Exploring the Remote Reactivity of π-Extended Carbonyl Compounds: the Vinylogous Alkylidene Malononitrile Activation Strategy

The development of enabling chemical transformations which exploit highly functionalized polydentate substrates – e.g. π-extended carbonyl compounds – with maximum efficiency and chemo-, regio-, and stereocontrol is a main challenge at the forefront of organic synthesis. To this end, merging the vinylogy concept with the malononitrile activation strategy, and the chiral iminium ion LUMO-lowering catalysis turned out to be a successful option, and several achievements were recently obtained on the exploitation of these concepts in asymmetric synthesis. We herein emphasize the role of the malononitrile handle as a crucial (and optionally traceless) ingredient enabling the selective activation of polyunsaturated carbonyl pro- nucleophiles. In particular, the synthetic potential of previously uncharted vinylogous alkylidene malononitriles I-III is highlighted, together with the modalities by which the efficient and chemo-, regio-, diastereo-, and enantioselective synthesis of collections of valuable carbocyclic and heterocyclic compounds were realized.