Organocatalytic Michael reaction malonate

L-Proline was also used by Zhong et aL to promote a highly stereoselective organocatalytic domino aminoxylation-aza-Michael reaction occurring between 2-(5-oxopentylidene) malonate derivatives and aromatic nitroso compounds. This process furnished chiral multifunctionalised tetrahydro-1,2-oxazines in good to high yields, an excellent enantioselectivity of 99% ee in general and exceptional levels of diastereoselectivity of >98% de, as summarised in Scheme 4.8. 

A wide variety of carbon nucleophiles have been successfully used in the organocatalytic asymmetric inter- and intramolecular Michael addition to different a,p-unsaturated systems. Among them, the addition of aldehydes to diverse Michael acceptors such as, a,p-unsaturated ketones, alkylidene malonates, P-nitrostyrenes, and vinyl sulfones, is one of the most studied reactions. Enamine catalysis is the most frequently employed chiral activation found in the literature. 

An organocatalytic conjugate Michael addition of malonates to various ,/ -unsaturated aldehydes in the presence of an organocatalyst derived from proline in aqueous reaction media has been developed. The common feature of the modified 0 diaryl prohnol silyl ether catalysts (2) consist of long alkyl chains in their sttuctures. 

The synthesis of functionalized tetrahydro-1,2-oxazines 76 from nitroolefins 75 and nitrosoarenes has been studied by Zhong and coworkers. This enantio and diastereoselective organocatalytic process takes place via a domino sequence comprising an initial proline-catalyzed enantioselective aminoxylation of the starting material taking place by addition of the enamine onto the 0=N nitroso bond, followed by a final aza-Michael addition (Scheme 3.20) [57]. The same group has reported a very similar reaction starting from 2-alkylidene derivatives of malonic ester [58]. 

---