Ugis seven component reaction

Many combinatorial libraries are not as easily described as that in Subsection 5.3.1. Often the reactants belong to various classes of compounds and react with each other via complex mechanisms. As an example, consider Ugi s seven component reaction [310]. The reactants are a central building block, pyridine-2,6-dicarboxylic acid 

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The combination of a Mannich-3CR with an Ugi-4CR results in a seven-component reaction (7CR), as shown in Scheme 9.8. Reaction of dimethylamine, formaldehyde and isobutyraldehyde led to the 3-aminoaldehyde 9-40, which was treated with valine, methyl isocyanide, and methanol to give the anticipated product 9-41 [3],... 

Synthesis of an amino acid derivative by using a seven-component reaction A. Domling, I. Ugi, Angew. Chem. 1993, W5, 634-635 Angew. Chem. Int. Ed. Engl 1993, 32, 563-564. 

Scheme 5.5 Union of Asinger and Ugi MCRs leading to a seven-component reaction.

The functional groups characterizing the sets of reactants are highlighted in grey. A stepwise procedure to construct the library described by Ugi s seven component reaction is given in [337]. Figure 5.6 shows how the pyridine-carboxylic acid is extended successively by the amine, aldehyde and isocyanide building blocks. The reaction schemes used are... 

In 1993, Ugi described the seven-component reaction [63] and pointed out the possibility of carrying out 7-MCR based on this strategy. However, it was not until 2009 when an efficient one-pot reaction of eight-components was described by Orru et al. [64]. This process involved the formation of 9 new bonds and 11 points of diversity. In this study, a sequential development from six- to eight-component reaction was carried out. The MCR was initiated with... 

More recently, Westermann et al. have described a seven-component reaction by a sequential Ugi-Mumm/Ugi-Smiles reaction [105]. In this work, the authors proposed the use of a different nitroaryl acid derivative (e.g., 116 or 118 ... 

SCHEME 7.48 Seven-component reactions by sequential chemoselective Ugi-Mumm/Ugi-Smiles reactions. 

FIVE-, SIX-, SEVEN-, AND EIGHT-COMPONENT REACTIONS BASED ON THE UGI REACTION... 

A further small tweaking of the reaction conditions involves great changes a further new cascade channel is breaking. This is accomplished by modulation of the nucleophilicity of the activated methylene compounds applied. When used with isocyanoacetate 87 instead of cyanoacetates 86 as a methylene-activated component, an Ugi-like multicomponent cascade reaction is observed. This reaction was first detected by deployment of ethyl isocyanoacetate 87 in reactions of ribose and proline. In these experiments, proline—once the catalyst in the Knoevenagel condensation/ketalization/oxa-Michael cascade reactions—is directly incorporated into the product. As a result of that, seven-membered lactone 89 is formed. This sharp difference is demonstrated in Scheme 2.18 [40]. 

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