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Synfacts 2015; 11(1): 0068
DOI: 10.1055/s-0034-1379692
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Reaction of Tertiary Enamides with Salicylaldehydes

Contributor(s):
Mark Lautens
,
Thomas Johnson
He L, Zhao L, Wang D.-X, Wang M.-X * Institute of Chemistry, Chinese Academy of Sciences and Tsinghua University, Beijing, P. R. of China
Catalytic Asymmetric Difunctionalization of Stable Tertiary Enamides with Salicylaldehydes: Highly Efficient, Enantioselective, and Diastereoselective Synthesis of Diverse 4-Chromanol Derivatives.

Org. Lett. 2014;
16: 5972-5975
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Publication History

Publication Date:
15 December 2014 (online)

 
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Key words

enamides - titanium - BINOLs

Significance

Tertiary enamides are related to enamines by replacement of an N-alkyl substitutent with an electron-withdrawing group. Despite this change, they remain nucleophilic. Taking advantage of this characteristic and of the electrophilicity of the transient iminium, the authors developed a modular titanium(IV)-catalyzed synthesis of 4-chromanol derivatives, by reaction with salicylaldehydes.


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Comment

The use of a titanium–(R)-BINOL complex enabled the synthesis of diverse 4-chromanol products with good to excellent enantio- and dia­stereoselectivity. Water was found to have a marked effect on enantioselectivity: under anhydrous conditions, the ee decreased to 50.8%, whereas it was measured at 96.5% in the presence of 20 mol% water, in the model reaction. The exact mechanism remains to be elucidated.


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