Catalytic asymmetric inverse-electron-demand

Example 3, Catalytic asymmetric inverse-electron-demand Diels—Alder reaction" ... 

Example 1, Catalytic asymmetric inverse electronic demand Diels-Alder reaction ... 

X. Jiang, R. Wang, Recent developments in catalytic asymmetric inverse-electron-demand Diels—Alder reaction, Chem. Rev. 113 (7) (2013) 5515—5546. 

The application of bis- and monooxazoline ligands in the catalytic asymmetric inverse-electron demand Diels-Alder reactions has been reviewed (13CRV5515). 

The binuclear BINOL-Al complex 39 was developed by the Yamamoto group and was applied in the catalytic asymmetric inverse-electron-demand Diels-Alder reaction between tropones and ketene diethyl acetal (Scheme 19.48). Various tropone derivatives underwent the reaction well, affording the corresponding functionalised bicycle[3.2.2] ring adducts in 36-98% yields and 46-97% enantiomeric excess. 

Although the diversity of asymmetric inverse-electron-demand hetero-Diels-Alder reactions has been weU established, examples of aU-carbon-based catalytic asymmetric versions have rarely been reported, and aU faU into the LUMO-lowering strategy. Based on previous applications of dienamine catalysis in asymmetric inverse-electron-demand hetero-Diels-Alder reactions, Li et al. extended this strategy to all-carbon-based asymmetric inverse-electron-demand Diels-Alder reactions (Scheme 1.28) [36]. The products of cyclohexene derivatives with substantial substitution diversity of electron-deficient dienes and crotonaldehyde were obtained with high diastereo- and enantioselectivities (up to 99% ee, dr up to 95 5). 

Marko I. E., Evans G. R., Declercq J. P., Tinant B., Feneau-Dupont J. Asymmetric, Catalytic, Inverse Electron-Demand Diels-Alder Reactions of 3-Carboalk-oxy-2-Pyrone Derivatives Acros Org. Acta 1995 1 63 6... 

The aza-Diels-Alder reaction is an important and versatile tool for the preparation of nitrogen-containing heterocycles present in numerous natural products and drug candidates. It involves the [4 + 2] cycloaddition of either an imine with an electron-rich diene or an azabutadiene with an electron-rich alkene (inverse electron demand). Catalytic asymmetric variants employing not only metal complexes, but also organic molecules were disclosed over the last few years. 

J0rgensen and Juhl reported the first organocatalytic enantioselective inverse-electron-demand hetero-Diels-Alder reaction of aldehydes (e.g., 71) and enones (e.g., 72) with excellent diastereo- and enantioselectivity. Scheme 3.26 [41], The reaction utilizes a chiral enamine intermediate as an alkene in catalytic asymmetric cycloaddition reactions. 

Compared to the hetero-Diels-Alder reaction of carbonyl compounds and derivatives with dienes, where only a limited number of catalytic and enan-tioselective reactions have been reported, the number of asymmetric hetero-Diels-Alder reactions in which the ketone or imine functionality is part of a heterodiene is much higher. In contrast, there are only a few examples of using a,p-unsaturated aldehydes in inverse hetero-Diels-Alder reactions. In the case of the inverse electron demand hetero-Diels-Alder reaction, the ketone or imine functionality is part of an a,(I-unsaturated system, which reacts in a cycloaddition reaction with an electron-rich alkene. The inverse electron demand hetero-Diels-Alder reaction is primarily controlled by a LUMOdiene-HOMOdienophiie interaction, which can be found, for example, in the reactions... 

The catalytic asymmetric /-selective Diels-Alder annulation of a, -unsaturated /-butyrolactams with enones provided a synthesis of, y-functionalized bridged bi-or tri-cyclic dihydropyranopyrrolidin-2-ones in one step (up to 98% yield, >20 1 dr, and 99% ee) The inverse-electron-demand aza-Diels-Alder cycloaddition 0 of A-aryl-a,/0-unsaturated ketimines with enecarbamates in the presence of chiral bifunctional phosphoric acids produced 4,5,6-trisubstituted 1,4,5,6-tetrahydropyridines having three contiguous stereogenic centres in up to 84% yield, 95 5 dr, and 95% 5-Alkenylthiazoles react as in-out dienes with e-poor dienophiles in polar 44-2- 0 cycloaddition reactions. The cycloadditions are site selective. The mechanism is thought to lie between a concerted but highly asynchronous process and a stepwise process. 

Thus, we have developed catalytic asymmetric aza Diels-Alder reactions of imines with alkenes using a chiral lanthanide Lewis acid, to afford 8-hydroxyquinoline derivatives in high yields with high diastereo- and enan-tioselectivities. The characteristic points of this reaction are as follows, (i) Asymmetric aza Diels-Alder reactions between achiral azadienes and dienophiles have been achieved using a catalytic amount of a chiral source, (ii) The unique reaction pathway, in which the chiral Lewis acid activates not dienophiles but dienes, is revealed. In most asymmetric Diels-Alder reactions reported using chiral Lewis acids, the Lewis acids activate dienophiles [64, 65]. However, inverse electron-demand asymmetric Diels-Alder reactions of 2-pyrone derivatives have been reported [72]. (iii) A unique lanthanide complex including an azadiene and an additive, which is quite different from the conventional chiral Lewis acids, has been developed. 

---