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Diastereodivergent Asymmetric 1,3‐Dipolar Cycloaddition of Azomethine Ylides and β‐Fluoroalkyl Vinylsulfones: Low Copper(II) Catalyst Loading and Theoretical Studies
Author(s) -
Cheng Feng,
Kalita Subarna Jyoti,
Zhao ZhenNi,
Yang Xing,
Zhao Yan,
Schneider Uwe,
Shibata Norio,
Huang YiYong
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201908227
Subject(s) - azomethine ylide , chemistry , cycloaddition , pyrrolidine , 1,3 dipolar cycloaddition , stereoselectivity , catalysis , adduct , enantioselective synthesis , michael reaction , organocatalysis , medicinal chemistry , polymer chemistry , stereochemistry , organic chemistry
A Cu II ‐catalyzed asymmetric 1,3‐dipolar cycloaddition using β‐fluoroalkyl alkenyl arylsulfones as dipolarophiles and glycine/alanine iminoesters as azomethine ylide precursors has been developed. Remarkably, a catalyst loading as low as 0.5 mol % is highly efficient. Accordingly, a wide range of enantioenriched 3‐fluoroalkyl pyrrolidines, as well as Δ 2 ‐pyrroline and pyrrole derivatives, are generated in good to excellent yields with high asymmetric induction. This synthetic approach is diastereodivergent in that exo ‐adducts could be converted into the corresponding exo′ ‐adducts by 1,8‐diazabicyclo[5.4.0]undec‐7‐ene mediated epimerization at C2 of the pyrrolidine core. The free‐energy profiles from DFT calculations suggest the Michael addition of the 1,3‐dipole to be the rate‐ and enantiodetermining step, and the origin of stereoselectivity is studied by means of the noncovalent interaction (NCI) analysis.