Development of domino cyclization reaction for one-pot synthesis of pyrroloindolizines and its application to total syntheses of related alkaloids

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We could find a gold-catalyzed domino reaction including an activation of triple bond, 6-exo-dig cyclization from imine nitrogen, generation of azomethine ylide, and enamine cyclization.Alkynyl iminoesters could be transformed into indolizines as a sole diastereomer. The X-ray crystallographic analysis on phenylmenthyl ester derivative revealed the configuration of the products and the mechanism on the observed stereoselectivities. However, the enamine cyclization, the final step for pyrroloindolizine formation, could not proceed at all because of the isomerization of the exo-enamine into the inappropriate endo-enamine via a conjugation with aromatic ring. After the investigations on the enamine cyclization step with intermolecular approach for a preclusion of undesired isomerization, we finally realized that trifluoroethyl ester worked best as an electrophile to give hydroxypyrroles in one-pot process. Based on these findings, synthetic studies on myrmicarins are now in progress.