Reactions of allyl alcohols and boronic acids with trifluoromethanesulfonyl hypervalent iodonium ylide under copper-catalysis

Article abstract of DOI:10.1039/c5dt02214b

Trifluoromethylsulfinyl and trifluoromethylthio groups are both important substituents for pharmaceuticals, agrochemicals and functional materials. We herein report the trifluoromethylthiolation of allyl alcohols 2 with trifluoromethanesulfonyl hypervalent iodonium ylide 1 under copper catalysis to provide trifluoromethylsulfinyl compounds 3. Trifluoromethylthiolation of boronic acids 4 with 1 furnished trifluoromethylthio compounds 5.

Full text of DOI:10.1039/c5dt02214b

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DOI: 10.1039/C5DT02214B
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Reactions of allyl alcohols and boronic acids with
trifluoromethanesulfonyl hypervalent iodonium ylide under
copper-catalysis
Sadayuki Arimori, Masahiro Takada and Norio Shibata*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/dalton
Trifluoromethylsulfinyl and trifluoromethylthio groups are both functionalization in preparing potential candidates in a class of
important substituents for pharmaceuticals, agrochemicals and medicinal significance. The trifluoromethanesulfonyl hypervalent
functional
trifluoromethylthiolation
materials.
We
of
herein
allyl alcohols
report
the iodonium ylide
1
we developed is useful for the
2
with trifluoromethylthiolation of enamines, indoles, β-keto esters,5
trifluoromethanesulfonyl hypervalent iodonium ylide 1 under pyrroles,9 arylamines,10 allylsilanes and silyl enol ethers.11 Reagent 1
copper catalysis to provide trifluoromethylsulfinyl compounds 3. is very stable, and crucial for the fact that the
Trifluoromethylthiolation of boronic acids 4 with 1 furnished trifluoromethylthiolation by 1 is the in-situ activation of 1 under
trifluoromethylthio compounds 5.
copper catalysis to a carbene intermediate. Our interest in the
utility of 1 prompted us to investigate the reactions of other
substrates, allyl alcohols 2 and boronic acids 4. We demonstrate
herein that the reaction of allyl alcohols 2 with 1 under copper
catalysis can furnish allylic trifluoromethyl sulfoxides12 3, instead of
In recent decades, there has been tremendous interest in
organofluorine compounds due to their great achievements as
pharmaceuticals, agrochemicals and functional materials. 1 The vast
majority of successful works reported in this area have dealt with
trifluoromethylthio compounds in good yields via
sigmatropic rearrangement.13 The reaction of boronic acids14 4 with
under the same copper catalysis provided cross coupling
a [2,3]-
fluorinated and trifluoromethylated compounds, and
a huge
number of effective methods have been developed for the
synthesis of these fluorinated molecules.2 Our group has also
contributed to this area by developing shelf-stable reagents for
fluorination3 and trifluoromethylation reactions.4 In 2013, we
reported a novel reagent, trifluoromethanesulfonyl hypervalent
iodonium ylide 1, for the electrophilic trifluoromethylthiolation
reaction.5 Trifluoromethylthio (SCF3) compounds are becoming
rather attractive after fluorinated and trifluoromethylated
compounds in the same research fields, since the introduction of
SCF3 entities into the target compounds greatly changes or
improves the lipophilicity of parent molecules6 without altering the
original framework much; and this effect is higher than that by the
trifluoromethyl substitution. In contrast to trifluoromethyl
compounds, SCF3 compounds can be further elaborated to exhibit
more suitable lipophilic profiles by the stepwise oxidation into
corresponding sulfoxides (S(O)CF3) and sulfones (SO2CF3, triflones).
In this context, the synthesis of SCF3 compounds has received great
attention.7 In particular, the development of electrophilic
trifluoromethylthiolation reagents8 is going to be prevalent in the
next several years, because it should be a key to realizing late-stage
1
trifluoromethylthio compounds 5 in moderate yields (Scheme 1).
Scheme 1 Utilization of trifluoromethanesulfonyl hypervalent
iodonium ylide 1.
Results and Discussion
We first examined the reaction of 1-phenyl-2-propen-1-ol (2a)
with 1 as a model substrate to optimize the reaction conditions by a
[2,3]-sigmatropic rearrangement to provide S(O)CF3-product 3a
instead of regular SCF3-products. The reaction was initially
*Department of Frontier Materials, Nagoya Institute of Technology, Gokiso,
Showa-ku, Nagoya 466-8555, Japan.
E-mail; nozshiba@nitech.ac.jp
† Electronic Supplementary Information (ESI) available: Synthetic methods and
experimental data of synthesized compounds. See DOI: 10.1039/x0xx00000x
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J. Name., 2013, 00, 1-3 | 1
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examined under similar conditions for the trifluoromethylthiolation
of allylsilanes and silyl enol ethers in our previous work11 (Table 1,
runs 1-2). The desired S(O)CF3-product 3a was obtained in 67%
yield. A longer reaction time gave 3a in higher yield (72%, Table 1,
run 2). When it comes to screening solvents, amide solvents (NMP,
DMF) gave 3a in comparatively favorable yields (43-58%, runs 3-4),
but a halogenated solvent (CH2Cl2), an ether solvent (THF), an ester
solvent (AcOEt) and other polar solvents (MeCN, DMSO, EtOH) were
not suitable for this transformation (runs 5-10). We next optimized
the copper catalysts (runs 11-16). The use of Cu (II) species was
found to be better than Cu (I) species (CuCl vs CuCl2, CuOAc vs
Cu(OAc)2), but no improvement was observed. A higher reaction
temperature did not improve the yield of 3a (run 17). The reaction
did not proceed in the absence of CuF2 (run 18).
alcohols 2l-n were applied, the reaction proceeded to give the
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sulfinates, although in moderate yields (15-4D2O%I):.10.1039/C5DT02214B
Table 1 Optimization of transformation of 1-phenyl-2-propen-1-ol
(2a) into 3a.a
run
CuX
solvent
temp
(C)
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
time (h)
yield
(%)b
67
72
58
43
trace
0
23
0
0
trace
0
6
36
12
50
13
54
0
1
2
3
4
5
6
7
8
CuF2
CuF2
CuF2
CuF2
CuF2
CuF2
CuF2
CuF2
CuF2
CuF2
CuCl
CuCl2
CuBr2
CuOAc
Cu(OAc)2
Cu(OTf)2
CuF2
DMAc
DMAc
NMP
DMF
CH2Cl2
THF
MeCN
DMSO
EtOH
AcOEt
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
10
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
Scheme 2 Transformation of allyl alcohols 2a-n into 3a-n (isolation
yields, reaction conditions: 2 (0.25 mmol), 1 (0.50 mmol) and CuF2 (0.05
mmol) in DMAc (1.25 ml), rt, 24 h under N2).
a The reaction time was 5 h. b E/Z =22/3. c d.r. = 3/2. d The reaction time
was 2 h.
9
We next attempted the cross coupling trifluoromethylthiolation
reaction of boronic acids 4 with 1. 4-Phenoxy-phenyl boronic acid
(4a) was first examined in the reaction with 1 under the same
conditions as in scheme 2, i.e., with a catalytic amount of CuF2 in
DMAC. The reaction did not proceed at rt, but 13% of the desired
SCF3 cross coupling product 5a was obtained at 80 C using a higher
amount of CuF2 (1.2 equiv.) (runs 1-2, Table 1S, ESI). When
Cu(OAc)2 (1.2 equiv.) was used, the yield of 5a improved to 47%
(run 7, Table 1S, ESI). The substrate scope was next examined for
the trifluoromethylthiolation reaction of aryl- and vinylboronic acids
(Scheme 3). Although the yields were moderate, various boronic
acids were applicable in the cross coupling reaction. Simple
arylboronic acid 4b-c were converted into the desired
trifluoromethylthiolated products 5b-c in modest yields (25-29%).
The electron-donating and -withdrawing substituted arylboronic
acids 4d-e were also transformed into 5d-e in 27-38% yield.
Furthermore, hetero arylboronic acid 4f-g were applied to the
trifluoromethylthiolation reaction, although the yield of 5f-g was
low (12-15%). Both arylboronic acids and vinylboronic acids 4h-i
also could be transformed into the F3CS-products 5h-i in good yields
(45-55%).
10
11
12
13
14
15
16
17
18
rt
50
rt
-
a The reactions were carried out with 2a (0.25 mmol), 1 (0.50 mmol)
and CuX (0.05 mmol) in each solvent (1.25 ml). b 19F NMR yields with
PhF (0.75 mmol) as an internal standard.
With the optimized reaction conditions in our hand (Table 1, run
2), we next investigated the substrate scope of allyl alcohols
(Scheme 2). Applying the reaction of 2 having naphthyl or alkyl
substituted phenyl groups, the desired trifluoromethyl sulfinyl
products 3b-d were obtained in good to high yields (61-85%,
Scheme 2). The electron-donating group (OMe) could be applied
without a high steric effect in the reaction (3e-g). Phenyl allyl
alcohols substituted with electron-withdrawing groups (Cl, CF3)
gave the desired products 3h-i in modest to high yield (44-75%).
Additionally, hetero aromatic allyl alcohols 3j-k were also relevant
in this transformation, providing the corresponding trifluoromethyl
sulfinates without any functionalization of the heteroaryl moieties.
It is interesting to note that even when alkyl and branched allyl
2 | J. Name., 2012, 00, 1-3
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Conclusions
We have succeeded in the synthesis of both
trifluoromethylsulfinyl and trifluoromethylthio compounds using
trifluoromethanesulfonyl hypervalent iodonium ylide
copper catalysis. The reaction of various allyl alcohols 2 with 1 in
the presence of catalytic amount of CuF2 furnished
trifluoromethylsulfinyl compounds instead of trifluoromethylthio
compounds via a [2,3]-sigmatropic rearrangement. On the other
hand, trifluoromethylthiolation of boronic acids 4 with 1 under
1 under
a
5 Y. -D. Yang, A. Azuma, E. Tokunaga, M. Yamasaki, M. Shiro and
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similar
reaction
conditions
using
Cu(OAc)2
provided
trifluoromethylthio compounds in moderate yields via a cross
coupling reaction. Although the same reactions providing 3 and 5
have been reported using “other trifluoromethylthiolation reagents”
under different conditions, these “trifluoromethylthiolation
reagents” themselves should be prepared in advance by
“trifluoromethylthiolation or related trifluoromethylation”. On the
other hand, our reagent 1 can be prepared form ubiquitous CF3SO2
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compounds
trifluoromethylthiolation reagent. These results show the further
expansion of the scope and utility of reagent for
such
as
CF3SO2Na,
without
using
any
1
trifluoromethylthiolations. A separate study will focus on this
aspect of the chemistry of 1 as well as further applications to
accommodate a broader range of reactions.
Acknowledgements
This research was financially supported in part by the Platform for
Drug Discovery, Informatics, and Structural Life Science from MEXT
Japan, the Advanced Catalytic Transformation (ACT-C) from the
Japan Science and Technology (JST) Agency, and the Kobayashi
International Foundation.
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4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5DT02214B
O
R''
R'''
S
SCF3
SO2CF3
CF3
Ph
R
boronic
acids 4
I
allyl
alcohols 2
R'
O
1
R
Ph
3
Cu-catalysis
Sulfone
5
Sulfoxide
Sulfide
Trifluoromethylsulfinyl 3 and trifluoromethylthio 5 compounds are independently
obtained by the sulfone-type reagent 1 under Cu catalysis.