Angewandte
Chemie
DOI: 10.1002/anie.201207304
Organofluorine Chemistry
À
C F Bond Activation of Unactivated Aliphatic Fluorides: Synthesis of
Fluoromethyl-3,5-diaryl-2-oxazolidinones by Desymmetrization of 2-
Aryl-1,3-difluoropropan-2-ols**
Gꢀnter Haufe,* Satoru Suzuki, Hiroyuki Yasui, Chisato Terada, Takashi Kitayama, Motoo Shiro,
and Norio Shibata*
The selective synthesis of fluorinated organic compounds and
the investigation of their properties have become major topics
in all fields of the chemical sciences, as well as in technological
b-trifluoromethyl-b-halostyrenes with primary amines to
form vinylogous guanidinium salts.[9] As part of our research
program related to the development of biologically relevant
fluorine-containing molecules,[10,11] we have been interested in
3,5-diaryl-2-fluoromethyl-oxazolidin-2-ones (1). 3,5-Diaryl-2-
trifluoromethyl-oxazolidin-2-ones (2) are promising agro-
chemicals which can act as insecticides, acaricides, ectopar-
asiticides, and control agents for animal parasites.[12] Although
more than 4400 compounds related to 2 are registered in the
SciFinder database (most of them patented),[13] no mono-
fluoromethyl analogues, 1, have yet been reported (Figure 1).
applications.[1] Whereas methods for the formation of C F
À
bonds have been developed from the beginning of organic
fluorine chemistry,[2] the application of C F bond cleavage in
À
poly-fluorinated carbon compounds for the preparation of
partially fluorinated molecules has been less developed.[3]
À
This is apparently due to the fact that C F bonds are the
strongest that carbon can form.[4] Research into the activation
[5]
À
of C F bonds of arylfluorides has a long history, but
aliphatic fluorides have been less frequently involved in such
processes and quite forcing conditions, such as organometallic
reagents or strong nucleophiles, have to be applied.[6] Thus,
the development of mild and effective methods for the
À
activation of aliphatic C F bonds has become a stimulating
À
topic in general organic chemistry. Although the C F bond
Figure 1. Biologically relevant 3,5-diaryl-2-(trifluoromethyl)-oxazolidin-2-
ones.
activation of several aliphatic fluorides with lithium reagents,
Brønsted acids, Lewis acids, transition metals, or Grignard
reagents has been reported in recent years,[3a,7] most of these
methods require that the fluorine atom(s) should be bound in
an activated position such as benzylic, allylic, a to a carbonyl
Herein, we disclose the first general synthesis of a series of
3,5-diaryl-2-fluoromethyl-oxazolidin-2-ones 1 by a conceptu-
ally new desymmetrization of unactivated aliphatic di-fluo-
À
(or an equivalent), on a halogenated carbon, and so on. C F
À
bond cleavage in an unactivated aliphatic position under mild
conditions is still a challenge,[8] although the substitution of
CH2F groups by phosphine groups using R2PLi was reported
30 years ago.[8h] Very recently, we have been able to substitute
all three fluorines and another b-halogen substituent of
rides with silicon-induced catalytic C F bond-cleavage as
a key step (Scheme 1). Namely, 2-aryl-1,3-difluoropropan-2-
ols 3 were transformed into 3,5-diaryl-2-fluoromethyl-oxazo-
lidin-2-ones 1 through their carbamates 4 by a mild, BSA/CsF
system (BSA = bis(trimethylsilyl)acetamide) catalytic in CsF.
One of the enantiotopic fluorine atoms of 4 was intramolec-
ularly substituted to afford monofluoromethyl-oxazolidin-2-
[*] Prof. Dr. G. Haufe
Organisch-Chemisches Institut, Westfꢀlische Wilhelms-Universitꢀt
Mꢁnster, 48149 Mꢁnster (Germany)
E-mail: haufe@uni-muenster.de
S. Suzuki, H. Yasui, C. Terada, T. Kitayama, Prof. Dr. N. Shibata
Department of Frontier Materials, Nagoya Institute of Technology
Gokiso, Showa-ku, Nagoya 466-8555 (Japan)
E-mail: nozshiba@nitech.ac.jp
Dr. M. Shiro
Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima
Tokyo 196-8666 (Japan)
[**] This study was financially supported in part by Grants-in-Aid for
Scientific Research from MEXT (Ministry of Education, Culture,
Sports, Science and Technology) (24105513, Project No. 2304:
Advanced Molecular Transformation by Organocatalysts) and by the
Deutsche Forschungsgemeinschaft (DFG). We thank the Asahi
Glass Foundation for partial support.
Scheme 1. Synthesis of 3,5-diaryl-2-fluoromethyl-oxazolidin-2-ones by
Supporting information for this article is available on the WWW
the desymmetrization of unactivated aliphatic fluorides using silicon-
À
induced or sodium-assisted C F bond-cleavage as a key step.
Angew. Chem. Int. Ed. 2012, 51, 12275 –12279
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12275