Total synthesis of (−)-codonopsinine via regioselective and diastereoselective amination using chlorosulfonyl isocyanate

Abstract The total synthesis of (−)-codonopsinine ( 1 ) from the readily available ( S )-3-chloropropan-1,2-diol is described. The key steps for the preparation of (−)-codonopsinine ( 1 ) involve the regioselective and diastereoselective amination of anti -1,2-dibenzyl ether 11 using chlorosulfonyl isocyanate and intramolecular amidomercuration to form the pyrrolidine ring. Notably, the reaction between anti -1,2-dibenzyl ether and chlorosulfonyl isocyanate in toluene at 0 °C produced the corresponding anti -1,2-amino alcohol 12a as a major product with excellent diastereoselectivity ( anti : syn  = 29:1). This observation can be explained by the neighboring group participation leading to the retention of stereochemistry.