Enamine organocatalyzed conjugate addition

Mosse and Alexakis [66] reported in 2005 the first organocatalyzed 1,4-conjugate addition of aldehydes to vinyl sulfones. The organocatalyst, N-tPr-2,2 -bipyrrolidine (2), induced a good enantioselectivity when using l,l-bis(benzenesulfonyl) ethylene (72) while phenyl vinyl sulfone (73) was not reactive under the same conditions (Scheme 34.26). As product 74 is sensitive to silica gel, it is accompanied by byproduct 75. To explain the observed selectivity, the authors suggested a transition state where the pyrroUdine moiety bearing the isopropyl substituent shields the Re face of the enamine and locks the conformation of the enamine intermediate. 

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. 

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