…”