Bases proton sponges

The liberation of HC1 during the Yoshikawa phosphorylation can lead to undesired side reactions of unsaturated side chains of modified pyrimidines. Protocol 11 describes a modified procedure for the phosphorylation step, whereby a strong, non nucleophilic base (proton-sponge , l,8-bis(dimethylamino)naph-thalene) is added. We have found that addition of proton-sponge also increases the rate of phosphorylation and in circumstances even when it is not specifically required, its addition can also be beneficial for particularly slow phosphorylation reactions. 

Larhed et al. investigated enantioselective Heck reactions with 2,3-dihydrofuran as alkene [86]. In the coupling with phenyl triflate, conditions previously reported by Pfaltz [87] were attempted under microwave irradiation. Interestingly, the catalytic system Pd2(dba)3/(4S)-4-t-butyl-2-[2-(diphenylphosphanyl)phenyl]-4,5-dihydro-l,3-oxazole, identified by the Swiss team, was found suitable for high-temperature microwave-assisted enantioselective Heck reactions (Scheme 76). Using a proton sponge as a base and benzene as a solvent gave the best conversions (Scheme 76). At tempera-... 

Compounds such as 2, 4, and 5 are known as proton sponges. Another type of proton sponge is quino[7,8-A]quinoline (6). Protonation of this compound also gives a stable monoprotonated ion similar to 3, but the steric hindrance found in 2, 4, and 5 is absent. Therefore 6 is a much stronger base than quinoline (7) (p/fg values of the conjugate acids are 12.8 for 6 and 4.9 for 7), but proton transfers are not abnormally slow. 

The proton sponges are exceptionally strong bases (see Section 4, p. 321 for a discussion) and one of the reasons for this is the strong hydrogen bonds with double-minimum potentials (A[8( H) — 8( H)] 0.5 present in the... 

Some consideration was given to appropriate bases for this oxidation system. Pyridine and sodium bicarbonate had been shown to be useful earlier and were included. Additional bases considered were a proton sponge (1,8-Bis(dimethylamino)naphthalene) and, as stated above, pyridine N-oxide. Because of the low solubilities in CXL systems of NaHCOs and the proton-sponge, pyridine was selected for these exploratory studies. 

Quino[7,8-/i]quinoline (50) and benzo[l, 2-h 4,3-/r Jdiquinoline (52) belong to the so-called proton sponges and possess abnormally high basicities, pKa= 12.8 and 10.3, respectively (89AG(E)84, 89AG(E)86). This is mostly due to strong destabilization of both bases because of electrostatic repulsion... 

Protection2 and activation1 of carboxylic acids. Carboxylic acids react with 1 in the presence of a 2-chloropyridinium salt, proton sponge, and DMAP to form amides (2). These amides are stable to acids and bases but deprotection is possible with oxidative hydrolysis with ceric ammonium nitrate (CAN). If the oxidation is carried out in the presence of an amine, an amide is obtained in 70-95% yield. For this purpose, the combination of copper(II) oxide and ceric pyridinium chloride is far superior to CAN.4 No racemization was observed in the benzoylation of an a-amino ester. 

Under optimized reaction conditions this two step synthesis for asymmetric preparation of /1-lactams is performed as follows. First, the organocatalyst 46 is added as a shuttle base to a solution of the acid chloride, 47, and the proton sponge , 49, at low temperature. Within a few minutes the soluble ketene and the hydrochloride salt, 49 HC1, as a white precipitate, are formed. Subsequently, the imino ester 44 is added to this solution at —78 °C, which results in the asymmetric formation of the /Mactam. Thus, the alkaloid 46 acts both as a dehydrohalogena-tion agent and as an organocatalyst for subsequent lactam formation [49, 52]. 

H.A. Staab, T. Saupe, Proton sponges and the geometry of hydrogen bonds aromatic nitrogen bases with exceptional basicities. Angew. Chem. Int. Ed. Engl. 27, 865-1008 (1988)... 

Examples Acid salts, acids, proton sponges, HF complexes Acids, alcohols, hydrates, phenols, biological molecules Weak base, basic salts C-H- O/N O/N-H- ji... 

The proton sponge, l,8-bis(dimethylaminonaphthalene) (DMAN), has been anchored onto amorphous and pure silica MCM-41.[182] DMAN supported on MCM-41 is an excellent base catalyst for the Knoevenagel condensation between benzaldehyde and different active methylene compounds, as well as for the Claisen-Schmidt condensation of benzaldehyde and 2 -hydroxyacetophenone to produce chalcones and flavanones. It was found that the activity of the supported catalyst is directly related to the polarity of the inorganic support. Moreover, the support can also preactivate the reagents by interaction of the carbonyl groups with the weakly acidic silanol groups of MCM-41. This preactivation step enables DMAN, anchored onto MCM-41, to abstract protons with a higher pK than that of the DMAN. 

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