Novel chemoselective and diastereoselective iron(III)-catalysed Michael reactions of 1,3-dicarbonyl compounds and enones

Iron(III) chloride hexahydrate catalyses the Michael reaction of 1,3-dicarbonyl compounds with alpha,beta-unsaturated ketones under mild and neutral conditions with extraordinary efficiency. The chemoselectivity of this Fe-III-catalysed process is superior to that of the classic base-catalysed Michael reaction, since the latter suffers from various side reactions, namely drawbacks such as aldol cyclisations and ester solvolysis. Excellent yields and chemoselectivities; together with the environmentally friendly nature of Fe-III catalysis makes this an important alternative to classic base catalysis. Moreover, the reaction procedure is reasonably easy: Fe-III catalysis does not require inert or anhydrous conditions, and in most cases no solvent is needed. In terms of diastereoselectivity, the Fe-III-mediated reaction may also prove superior to a base-catalysed one. In at least one example, Fe-III catalysis forms a diastereoisomer as the major kinetic product, which is disfavoured in the base-mediated Michael reaction, where a thermodynamic mixture is obtained. The relative configuration of the diastereoisomeric Michael products has been determined for two examples by synthesis and structure elucidation of the cyclic aldol derivatives.