Premium
Chiral N,O‐Ligand/[Cu(OAc) 2 ]‐Catalyzed Asymmetric Construction of 4‐Aminopyrrolidine Derivatives by 1,3‐Dipolar Cycloaddition of Azomethine Ylides with α‐Phthalimidoacrylates
Author(s) -
Wang Zheng,
Yu Xingxin,
Tian BoXue,
Payne Daniel T.,
Yang WuLin,
Liu YangZi,
Fossey John S.,
Deng WeiPing
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201500966
Subject(s) - cycloaddition , chemistry , catalysis , ligand (biochemistry) , stereoselectivity , pyridine , 1,3 dipolar cycloaddition , medicinal chemistry , stereochemistry , combinatorial chemistry , organic chemistry , receptor , biochemistry
A protocol to access useful 4‐aminopyrrolidine‐2,4‐dicarboxylate derivatives has been developed. A variety of chiral N,O‐ligands derived from 2,3‐dihydroimidazo[1,2‐a]pyridine motifs have been evaluated in the asymmetric 1,3‐dipolar cycloaddition of azomethine ylides to α‐phthalimidoacrylates. Reactions catalyzed by copper in combination with ligand 7‐Cl‐DHIPOH provided the highest level of stereoselectivity for the 1,3‐dipolar cycloaddition reaction. The reaction tolerates both β‐substituted and β‐unsubstituted α‐phthalimidoacrylate as dipolarophiles, affording the corresponding quaternary 4‐aminopyrrolidine cycloadducts with excellent diastereo‐ (>98:2 d.r.) and enantioselectivities (up to 97 % ee ). Removal of the phthalimido protecting group can be accomplished by a simple NaBH 4 reduction. Theoretical calculations employing DFT methods show this cycloaddition reaction is likely to proceed through a stepwise mechanism and the stereochemistry was also theoretically rationalized.