Replacement of a carbon atom of the classical Diels–Alder pair by nitrogen defines the aza-Diels–Alder reaction, a [4+2] cycloaddition that constructs a six-membered nitrogen heterocycle. Either the diene (1-azadiene) or the dienophile (imine) may carry the nitrogen. Inverse-electron-demand variants pair an electron-deficient azadiene with an electron-rich dienophile and are frequently catalyzed by chiral Brønsted acids [1]. Organocatalytic regio- and stereoselective inverse-electron-demand aza-Diels–Alder reactions of α,β-unsaturated aldehydes with N-tosyl-1-aza-1,3-butadienes proceed through a chiral enamine or related covalent intermediate [2]. Three-component asymmetric implementations generate ring-fused tetrahydroquinolines by assembling the azadiene or dienophile in situ [3]. The bonding event is a concerted or highly asynchronous cycloaddition that forms two new σ bonds and a six-membered ring, distinguishing the process from stepwise Mannich–Michael sequences that reach the same connectivity without a cycloaddition transition state. Normal-electron-demand aza-Diels–Alder reactions invert the electronic roles but share the same [4+2] topology.
- aza-Diels–Alder reaction
- inverse-electron-demand cycloaddition
- nitrogen heterocycles
- organocatalysis
Cyclization and Aryne Chemistry • Organic Chemistry • Chemistry • Physical Sciences
References
- Takahiko Akiyama; Hisashi Morita; Kohei Fuchibe; Chiral Brønsted Acid-Catalyzed Inverse Electron-Demand Aza Diels−Alder Reaction. J. Am. Chem. Soc. 2006, 128, 13070-13071, 10.1021/ja064676r.
- Bo Han; Zhao‐Quan He; Jun‐Long Li; Rui Li; Kun Jiang; Tian‐Yu Liu; Ying‐Chun Chen; Organocatalytic Regio‐ and Stereoselective Inverse‐Electron‐Demand Aza‐Diels–Alder Reaction of α,β‐Unsaturated Aldehydes and N‐Tosyl‐1‐aza‐1,3‐butadienes. Angew. Chem. Int. Ed. Engl. 2009, 48, 5474-5477, 10.1002/anie.200902216.
- Mingsheng Xie; Xiaohong Chen; Yin Zhu; Bo Gao; Lili Lin; Xiaohua Liu; Xiaoming Feng; Asymmetric Three‐Component Inverse Electron‐Demand Aza‐Diels–Alder Reaction: Efficient Synthesis of Ring‐Fused Tetrahydroquinolines. Angew. Chem. Int. Ed. Engl. 2010, 49, 3799-3802, 10.1002/anie.201000590.