control model for high-valence iodine catalyzed olefin bifunctionalization with
C2 axis symmetry
Network (Reporter Ma Chao) Recently, Academician Cheng Jinpei and Associate
Professor Xue Xiaosong from Nankai University collaborated with Prof. Hawke of
the University of California, Los Angeles, and Professor Eric Jacobson of
Harvard University to catalyze olefin asymmetry in high-valence iodine achieved
significant breakthrough in illuminating the mechanism of chiral geminal difluorination
reaction catalyzed by aryl iodide. The research results were published in Journal of the American Chemical Society.
Hawke and Xue Xiaosong are co-authors.
element is called the “the little giant” in the periodic table. The
introduction of a fluorine atom or a fluorine-containing group into an organic
compound tends to dramatically change its physical, chemical, and physiological
properties. Therefore, fluorine-containing organic compounds are widely applied
in the fields of medicines, pesticides, and materials. Among the many
fluorine-containing groups, difluoromethyl groups are generally considered to
be "bioisosteres" of hydroxyl groups and mercapto groups. The
introduction of such groups into drug molecules generally improves their
metabolic stability and oral bioavailability. .
"A series of
problems caused by the clinical use of racemic drugs, such as drug efficacy,
drug transport, metabolism, toxicity, etc., have attracted more and more
attention. For the synthesis of drug molecules, the development of chiral
catalytic synthesis of difluoromethyl-containing functional groups is of great
significance." Xue Xiaosong introduced.
In 2016, the Eric
Jacobson team used the chiral aryl iodide catalytic strategy to efficiently and
selectively to construct a quaternary carbon chiral center containing
difluoromethyl groups under mild conditions. However, how does chiral aryl
iodide catalyze this reaction and how can it result in such high selectivity?
These two key issues remain unsolved. High-valence iodine has similar reaction
properties to transition metals, and its non-toxic safety and economical cost
are in line with the development trend of modern chemistry. However, the
high-valence iodine catalyzed asymmetric transformation has always been one of
the most challenging research topics in the field of high-valence iodine
chemistry. The key problem that restricts the development of this field is the
ambiguity of the relevant reaction mechanism and the lack of understanding of
the chiral control mechanism.
Academician Cheng guided us to study the mechanism of geminal difluoride of styrene
derivatives mediated by high-valence iodine reagents through DFT calculation,
and we found a new activation model of the reagent." Xue said. On the
basis of previous research, the research team cooperated with Prof. Hawke and
Professor Eric Jacobson to investigate the mechanism of asymmetric geminal fluorination
of styrene derivatives by chiral aryl iodide, conducting in-depth theoretical
research in the chiral control mechanism. “We examined the mechanism of the
reaction in detail, including various possible activation mechanisms of the
catalyst, how the difluoromethyl functional group formed, and finally proposed
a chiral control model suitable for understanding and predicting C2 axis
symmetry of high-valence iodine catalyzing olefin bifunctionalization reaction."
In this model, the
chiral pocket of the catalyst enables the recognition of the substrate and the Latent
chiral surface, which not only
explains and predicts the substituent effects of the catalyst and substrate
observed in this experiment, but also provide a theoretical basis for the
rational design of high-valence iodine catalyzed asymmetric conversion of
olefins. The study will also deepen people's understanding of the chemical
reactivity of high-valence iodine helping develop greener and cleaner chemistry
based on high-valence iodine.
It is understood
that Journal of the American Chemical
Society published this achievement for the 70th birthday of Academician
The research was funded by the National Natural Science Foundation of China and