Total Synthesis of Indolizidine Alkaloids (–)‐167B, (–)‐209I, and (–)‐223A by Using a Common Tricyclic Lactone

Abstract

AbstractHighly stereocontrolled total synthesis of dart frog indolizidine alkaloids (–)‐167B, (–)‐209I, and (–)‐223A was accomplished, with a common tricyclic lactone intermediate as the starting compound, in overall yields of 17 %, 14 %, and 17 %, respectively. The C7–C8 bond of the 167B, without a C8 chiral substituent, was formed through ring closure metathesis followed by hydrogenation. In 209I and 223A, which have a C8 chiral substituent, highly substrate‐controlled asymmetric radical cyclization was used to form the C7–C8 bond, and the correct stereochemistry of the C8 substituents was obtained in both molecules. Ethyl substituent at the C6 position of 223A was obtained with correct stereochemistry through asymmetric alkylation/epimerization sequences of the tricyclic lactone. Cleavage of the excess carbon on the C5 position of all three indolizidines was performed by using a Barton decarboxylation protocol. Reduction of the corresponding indolizidin‐3‐ones by LAH completed the total synthesis of (–)‐167B, (–)‐209I and (–)‐223A.