Michael additions of propionaldehyde

On the other hand, a computational study [159] of the Michael addition of propionaldehyde lithium enolate adding to E-crotonaldehyde indicates an anticlinal conformation around the forming bond (i.e. A eclipsing R2 in the ul topicity and A eclipsing H in the Ik topicity of Figure 5.9). 

Bolm and coworkers exploited (5)-35c in the Michael addition of propionaldehyde or butyrraldehyde to aromatic nitroalkenes, obtaining excellent yields and stereoselectivities (Scheme 11.34). ... 

Christmann, Strohmann and coworkers compared (S )-35c and (5)-35d with Maruoka s pyrrolidine (.S)-34 in the Michael addition of propionaldehyde to ( )-p-nitrostyrene. (S)-35c gave the desired product in excellent yields and selectivity, not surprisingly affording the opposite enantiomer with respect to the use of (S)-34 (Scheme 11.35A). Finally, the authors examined the organocatalytic asymmetric a-allqrlation of n-octanal. In this reaction (5)-35c was less reactive than (.S)-34, albeit maintaining almost the same level of stereocontrol (Scheme 11.35B). °... 

Scheme 11.35 Michael addition of propionaldehyde to ( )-p-nitrostyrene (A) and asymmetric a-alkylation of /2-octanal (B) using pyrrolidines (5)-35c and (5)-35d.

In 2011, Moreau, Greek and coworkers reported a multicatalytic process [6] merging two consecutive enamine catalytic cycles based on a Michael addition/a-amination cascade reaction [7]. The Michael addition of aldehydes to p-nitrostyrene followed by the electrophilic amination were catalyzed, respectively, by the diphenylprolinol silylether 5 and the 9-amino-(9-deoxy)-cpf-cinchonine 6 (Scheme 12.4), both previously described by Hayashi and coworkers [8] and Melchiorre and coworkers [9]. One interesting feature of this reaction is that diphenylprolinol silylether 5 can specifically catalyze the Michael addition, while 9-amino-(9-deoxy)-ep/-cinchonine 6 is required to promote the electrophilic amination. The Michael addition of propionaldehyde to p-nitrostyrene was achieved by using only 5 mol% of catalyst 5 in chloroform at 0 C. After completion of the reaction, dibenzyl azodicarboxylate (DEAD, 1.5 equiv), trifluoroacetic acid (15 mol%) and the second catalyst 6 (5 mol%) were added. The expected product 7 was obtained as a single diastereomer in good yield (80%) and with excellent enantioselectivity (ee 96%). Various nitroalkenes bearing electron-rich and electron-deficient aryl... 

Indoles undergo Michael additions in the presence of acid catalysts. Gold-catalyzed conjugate additions of indoles with enones led to the formation of indol-3-yl propanones <04SL944>. With 3-substituted indole substrates, the reactions proceeded to give the corresponding 2-substituted indoles. Homotryptamines were formed in a one-pot sequence that involved a Michael addition by indole substrates to acrolein imine derivatives followed by a reductive amination of the indole propionaldehyde intermediates <04TL3803>. 

Interesting examples for conjugate additions mediated by chiral amines have been described by Alexakis et al. (Scheme 36), who used the nitroalkene 151 as a Michael acceptor in organocatalytic enamine-catalyzed conjugate addition reactions 149, 150, 153). Michael reaction of 151 with propionaldehyde 60 in the presence of the diamine catalyst 152 (15 mol%) gave 153 as a mixture of four diastereomers in good yield. Subsequent aldehyde protection and conversion of the... 

Scheme 12.4 Michael addition/a-amination sequence of propionaldehyde with different nitroalkenes.

---