Proton sponges organic synthesis

The main area of application of proton sponges, primarily compound 1, is in organic synthesis as strong but low-nucleophilicity bases. Besides, the proton sponges and their salts are a favourite model of physical chemists and theoreticians for investigating hydrogen bonds and a number of other interesting phenomena. 

Until recently, there had been no reports on the application of 2,7-disubstituted proton sponges like 44 and 65 in organic synthesis. Their advantage in comparison with compound 1 is their increased basicity coupled with their extremely low C-nucleophilicity. Lately, the 2,7-dimethoxy compound 44 was used for deprotonation of salts of other proton sponges, in particular of 88 and 89 (Section n.C.2)67. In another example, when the proton sponge 1 participated in the azo-coupling reaction, the addition of base 44 increased the degree of interaction (equation 30)56. The yield of the azo compound 269 was nearly quantitative, and the base 44 could be easily recovered. 

The pA" of several common amines used in synthesis have been determined in THF at 25°C. All will be used as bases in reactions used later in this book. 4-Al,Al-Dimethylaminopyridine (DMAP, 16), proton sponge (17), quinuclidine, (18), DBU (l,8-diazabicyclo-[5.4.0]-undec-7-ene, 19), and diazabicyclo-[2.2.2]octane (DABCO, 20) are shown, along with triethylamine, tributylamine, and tribenzylamine for comparison. The p/T values for these compounds are shown in THF, DMSO, and acetonitrile in Table 2.4.27 These values were determined from proton-transfer ion pairs of the type BH" " with acidic indicator hydrocarbons in THF. The values obtained in THF differ substantially from the ionic pKa values for NH+ in DMSO or acetonitrile. Streitwieser and co-workers27 states that "at the present time amines cannot be placed quantitatively on any of the ion pair acidity scales currently in use for neutral acids in THF". The realization that it may be necessary to use different bases in different solvents, despite the fact that all are considered to be good bases in organic reactions, makes it clear why a quantitative comparison of bases would be useful. 

In this chapter, the synthetic utility of Proton Sponge (1) was reviewed. This superbase, although not a main player, is indispensable for various mild and selective transformations in organic synthesis. Despite the unique characteristics of superbases, their exploitation is still limited. Recently, various types of proton sponges, including chiral ones, have been developed, and are likely to have a wide range of applications in organic and asymmetric synthesis. 

Martfnez-Franco R, Moliner M, Yun Y, Sun J, Wan W, Zou X, et al. Synthesis of an extra-large molecular sieve using proton sponges as organic structure-directing agents. Proe Natl Aead Sci U S A 2013 110 3749-54. 

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