Synthesis of Indolizidines Bearing Quaternary Stereocenters

Significance

The synthesis of two new polyhydroxylated indolizidines by stereoselective allyl­silane addition to tertiary N-acyliminium ions at a bicyclic ring junction is described. Starting from readily available A (N. Langlois, B. K. Le Nguyen J. Org. Chem. 2004, 69, 7558-7564), a two-step procedure leads stereoselectively to B bearing a quaternary allyl group. Chiral auxiliary removal followed by simple silicon protection and N-allylation affords intermediate C, which, upon subjection to metathesis, dihydroxylation and further manipulation, furnishes isomeric products D and E in 10 steps and 2% and 15% overall yields, respectively. The structure and absolute configuration of the products was established on the basis of the X-ray single-crystal structure analysis of intermediate F and NMR spectral correlations.