Smile reaction

Empath is a Cabinet database of metabolic pathways that models a metabolic pathway chart. It initially models the Boehringer Mannheim wall chart [35] but other pathway layouts are possible. It currently includes 1462 steps (metabolic reactions). The Empath database consists of more than 8000 live objects. Every object has an exact geometric location, that is, x, y coordinate, which is optionally indicated by visible hotspots. The chart is clickable everywhere and the image recenters itself around the selected point. The current object is the one closest to the center of the image and is identified by a bull s eye. A summary of the object is given (e.g., its structure, EC number, SMILES, reaction stoichiometry, etc.). Empath provides navigational features such as zoom in/out, wider, thinner, taller and shorter. 

Transformation of phenol to the corresponding thiophenol, a variant of the Smile reaction (page 549). 

Wittig-Smiles reaction.l The reaction of a triarylmethylphosphonium halide and a base with an a-keto dicarboxylic acid halide imide such as 1 results in a Wittig reaction followed by a Smiles rearrangement to provide a pyrrolidine dione... 

The analogous primary amine had been earlier studied by Wubbels and gave only the photo-Smiles reaction, but this process was not observed for the present system and the reaction is suggested to proceed by a photo-electron transfer mechanism to yield the radical ion pair. Photoaddition of N-H bonds to aromatic compounds has been known for some years, and the intramolecular process which leads to cyclization products has been reported for the reaction of 9-(aj-anilinolalkyl)phenanthrenes (220). The formation of the spiro-compounds (221) by addition of the N-H bond across the phenan-threne 9,10-positions is suggested to arise from the intramolecular exciplex in... 

The binding calculator computes the feasibility of a particular vMol binding to a vEnz, based on quantitative structure-activity relationships (or decision tree) derived from properties of known substrates for each enzyme. Transformations are stored as a list of SMIRKS (SMILES Reaction Specification)... 

TBSO h n-BUjSnH TBSO 1 Step 1 of radical Smiles reaction TBSO... 

Scheme 19.40 Mercaptobenzothiazoles and benzoxazoles in Ugi-Smiles couplings. Scheme 19.41 Passerini-Smiles reaction of 2-nitrophenol.

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

The related Passerini-Smiles reaction, an analogous three-component coupling performed in the absence of the amine parmer, affords O-aryl carboxamides 76 via O to O aryl transfer fScheme 19.411. ... 

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. ... 

Kimbaris et al performed the reduction of sulfone 113 using zinc-sodium hydroxide anticipating the formation of the sulfone derivative of pyrrolobenzothiadiazepine 119. However, the reaction afforded a mixture of two compounds 117 and 118. The formation of 118 is proposed to follow a Truce-Smiles reaction via the initial addition of the hydroxide ion on the... 

The Truce-Smiles rearrangement involves reaction of an internal carbon nncleophile [109] and differs from the Smiles reaction in that an activating group, such as a nitro group, may not be necessary. An early example, shown in Scheme 6.20, was the rearranganent of a phenyl sulfone to a sulfinic acid and involves carbanion formation by deprotonation of a methyl group by butyl lithium [110]. 

Snape s work developing the scope of the Truce-Smiles reaction toward new asymmetric reactions FIGURE 18,2 Worthy exan rles of the versatility of the Truce-Smiles rearrangement. 

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. 

---