Communication
and a neighboring ylide group) as an effective trifluorome-
thylthiolation reagent,[12] we were excited about the possibility
to exploit the simpler reagent CF3SO2Na for the synthesis of
CuSCF3 under appropriate deoxygenative conditions in the ab-
sence of external sulfur sources.
Table 2. Optimization of synthesis of CuSCF3 from CF3SO2Na.[a]
Initial studies were focused on searching for reductants ca-
pable of abstracting the oxygen atoms from CF3SO2Na. We
found that simple phosphine compounds (Table 1; 3a–e) could
Entry
Reductant
Copper Source
Solvent
Yield[b]
1
2
3
4
5
6
7
8
9
Ph3P (3a)
Ph3P (3a)
Ph3P[d] (3a)
Cu powder[c]
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
trace
70%
83%
79%
[d]
MePPh2 (3b)
Me2PPh[d] (3c)
Me3P[d] (3d)
Bu3P[d] (3e)
Ph3P[d] (3a)
Ph3P[d] (3a)
75%
Table 1. Comparison of deoxygenation reagents for CF3SO2Na.[a]
None[e]
None[e]
None[e]
None[e]
CuCl
DMI
[b]
Entry
PR3
Yield of CF3SSCF3
[a] General conditions: CF3SO2Na (0.2 mmol, 1.0 equiv) and copper source
(0.2 mmol, 1.0 equiv) were dissolved in solvent (1.0 mL), then reductant
(0.4 mmol, 2.0 equiv) was added and stirred under N2/RT. [b] Yield was de-
termined by 19F NMR spectroscopy of the crude product mixture using
PhCF3 as internal standard. [c] Unactivated Cu powder was utilized. [d] Re-
ductant was added in a pre-cooled CuCl/CF3SO2Na/CH3CN mixture (ap-
proximately À258C), and then returned to RT for stirring. This addition
procedure works well on a multiple-gram scale synthesis of CuSCF3.
[e] No conversion of CF3SO2Na was detected, and the coordination com-
plexes between phosphines and CuCl was observed.
1
2
3
4
5
6
7
Ph3P (3a)
27%
22%
20%
13%
Ph2PMe (3b)
PhPMe2 (3c)
PMe3 (3d)
PBu3 (3e)
P(NEt2)3 (3 f)
Zinc powder
18%
None[c]
None[c]
[a] Yield was determined by 19F NMR spectroscopy of the crude product
mixture using PhCF3 as internal standard; PR3 (1.5 equiv). [b] The moder-
ate yield could be caused by the volatile properties of CF3SSCF3. [c] No
conversion of CF3SO2Na and no formation of CF3SSCF3.
ing CuSCF3 in 72% yield [Eq. (1)]. The reason why the [ClCu-
(PMe3)x] and [ClCu(PBu3)x] species show poor reactivity towards
CF3SO2Na is still not very clear. A possible explanation could be
the stronger bonding of the electron-rich trialkylphosphines
(3d or 3e) to the copper(I) center that prevents the dissocia-
tion of trialkylphosphines for deoxygenative reduction.
convert CF3SO2Na to CF3SSCF3 with moderate success, whereas
hexaethylphosphorous triamide (P(NEt2)3; 3 f) and metal-based
reductants, like zinc powder, were inert, even at elevated tem-
peratures (Table 1). The ability of phosphines to extrude
oxygen atoms from CF3SO2Na is consistent with the strong
thermodynamic
impetus
of
P=O
bond
formation
(ꢀ544 kJmolÀ1).[13] With the phosphine reducing agents identi-
fied, we investigated whether this deoxygenative process
could be exploited for the construction of desired CuSCF3
(Table 2). Initially, copper powder was used to trap the
CF3SSCF3 generated in situ. However, only trace amount of
CuSCF3 was observed, even when stirred for several days at
room temperature or heated at 50–608C, overnight (entry 1).
Gratifyingly, CuSCF3 was generated in 70% yield according to
19F NMR analysis (signal at À27.5 ppm) when the copper
source was CuCl (entry 2). Addition of Ph3P to a pre-cooled
CuCl/CF3SO2Na solution in CH3CN, and then warming to room
temperature minimized side reactions and improved the yield
to 83% (entry 3). Further solvent and reducing agent screening
confirmed that CuCl/CF3SO2Na/Ph3P combination in a 1:1:2
equivalent ratio, respectively, in acetonitrile solvent represent-
ed the optimal conditions for the efficient production of
CuSCF3 in terms of low cost, air stability and yield (entries 3–9).
Notably, the phosphines (3a–c) bearing a phenyl ring showed
good reaction efficiency in the generation of CuSCF3, whereas
the more electron-rich Me3P (3d) and Bu3P (3e) displayed slug-
gish reactivities (entries 6–7), and formation of the correspond-
ing inert [ClCu(PMe3)x] and [ClCu(PBu3)x] species indicated by
31P NMR was observed. In contrast, preformed [ClCu(PPh3)2]
(3)[14] reacted smoothly with CF3SO2Na in acetonitrile, furnish-
With the optimized reaction conditions for generating
CuSCF3 from CF3SO2Na established, we sought to use this
chemistry to prepare a series of air-stable, ligated, and synthet-
ically useful trifluoromethylthiolating agents [LCu(SCF3)]
(Scheme 3). Initially, 2,2’-bipyridine was selected as the sup-
porting ligand for the preparation of [(bpy)CuI(SCF3)] (5a),
which is a versatile trifluoromethylthiolation agent for various
R–X substrates.[7c–e] Gratifyingly, 5a was afforded as red crystals
in 60% yield. Its structure was confirmed by NMR spectrosco-
py, elemental analysis, and single-crystal X-ray crystallography
(see the Supporting Information). Next, several related deriva-
tives [(dtbpy)CuI(SCF3)] (5b),[7c] [{(phen)CuI(SCF3)}2] (5d),[7c] and
[(Ph3P)2CuI(SCF3)] (5e)[7d] were also efficiently obtained by simi-
lar procedures. When 6,6-dimethylbipyridine was employed as
the chelating ligand, the dimer 5c was obtained in 58% yield.
The dimeric structure of 5c (Figure 2, left)[15] differs remarkably
from the other reported bipyridine-based complexes 5a and
5b. Similarly, treatment of CuSCF3 with 1,1’-bis(diphenylphos-
phino)ferrocene (dppf) provided [(dppf)CuI(SCF3)] (5 f) as
a yellow solid in 69% yield, and its structure was also verified
by single-crystal X-ray crystallography (Figure 2, right).[15] It is
Chem. Eur. J. 2016, 22, 858 – 863
860
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