Transition States of the Asymmetric Michael Reactions of Aldehydes Catalyzed by Trimethylsilyl-Protected Diphenylprolinol

The asymmetric Michael reactions of aldehydes and nitroalkenes catalyzed by trimethylsilyl-protected diphenylprolinol were investigated by using density functional theory calculations. As a result of the stereospecific blockade of the bulky diphenylsiloxymethyl group on the pyrrolidine ring, the Re face of the enamine double bond is effectively shielded. For acetaldehyde, there are two different conformers of the enamine intermediate. On the basis of the two conformers of the enamine intermediate, four different reaction pathways were considered and four different transition states were searched for the enantioselective asymmetric Michael reaction of acetaldehyde and nitroalkene. The lowest- and second-lowest-energy transition states are both formed via the same intermediate IM2. The enantiomeric excess, calculated to be 96 % ee, is in good agreement with the experimental value. For propanal, on the basis of the four different conformers of the prolinol-enamine intermediate, eight different reaction pathways were considered and eight transition states were searched for the enantioselective asymmetric Michael reaction. The calculated ee value is 99.5%, which is in good agreement with the experimental ee value of 99 %. The lowest- and second-lowest-energy transition states are formed via different enamine intermediates, which is different from the case of acetaldehyde. The calculations also reveal that the intermediates play an important role in the reactions. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)