N-Heterocyclic carbene catalysis: Application to the total synthesis of cephalimysin A, and development of multicatalytic cascade reactions

Application of the N-Heterocyclic carbene catalyzed Stetter reaction to the total synthesis of 9-epi-cephalimysin A has been realized. The approach centers on the use of an asymmetric catalytic Stetter reaction to access the spirocyclic core of cephalimysin A. Specifically it was found that a photoisomerization/Stetter protocol allows rapid access to an intermediate readily amenable for further functionalization. This intermediate was further elaborated to three stereoisomers of the naturally occurring cephalimysin A.;During the investigation of cephalimysin A an interesting side product was observed that led to the development of several multicatalytic cascade reactions utilizing N-heterocyclic carbenes. Specifically the pairing of secondary-amine catalysts with N-heterocyclic carbenes allowed for the synthesis of densely functionalized cyclopentanones in a single step. Moreover, a synergistic relationship was observed between the two catalysts. This partnership allowed for the products to be achieved in higher selectivity than would have been possible if conducting the reactions in a stepwise fashion.