Direct asymmetric vinylogous Michael addition of cyclic enones to nitroalkenes via dienamine catalysis.
In spite of the many catalytic methodologies available for the asymmetric functionalization of carbonyl compounds at their α and β positions, little progress has been achieved in the enantioselective carbon-carbon bond formation γ to a carbonyl group. Here, we show that primary amine catalysis provides an efficient way to address this synthetic issue, promoting vinylogous nucleophilicity upon selective activation of unmodified cyclic α,β-unsaturated ketones. Specifically, we document the development of the unprecedented direct and vinylogous Michael addition of β-substituted cyclohexenone derivatives to nitroalkenes proceeding under dienamine catalysis. Besides enforcing high levels of diastereo- and enantioselectivity, chiral primary amine catalysts derived from natural cinchona alkaloids ensure complete γ-site selectivity: The resulting, highly functionalized vinylogous Michael adducts, having two stereocenters at the γ and δ positions, are synthesized with very high fidelity. Finally, we describe the extension of the dienamine catalysis-induced vinylogous nucleophilicity to the asymmetric γ-amination of cyclohexene carbaldehyde.
Bencivenni
Giorgio
G
Dipartimento di Chimica Organica "A. Mangini," Università di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy.
Galzerano
Patrizia
P
Mazzanti
Andrea
A
Bartoli
Giuseppe
G
Melchiorre
Paolo
P