Highly Diastereo‐ and Enantioselective Michael Addition of Nitroalkanes to 2‐Enoyl‐Pyridine N‐Oxides Catalyzed by Scandium(III)/Copper(II) Complexes

Abstract

A C2 -symmetric Schiff-base ligand, derived from tridentate-Schiff-base, was developed and successfully applied to the asymmetric Michael addition of nitroalkanes to 2-enoyl-pyridine N-oxides. With this newly catalytic system, an unprecedented diastereoselectivity was obtained in the asymmetric Michael addition of nitroalkanes to 2-enoyl-pyridine N-oxides. In addition, a switch in enantioselectivity was achieved by using this newly catalytic system and our previous catalyst. After a facile reduction, the optically active adduct was converted to a biologically active dihydro-2H-pyrrol 4 a. Furthermore, a connection of two tridentate-Schiff-base subunits proved to be an effective strategy in ligand design.

Organocatalytic Enantioselective Michael Addition of Oxazolones to 2‐Enoylpyridine N‐Oxides for Assembling of Pyridine N‐Oxides Featuring Vicinal Oxygen‐Containing Tetrasubstituted Stereocenters

“…As a direct and efficient access to those chiral pyridine N ‐oxide frameworks, catalytic enantioselective transformation of 2‐enoylpyridine N ‐oxides has been developed . Particularly, impressive results have been achieved from the chiral metal complexes catalyzed reactions of 2‐enoylpyridine N ‐oxides with the aid of copper, zinc, and scandium/copper . In sharp contrast, the organocatalytic asymmetric reactions of 2‐enoylpyridine N ‐oxides are very limited.…”

Recent Developments in Highly Stereoselective Michael Addition Reactions Catalyzed by Metal Complexes

“…The catalytic system Sc(OTf) 3 /polydentate ligand 116 was applied for the asymmetric Michael addition of nitroalkanes 115 to 2-alkenoylpyridine N-oxides 114 with good enantio-and diastereoselectivity (Scheme 33). 38…”

Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

“…Recently, Pedro and Blay's group synthesized pyBOX (pyridine‐2,6‐bis(oxazolines))‐derived ligand‐La III complex and performed the Michael addition of nitroethane or nitropropane to azachalcone (( E )‐3‐phenyl‐1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one) in moderate enantio‐ and diastereoselectivity . Recently, a similar system involving Sc III complex with C 2 ‐symmetric Schiff base ligands has been developed for the catalytic asymmetric Michael addition of nitroalkanes to azachalcone N ‐oxides by Wang's group with good diastereo‐ and enantioselectivity . Thus, owing to the synthetic versatility of nitro groups, immense progress of the asymmetric Michael additions of nitroalkane has been reported, but the control of diastereoselectivity and enantioselectivity, and catalytic efficiency were still limited.…”