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

The asymmetric one-pot 6π-azaelectrocyclization
of alkenyl
vinyl stannane, ethyl (Z)-2-iodo-4-oxobutenoate,
and (−)-7-isopropyl-cis-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.