Direct Catalytic Asymmetric Aldol-Tishchenko Reaction
Vijay Gnanadesikan, Yoshihiro Horiuchi, Takashi Ohshima and Masakatsu Shibasaki*
*Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo
113-0033, Japan, Email: mshibasa
mol.f.u-tokyo.ac.jp
V. Gnanadesikan, Y. Horiuchi, T. Ohshima, M. Shibasaki, J. Am. Chem. Soc., 2004, 126, 7782-7783.
DOI: 10.1021/ja047906f
Abstract
A direct catalytic asymmetric aldol reaction of propionate equivalent was achieved via the aldol-Tishchenko reaction. Coupling an irreversible Tishchenko reaction to a reversible aldol reaction overcame the retro-aldol reaction problem and thereby afforded the products in high enantio and diastereoselectivity.
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proposed mechanism
Details
The document discusses the development of a direct catalytic asymmetric aldol-Tishchenko reaction by Vijay Gnanadesikan, Yoshihiro Horiuchi, Takashi Ohshima, and Masakatsu Shibasaki from the University of Tokyo. This reaction aims to achieve high product yields and enantioselectivity without the need for stoichiometric preactivation of ketones. The researchers focused on ethyl ketones, which are challenging due to their tendency towards retro-aldol reactions. They utilized a lanthanoid-based heterobimetallic catalyst to facilitate the reaction, inspired by previous work on SmI2-catalyzed Tishchenko reactions and yttrium-salen complex catalyzed reactions. Optimization studies revealed that using La(OTf)3, (R)-BINOL, and BuLi in a 1:3:5.6 ratio provided the best results. The reaction was effective with various aldehyde and ketone substrates, achieving high enantioselectivity (up to 95% ee) and yields (up to 96%). The mechanism involves reversible aldol formation followed by an irreversible Tishchenko reaction, preventing retro-aldolization. This method offers a practical and efficient approach for synthesizing enantioselective aldol products, with potential applications in the synthesis of polypropionate natural products. Further studies are ongoing to expand the substrate scope and understand the reaction mechanism better.
Key Words
Tishchenko Reaction, 1,3-Diols
ID: J48-Y2004-1520
