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. Issue 29 (3rd June 2015)

• Record Type: Journal Article
• Authors: Wang, Zheng; Yu, Xingxin; Tian, Bo‐Xue; Payne, Daniel T.; Yang, Wu‐Lin; Liu, Yang‐Zi; Fossey, John S.; Deng, Wei‐Ping
• Is Part Of: Chemistry. Volume 21:Issue 29(2015)
• Page Start: 10457
• Page End: 10465
• Publication Date: 2015-06-03
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201500966
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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‐ (&gt;98:2 d.r.) and enantioselectivities (up to 97 % <italic>ee</italic>). 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.</p> </abstract>