Research Achievements

October 3, 2019 

Teaching an old compound new tricks: Enabling selective carbon-carbon bond formation at the inherently inert position of enol silyl ethers

Chemists open the door to new transformations of a compound commonly used for drug development.


Nagoya University researchers have discovered a new way to modify reactants that have been widely studied and utilized for over 50 years, enabling more efficient production of some complex organic molecules used in medical drugs. The work was published in Nature Communications.


Synthetic chemists often use a class of molecules called enol silyl ethers, in which silicon atom (Si), oxygen atom (O), and carbon atom (C) are connected as Si-O-C=C (- is a single bond, and = is a double bond). These molecules are reactive to form a new bond at the carbon atom not attached to the oxygen atom, serving as reliable substrates for efficient and selective synthesis of functionalized carbonyl compounds, and thus has been widely utilized in synthetic organic chemistry over 50 years. 


Professor Takashi Ooi and colleagues from Nagoya University's Institute of Transformative Bio-Molecules in Japan wanted to find out if selective C-C bond formation at an inherently inert position of enol silyl ethers could be accomplished to form more complex enol silyl ethers, which are then available for further chemical transformations.


They developed a chemical reaction by the combined use of two catalysts, a photosensitizer and an organic base, under visible-light irradiation (blue LED). The new reaction does not eliminate a silyl group, which normally leads to the formation of simple carbonyl compounds. Rather, it cleaves a relatively stable carbon-hydrogen bond, which enables the replacement of the hydrogen with an alkyl group. The new process allows chemists to synthesize previously difficult-to-access complex carbonyl compounds, and it can accelerate the discovery of new drugs.


This catalytic strategy is expected to help streamline synthesis of a variety of other organic molecules as well. "Our strategy is not limited to enol silyl ethers," says Ooi. "We would like to apply it to other organic compounds to enable bond-forming reactions at previously difficult-to-functionalize positions in molecules."


Figure: A new transformation for efficient synthesis of complex organic molecules



The article, "Direct allylic C-H alkylation of enol silyl ethers enabled by photoredox-Brønsted base hybrid catalysis" was published in Nature Communications at DOI:10.1038/s41467-019-10641-y


Authors: Kohsuke Ohmatsu, Tsubasa Nakashima, Makoto Sato, and Takashi Ooi


For more information, contact:

Professor Takashi Ooi


Institute of Transformative Bio-Molecules, Nagoya University



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About Nagoya University

Nagoya University has a history of about 150 years, with its roots in a temporary medical school and hospital established in 1871, and was formally instituted as the last Imperial University of Japan in 1939. Although modest in size compared to the largest universities in Japan, Nagoya University has been pursuing excellence since its founding. Six of the 18 Japanese Nobel Prize-winners since 2000 did all or part of their Nobel Prize-winning work at Nagoya University:  four in physics - Maskawa and Kobayashi in 2008, and Akasaki and Amano in 2014  - and two in Chemistry - Noyori in 2001 and Shimomura in 2008. In mathematics, Mori did his Fields Medal-winning work at Nagoya University. A number of other important discoveries have been made at Nagoya University, including the Okazaki DNA Fragments by Reiji and Tsuneko Okazaki in the 1960s; and depletion forces by Asakura and Oosawa in 1954.



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