Imidazolidinone organocatalysts iminium activation

The synthesis is initiated by the organocatalyzed cascade that activates a,p-unsaturated aldehyde 8 with the formation of an iminium ion (Scheme 14.2). In this way, the imidazolidinone catalyst allows hydride transfer from the Hantzsch dihydropyridine 9 onto the highly activated conjugated alkene 11, which creates the nucleophilic enamine intermediate 12. Because of the chirality of the organocatalyst, stereoselective Michael addition (97% ee) to the adjacent enone occurs, with minor preference for the cis diastereomer (2 1 dr). Fortunately, this undesired diastereomer slowly epimerizes to the required trans isomer, which produces (-l-)-ricciocarpin A when treated with samarium triisopropoxide. Besides the Cannizzaro-like redox disproportionation, which allows the lactone producing Evans-Tihchenko reaction to occur, samarium(III) also enhances the epimerization to the trans isomer and therefore produces the desired isomer in high selectivity. 

In a similar manner, Waldmann and coworkers described the activation of cinnamaldehyde by prolinol derivative 17 to achieve enantio- and diastereoselective Michael addition of the malonic derivative 16 to the a,p-unsaturated iminium 18 (Scheme 14.3) [9]. In order to accomplish selectivity, four organocatalysts were screened, of which were three prolinol derivatives and the previously discussed MacMillan s imidazolidinone 10. In contrast to List s example, the imidazolidinone gave poor enantioselectivity (58/53% ee), but good diastereoselectivity (4 1 dr) when... 

Organocatalysts To date, the main classes of organocatalysts that have been used are [42] imidazolidinone, diarylprolinol silyl ether, cinchona alkaloid, and phosphoric acid and thiourea derivatives. Essentially, two modes of activation can be considered the reversible formation of iminiums/enamines (covalent activation) with a,P-unsaturated aldehydes and ketones in the presence of primary or secondary chiral amines (Figure 35.1), and activation via hydrogen-bond formation (non-covalent activation) when chiral catalysts bearing hydrogen-bond donors are used (Figure 35.2). 

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