Solvent-Dependent Guanidine Base Catalyzed Mannich Reactions

1 Solvent-Dependent Guanidine Base Catalyzed Mannich Reactions 

Conformationally flexible guanidine-thiourea catalyst 174 has unique solvent-dependent properties in the catalytic Mannich-type reaction. Based on detailed kinetic analyses, the origin of solvent-dependent stereo-discrimination is controlled by enthalpy-entropy compensation. The stereoselectivities of (S)-selective Mannich-type reactions in non-polar solvents such as m-xylene are predominantly due to differences in the entropies of activation (Table 28.9, entries 1-3), whereas the stereo-discrimination of (R)-selective reactions in polar solvents such as acetonitrile result from differences in the enthalpies of activation (Table 28.9, entries 4-6) [89]. 

2 Chiral Ammonium Betaine-Cataiyzed Mannich Reactions 

Quaternary ammonium betaines possessing an anion moiety have emerged as Bronsted base catalysts. The C2-symmetric axially chiral ammonium betaine 177 deprotonates the a-substituted a-nitrocarboxylates (176) to form a structured ion pair that reacts with imines (173) to furnish the corresponding anti-Mannich 

3 Quaternary Phosphonium Salt-Catalyzed Mannidi Reactions 

---

Table 28.9 Solvent-dependent guanidine base-catalyzed Mannich reactions.

---