Stereodivergent Synthesis of Piperidine Alkaloids by Ring-Rearrangement Metathesis/Reductive Lactam Alkylation of Nitroso Diels-Alder Cycloadducts

A general methodology for the stereoselective synthesis of 2-(2-hydroxyalkyl)piperidine alkaloids by ring-rearrangement metathesis of nitroso Diels-Alder cycloadducts is reported. The approach is illustrated by the formal synthesis of porantheridine and the total synthesis of andrachcinidine through a diastereodivergent allylation of an N-alkoxy bicyclic lactam. The asymmetric synthesis of the latter alkaloid provides new insights into the configurational stability of cycloadducts between chloronitroso reagents and cyclopentadiene.