Ni(II)-Bis[(R,R)-N,N'-dibenzylcyclohexane-1,2-diamine]Br2 Catalyzed Enantioselective Michael Additions of 1,3-Dicarbonyl Compounds to Conjugated Nitroalkenes
David A. Evans* and Daniel Seidel
*Department of Chemistry and Chemical Biology, Harvard University,
Cambridge, Massachusetts 02138, Email: evanschemistry.harvard.edu
D. A. Evans, D. Seidel, J. Am. Chem. Soc., 2005, 127, 9958-9959.
DOI: 10.1021/ja052935r
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Abstract
A Ni(II)-(bis)diamine-catalyzed, highly enantioselective Michael addition of substituted and unsubstituted malonates and β-ketoesters to nitroalkenes bearing aromatic and aliphatic residues has been developed.
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Details
The document discusses the development of a new chiral Ni(II) catalyst for enantioselective Michael additions of 1,3-dicarbonyl compounds to conjugated nitroalkenes. This catalyst, Ni(II)-Bis[(R,R)-N,N′-dibenzylcyclohexane-1,2-diamine]Br2, facilitates the transformation at ambient temperatures, producing synthetically useful chiral building blocks. The catalyst design involves a moderately Lewis acidic metal salt bound to two chiral ligands, which enolize the substrate without needing an ancillary base. The study shows that the dibenzyl substituted cyclohexanediamine ligand performs best, with NiBr2 yielding optimal results in toluene. The reaction conditions were optimized, achieving high yields and enantioselectivities for various substituted and unsubstituted malonates and nitroalkenes. The scope extends to β-ketoester nucleophiles, providing excellent yields and selectivities. Large-scale experiments demonstrated the catalyst's efficiency at low concentrations. The proposed transition structure suggests that dipole reduction and minimized ligand-substrate interactions contribute to high enantioselectivities. Further studies are needed to fully understand the mechanism. The research was supported by the NSF and NIH, with additional postdoctoral fellowship support from the Ernst Schering Research Foundation. Experimental procedures and data are available online.
Key Words
Michael Addition, Nitro Compounds
ID: J48-Y2005-2450