Conversion of MT-sulfone to a trifluoromethyl group by IF5: The application of an MT-sulfone anion as a trifluoromethyl anion equivalent

Article abstract of DOI:10.1039/c1cc13232f

An MT-sulfone group was converted to a trifluoromethyl group by treatment with IF₅ after an alkylation reaction. Therefore, an MT-sulfone anion can be used as a trifluoromethyl anion equivalent. The formal asymmetric Michael-addition of a trifl

Full text of DOI:10.1039/c1cc13232f

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Conversion of MT-sulfone to a trifluoromethyl group by IF5: the
application of an MT-sulfone anion as a trifluoromethyl anion
equivalentw
Yosuke Imagawa, Syuhei Yoshikawa, Tadahito Fukuhara and Shoji Hara*
Received 1st June 2011, Accepted 28th June 2011
DOI: 10.1039/c1cc13232f
An MT-sulfone group was converted to a trifluoromethyl group
by treatment with IF5 after an alkylation reaction. Therefore, an
MT-sulfone anion can be used as a trifluoromethyl anion
equivalent. The formal asymmetric Michael-addition of a
trifluoromethyl anion to crotonaldehyde was also performed.
The introduction of a trifluoromethyl group into a molecule
is a challenging area of organic chemistry because both a
trifluoromethyl anion and its cation are difficult to generate
and use.1 A carbon–carbon bond forming reaction between a
Scheme 1
trifluoromethyl anion and alkyl halides is the most funda-
proceeds as follows: the oxidative fluorination of 1 by IF5
mental method for introducing a trifluoromethyl group into
the molecules, and a trifluoromethyl copper species was most
successfully used, especially, for the introduction of a trifluoro-
methyl group into the aromatic ring or vinylic carbon.2,3
However, a good yield cannot be expected from a reaction
of the trifluoromethyl copper species with aliphatic alkyl halides.4
Although trifluoromethyltrimethylsilane has been used as a
trifluoromethyl anion equivalent,5 it is rarely used in the SN2
reaction with alkyl halides owing to the low yield of the expected
products and the formation of inseparable by-products.4c,6 On
the other hand, MT-sulfone {(methylsulfanyl)methyl tolyl
sulfone} is known to afford a stable anion species by treatment
with a base under mild conditions, and its subsequent reaction
with alkyl halides gives alkylated derivatives 1.7 We found that
the MT-sulfone group in 1 can be converted to a trifluoro-
methyl group by the reaction with IF5.8 Therefore, the
MT-sulfone can be used to introduce the trifluoromethyl
group into the substrate (Scheme 1).
initially occurred to afford 3.10 In the second step, the tosyl
group was eliminated as tosyl fluoride to afford a sulfonium
salt 4, which was converted to difluorosulfide 5 by the attack
of a fluoride ion. Finally, the methylsulfanyl group in 5 was
substituted by a fluoride ion to afford the trifluoromethylated
product 2 (Scheme 2).
Under these conditions, an alkylated MT-sulfone 1a was
converted to 1,1,1-trifluoroalkane 2a in good yield. Furthermore,
a functional group such as an ester, an amide, and a chloride in
1 is tolerable under these conditions, and the functionalized
trifluoromethyl compounds could be obtained as shown in
Table 1.
The reaction of 1 with IF5 was performed under various
conditions, and the best result was obtained by carrying out
the reaction in Et3N–5HF using 6 eq. of IF5 at 60 1C for 48 h.9
In this reaction, the presence of a methylsulfanyl group in 1 is
critical, and the phenyl alkyl sulfone is inert to IF5. During the
reaction, the formation of tosyl fluoride was observed.
From these observations, it can be assumed that the reaction
Division of Chemical Process Engineering, Graduate School of
Engineering, Hokkaido University, Sapporo 060-8628, Japan.
E-mail: shara@eng.hokudai.ac.jp; Fax: +81 11 706 6556;
Tel: +81 11 706 6556
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c1cc13232f
Scheme 2
c
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Chem. Commun., 2011, 47, 9191–9193 9191

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a
Table 1 The reaction of MT-sulfone derivative with IF5
Substrate
Product
Yieldb (%)
C12H25–CF3
87
2a
EtOOC–(CH2)5–CF3
75
81
71
2b
Cl–(CH2)12–CF3
2c
CF3–(CH2)10–CF3
2d
BzO–(CH2)6–CF3
73
2e
Scheme 3
78c
We found that the MT-sulfone group can be converted to
a trifluoromethyl group by the reaction with IF5. As the
MT-sulfone affords a stable anion species by treatment with
a base, and its subsequent reaction with alkyl halides gives
alkylated derivatives, an MT-sulfone anion can be used as a
trifluoromethyl anion equivalent. We also performed the formal
asymmetric Michael-addition of a trifluoromethyl anion to
crotonaldehyde, where the trifluoromethyl group was introduced
at the b-position of crotonaldehyde enantioselectively.
a
If otherwise not mentioned, the reaction was carried out using 6 eq.
b
of IF5/Et3N-5HF at 60 1C for 48 h. Isolated yield based on the
substrate used. 8 eq. of IF5/Et3N-5HF was used.
c
Recently, the asymmetric trifluoromethylation reaction
has received much attention and many elegant methods for
producing a compound having a trifluoromethyl group at its
asymmetric center have been reported.11 However, the asymmetric
Michael-addition of the trifluoromethyl anion to a,b-unsaturated
carbonyl compounds has not yet been reported. Therefore, we
applied our method to introduce a trifluoromethyl group at
the b-position of the carbonyl group enantioselectively. The
asymmetric Michael-addition of MT-sulfone catalyzed by
an organocatalyst was unsuccessful owing to the low acidity
of MT-sulfone (pKa = 23.4).12 On the other hand, the
organocatalyst-catalyzed asymmetric Michael-addition of
bis(phenylsulfonyl)methane (pKa = 12.5)13 to a,b-unsaturated
aldehydes is known.14 Therefore, the Michael-addition of
bis(phenylsulfonyl)methane to crotonaldehyde was performed
in the presence of (S)-2-(diphenyltrimethylsiloxy)methyl-
pyrrolidine, and the resulting adduct 6 was reduced to an
alcohol.15 After the protection of alcohol with TBDMS, one
Notes and references
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c
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Chem. Commun., 2011, 47, 9191–9193 9193