Prolinol derivatives, catalysis

An organo-metal synergistic catalysis has been developed (Scheme 19) for the construction of the spirocyclopentene oxindole derivatives (502). Here, the cinnamic aldehyde (498) is first activated through the in situ catalytic formation of the highly electrophilic iminium ion (499) with the Hayashi-Jprgensen prolinol-derived catalyst (325)... 

In 2008, the groups headed by Jprgensen and Rueping contemporaneously reported the use of 1,3-diketones reacting as bis-nucleophiles with a,p-unsaturated aldehydes under iminium catalysis with a diaryl prolinol sdyl ether catalyst (Scheme 16.13) [27, 28]. This domino reaction allowed the formation of 3,4-dihydropyrans with good yields and enantioselectivities but variable diastereoselectivities in favor of the 1,3-trans derivatives, precursors of indoloquinoUzidines [29]. 

Other proline-derived catalysts promoting the selective formation of the fl/iti-diastereomer have been developed, for example, by the groups of Maruoka (axially chiral amino sulfonamides 98, symmetric chiral pyrrolidine-based amino sulfonamides 99) [66, 67] and Cdrdova (diaryl-prolinols 100) [68], among others, involving Coulombic or steric interactions (or both) as well to lock the transition state in the conformation required for stereoselective catalysis (Figure 11.3). 

Later, the same group succeeded in achieving a cascade Michael/nitro-Mannich/ acetalization reaction by the combination of covalent enamine catalysis and noncovalent bifunctional base/Br0nsted acid catalysis [32]. The fuUy substituted piperidines with diverse substitution patterns were prepared efficiently starting from simple aliphatic aldehydes, Ts-protected imines, and trani -P-nitro alkenes (Scheme 9.36). This finding effectively incorporated prolinol silyl ether-catalyzed Michael addition of aldehyde 65 to nitroalkene 75 and valine-derived bifunctional thiourea-mediated nitro-Mannich reaction of y-nitro aldehyde 106 to imine 105 in the cascade process, providing a complementary contribution to the well-known single catalyst-promoted triple cascade reactions and two catalyst-promoted reaction cascades. 

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