Guanidine catalysis

Ishikawa and co-workers also reported a class of structurally modified guanidines for promotion of the asymmetric Michael reaction of ierf-butyl-diphenylimino-acetate to ethyl acrylate [124,125]. In addition to a polymer support design (Scheme 69), an optical resolution was developed to achieve chiral 1,2-substituted ethylene-l,2-di-amines, a new chiral framework for guanidine catalysis. The authors discovered that incorporating steric bulk and aryl substituents in the catalyst did improve stereoselec-tivitity, although the reactivity did suffer (Scheme 70, Table 4). 

The complexity of the supported guanidine catalysis, the dilTiculty frequently encountered by reactants in reaching the active sites and the role played by the unfunctionali/cd surface of the support are also discussed. 

A useful route to 2,1,3-benzothiadiazoles is the F -catalyzed cyclization of l-(4-X-C6F4)-3-trimethylsilyl-l, 3-diaza-2-thiallenes [90JFC(50)359]. Fluoride ion catalysis is also used in the formation of heterocycles from pentafluorobenzoyl and -phenoxy compounds (81BCJ3447). Pentafluoro-phenylcarbonimidoyl dichloride with primary amines gave guanidines,... 

Aminosilicas have been widely studied for use in catalysis, either as a base catalyst or as a support for metal complexes (12). For example, amine functionalized silica can be used to catalyze the Knoevenagel condensation, an important C-C bond forming reaction. Also, the amine sites on the silica can be further functionalized to form supported imines, guanidine, and other species... 

Furthermore, the same sol-gel matrices have been used in a system where acid and base catalysis occur in the same pot without quenching either catalyst [29]. In this case, the acids were either entrapped Nafion (perfluorinated resin sulfonic super acid, a3) or entrapped molybdic acid (M03-Si02, a2), while the bases were two ORMOSILs (organically modified silica sol-gel materials), one with H2N (CH2)2NH(CH2)3 groups (bi) and the other guanidine base residues (b2) (Scheme 5.12). 

While the significance of the bifunctional Brpnsted base catalysts has been illustrated in the previous sections, few examples rely solely on a Brpnsted base interaction for asymmetric catalysis. However, in the past few decades, a novel catalyst system has emerged as a powerful promoter of chiral transformations. The guanidines have gained the reputation as super bases in organic transformations. 

It was not until 1994 that Chinchilla and co-workers identified a synthesized a chiral guanidine for asymmetric catalysis [115],... 

The authors reported the first chiral guanidine catalyzed addition of nitro-olefms to aldehydes (Scheme 62, Table 3). While reactivity and selectivity were not optimal, the discovery led to great developments in the field of asymmetric Brpnsted base catalysis. 

Ooi has recently reported application of chiral P-spiro tetraaminophosphonium salt 37 as a catalyst for the highly enantio- and diasterioselective direct Henry reaction of a variety of aliphatic and aromatic aldehydes with nitroalkanes (Scheme 5.51) [92]. Addihon of the strong base KO Bu generates in situ the corresponding catalyhcally active triaminoiminophosphorane base A. Ensuing formation of a doubly hydrogen-bonded ion pair B positions the nitronate for stereoselective addition to the aldehyde. This catalyst system bears many similarities to guanidine base catalysis. 

The combination of his-electrophilic and his-nucleophilic components is the basis of general pyrimidine synthesis. A reaction between an amidine (urea or thiourea or guanidine) and a 1,3-diketo compound produces corresponding pyrimidine systems. These reactions are usually facilitated by acid or base catalysis. 

Pyran-4-ones, chromones and flavones are converted into pyrimidines, usually under base catalysis, by reaction with compounds which contain the grouping N—C—N urea, thiourea, guanidine, aminoguanidine, acetamidine and dicyandiamide are examples of this type. Scheme 24 shows some typical examples (77BSF369, 81JHC619). 

Where R4 is a hydrogen or carbon atom, 10.15 is simply an amidine. However, urea 10.16, thiourea 10.17, or guanidine 10.18 and their derivatives may be used. These nucleophiles may be condensed with ester and nitrile functionalities as well as with aldehydes and ketones. Such condensations to afford pyridimidine derivatives are usually facilitated by acid or base catalysis, although certain combinations of reactive electrophilic and nucleophilic compounds require no catalyst at all. Some examples are shown below. 

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