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
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.
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.
