Guanidine bases

To a solution of nitroolefin 4 (200 mg) and isocyanide 16 (169 mg) in a 1 1 mixture of THF and isopropanol (5 mL) was added the guanidine base A -t-BuTMG (180 mg). The resulting solution was heated to 50°C for 3 h, poured into water, and extracted with dichloromethane. The organic layer was dried over sodium sulfate and filtered through a short column of silica gel (eluent dichloromethane). Evaporation under vacuum of the solvent gave the desired pyrrole as a pale crystalline solid (272 mg, 90%) mp... 

The wide applicability of the PK reaction is apparent in the synthesis of pyrroles, for example, 45, en route to novel chiral guanidine bases, levuglandin-derived pyrrole 46, lipoxygenase inhibitor precursors such as 47, pyrrole-containing zirconium complexesand iV-aminopyrroles 48 from 1,4-dicarbonyl compounds and hydrazine derivatives. The latter study also utilized Yb(OTf)3 and acetic acid as pyrrole-forming catalysts, in addition to pyridinium p-toluenesulfonate (PPTS). 

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). 

Virnig, M. J. Mackenzie, J. M. W. Adamson, C. The use of guanidine-based extractants for the recovery of gold. Symposium Series—South African Institute of Mining and Metallurgy 1996, S16, 151-156. 

Figure 11.18 The diazonium group of p-diazobenzoylbiocytin can couple to the C-8 position of guanidine bases in nucleic acids, forming diazo bonds.

Reaction is terminated at the desired monoaddition-stage by using free guanidine (base), and acetone as solvent (376, 377). Guanidine salts and carbodiimides in dimethylformamide, in spite of the presence of excess of the former, yield 1,2,6-trisubstituted isomelamines (XLIII), presmnably by loss of arylamine from the intermediate labile triguanide (XLII) (375). 

Two groups [451,452] have discussed the restricted rotation revealed by nuclear magnetic resonance in some penta-substituted guanidine bases, but which is not apparent [452] in the hexa-substituted guanidinium salts. Further work on the chromatography [453, 454] and mass spectra [455] of guanidines has appeared (see p. 129). 

For an example of asymmetric Michael reaction using guanidine-based catalysts, see Ma, D. Cheng, K. Tetrahedron Asym. 1999, 10, 713-719. 

Thereafter, Terada applied related binaphthyl guanidine base catalyst 24 to the asymmetric 1,4 addition of diphenylphosphite to nitroalkenes (Scheme 5.45) [81]. 

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. 

Figure 6.53 Structurai concept for the design of guanidine-based bifunctionai thiourea organocataiysts 179-189 and mode of bifunctionai substrate activation.

Figure 6.54 Structures of guanidine-based thiourea derivatives screened in the Henry reaction of nitromethane with cyclohexane carboxaldehyde under phase-transfer conditions.

A polymer-bound guanidine base 31 has been used for the formation of aryl ethers from suitable phenols and alkyl halides. In addition to serving as a base to affect deprotonation, reagent 31 also acts as a sequestering agent for excess starting phenol (reaction 11).26... 

An unsuccessful attempt has been made to determine the separate electronic and steric effects of alkyl groups on the acidities of hydrocarbons, acetophenone derivatives, and acetone derivatives CH3COCHR1R2 (at either site) by multivariational analyses of experimental and theoretical acidities for each set.15 A thermodynamic cycle has been used to estimate the aqueous phase p/C, = 22.7 1.0 for the methyl group of acetic acid and p/C, = 3.3 1.0 for the corresponding enol.16 Equilibrium acidities have been determined for several nitroaryl substituted nitroalkanes and cyanomethanes, 2,4,6-TNT, and 9-cyanofluorene17 in acetonitrile the influence of common cation BH+ on the electronic spectra of the anions obtained in the presence of strong guanidine bases (B) has been attributed to formation of two types of ion pair.18... 

A further development, by the Grigg group, was the use of menthyl acetal 48 26 This chiral acetal reacted with aromatic iminoesters 43c-g in the presence of silver acetate (1.5 equiv) and guanidine base 47 (1.2 equiv) in acetonitrile, to give cycloadducts 49 in good yields and as a single diastereoisomer in each case (Scheme 2.13). In contrast, toluene was the preferred solvents for aliphatic iminoesters 43e and 43m-p. 

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