Organocatalysis [1] has expanded widely within the last few years, since the rediscovery of the proline-catalyzed aldol reaction. [2] Since then, several different methods, such as fluorination, [3] chlorination, [4] bromination, [5] sulfenylation, [6] amination, [7] and Mannich reactions, [8] have been developed for the a-functionalization of aldehydes and ketones with high stereoselectivity. The catalysts for these reactions are mainly chiral secondary amines and imidazolidinones, which activate the carbonyl compounds by an enamine mechanism. [9] Chiral secondary amines are also effective catalysts for enantioselective b addition to a,b-unsaturated carbonyl compounds. In the case of these a,b-unsaturated systems, the catalyst activates the substrate through the iminium-ion mechanism, thereby facilitating the addition of the nucleophile to the b-carbon atom. This reaction protocol has been developed organocatalytically for a number of different reactions such as cycloaddition reactions, [10] reductions, [11] and Michael additions. [12] Recently, several organocatalyzed nucleophilic nitrogen addition reactions to a,b-unsaturated carbonyl compounds have been presented. For example, Miller and co-workers [13] accomplished the addition of azide to unsaturated imides with moderate to good enantioselectivity, and MacMillan and coworkers [14] demonstrated the enantioselective formation of bamino aldehydes by addition of O-tert-butyldimethylsilylprotected carbamates to a,b-unsaturated aldehydes. Furthermore, Jacobsen and Gandelman [15] succeeded with the addition of a range of different aromatic N-heterocyclic compounds to unsaturated ketones and imides with high enantioselectivities using a chiral Al-salen catalyst.
The products of the addition of N-heterocyclic compounds to a,b-unsaturated aldehydes have shown important biological activities. [16] Several compounds containing Nheterocyclic groups such as 1,2,4-triazoles and tetrazoles are, for example, included in drugs such as Voriconazole (antifungal), Fluconazole (antifungal), and Losartan (high blood pressure).