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Synfacts 2014; 10(5): 0492
DOI: 10.1055/s-0033-1341182
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Zinc-Catalyzed Aldol Reaction of Glycinate Schiff Bases and Aldehydes

Contributor(s):
Mark Lautens
,
David A. Petrone
Trost BM, * Miege F. Stanford University, USA
Development of ProPhenol Ligands for the Diastereo- and Enantioselective Synthesis of β-Hydroxy-α-amino Esters.

J. Am. Chem. Soc. 2014;
136: 3016-3019
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Further Information

Publication History

Publication Date:
17 April 2014 (online)

 
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Key words

zinc - ProPhenol - aldols

Significance

The synthesis of optically active β-hydroxy-α-amino acids represents an important challenge, as they are common motifs in complex natural products. Despite the numerous attempts to access this substructure via direct asymmetric aldol reaction between glycinate Schiff bases and aldehydes, selectivities remain low. Another common issue seen with this transformation is the difficulty in selectively obtaining the syn stereoisomer. Here, the authors report a new catalytic asymmetric avenue to this desired isomer via a similar aldol strategy using a Zn/ProPhenol ligand combination.


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Comment

The authors report the direct zinc-catalyzed asymmetric synthesis of β-hydroxy-α-amino acid esters via the aldol reaction between ­glycinate Schiff bases and aldehydes. After undertaking a ligand structure optimization, the authors found [(S,S),(S,S)]-L1 to be superior. Products were afforded in good to excellent yields, with moderate to excellent levels of both diastereoselectivity and enantioselectivity. Additionally, the authors applied this transformation to α-chiral aldehydes, which generated products with three contiguous stereocenters with high levels of diastereoselectivity.


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