Abstract
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 NaBH4 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.
Original language | English |
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Pages (from-to) | 10457–10465 |
Number of pages | 9 |
Journal | Chemistry: A European Journal |
Volume | 21 |
Issue number | 29 |
Early online date | 3 Jun 2015 |
DOIs | |
Publication status | Published - 13 Jul 2015 |
Bibliographical note
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Keywords
- Asymmetric synthesis
- Copper
- Cycloaddition
- Density functional calculations
- Ligands
ASJC Scopus subject areas
- General Chemistry