Ligand binding reactions, solvent role

Dialkylzinc derivatives are inert towards conjugated enones (e.g. 181) in hydrocarbon or ethereal solvents. The discovery that a conjugate addition can be promoted by Cu(I) salts in the presence of suitable ligands L (e.g. sulphonamide 182) opened a new route to zinc enolates (e.g. 183), and hence to the development of three-component protocols, such as the tandem 1,4-addition/aldol addition process outlined in equation 92186. If the addition of the aldehyde is carried out at —78 °C, the single adduct 184 is formed, among four possible diastereomeric products. The presence of sulphonamide is fundamental in terms of reaction kinetics its role is supposed to be in binding both Cu(I) and Zn(II) and forming a mixed metal cluster compound which acts as the true 1,4-addition catalyst. 

The development of a viable catalytic enantioselective variant of this transformation is clearly a worthy objective. While it is clear that donor solvents are crucial for the success of the reaction, the actual role of the solvent is not clear. In addition, the use of chiral agents to modulate the stereochemical course of reaction is complicated by the weak affinity of Cr(IT) for common chiral ligands. Identifying that class of ligand that can compete with solvent for the Cr(II) center, accelerate the addition, and not irreversibly bind to Cr(II) constitutes a significant challenge. 

The role of extra water in such recipes has turned out to be complex and again a question of supramolecular chemistry. It seems to be safe to state that its stmcture and chemical reactivity is far from that of bulk water, as it is tightly bound and activated in the H-bonded system of the IL. Therefore, reactions with water take place quite rapidly. On the other hand, water as a solvating ligand seems to be excluded due to the IL-binding, as for instance deduced from the absence of so-called solvent pores [30]. This is a quite unique situation for colloid chemistry and material synthesis. 

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