Stereocontrolled Synthesis of Substituted Chiral Piperidines via One-Pot Asymmetric 6π-Azaelectrocyclization: Asymmetric Syntheses of (−)-Dendroprimine, (+)-7-Epidendroprimine, (+)-5-Epidendroprimine, and (+)-5,7-Epidendroprimine

Abstract

The asymmetric one-pot 6π-azaelectrocyclization of alkenyl vinyl stannane, ethyl (<i>Z</i>)-2-iodo-4-oxobutenoate, and (−)-7-isopropyl-<i>cis</i>-aminoindanol in the presence of a Pd(0) catalyst stereoselectively produced the tetracyclic aminoacetal compounds, resulting from the four-bond formation accompanying by controlling the stereochemistry at the two asymmetric centers. The produced cyclic aminoacetals can be regarded as synthetic precursors of substituted chiral piperidines, and the syntheses of 2,4- and 2,4,6-substituted piperidines were realized from the obtained aminoacetals by the stereoselective hydrogenation of the double bond conjugated with the C-4 ester group and alkylation at the aminoacetal moiety. In addition, the stereoselective synthesis of an indolizidine alkaloid, (−)-dendroprimine, and its three stereoisomers, (+)-7-epidendroprimine, (+)-5-epidendroprimine, and (+)-5,7-epidendroprimine, were achieved