Dihydrooxazine Oxides as Key Intermediates in Organocatalytic Michael Additions of Aldehydes to Nitroalkenes

The organocatalytic enantioselective Michael addition of aldehydes to nitroalkenes through enamine catalysis has been studied intensively in recent years. Pioneering mechanistic studies by Seebach and Hayashi and co-workers, as well as by the Blackmond group, on reactions catalyzed by diaryl prolinol ethers have identified cyclobutane (CB) species 6a (Scheme 1) as a key intermediate and the resting state of the amine catalyst. Although these studies clearly demonstrated that the rate-determining step in the catalytic cycle takes place after the formation of 6a, and possibly involves the protonation of the iminium nitronate 5a, the detailed mechanism of the rate-determining step was not addressed. More recently, the Blackmond group suggested a modified catalytic cycle where the cyclobutane species 6a is first deprotonated to give the anion 10 a, followed by protonation to form the enamine 8a. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.