Synthesis of (−)‐8a‐<i>epi</i>‐Lentiginosine via Tsuji–Trost Reaction of <scp>d</scp>‐Glucose‐Derived Allylic Alcohols and Crystal Structure Analysis

Abstract An indolizidine alkaloid, (−)‐8a‐ epi ‐lentiginosine was synthesized from d ‐glucose using the Pd‐BiPhePhos catalyzed intramolecular Tsuji–Trost reaction of non−derivatized allylic alcohol as a key construction of the hydroxylated pyrrolidine ring to give the desired product in good yield and high stereospecificity ( dr = 97:3). The absolute configuration and structure of (−)‐8a‐ epi ‐lentiginosine were confirmed by NMR and X‐ray crystal structure analysis. The crystal structure of (−)‐8a‐ epi ‐lentiginosne showed the envelope conformation of the five‐membered ring, which is an N‐atom in the endo‐position, and the fused six‐membered ring adopts a chair conformation similar to the DFT optimized structure. The solid‐state packing is dominated by a 1D‐hydrogen‐bonded network along the a‐axis involving both hydroxyl groups and the amine. The large HOMO–LUMO energy gap indicated the high stability of the compound.