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.
- Computational chemistry
- Intermediate characterization
- NMR spectroscopy
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