MacMillan’s Imidazolidinones: Powerful Chiral Organocatalysts

Introduction

During the last seven years, many research groups have developed the concept of iminium activation. The advantage of this approach is that the iminium generated in situ by equilibrium between an α,β-unsaturated carbonyl compound (ketone or aldehyde) and a secondary amine salt can replace the traditional use of Lewis acid to lower the LUMO of the electrophile (Figure [1] ). [1]

Figure 1 Lewis acid activation vs iminium activation

A small collection of chiral imidazolidinone salts have been shown to be widely efficient for a broad range of asymmetric transformations such as Friedel-Crafts alkylation, [2] Diels-Alder cycloaddition, [3] hydrogenation of α,β-unsaturated carbonyl compounds [4] and cascade catalysis. [5]

Furthermore, these chiral imidazolidinones can be used for the classical enamine activation of ketone or aldehyde [6] in aldol or addition reactions. [5]

This concept first reported by MacMillan [3] is now an efficient tool in organocatalysis. [7] Indeed, this reagent is a good alternative to toxic, hazardous and expensive metals.

Numerous catalysts are commercially available (Figure [2] ), or can be easily prepared from inexpensive natural amino acids. [3]

Moreover, it has been recently reported that the commercially available chiral amine salts derived from these imidazolidinones can be used for iminium activation in total synthesis, demonstrating that this concept can be applied to the preparation of complex target molecules. [8]

Figure 2 Commercially available chiral imidazolidinone catalysts

References

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