Synfacts 2008(3): 0278-0278  
DOI: 10.1055/s-2008-1042694
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Nd/Na-Catalyzed Anti-Selective Nitroaldol Reaction

Contributor(s):Mark Lautens, Praew Thansandote
T. Nitabaru, N. Kumagai*, M. Shibasaki*
The University of Tokyo, Japan
A Catalytic Asymmetric anti-Selective Nitroaldol Reaction with a Neodymium-Sodium Heterobimetallic Complex
Tetrahedron Lett.  2008,  49:  272-276  
Further Information

Publication History

Publication Date:
21 February 2008 (online)


Significance

A catalytic asymmetric anti-selective nitroaldol reaction has been developed using a Nd/Na/amide heterobimetallic catalyst. The yields, diastereoselectivities, and enantioselectivities are highest with aromatic aldehydes with an ortho-alkyl substituent. The products are useful anti-1,2-nitro alkanols, which can be rapidly converted into synthetically useful anti-1,2-amino alcohols.

Comment

Most asymmetric nitroaldol reactions are syn-selective, which makes this anti-selective methodology noteworthy. The key to the anti-­diastereoselectivity is the heterobimetallic complex, which discourages chelation in a cyclic transition state and encourages the extended transition state (shown above) leading to the anti-product. Though the ee values for this reaction are moderate, the diastereoselectivities are usually high. For other anti-selective nitroaldol reactions, see: T. Risgaard, K. V. Gothelf, K. A. Jørgensen Org. Biomol. Chem. 2003, 1, 153; D. Uragachi, S. Sakaki, T. Ooi J. Am. Chem. Soc. 2007, 129, 12392.