Direct, Organocatalytic, Enantioseletcive Michael Reactions: Turning Common Michael Acceptors Into Vinylogous Carbon Nucleophiles

alpha,beta-Unsaturated carbonyl or carbonyl-like moieties are usually envisaged as privileged electrophilic functionalities to be exploited, among others, in Michael addition reactions as well as synchronous or stepwise cycloadditions, opening the way to a wide range of highly valuable beta-functionalized scaffolds. However, behind this common reactivity pattern, an “umpolung” option can be unveiled when an enolizable alkyl group is present at the beta-position of the ylidene. In fact, using a suitable activating catalyst and capitalizing on the vinylogous pro-nucleophilic character of the alkyl group, an addition reaction of these substrates to proper electrophilic acceptors can be fostered to yield olefinic products functionalized at the most distant point of the molecule (C-gamma). We were able to proof this concept on several multidentate scaffolds, namely 3-alkylidene oxindoles,[1] alpha-alkylidene pyrazolinones[2] and dicyano-olefins,[3] by developing direct, organocatalytic, asymmetric, vinylogous Michael addition reactions using nitroolefins or unsaturated aldehydes as electrophilic counterparts. Based on stereocontrolled, covalent or non-covalent dual activation modes, the Cinchona- or prolinol-based organocatalysts performed well, promoting the reactions in high yields and with remarkable control of the regio-, diastereo- and enantioselectivity. References 1. (a) Curti, C.; Rassu, G.; Zambrano, V.; Pinna, L.; Pelosi, G.; Sartori, A.; Battistini, L.; Zanardi, F.; Casiraghi, G. Angew. Chem. Int. Ed. 2012, 51, 6200. (b) Rassu, G.; Zambrano, V.; Pinna, L.; Curti, C.; Battistini, L.; Sartori, A.; Pelosi, G.; Zanardi, F.; Casiraghi, G. Adv. Synth. Catal. 2013, 355, 1881. 2. Rassu, G.; Zambrano, V.; Pinna, L.; Curti, C.; Battistini, L.; Sartori, A.; Zanardi, F.; Casiraghi, G. Adv. Synth. Catal. 2014, accepted. 3. Dell’Amico, L.; Curti, C.; Zanardi, F. et al. manuscript in preparation.