Enantioselective Conjugate Addition of Donor–Acceptor Hydrazones to α,β-Unsaturated Aldehydes through Formal Diaza–Ene Reaction: Access to 1,4-Dicarbonyl Compounds

• Published in: Journal of the American Chemical Society 2012-07, Vol.134 (29), p.11872-11875
• Main Authors: Fernández, Maitane, Uria, Uxue, Vicario, Jose L, Reyes, Efraím, Carrillo, Luisa
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja3041042

Donor–acceptor monosubstituted hydrazones participate as suitable reagents able to undergo an enantioselective formal diaza–ene reaction with α,β-unsaturated aldehydes under chiral secondary amine catalysis. This constitutes a new approach for the enantioselective conjugate addition of hydrazones to enals under metal-free conditions and leads to the formation of γ-hydrazono carboxylic acids after oxidation/[1,3]-H shift. The methodology is also useful for the synthesis of enantioenriched β-substituted α-keto-1,5-diesters by using the hydrazone moiety as a masked carbonyl group.