[4+1] Heteroannulation to Form 1‐Pyrrolines through Alder‐Ene Reaction of in situ Generated Ynimines: Development and Application in Total Synthesis of Borrecapine
Year: 2024
Type: article
Abstract: We report in this paper a novel Cu‐catalyzed synthesis of polysubstituted 1‐pyrrolines. The reaction of β,γ‐unsaturated oxime esters 4 with terminal alkynes 5 in the presence of a catalytic amount of Cu(OAc) 2 and 2,2′‐biquinoline affords the corresponding 1,6‐enynimines, which undergo a highly stereoselective Alder‐ene reaction to afford 1‐pyrrolines with concomitant generation of a quaternary carbon and a 2‐azadiene motif. It represents an unusual [4+1] heteroannulation reaction wherein terminal alkynes act as a one carbon donor and are 1,1‐difunctionalized. Mechanistic studies suggest that the allylic hydrogen trans to the oxime ester main chain is selectively transferred to the electron‐rich alkyne during the pericyclic reaction. The resulting 1‐pyrrolines undergo facile acid‐catalyzed regioselective Wagner–Meerwein rearrangement to provide 2 H ‐pyrroles in excellent yields. The 2 H ‐pyrroles are also accessible from 4 and 5 in a one‐pot manner without isolation of the 1‐pyrrolines. Leveraging this heteroannulation reaction as a key step, the first total synthesis of borrecapine, a 2,3,3,5‐tetrasubstituted pyrrolidine, is accomplished.
Source: Angewandte Chemie
Authors: Rémi Lavernhe, Qian Wang, Jieping Zhu
Institution: École Polytechnique Fédérale de Lausanne
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,250
OpenAlex ID: W4401641256