10.1002/anie.201707375
Angewandte Chemie International Edition
COMMUNICATION
Scheme 4. Scope of the reaction with -phenyl diazoacetate 4a and
difluoromethylated olefins 2. [a] Reaction was carried out at –60 °C.
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The difluoromethyl styryl derivatives 2a,b bearing a methyl group
at the para and meta positions were readily converted into the
corresponding dilfuoromethylcylopropanes 6a and 6b in good
yields and excellent ee’s. The naphthyl-substituted olefin was
smoothly reacted to give 6c in 77% yield and a moderate 9:1 dr.
The major diasteroisomer was obtained in 93% ee. Finally, aryls
bearing a halogen or a nitro group were transformed into the
corresponding cyclopropanes 6d-g in good yield, excellent
diastereoselectivities and enantioselectivities. Note that the nitro
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a poor 28% yield, despite a complete
diastereoselectivity and a high enantioselection of the reaction.
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In summary, we reported herein the first asymmetric synthesis of
difluoromethylcyclopropanes. The methodology, using a unique
catalyst, allowed the formation of the difluoromethylated
cyclopropanes in high yields (up to 95%), high
diastereoselectivities (up to 20:1) and excellent enantiomeric
excess (up to 99%). Indeed, using either -aryl diazoacetates or
-nitro diazoketone with Rh2((S)-BTPCP)4 as a catalyst, -
difluoromethylated olefins were readily converted into the
corresponding highly decorated cyclopropanes. The scope of the
reaction is quite broad and offers a new access to this versatile
class of compounds.
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Acknowledgements
This work was supported by INSA Rouen, Rouen University,
CNRS, EFRD, Labex SynOrg (ANR-11-LABX-0029) and Région
Normandie (Crunch Network) as well as the Natural Science and
Engineering Research Council of Canada (NSERC), the Canada
Foundation for Innovation, the Canada Research Chair Program,
the FQRNT Centre in Green Chemistry and Catalysis and
Université de Montréal. M.B. thanks the Labex SynOrg (ANR-11-
LABX-0029) and Université de Montréal for a postdoctoral
fellowship. W.-S.H. thanks the Labex SynOrg (ANR-11-LABX-
0029) for a doctoral fellowship. A.B.C. thanks the Labex SynOrg
(ANR-11-LABX-0029) for a chair of excellence.
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Keywords: Difluoromethyl • Cyclopropane • Asymmetric
catalysis • Diazo derivatives • Chiral rhodium catalyst
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