Ugi-Smiles reaction

Scheme 19.46 Tandem I Jgi-Mumm/Ugi-Smiles reactions with hydroxybenzoic derivatives.

Westermann and coworkers have recendy reported on tandem Ugi-Mumm/Ugi-Smiles reactions using various phenol-substituted carboxylic acids tScheme 19.46i. As the Ugi-Mumm is very rapid, it is possible to perform sequential couplings to reach products with seven points of diversity. ... 

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. 

Once the Ugi-Smiles coupling was established, different woiks related to the derivatization of the products were carried out Some of the examples were performed in a one-pot manner, but most of them required previous isolation of the Ugi-Smiles adducts. One of the first examples was developed by El Kaun and Grimaud by combination of the Ugi-Smiles reaction and a ring-closure metathesis, affording interesting pyrintido azepine scaffolds 120 (Scheme 7.49) [ 106]. However, the one-pot procedure could not be carried out probably... 

Inspired in the combination of the Ugi-Smiles reaction with other transformations, the same group envisaged a new route for the construction of indole scaffolds 121 based on an extension of this novel Ugi-Smiles protocol with a subsequent Heck cyclization in an one-pot procedure (Scheme 7.50) [107]. 

Other metal-catalyzed reactions have been also combined with the Ugi-Smiles reaction. Thus, substituted pyrrolo[2,3-base-catalyzed intramolecular cyclization (Scheme 7.51) [108]. 

SCHEME 7.52 Ugi—Smiles reaction and palladium-catalyzed opening of furans. 

The combination of the Ugi-Smiles coupling with the reduction of the nitro group of the aryl group has been used for the synthesis of benzimidazolopiperazines 128 [110]. Thus, the use of aminoacetaldehyde dimethyl acetal 125 with 2-nitrophenol 107 in the Ugi-Smiles reaction yielded the piperazine 127 (Scheme 7.53) throngh the opened intermediate 126. Then, the hydrogenolysis of the piperazine 127 provided the fused system 128 at 60 C in the presence of acetic acid to ensure a faster cycUzation. 

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