10.1002/chem.201902927
Chemistry - A European Journal
COMMUNICATION
Scheme 2. Proposed mechanism for the generation of both isomers of biflavanone 2a.
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In order to rule out a thermodynamic-kinetic control, we performed
several control experiments. Thus, isolated biflavanone (R*,R*)-
2a was refluxed in THF for 24h, alone or in the presence of 1.1
equiv. of SmI2/MeOH, or 1.1 equiv. SmI3/MeOH, affording
unaltered starting (R*,R*)-biflavanone 2a. As a further control we
have also refluxed (R*,R*)-2a in the presence of flavone 1b and
1.1 equiv. of SmI2/MeOH. Under these conditions, unaltered
(R*,R*)-biflavanone 2a was again recovered.
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In summary, a remarkable example of a temperature-controlled
stereodivergent reaction promoted by SmI2 for the synthesis of
2,2’-biflavanones is herein described. The temperature-induced
reversal of selectivity and can be explained on the basis of a shift
in the mechanism of the process, where the key step is the
generation of a stabilized radical intermediate: low temperature
favors a radical coupling process, while at high temperature, the
anionic mechanism is preferred. Thus, when the reaction is
performed at -40 ºC, only (R*,R*)-stereoisomer is observed
whereas at reflux temperature (R*,S*)-isomer is generated as the
major product. Temperature dependent inversion of
diastereoselectivity is an interesting and unusual phenomenon
and these results offer important clues for the very attractive idea
of controlling stereochemistry by only altering the reaction
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conditions. The development of
a temperature-controlled
enantioselective version of this reaction is currently under
investigation in our research group.
Acknowledgements
Thanks are due to Principado de Asturias (FICYT
IDI/2018/000181) for financial support. University of Aveiro and
FCT/MEC for the financial support of the QOPNA research unit
(FCTUID/QUI/00062/2013) through national funds and, where
applicable, co-financed by the FEDER, within the PT2020
Partnership Agreement, and to the Portuguese NMR Network.
Authors also thank Prof. Francisco J. González and Prof. Ramón
Liz for their valuable discussions.
[11] Studies of different proton sources (H2O, MeOH, EtOH, i-PrOH, and t-
BuOH), including the effect of temperature, has been carried out. This study
showed that the best results, in terms of both yield and stereoselectivity, were
those obtained when methanol was used as the proton source (see tables at
the Supporting Information file). For reviews on the influence of additives on
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Keywords: Flavonoid • Natural Products • Radical coupling •
Samarium • Stereodivergent reaction
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