Counterion's Effect on the Catalytic Activity of Zn‐Prolinamide Complexes in Aldol Condensations

Abstract

The catalytic activity of complexes involving organic ligands and Lewis acids can be modulated by changing any of their components. In this work we have studied the influence on the stereoselectivity and catalytic activity exerted by the counterion of zinc salts employed as cocatalysts of L‐prolinamide in aldol condensations. The structures of the complexes have been determined both in solution and in the solid state.

Zn-Catalyzed Multicomponent KA2 Coupling: One-Pot Assembly of Propargylamines Bearing Tetrasubstituted Carbon Centers

“…We did not investigate ZnI 2 further, at this stage, because this salt is known for its ability to mediate the formation of trisubstituted allenes from pyrrolidine-derived tetrasubstituted propargylamines and, therefore, could lead to complications during the investigation of the reaction scope. 53b The activity of zinc halides correlates with their Lewis acidity; 57 however, no conclusions can be drawn based on this fact alone, as the relationship between the nature of the corresponding zinc acetylides and other intermediates involved in the cycle might be rather complex, especially in the absence of solvent. Of note, Zn(OTf) 2 is active under neat conditions as well; however, it also leads to unwanted side reactions, which inhibit efficient conversion to propargylamine 4a (result not shown).…”

“…66 Unfortunately, attempts to identify the compound by high resolution mass spectrometry (HRMS) analysis only confirmed the existence of N -phenylpiperazine. 57 The fact that N -phenylpiperazine and the acetate anions are present in a 1:1 ratio, as suggested by 1 H NMR analysis, prompted us to embark upon further investigations, in order to gain more insight regarding the components of this complex. IR analysis suggested that hydroxide species could also be present in this compound, 67 which can be explained considering that water is a byproduct of the KA 2 coupling (see Supporting Information).…”

Late‐Stage Hydrocarbon Conjugation and Cyclisation in Synthetic Peptides and Proteins

“…Other zinc(II) complexes were less effective in mediating alkylation of 1, suggesting that the ligand for Zn 2 + has an important role in the reaction, possibly by modulating its Lewis acid properties. [29,30] Interestingly, Ni 2 + and Cd 2 + acetates also promoted S-alkylation, but were accompanied by side reactions (Figure S4) or underperformed when carried out in DMAC. Thus, Zn 2 + was preferred for further experiments due to more efficient alkylation, less oxidative side reactions, and low toxicity.…”

“…A variety of metal complexes were examined for promoting S‐alkylation of cysteine by iodohexadecane (Figure 1D). Other zinc(II) complexes were less effective in mediating alkylation of 1 , suggesting that the ligand for Zn 2+ has an important role in the reaction, possibly by modulating its Lewis acid properties [29,30] . Interestingly, Ni 2+ and Cd 2+ acetates also promoted S‐alkylation, but were accompanied by side reactions (Figure S4) or underperformed when carried out in DMAC.…”

Dynamic assembly of a zinc-templated bifunctional organocatalyst in the presence of water for the asymmetric aldol reaction

“…The effect of the zinc counterion in zinc-prolinate catalysts had been found to be indeed remarkable, being chloride and acetate the most convenient salts. 19 Further experimentation led to the observation that the ZnCl 2 -pyridine ligands mixtures were not fully soluble in organic solvents. Nevertheless, the addition of a small amount of water to THF produced a fast dissolution of the system and an enhancement of the catalytic activity and specially stereoselectivity ( Table 1, entries 1-2 and 5-7).…”