Stereodivergent Hydrosilylation, Hydrostannylation, and Hydrogermylation of α-Trifluoromethylated Alkynes and Their Synthetic Applications

Article abstract of DOI:10.1055/s-0035-1561487

Stereoselective hydrometalation reactions of aryl- and alkyl-substituted trifluoromethylated alkynes with triethylsilane, tributylstannane, and triphenylgermane have been investigated. (E)-α-CF₃-Vinylsilanes, -stannanes, and -germanes were obta

Full text of DOI:10.1055/s-0035-1561487

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–N
paper
A
C. Tresse et al.
Paper
Synthesis
Stereodivergent Hydrosilylation, Hydrostannylation, and Hydro-
germylation of α-Trifluoromethylated Alkynes and Their Synthetic
Applications
Cédric Tressea
R1
M
R2
X
R1
R2
H
M
Stéphane Schweizera
Philippe Bisseretb
Jacques Lalevéec
Gwilherm Evanod
Nicolas Blanchard*b
R1
CF3
when
M = Ge
H
CF3
H
CF3
SiR3
GeR3
SnR3
M
a Laboratoire de Chimie Organique et Bioorganique, Université de Haute-Alsace,
Institut Donnet, 3bis rue Alfred Werner, 68093 Mulhouse, France
b Laboratoire de Chimie Moléculaire, Université de Strasbourg, CNRS UMR 7509,
ECPM, 25 rue Becquerel, 67087 Strasbourg, France
n.blanchard@unistra.fr
c Institut de Science des Matériaux de Mulhouse, Université de Haute-Alsace,
CNRS UMR 7361, 15 rue Jean Starcky, 68057 Mulhouse, France
d Laboratoire de Chimie Organique, Service de Chimie et PhysicoChimie
Organiques, Université libre de Bruxelles (ULB), Avenue F. D. Roosevelt 50,
CP160/06, 1050 Bruxelles, Belgium
Dedicated to the memory of Jean-François Normant, an outstanding scientist
and artist
Received: 20.05.2016
Accepted after revision: 08.06.2016
Published online: 22.07.2016
fludelone, thereby enhancing the therapeutic index of this
promising antimitotic compound (Scheme 1).2 In addition,
incorporation of 19F atoms into natural product derivatives
is also a unique strategy to investigate the biological mech-
anisms that the latter induce by multinuclear NMR owing to
the magnetic properties of the fluorine atom.3 Representa-
tive examples of such a fascinating endeavor have been re-
ported in fluorinated probes 1, 2, and 3 derived from am-
photericin,4 parthenolide,5 or bafilomycin, respectively
(Scheme 1).6 For the past few years, we have been investi-
gating Buruli ulcer, a neglected human mycobacterial dis-
ease caused by mycolactones A/B, the exotoxins of Myco-
bacterium ulcerans.7 We have reported several synthetic
strategies to finely modulate the different sectors of these
macrolides.8 The resulting library of mycolactone analogues
contributed not only to the elucidation of the structure–
activity relationships of these macrolides,9 but also to the
discovery that certain simplified analogues were able to
bind and activate a sub-domain of one of the proteic target
of mycolactone, the N-WASP protein.8b,10 To gain more in-
sight into the physical interactions of mycolactones and
their biological targets, the use of fluorinated mycolactones
probes should prove very useful in structural biology inves-
tigations using NMR spectroscopy. Following the lead of the
epothilone series, the stereoselective introduction of (E)-
and (Z)-trisubstituted trifluoromethylated alkenes in the
mycolactones scaffolds, as in 5, which is related to the pre-
viously reported analogue 4, was investigated on model
substrates.
DOI: 10.1055/s-0035-1561487; Art ID: ss-2016-c0368-op
Abstract Stereoselective hydrometalation reactions of aryl- and alkyl-
substituted trifluoromethylated alkynes with triethylsilane, tributyl-
stannane, and triphenylgermane have been investigated. (E)-α-CF3-Vi-
nylsilanes, -stannanes, and -germanes were obtained under palladium-
catalyzed conditions whereas the corresponding (Z)-α-CF3-vinylger-
manes were obtained under radical conditions. These reactions pro-
ceed in good to excellent yields and possess a broad functional group
tolerance. Applications of the (Z)- and (E)-α-CF3-vinylgermanes in palla-
dium-catalyzed cross-coupling reactions with aryl halides having di-
verse electronic requirements were also investigated. The correspond-
ing (Z)- and (E)-α-CF3-styrenes were obtained as single isomers, thus
demonstrating the utility of these versatile synthons for the synthesis
of stereodefined trifluoromethylated alkenes.
Key words hydrosilylation, hydrostannylation, hydrogermylation, tri-
fluoromethylated alkynes, trifluoromethylated alkenes, fluorinated
probes, natural products
The selective introduction of fluorine and fluoroalkyl
substituents into organic molecules has been central to the
fine modulation of their physicochemical as well as biologi-
cal activities and has found applications in numerous areas
of our daily life, ranging from material to life sciences.1 In
particular, the structural editing of natural products with
fluorinated motifs can lead to improved biological activi-
ties, as exemplified in the epothilone series wherein the
C12–C13 trisubstituted epoxide of the natural product was
replaced by a (E)-trifluoromethyl-substituted alkene in
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

B
C. Tresse et al.
Paper
Synthesis
Trifluoromethylated alkenes can be prepared with
O
S
N
moderate selectivity by a fluorine-induced Horner–
12
13
Wadsworth–Emmons olefination reaction,11 by transition-
metal-mediated electrophilic trifluoromethylation of alke-
nyl halides, vinylboron, vinyl halides (and pseudo-halides)
or acrylic acids,12 by radical processes,13 and by direct tran-
sition-metal-catalyzed sp2 C–H bond trifluoromethyla-
tion.14 Another strategy for the stereoselective synthesis of
the challenging trisubstituted trifluoromethylated alkenes
6 would call for the cross-coupling of a (Z)- or (E)-α-CF3-vi-
nylmetal species 7 that, in turn, could be obtained from the
HO
CF3
Fludelone
O
12
13
O
OH
O
Epothilone B
OH
R
HO
O
O
OH
HO
O
OH OH
OH OH
stereoselective hydrometalation of α-CF3-alkynes
8
CO2H
(Scheme 2).
O
R2
X
X
O
R1
H
CF3
M
R1
CF3
R2
OH
Amphotericin B, R = H
1, R = F
NH2
OH
H
(Z)-6
(E)-7
R1
CF3
+
H
M
R1
M
R2
R1
R2
8
SiR3
M
GeR3
SnR3
H
CF3
H
CF3
N
O
(E)-6
(Z)-7
O
O
O
Scheme 2 Synthetic blueprints for the synthesis of trifluoromethylat-
ed alkenes 6 from trifluoromethylated alkynes via regio- and stereo-
selective hydrometalation and cross-coupling reactions
2
CF3
O
Parthenolide
OMe
Indeed, hydrometalation reactions of α-CF3-alkynes15
have the potential to craft, in a single step, valuable α-CF3-
vinylmetal building blocks, either partners of metal-cata-
lyzed cross-couplings or precursors of the corresponding α-
CF3-vinyl halides. Provided that the regio- and stereoselec-
tivity of the hydrometalation could be controlled, this strat-
egy would afford a straightforward entry into the selective
formation of polysubstituted CF3-alkenes.16 Among the re-
ports of hydrometalation of α-CF3-alkynes, Konno has de-
scribed that hydroboration of aryl-substituted α-CF3-
alkynes 9 proceeded mainly with (Z)-stereoselectivity and
that the intermediate vinylborane 10 could be submitted to
Suzuki–Miyaura cross-coupling with aryl iodides (Scheme
3, eq. 1).17 Similarly, hydrosilylation of 9 (aryl-, benzyl- or
propargyl-substituted) was efficiently catalyzed by
Co2(CO)8 in refluxing 1,2-dichloroethane, but the regiose-
lectivity was lower than that obtained with the hydrobora-
tion reaction (Scheme 3, eq. 2).18 Hydro- and carbocupra-
tion of 9 were also developed by the same group and excel-
lent regio- and stereoselectivities were noticed.19 However,
only potent electrophiles could be used to trap the interme-
diate vinylcopper species 13 (Scheme 3, eq. 3). The same
trend was observed with the hydroalumination of 9
(Scheme 3, eq. 4).19
R
O
OH
24
O
OH
O
HO
OH
OMe
Bafilomycin A1 (Baf), R = i-Pr
3, 24-F-Baf, R = CF3
OH OH
O
O
R1
OH
O
Mycolactone A/B, R1 = Me
O
OH OH
O
R2
OH
O
OH OH
4, R1 = H, R2 = H
Rare examples of hydrostannylation reactions of α-CF3-
alkynes have been reported since the seminal work of
Cullen and Styan in 1966,20,21 but it is under the impulsion
5, R1 = H or Me, R2 = CF3
Scheme 1 Selection of fluorinated analogues of natural products
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

C
C. Tresse et al.
Paper
Synthesis
cerning the hydrometalation of α-CF3-alkynes using group
14 element hydrides, namely silanes, germanes, and stan-
nanes. In addition, selected synthetic applications of the re-
sulting α-CF3-vinylgermanes and α-CF3-vinylstannanes are
discussed.
Ar
I
Pd(PPh3)2Cl2
(10 mol%)
NaOH
R
H
CF3
Ar
CF3
(eq. 1)
Cy2BH
Ar
CF3
BCy2
toluene
r.t.
reflux
H
Ar
9
11
(E)-10 (major)
We indeed recently reported that terminal alkynes 18,
whether alkyl- or aryl-substituted, could be easily trans-
formed into the corresponding α-CF3-alkynes 8 in good to
excellent yields using two practical procedures.29 In the
first one (Scheme 4, eq. 1), copper acetylides are synthe-
sized by direct cupration of the terminal alkyne 18 (CuI,
NH4OH or K2CO3, DMF) followed by their trifluoromethyla-
tion using an excess of the Ruppert–Prakash reagent and
TMEDA under an atmosphere of oxygen, in petroleum ether
(PE)/DMF (95:5) at room temperature. In the second proce-
dure (Scheme 4, eq. 2), terminal alkynes 18 are treated with
CuI, TMEDA, the Ruppert–Prakash reagent, and K2CO3 in
DMF at room temperature. These two protocols are unique
with regards to functional group tolerance and were thus
selected for the synthesis of a range of α-CF3-alkynes 8, pre-
cursors of the hydrometalation reaction with group 14 ele-
ment hydrides.
Et3SiH
Co2(CO)8
(5 mol%)
Ar
H
CF3
(eq. 2)
9
9
9
DCE
reflux
SiEt3
(E)-12 (major)
[CuH2]–
Ar
CF3
E+
Ar
CF3
E
(eq. 3)
(eq. 4)
(H2O, I2
allylBr
or BnBr)
H
Cu
H
THF
–78 °C
13
14
Ar
H
E+
Ar
H
Red-Al
Et2O
(H2O, I2
allylBr
or BnBr)
E
CF3
Al
CF3
16
15
Bu3SnH
Et3B
(20 mol%)
Ar
SnBu3
CF3
TMSCF3
TMEDA
O2
CuI
NH4OH
or
(eq. 5)
9
toluene
0 °C
H
R
CF3 (eq. 1)
R
H
R
Cu
PE/DMF
(95:5)
r.t.
CuI
K2CO3
DMF
(Z)-17 (major)
18
19
8
Scheme 3 Reported hydroboration, hydrosilylation, hydrocupration,
hydroalumination, and hydrostannylation reactions of α-CF3-alkynes 9
TMSCF3
TMEDA
CuI
of the group of Konno that the scope was more thoroughly
explored.19,22 Indeed, they demonstrated that moderate to
excellent yields of α-CF3-vinyl stannanes 17 could be ob-
tained from the aryl-substituted trifluoromethylated
alkynes 9 using tributyltin hydride and a catalytic amount
of triethylborane as a radical initiator (Scheme 3, eq. 5). The
stereoselectivity of the process was directly linked to the
electronics of the aryl substituent. Iodolysis or copper-cata-
lyzed cross-coupling of related vinylstannanes with activat-
ed electrophiles were also reported by Abarbri.23 Strangely,
a hydrometalation that has not been yet investigated in the
context of α-CF3-alkynes is hydrogermylation24 although
germanium also belongs to group 14, together with silicon
and tin, and has been reported to react with alkynes under
transition-metal25 or Lewis acid catalysis,26 and also under
radical conditions as elegantly reported by Oshima.25f,27
Although an arsenal of hydrometalation reactions of
aryl-substituted α-CF3-alkynes 9 have been reported, it
should be noticed that stereoselective access to (Z)- or (E)-
alkyl-substituted α-CF3-vinylmetal is still challenging. In
addition, a practical access to valuable (E)-α-CF3-vinylstan-
nanes, not accessible by reported methods, would be ste-
reocomplementary to existing methods. We report herein
the full account of our preliminary investigations28 con-
K2CO3
(eq. 2)
R
CF3
R
H
DMF
r.t.
18
8
Scheme 4 Two practical protocols for the copper-mediated synthesis
of α-CF3-alkynes 8 from terminal alkynes 18
Our investigations of the hydrometalation reactions of
α-CF3-alkynes began with the platinum-catalyzed hydrosi-
lylation reaction (Scheme 5). Based on the pioneering work
of Tsipis,30 in 2012 the group of Ferreira reported a cis-hy-
drosilylation of internal alkynes catalyzed by PtCl2 or
Pt(dvds).31 Inspired by this work, Pt(dvds) (1 mol%) {dvds =
[(H2C=CH)Me2Si]2O]} was used in the hydrosilylation of 20a
in toluene at room temperature for 18 h (Scheme 5, eq. 1). A
moderate yield of the desired (E)-α-CF3-vinylsilane 21a was
obtained (69%) together with protodesilylation product 22.
On the other hand, the use of PtCl2 (5 mol%) in toluene at
room temperature for 24 h afforded cleanly the desired (E)-
α-CF3-vinylsilane 21a with only traces of the other regio-
isomer 23a and the protodesilylated alkene 22 (21a/23a/22
94:3:3) as measured by 19F NMR of the crude reaction mix-
ture (see the Supporting Information). The vinylsilane 21a
was then submitted to iodolysis in dichloromethane at
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

D
C. Tresse et al.
Paper
Synthesis
40 °C for 12 h, but no trace of the desired α-CF3-vinyl iodide
was obtained thus demonstrating that this π-system is too
electron-deficient to undergo an efficient iododesilylation.
3, eq. 5), the examples in Scheme 6 constitute the first re-
port of a palladium-catalyzed hydrostannylation of α-CF3-
alkynes to the best of our knowledge.
The connectivity of the major compound 24a was estab-
lished through the measurement of its coupling constants
in 1H, 19F, and 13C NMR (Scheme 6), while the configuration
of the π-system was determined by chemical correlation.
Indeed, when the mixture of the two regioisomeric vinyl-
stannanes 24a and 25a were treated with p-toluenesulfonic
acid in dichloromethane,22b a single α-CF3-alkene (Z)-22
was obtained in 88% (Scheme 6, eq. 2; see the Supporting
Information). The (Z)-configuration of the alkene 22 was
unambiguously determined by the measure of its coupling
constants. Contrary to the vinylsilane 21a, vinylstannanes
24a and 25a are excellent precursors of the corresponding
vinyl iodides 26a and 27a upon treatment with I2 in di-
chloromethane, a fact that could be attributed to the higher
intrinsic nucleophilicity of stannanes compared to silanes
(Scheme 7). After the simple treatment of the crude reac-
tion mixture with the Roush KF on Celite® protocol32 and a
short filtration on silica gel, an excellent 92% yield of 26a
and 27a was obtained (see the Supporting Information).
Et3SiH
Pt(dvds)
(1 mol%)
C10H21
CF3
C10H21
CF3
H
+
C10H21
CF3
toluene
r.t.
18 h
98%
H
SiEt3
H
(eq. 1)
20a
20a
21a
(Z)-22
21a/22 = 69:31
Et3SiH
PtCl2
(5 mol%)
C10H21
CF3
C10H21
CF3
+
+
C10H21
CF3
22
toluene
r.t.
24 h
92%
H
SiEt3 Et3Si
21a
21a/23a/22 = 94:3:3
H
(eq. 2)
23a
Scheme 5 Platinum-catalyzed hydrosilylation of α-CF3-alkyne 20a
We next turned our attention to another element of
group 14 and focused on the transition-metal-catalyzed hy-
drostannylation of α-CF3-alkynes (Scheme 6). When alkyne
20a was treated with tributyltin hydride and Pd(PPh3)4 (1
mol%) in THF at room temperature for 2 h, a good yield of
two isomeric (E)-α-CF3-vinylstannanes 24a and 25a was
obtained (24a/25a 89:11) (Scheme 6, eq. 1). A better regio-
isomeric ratio was obtained at 0 °C under the same condi-
tions (24a/25a 95:5). This high regioselectivity is presum-
ably largely electronically driven although a steric contribu-
tion might also be at play. Although the radical
hydrostannylation of α-CF3-alkynes was reported (Scheme
C10H21
H
CF3
C10H21
CF3
C10H21
CF3 C10H21
+
CF3
H
I2
+
CH2Cl2
r.t.
SnBu3 Bu3Sn
24a
24a/25a = 89:11
H
H
I
I
25a
26a
27a
2 h
92%
26a/27a = 89:11
Scheme 7 Iodolysis of α-CF3-vinylstannanes 24a and 25a
This hydrostannylation of α-CF3-alkynes can be extend-
ed to a more complex substrate as exemplified in Scheme 8.
The α-CF3-alkyne 20b bearing a p-methoxybenzyl ether in
the homopropargylic position was also found to undergo a
clean hydrostannylation in refluxing THF for 2 h (Scheme 8,
eq. 1). Although the ratio of the two regioisomeric and
chromatographically separable stannanes was low
(24b/25b 73:27 as determined by 19F NMR of the crude re-
action mixture), it could be further increased to 92:8 at 0 °C
(slightly eroded compared to the hydrostannylation of 20a
at 0 °C in Scheme 6) and to 96:4 at –30 °C. The yield of the
latter transformation was only slightly decreased upon a
three-fold increase in the scale of the –30 °C reaction (96%
on 0.5 mmol and 85% on a 1.5 mmol) thus showing that this
process is not only simple to set up, but also reliable.
As in the case of the hydrostannylation of the α-CF3-do-
decyne 20a, the determination of the structures of the two
regioisomers 24b and 25b was based on a combination of
NMR studies (1H, 19F, and 13C) and chemical correlation
(Scheme 8). Actually, treatment of a pure sample of 24b
with p-toluenesulfonic acid in dichloromethane for 24
hours delivered the (Z)-α-CF3-alkene 28 in 65% yield
(Scheme 8, eq. 2).
Bu3SnH
Pd(PPh3)4
(1 mol%)
C10H21
H
CF3
C10H21
CF3
H
+
C10H21
CF3
(eq. 1)
THF
2 h
SnBu3 Bu3Sn
20a
24a
25a
20 °C, 85%, 24a/25a = 89:11
0 °C, 99%, 24a/25a = 95:5
H
JH-H = 7.9 Hz
H
C10H21
H
CF3
C10H21
CF3
H
p-TsOH
C9H19
CF3
+
(eq. 2)
CH2Cl2
r.t.
24 h
88%
SnBu3 Bu3Sn
H
F
H
24a/25a = 89:11
24a
25a
(Z)-22
JH-H = 11.6 Hz
JC-F = 7.8 Hz
H
H
F
JCq-F = 274.8 Hz
C9H19
F
C9H19
CF3
JSn-F = 21.3 Hz
JCq-F = 33.2 Hz
JH-H = 7.4 Hz
SnBu3
H
SnBu3
JSn-H = 55.1 and 57.4 Hz
Scheme 6 Palladium-catalyzed hydrostannylation of α-CF3-alkyne 20a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

E
C. Tresse et al.
Paper
Synthesis
Bu3SnH
Pd(PPh3)4
(1 mol%)
PMBO
i-Pr
PMBO
CF3
CF3
H
CF3
i-Pr
+
(eq. 1)
PMBO
H
SnBu3
Bu3Sn
(E)-25b
THF
i-Pr
20b
(E)-24b
65 °C, 2 h, 85%a
0 °C, 2 h, 99%a
24b/25b = 73:27
24b/25b = 92:8
–30 °C, 12 h, 96%a (85%)b
24b/25b = 96:4
JH-H = 7.5 Hz
H
H
PMBO
PMBO
H
CF3
H
CF3
p-TsOH
i-Pr
(eq. 2)
i-Pr
CH2Cl2
r.t.
24 h
65%
H
SnBu3
(E)-24b
JH-H = 11.9 Hz
28
JH-H = 7.0 Hz
JCtert-F = 7.8 Hz
H
PMBO
PMBO
F
F
JCq-F = 274.7 Hz
H
JSn-F = 20.6 Hz
CF3
F
i-Pr
i-Pr
JCq-F = 33.2 Hz
H
SnBu3
SnBu3
(E)-24b
(E)-24b
JSn-H = 56.3 and 57.3 Hz
nOe
X
JCq-F = 4.9 Hz
PMBO
PMBO
F
F
JCq-F = 276.5 Hz
H
CF3
F
i-Pr
JH-F = 8.6 Hz
i-Pr
JCtert-F = 31.1 Hz
Bu3Sn
H
Bu3Sn
(E)-25b
H
(E)-25b
JSn-H = 61.4 and 62.8 Hz
Scheme 8 Palladium-catalyzed hydrostannylation of α-CF3-alkyne 20b. a 0.5 mmol of 20b. b 1.5 mmol of 20b.
Having in hand the two regioisomeric α-CF3-vinylstan-
nanes 24b and 25b, their behavior in iododestannylation
was investigated (Scheme 9). As anticipated, 24b led to a
clean and high-yielding reaction that offered 26b, in only 2
h, in 94% yield. On the other hand, iododestannylation of
the minor regioisomer 25b was very slow in dichlorometh-
ane at room temperature for 4 h and only 18% yield of the
(E)-α-CF3-β-iodoalkene 27b was obtained. This could be ex-
plained by the electronically disfavored formation of an in-
termediate carbocation adjacent to the CF3 group.
While the hydrosilylation and hydrostannylation reac-
tions of α-CF3-alkynes were being investigated in our
group, we also became interested in another element of the
group 14, the chemistry of which has been underexplored
from our own point of view, namely germanium. While or-
ganogermanes are slightly more expensive than the corre-
sponding organostannanes,33 they possess much lower tox-
icity,24 greater stability, and can be used in cross-coupling
reactions (provided that the electronics of the germanium
atom are adequately tuned).34 The latter properties were of
special interest for us as they could represent a unique bal-
ance not found in the silane- or stannanes series investigat-
ed in Schemes 5 to 9.
Inspired by Konno’s radical hydrostannylation of aryl-
substituted α-CF3-alkynes,19,22 conditions for the efficient
generation of germyl radicals were screened. It was quickly
PMBO
PMBO
CF3
CF3
I
I2
i-Pr
i-Pr
CH2Cl2
r.t.
2 h
94%
H
SnBu3
H
(E)-24b
(E)-26b
PMBO
PMBO
CF3
H
CF3
H
I2
i-Pr
i-Pr
CH2Cl2
r.t.
4 h
18%
Bu3Sn
I
(E)-25b
(E)-27b
Scheme 9 Iodolysis of α-CF3-vinylstannanes (E)-24b and (E)-25b
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

F
C. Tresse et al.
Paper
Synthesis
found that commercially available triphenylgermane could
be oxidized to the corresponding radical cation using am-
monium persulfate35 in aqueous acetonitrile (Scheme 10).
In addition, the germyl radical could be trapped by N-tert-
butyl-α-phenylnitrone leading to the adduct whose struc-
ture has been confirmed by EPR spectroscopy (aN = 14.6 G
and aH = 5.4 G), thus demonstrating the intermediacy of the
triphenylgermyl radical.28
Much to our pleasure, implementation of these practical
conditions to α-CF3-alkynes 8 delivered (Z)-α-CF3-vinylger-
manes 29 as single stereoisomers (Scheme 10). As a model
substrate, 1,1,1-trifluorotridec-2-yne (20a) was investigat-
ed and its hydrogermylation delivered α-CF3-vinylgermane
29a in 87% yield as a single regio- and stereoisomer. The
structure of the latter was determined by a combination of
19F NMR and nuclear Overhauser effects and was in line
with the (Z)-selectivity observed for the related radical hy-
drostannylation (Scheme 3).
The scope of this (Z)-selective radical hydrogermylation
was next explored with diverse α-CF3-alkynes 20b–g in
aqueous acetonitrile (Method A) or in DMF (Method B) at
20 °C. Indeed, it was observed that Method B led to higher
yields for aromatic substituted CF3-alkynes. In all the cases
investigated, a single regio- and stereoisomer 29b–g was
produced, as determined by 19F NMR analysis of the crude
reaction mixture, in 71–87% yield. Alkyl-substituted α-CF3
alkynes were tolerated (29a and 29b) as well as aryl-substi-
tuted ones (29c–g).
Although this (Z)-selective hydrogermylation delivered
unique fluorinated building blocks, a stereocomplementary
access to the corresponding (E)-α-CF3-vinylgermanes 30
would be also essential. Inspired by the palladium-cata-
lyzed hydrosilylation and hydrostannylation reactions re-
ported in Schemes 5 to 9, we explored the corresponding
transition-metal-catalyzed hydrogermylation of α-CF3-
alkynes 8 (Scheme 10). Once again, 1,1,1-trifluorotridec-2-
yne (20a) was elected as a model compound and screening
of reaction conditions identified Pd(PPh3)4 as the optimal
catalyst at a loading of 1 mol% in THF at 20 °C. Inspection of
the crude reaction mixture by 1H and 19F NMR revealed that
the major α-CF3-vinylgermane 30a was indeed the antici-
pated (E)-α-CF3-isomer (74% isolated yield), and that only
traces (4%) of the (E)-β-CF3-vinyl were obtained.
Upon investigation of the scope of this palladium-cata-
lyzed process, it was found that only alkyl-substituted
alkynes were reactive. Even under forcing conditions
(100 °C in THF, microwave irradiation), the aryl-substituted
derivatives were unreactive, although the reasons are un-
clear at present. Nevertheless, alkyl-substituted α-CF3-
alkynes (30b,d–f) and enyne (30c) were good partners as
demonstrated in Scheme 10. The desired (E)-α-CF3-vinyl-
germanes 30 were obtained in 43–91% with only traces of
the β-vinylgermanes. Worthy of note is the functional
group tolerance of the reaction since silyl ethers, p-meth-
oxybenzyl ether, and 1,2-disubstituted cyclopropanes were
tolerated.
R
H
GePh3
CF3
R
H
CF3
(NH4)2S2O8
Pd(PPh3)4 (1 mol%)
+
R
CF3
H GePh3
method A (MeCN/H2O)
or B (DMF)
THF
20–100 °C
1–12 h
GePh3
(Z)-29
(E)-30
8
Br
TBDPSO
GePh3
CF3
OTBDPS
TBDPSO
C10H21
H
GePh3
CF3
GePh3
CF3
GePh3
CF3
C10H21
H
(E)-30a, 74%c
CF3
CF3
GePh3
CF3
H
H
H
GePh3
H
H
GePh3
(Z)-29a, 87%a (Z)-29b, 71%a
MeO
(E)-30b, 57%c
(E)-30c, 43%d
(Z)-29c, 84%b
(Z)-29d, 72%b
O
PMBO
i-Pr
H
H
H
CF3
CF3
CF3
GePh3
CF3
GePh3
CF3
GePh3
H
MeO
H
GePh3
H
GePh3 TBDPSO
H
GePh3
H
H
H
CF3
(E)-30f, 83%e
(E)-30d, 91%c
(Z)-29e, 82%b
(Z)-29f, 82%b
(Z)-29g, 82%b
(E)-30e, 65%d
Scheme 10 Regio- and stereoselective hydrogermylation of α-CF3-alkynes 8. a Method A. b Method B. c 20 °C, 12 h. d 50 °C, 2 h. e 100 °C (microwave
irradiation), 2 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

G
C. Tresse et al.
Paper
Synthesis
lides. The prerequisite for such a process is to finely tune
the electronics of the germanium center to render it suffi-
ciently electron-deficient.34 To achieve this goal, various
electrophiles potentially able to promote a preferential re-
action on the phenyl substituent of the germanium [versus
the more electron-deficient (trifluoromethyl)alkene] were
screened (Scheme 12). Mineral acids such as HCl and HBr
proved to be the most efficient in this regard. Indeed, when
α-CF3-vinylgermanes (Z)-29a and (E)-30a were treated
with HCl (37% in water) or HBr (48% in water) in dioxane at
160 °C for 1 h, quantitative conversion to the moisture sen-
sitive mono-chloro (Z)-32a-Cl/Br and mono-bromo (E)-
33a-Cl/Br derivatives was observed.
On the other hand, the replacement of two phenyl sub-
stituents on the germanium center by two chlorine atoms
was cleanly promoted by iodine monochloride in chloro-
form at 55 °C for 12 hours, thus leading to (Z)-34a (88%) and
(E)-35a (98%). Running the reaction neat at 85 °C delivered
exclusively the α-CF3-trichloro(vinyl)germanes (Z)-36a
(77%) and (E)-37a (72%). Although the latter derivatives
proved to be readily hydrolyzed to the corresponding trihy-
droxygermanes in the presence of traces of water, they
could be converted into the bench-stable germanium ses-
quioxides when treated with aqueous ammonia, as shown
in Scheme 13.36
Conditions screened
I2, CH2Cl2, r.t., 12 h
I2, neat, r.t., 4 h
I2, CuI, Et2O, 20–50 °C, 5 h
I2, CuI, THF, 100 °C (MW), 1 h
C10H21
GePh3
CF3
C10H21
H
I
X
H
(Z)-29a
Scheme 11 Lack of reactivity of (Z)-29a in the iodolysis reaction
CF3
(Z)-31a
As with α-CF3-vinylstannane (E)-24b, the iododemeta-
lation of (Z)-29a with iodine in dichloromethane was ex-
plored. However, no reaction took place even in the absence
of solvent (Scheme 11). In addition, neither Abarbri’s condi-
tions (CuI, I2, up to 100 °C)23 nor ICl at room temperature
were able to convert (Z)-29a into the desired α-CF3-vinyl io-
dide (Z)-31a. This lack of reactivity is reminiscent of the
previously investigated iodolysis of α-CF3-vinylsilane 21a.
Overall in this series, only the α-CF3-vinylstannane (E)-24b
underwent smooth iodolysis, thus stressing the enhanced
reactivity of stannane derivatives toward iodolysis reac-
tions.
In a last part of our investigations, we focused on the
synthetic use of these unique (Z)- and (E)-α-CF3-vinylger-
manes 29 and 30 in cross-coupling reactions with aryl ha-
X–
Y
X
Ph Ph
Ge
R1 R2
Y = H or I
X = Cl or Br
H
GePh3
CF3
H
H
Ge X
– PhY
Y
conditions
C10H21
C10H21
CF3
C10H21
CF3
(Z)-32a-Cl/Br, R1 = R2 = Ph
(E)-33a-Cl/Br, R1 = R2 = Ph
(Z)-34a, R1 = Ph, R2 = Cl
(E)-35a, R1 = Ph, R2 = Cl
(Z)-36a, R1 = R2 = Cl
(Z)-29a
(E)-30a
(E)-37a, R1 = R2 = Cl
H
CF3
GePh2Cl
H
CF3
H
GePh2Cl
CF3
H
GePh2Br
C10H21
C10H21
GePh2Br
C10H21
C10H21
CF3
(Z)-32a-Cl
(Z)-32a-Br
(E)-33a-Cl
(E)-33a-Br
HCl, dioxane,
160 °C, 1 h
100% conversion
HBr, dioxane,
160 °C, 1 h
100% conversion
HCl, dioxane,
160 °C, 1 h
100% conversion
HBr, dioxane,
160 °C, 1 h
100% conversion
H
CF3
H
GePhCl2
H
CF3
H
GeCl3
C10H21
GePhCl2
C10H21
CF3
C10H21
GeCl3
C10H21
CF3
(Z)-34a
(E)-35a
(Z)-36a
(E)-37a
ICl, CHCl3
55 °C, 12 h
100% conversion
88% isolated yield
ICl, CHCl3
55 °C, 12 h
100% conversion
98% isolated yield
ICl, neat
85 °C, 4 h
100% conversion
77% isolated yield
ICl, neat
85 °C, 4 h
100% conversion
72% isolated yield
Scheme 12 Electronic tuning of the germanium center of (Z)-29a and (E)-30a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

H
C. Tresse et al.
Paper
Synthesis
NO2
H
GeCl3
CF3
H
GeO1.5
CF3
NH4OH
1
Pd(OAc)2
(5 mol%)
NaOH
/
NO2
n
20 °C
3 h
100% conversion
C10H21
C10H21
H
GeCl3
CF3
H
n
+
(E)-37a
(E)-38a
(eq. 1)
CF3
dioxane/H2O
80 °C
C10H21
C10H21
Scheme 13 Synthesis of germanium sesquioxide (E)-38a from (E)-37a
I
(E)-37a
(Z)-40a, 95%
39a
We next turned our attention to the use of these elec-
tron-deficient vinylgermanes in palladium-catalyzed cross-
couplings with aryl iodides and bromides under the condi-
tions reported by Fugami and Kosugi in the cases of aromat-
ic trichlorogermanes and aromatic germanium sesqui-
oxides.34 It should be noted that only α-CF3-trichloroger-
manes (Z)-36a and (E)-37a and sesquioxide (E)-38a proved
to be reactive under these conditions. In a first series of
cross-couplings, 1-iodo-4-nitrobenzene (39a) was reacted
with (E)-α-CF3-trichlorogermane (E)-37a (Scheme 14, eq.
1), the corresponding (Z)-isomer (Z)-36a (Scheme 14, eq. 2)
and the (E)-sesquioxide 38a (Scheme 14, eq. 3), thus deliv-
ering the α-CF3-styrene derivatives (Z)-40a and (E)-42a as
single isomers in 95%, 90%, and 62% yields, respectively. Use
of the 1-bromo-4-nitrobenzene (39b) was less efficient,
styrene (E)-42a being obtained only in 46% yield (Scheme
14, eq. 2).
NO2
Pd(OAc)2
(5 mol%)
NaOH
H
CF3
H
CF3
(eq. 2)
+
dioxane/H2O
80 °C
C10H21
GeCl3
C10H21
X
39a, X = I
39b, X = Br
(E)-42a
(Z)-36a
90% from 39a
46% from 39b
NO2
NO2
NO2
Pd(OAc)2
(5 mol%)
NaOH
H
GeO1.5
CF3
H
1
+
/
n
(eq. 3)
dioxane/H2O
80 °C
C10H21
C10H21
CF3
n
I
(E)-38a
(Z)-40a, 62%
39a
OMe
Finally, 4-iodoanisole (41) was employed as the electro-
phile in these palladium-catalyzed cross-couplings with
(E)-37a and (Z)-36a (Scheme 14, eqs. 4 and 5). The expect-
ed α-CF3-styrenes (Z)-43a and (E)-44a were obtained in
moderate yields (60% and 56%, respectively), but as single
isomers as shown by inspection of the crude reaction mix-
ture by 19F NMR.
In conclusion, we have demonstrated that α-CF3-
alkynes are reactive partners in regio- and stereoselective
hydrosilylation, hydrostannylation, and hydrogermylation
reactions. The corresponding α-CF3-vinylmetals are stable
derivatives that could be further transformed into the cor-
responding α-CF3-vinyl halides (in the case of the stannane
series) or engaged in palladium-catalyzed cross-couplings
with aryl halides, thus delivering valuable fluorinated
building blocks that were previously difficult to access.
OMe
Pd(OAc)2
(5 mol%)
NaOH
H
GeCl3
H
(eq. 4)
+
dioxane/H2O
C10H21
CF3
C10H21
CF3
80 °C
I
I
(E)-37a
(Z)-43a, 60%
41
OMe
Pd(OAc)2
(5 mol%)
NaOH
H
CF3
H
CF3
+
(eq. 5)
dioxane/H2O
80 °C
C10H21
GeCl3
C10H21
(E)-44a, 56%
(Z)-36a
38
OMe
Scheme 14 Cross-coupling reactions of (E)- and (Z)-α-CF3-vinylger-
manes and (E)-vinylgermane sesquioxide with aryl halides
Büchi 510 melting point apparatus. THF was distilled under N2 from
Na/benzophenone. Reagents were purchased from Aldrich or Alfa
Aesar and used without further purification, unless otherwise noted.
All α-CF3-alkynes were synthesized from the corresponding terminal
alkynes according to the literature.29a Microwave reactions were per-
formed in a CEM Intelligent Explorer (Model 541416) microwave.
NMR spectra were recorded on Bruker AV 300 or AV 400 spectrome-
ters at 300 or 400 MHz for 1H NMR, 75 or 100 MHz for 13C NMR, and
376 or 282 MHz for 19F NMR. The spectra were calibrated using un-
deuterated solvent as the internal reference, unless otherwise indi-
cated. HRMS in positive mode were recorded using a 6520 series
quadrupole time-of-flight (Q-TOF) mass spectrometer (Agilent) fitted
with a multimode ion source (in mixed mode that enables both elec-
trospray ionization, ESI, and atmospheric pressure chemical ioniza-
tion, APCI). Samples were directly infused into the source using
MeOH/0.2% aq HCO2H 50:50. The HRMS of 24a, 29e, 29g, 30c, and 40a
could not be obtained despite our efforts; they do not ionize under
either ESI or APCI techniques. Melting points were recorded on a
Yields refer to chromatographically and spectroscopically (1H and 19
F
NMR) homogeneous materials, unless otherwise noted. Reactions
were monitored by TLC carried out on Merck TLC silica gel 60 F254 alu-
minum plates, using UV light or KMnO4 as visualizing agents. All sep-
arations were performed by chromatography on Merck silica gel 60
(40–63 μm), on a Combiflash Companion from Teledyne Isco or by
preparative TLC chromatography (layer thickness of 500 μm).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

I
C. Tresse et al.
Paper
Synthesis
For the sake of completeness, experimental procedures leading to
compounds 29a–g, 30a–f, 32a–37a, 40a and 42a–44a that have been
published in the preliminary communication28 are reproduced here.
Detailed procedures for the synthesis of 21a, 22, 26a,b, 27b, 28, 32a-
Cl/Br, 38a, 42a, 44a and the hydrolyzed organogermanes from 32a-
Cl/Br and 33a-Cl/Br can be found in the Supporting Information.
Tributyl[(E)-1,1,1-trifluoro-5-(4-methoxybenzyloxy)-6-methyl-
hept-2-en-3-yl]stannane [(E)-25b]
Obtained from 20b (100 mg, 0.33 mmol) following a slight modifica-
tion of TP A (the mixture was heated to reflux for 1 h), which led to a
ratio of 24b/25b of 73:27. After separation of the two isomers by pre-
parative TLC (cyclohexane/toluene 7:3), 25b (41 mg, 0.069 mmol,
21%) was isolated as a pale yellow oil.
Tributyl[(E)-1,1,1-trifluorotridec-2-en-2-yl]stannane [(E)-24a]
and Tributyl[(E)-1,1,1-trifluorotridec-2-en-3-yl]stannane [(E)-
25a]; Typical Procedure A (TP A)
1H NMR (300 MHz, CDCl3): δ = 7.26 (d, J = 8.7 Hz, 2 H), 6.87 (d, J = 8.7
Hz, 2 H), 5.75 (q, J = 8.6 Hz, J1H-117Sn = 61.4 Hz, J1H-119Sn = 62.8 Hz, 1
H), 4.47 (d, J = 11.3 Hz, 1 H), 4.41 (d, J = 11.3 Hz, 1 H), 3.81 (s, 3 H),
3.37 (m, 1 H), 2.73 (m, 2 H), 1.93 (m, 1 H), 1.54–1.40 (6 H), 1.38–1.25
(6 H), 1.00–0.85 (21 H).
13C NMR (100 MHz, CDCl3): δ = 161.8 (q, J = 4.9 Hz), 158.9, 131.1,
128.8 (2 C), 127.1 (q, J = 31.1 Hz), 121.9 (q, J = 276.5 Hz), 113.5 (2 C),
84.1, 70.9, 55.2, 30.1 (J13C-117Sn = J13C-119Sn = 21.9 Hz), 30.3, 28.9
(J13C-117Sn = J13C-119Sn = 19.8 Hz, 3 C), 27.3 (J13C-117Sn = J13C-119Sn =
60.7 Hz, 3 C), 17.7, 17.5, 13.6 (3 C), 10.4 (J13C-117Sn = 332.0 Hz, J13C-
119Sn = 339.1 Hz, 3 C).
A round-bottom flask equipped with a magnetic stirring bar, a dry N2
inlet and a septum, was successively charged with 20a (100 mg, 0.43
mmol), THF (2.1 mL, 0.2 M), Bu3SnH (126 μL, 0.47 mmol, 1.1 equiv),
and Pd(PPh3)4 (5.0 mg, 4.3 μmol, 1 mol%). The mixture was then
stirred under N2 atmosphere at 20 °C for 2 h. The solvent was re-
moved under reduced pressure and analysis of the crude mixture by
19F NMR revealed a ratio of 24a/25a of 89:11. After purification of the
crude material by column chromatography (100% cyclohexane), 24a
(223 mg, 0.425 mmol, 99%) was isolated as a pale yellow oil. Due to
the weak proportion of 25a, this compound was not fully character-
ized. However, diagnostic signals are given.
19F NMR (376 MHz, CDCl3): δ = –52.5 (d, J = 8.6 Hz, CF3).
Triphenyl[(Z)-1,1,1-trifluorotridec-2-en-2-yl]germane [(Z)-29a];
Typical Procedure B (TP B)
1H NMR (400 MHz, CDCl3): δ = 5.98 (t, J = 7.4 Hz, J1H-117Sn = 55.1 Hz,
J1H-119Sn = 57.4 Hz, 1 H, diagnostic signal of minor isomer), 5.64 (q, J =
8.5 Hz, 1 H, diagnostic signal of minor isomer), 2.37–2.28 (m, 2 H),
1.56–1.39 (8 H), 1.34–1.26 (20 H), 1.06–0.93 (6 H), 0.93–0.86 (12 H).
13C NMR (100 MHz, CDCl3): δ = 152.8 (q, J = 7.8 Hz), 132.7 (q, J = 33.2
Hz), 127.1 (q, J = 274.8 Hz), 125.5 (q, J = 31.0 Hz, diagnostic signal of
minor isomer), 31.9, 31.3 (J13C-117Sn = J13C-119Sn = 35.3 Hz), 29.6, 29.5,
29.4, 29.3, 29.2 (2 C), 28.7 (J13C-117Sn = J13C-119Sn = 19.8 Hz, 3 C), 27.2
(J13C-117Sn = J13C-119Sn = 59.1 Hz, 3 C), 22.7, 14.1, 13.6 (3 C), 10.2 (J13C-
117Sn = 344.7 Hz, J13C-119Sn = 352.5 Hz, 3 C).
A round-bottom flask equipped with a magnetic stirring bar and a
septum was successively charged with 20a (21 mg, 0.09 mmol),
MeCN (450 μL), and H2O (180 μL). After addition of Ph3GeH (27.4 mg,
0.09 mmol) and ammonium persulfate (20.5 mg, 0.09 mmol), the
mixture was stirred under air (balloon) at 20 °C for 12 h. Sat. aq
NaHCO3 solution was then added and the mixture was extracted with
EtOAc (2 ×); the combined organic layers were dried (MgSO4) and fil-
tered, and the solvents were evaporated under reduced pressure. Af-
ter purification of the crude material by column chromatography (cy-
clohexane/EtOAc 95:5), (Z)-29a (42 mg, 87%) was isolated as white
crystals; mp 63–64 °C.
19F NMR (376 MHz, CDCl3): δ = –47.9 (s, J19F-117Sn = J19F-119Sn = 21.3
Hz, CF3), –52.5 (d, J = 8.2 Hz, CF3, minor isomer).
1H NMR (300 MHz, CDCl3): δ = 7.58–7.55 (m, 6 H), 7.43–7.37 (m, 9 H),
7.13–7.06 (m, 1 H), 1.95–1.85 (m, 2 H), 1.34–1.18 (m, 6 H), 1.17–1.05
(m, 6 H), 1.01–0.83 [m, 7 H, including 0.90 (t, J = 6.8 Hz, 3 H)].
13C NMR (75 MHz, CDCl3): δ = 151.1 (q, J = 8.9 Hz, CH), 135.5, 135.1,
129.4, 128.4, 125.6 (q, J = 273 Hz, CF3), 32.7, 32.0, 29.6, 29.5, 29.4,
29.3, 29.2, 28.3, 22.8, 14.3.
Tributyl[(E)-1,1,1-trifluoro-5-(4-methoxybenzyloxy)-6-methyl-
hept-2-en-2-yl]stannane [(E)-24b]
Obtained from 20b (100 mg, 0.33 mmol) following TP A (at –30 °C),
which led to a separable mixture of 24b and 25b. After purification of
the crude material by preparative TLC (cyclohexane/toluene 7:3), 24b
(189 mg, 0.32 mmol, 96%) was isolated as a pale yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.28 (d, J = 8.7 Hz, 2 H), 6.90 (d, J = 8.7
Hz, 2 H), 6.24 (t, J = 7.0 Hz, J1H-117Sn = 56.3 Hz, J1H-119Sn = 57.3 Hz, 1
H), 4.47 (s, 2 H), 3.82 (s, 3 H), 3.27 (m, 1 H), 2.60 (m, 2 H), 1.92 (sept d,
J = 6.8, 5.3 Hz, 1 H), 1.61–1.45 (6 H), 1.41–1.26 (6 H), 1.04–0.87 (21 H).
19F NMR (376 MHz, CDCl3): δ = –54.6 (d, J = 2.1 Hz, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C25H32F3Ge: 461.1674; found:
461.1691.
[(Z)-5-(tert-Butyldiphenylsiloxy)-1,1,1-trifluoropent-2-en-2-
yl]triphenylgermane [(Z)-29b]
13C NMR (100 MHz, CDCl3): δ = 159.1, 149.1 (q, J = 7.8 Hz), 134.2 (q, J =
33.2 Hz), 130.9, 129.2 (2 C), 127.1 (q, J = 274.7 Hz), 113.7 (2 C), 88.3,
71.3, 55.2, 32.0 (J13C-117Sn = J13C-119Sn = 34.6 Hz), 31.0, 28.7 (J13C-117Sn
= J13C-119Sn = 19.8 Hz, 3 C), 27.2 (J13C-117Sn = J13C-119Sn = 60.7 Hz, 3 C),
18.3, 17.8, 13.6 (3 C), 10.2 (J13C-117Sn = 344.7 Hz, J13C-119Sn = 352.5 Hz,
3 C).
Obtained from the corresponding α-CF3-alkyne (34 mg, 0.09 mmol)
following TP B. After purification of the crude material by column
chromatography (cyclohexane/CH2Cl2 9:1), (Z)-29b (44 mg, 71%) was
isolated as a white powder; mp 107–108 °C.
1H NMR (400 MHz, CDCl3): δ = 7.58–7.56 (m, 4 H), 7.52–7.50 (m, 6 H),
7.45–7.31 (m, 16 H), 3.40 (t, J = 6.0 Hz, 2 H), 2.16–2.10 (m, 2 H), 1.03
(s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 148.4 (q, J = 9.2 Hz, CH), 135.7, 135.3,
135.0, 133.5, 129.8, 129.7, 128.5, 127.8, 125.5 (q, J = 273 Hz, CF3), 62.1,
35.3, 26.9, 19.3.
19F NMR (376 MHz, CDCl3): δ = –48.1 (br s, J19F-117Sn = J19F-119Sn =
20.6 Hz, CF3).
HRMS-ESI: m/z [M + H]+ calcd for C28H48F3O2Sn: 593.2628; found:
593.2625.
19F NMR (376 MHz, CDCl3): δ = –54.9 (d, J = 2.4 Hz, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C33H34F3GeOSi: 605.1544;
found: 605.1558.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

J
C. Tresse et al.
Paper
Synthesis
[(Z)-3-(Biphenyl-4-yl)-1,1,1-trifluoroprop-2-en-2-yl]triphenylger-
mane [(Z)-29c]; Typical Procedure C (TP C)
1H NMR (400 MHz, CDCl3): δ = 8.19 (d, J = 2.3 Hz, 1 H), 7.47 (dd, J = 7.8,
1.5 Hz, 6 H), 7.32–7.24 (m, 9 H), 6.90 (t, J = 7.8 Hz, 1 H), 6.89 (d, J = 7.8
Hz, 1 H), 6.44 (d, J = 7.8 Hz, 1 H), 6.27 (t, J = 7.8 Hz, 1 H), 3.66 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.8, 146.0 (q, J = 9.2 Hz, CH), 135.8,
135.1, 130.4, 129.8, 129.0, 128.9 (q, J = 30 Hz, C), 128.0, 126.2 (q, J =
273 Hz, CF3), 124.5, 119.6, 109.7, 55.1.
A round-bottom flask equipped with a magnetic stirring bar and a
septum was successively charged with 20c (20 mg, 0.08 mmol) and
DMF (400 μL). After the addition of Ph3GeH (24.4 mg, 0.08 mmol) and
ammonium persulfate (18.3 mg, 0.08 mmol), the mixture was stirred
under air (balloon) at 20 °C for 4 h. Sat. aq NaHCO3 solution was then
added and the mixture was extracted with cyclohexane/CH2Cl2 (9:1,
2 ×); the combined organic layers were dried (MgSO4) and filtered,
and the solvents were evaporated under reduced pressure. After puri-
fication of the crude material by column chromatography (cyclohex-
ane/CH2Cl2 9:1), (Z)-29c (37 mg, 84%) was isolated as a white powder;
mp 176–177 °C.
19F NMR (376 MHz, CDCl3): δ = –52.7 (d, J = 2.1 Hz, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C22H18F3GeO: 429.0520; found:
429.0532.
Triphenyl[(Z)-1,1,1-trifluoro-3-(4-phenoxyphenyl)prop-2-en-2-
yl]germane [(Z)-29g]
1H NMR (400 MHz, CDCl3): δ = 8.18 (d, J = 2.0 Hz, 1 H), 7.50 (dd, J = 7.8,
1.8 Hz, 6 H), 7.40–7.28 (m, 14 H), 7.14 (d, J = 8.1 Hz, 2 H), 7.04 (d, J =
8.1 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 148.4 (q, J = 9.2 Hz, CH), 141.6, 140.5,
135.4, 135.2, 133.7, 129.7, 129.2, 128.8, 128.3, 127.6, 127.1, 126.3,
126.2 (q, J = 273 Hz, CF3).
Obtained from 20g (21 mg, 0.08 mmol) following TP C. After purifica-
tion of the crude material by column chromatography (cyclohex-
ane/CH2Cl2 9:1), (Z)-29g (37 mg, 82%) was isolated as a white powder;
mp 113 °C.
1H NMR (400 MHz, CDCl3): δ = 8.10 (d, J = 2.3 Hz, 1 H), 7.49 (dd, J = 7.8,
1.2 Hz, 6 H), 7.38–7.27 (m, 11 H), 7.11–7.06 (m, 3 H), 6.76 (dd, J = 8.8,
1.0 Hz, 2 H), 6.46 (d, J = 8.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 158.0, 156.6, 148.0 (q, J = 9.2 Hz, CH),
135.5, 135.2, 131.1, 129.8, 129.6, 129.3, 128.3, 127.8 (q, J = 30 Hz, C),
126.3 (q, J = 273 Hz, CF3), 123.7, 119.3, 117.7.
19F NMR (376 MHz, CDCl3): δ = –53.0 (d, J = 2.1 Hz, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C27H20F3Ge: 475.0729; found:
475.0736.
19F NMR (376 MHz, CDCl3): δ = –52.9 (d, J = 2.4 Hz, CF3).
[(Z)-3-(4-Bromophenyl)-1,1,1-trifluoroprop-2-en-2-yl]triphenyl-
germane [(Z)-29d]
Triphenyl[(E)-1,1,1-trifluorotridec-2-en-2-yl]germane [(E)-30a];
Typical Procedure D (TP D)
Obtained from 20d (20 mg, 0.08 mmol) following TP C. After purifica-
tion of the crude material by column chromatography (cyclohex-
ane/CH2Cl2 95:5), (Z)-29d (32 mg, 72%) was isolated as a white pow-
der; mp 135–136 °C.
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 2.3 Hz, 1 H), 7.45 (dd, J = 7.8,
1.2 Hz, 6 H), 7.37–7.27 (m, 9 H), 6.95–6.89 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 147.6 (q, J = 9.2 Hz, CH), 135.1, 133.6,
130.8, 130.6, 129.3, 128.4, 126.0 (q, J = 273 Hz, CF3), 123.2.
19F NMR (376 MHz, CDCl3): δ = –53.4 (d, J = 2.4 Hz, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C21H15BrF3Ge: 476.9514;
found: 476.9524.
A round-bottom flask equipped with a magnetic stirring bar, a dry N2
inlet, and a septum was successively charged with 20a (1.0 g, 4.27
mmol), THF (21.4 mL, 0.2 M), Ph3GeH (1.30 g, 4.27 mmol), and
Pd(PPh3)4 (46.2 mg, 0.04 mmol, 1 mol%). The mixture was stirred at
20 °C for 12 h. After purification of the crude material by column
chromatography (cyclohexane), (E)-30a (1.7 g, 74%) was isolated as a
colorless oil.
1H NMR (300 MHz, CDCl3): δ = 7.53–7.49 (m, 6 H), 7.43–7.36 (m, 9 H),
6.19 (t, J = 7.7 Hz, 1 H), 2.45–2.36 (m, 2 H), 1.39–1.25 m, 16 H), 0.89 (t,
J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.8 (q, J = 6.4 Hz, CH), 135.3, 135.2,
129.6, 129.1 (q, J = 31 Hz, C), 128.5, 126.1 (q, J = 276 Hz, CF3), 32.0,
31.2, 29.7, 29.6, 29.5, 29.4, 29.3, 29.0, 22.8, 14.3.
Triphenyl[(Z)-1,1,1-trifluoro-3-(4-methoxyphenyl)prop-2-en-2-
yl]germane [(Z)-29e]
19F NMR (376 MHz, CDCl3): δ = –47.3 (s, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C25H32F3Ge: 463.1667; found:
Obtained from 20e (16 mg, 0.08 mmol) following TP C. After purifica-
tion of the crude material by column chromatography (cyclohex-
ane/CH2Cl2 8:2), (Z)-29e (33 mg, 82%); was isolated as a white pow-
der; mp 107–108 °C.
463.1682.
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 2.3 Hz, 1 H), 7.50 (dd, J = 7.8,
1.5 Hz, 6 H), 7.35–7.27 (m, 9 H), 7.07 (d, J = 8.8 Hz, 2 H), 6.37 (d, J = 8.8
Hz, 2 H), 3.61 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 160.3, 148.2 (q, J = 9.2 Hz, CH), 135.6,
135.2, 131.3, 129.2, 128.2, 127.1, 126.4 (q, J = 273 Hz, CF3), 126.1 (q, J =
30 Hz, C), 113.1, 55.3.
[(E)-5-(tert-Butyldiphenylsiloxy)-1,1,1-trifluoropent-2-en-2-
yl]triphenylgermane [(E)-30b]
Obtained from the corresponding α-CF3-alkyne (34 mg, 0.09 mmol)
following TP D. The mixture was stirred at 50 °C for 2 h. After purifi-
cation of the crude material by preparative TLC chromatography (cy-
clohexane/CH2Cl2 8:2), (E)-30b (35 mg, 57%) was isolated as a white
powder; mp 87–88 °C.
19F NMR (376 MHz, CDCl3): δ = –52.6 (d, J = 2.1 Hz, CF3).
1H NMR (400 MHz, CDCl3): δ = 7.58–7.52 (m, 10 H), 7.44–7.31 (m, 15
H), 6.49 (t, J = 7.2 Hz, 1 H), 3.69 (t, J = 5.8 Hz, 2 H), 2.71–2.66 (m, 2 H),
0.96 (s, 9 H).
Triphenyl[(Z)-1,1,1-trifluoro-3-(2-methoxyphenyl)prop-2-en-2-
yl]germane [(Z)-29f]
13C NMR (100 MHz, CDCl3): δ = 153.6 (q, J = 6.4 Hz, CH), 135.6, 135.3,
135.0, 133.6, 130.7 (q, J = 31 Hz, C), 129.8, 129.5, 128.5, 127.8, 126.1
(q, J = 276 Hz, CF3), 62.5, 34.3, 26.9, 19.3.
Obtained from 20f (16 mg, 0.08 mmol) following TP C. After purifica-
tion of the crude material by column chromatography (cyclohex-
ane/CH2Cl2 9:1), (Z)-29f (33 mg, 82%) was isolated as a white powder;
mp 83 °C.
19F NMR (376 MHz, CDCl3): δ = –47.4 (s, CF3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

K
C. Tresse et al.
Paper
Synthesis
HRMS-APCI: m/z [M – C6H5]+ calcd for C33H34F3GeOSi: 606.1569;
found: 606.1558.
{(E)-cis-3-[2-(tert-Butyldiphenylsiloxymethyl)cyclopropyl]-1,1,1-
trifluoroprop-2-en-2-yl]triphenylgermane [(E)-30f]
Obtained from the corresponding α-CF3-alkyne (44 mg, 0.11 mmol)
following TP D. The mixture was stirred under MW at 100 °C for 1 h.
After purification of the crude material by column chromatography
(cyclohexane/CH2Cl2 95:5), (E)-30f (65 mg, 83%) was isolated as a col-
orless oil.
1H NMR (400 MHz, CDCl3): δ = 7.65–7.59 (m, 4 H), 7.48 (d, J = 6.5 Hz, 6
H), 7.38–7.29 (m, 15 H), 5.75 (d, J = 11.3 Hz, 1 H), 3.59 (dd, J = 11.4, 6.8
Hz, 1 H), 3.43 (dd, J = 11.4, 8.2 Hz, 1 H), 2.22–2.13 (m, 1 H), 1.51–1.42
(m, 1 H), 1.11–1.06 (m, 1 H), 1.01 (s, 9 H), 0.31 (dd, J = 11.4, 5.3 Hz, 1
H).
13C NMR (100 MHz, CDCl3): δ = 156.4 (q, J = 6.4 Hz, CH), 135.8, 135.7,
135.3, 135.2, 129.8, 129.4, 128.4, 127.8, 127.7, 126.6 (q, J = 276 Hz,
CF3), 64.0, 27.0, 23.9, 19.3, 18.0, 14.9.
19F NMR (376 MHz, CDCl3): δ = –47.1 (s, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C35H36F3GeOSi: 631.1805;
[(E)-6-(tert-Butyldiphenylsiloxy)-1,1,1-trifluorohexa-2,4-dien-2-
yl]triphenylgermane [(E)-30c]
Obtained from the corresponding α-CF3-alkyne (34 mg, 0.09 mmol)
following TP D. The mixture was stirred at 50 °C for 2 h. After purifi-
cation of the crude material by preparative TLC chromatography (cy-
clohexane/CH2Cl2 8:2), (E)-30c (27 mg, 43%) was isolated as a white
solid; mp 82 °C.
1H NMR (400 MHz, CDCl3): δ = 7.67 (dd, J = 7.6, 1.2 Hz, 4 H), 7.55–7.53
(m, 6 H), 7.45–7.37 (m, 15 H), 7.08–7–00 (m, 1 H), 6.61 (d, J = 11.6 Hz,
1 H), 5.89 (dt, J = 14.8, 4.0 Hz, 1 H), 4.30 (d, J = 1.8 Hz, 2 H), 1.08 (s, 9
H).
13C NMR (100 MHz, CDCl3): δ = 149.9 (q, J = 6.4 Hz, CH), 142.2, 135.7,
135.3, 135.0, 133.4, 129.9, 129.5, 128.5, 127.4 (q, J = 31 Hz, C), 127.9,
126.2 (q, J = 276 Hz, CF3), 124.9, 63.5, 26.9, 19.4.
19F NMR (376 MHz, CDCl3): δ = –46.7 (d, J = 1.3 Hz, CF3).
found: 631.1813.
Triphenyl[(E)-1,1,1-trifluoro-5-(4-methoxybenzyloxy)-6-methyl-
hept-2-en-2-yl]germane [(E)-30d]
Chlorodiphenyl[(E)-1,1,1-trifluorotridec-2-en-2-yl]germane [(E)-
33a-Cl]
Obtained from the corresponding α-CF3-alkyne (27 mg, 0.09 mmol)
following TP D. The mixture was stirred at 20 °C for 12 h. After purifi-
cation of the crude material by column chromatography (cyclohex-
ane/CH2Cl2 9:1), (E)-30d (50 mg, 91%) was isolated as a colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.51 (dd, J = 7.6, 1.6 Hz, 6 H), 7.44–7.33
(m, 9 H), 7.02 (d, J = 8.6 Hz, 2 H), 6.77 (d, J = 8.6 Hz, 2 H), 6.46 (t, J = 7.1
Hz, 1 H), 4.34 (d, J = 10.9 Hz, 1 H), 4.24 (d, J = 10.9 Hz, 1 H), 3.79 (s, 3
H), 3.23–3.18 (m, 1 H), 2.72–2.65 (m, 1 H), 2.60–2.52 (m, 1 H), 1.92–
1.80 (m, 1 H), 0.90 (t, J = 6.7 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 159.1, 154.0 (q, J = 6.4 Hz, CH), 135.5,
135.3, 135.1, 130.8, 130.1 (q, J = 31 Hz, C), 129.5, 129.2, 128.5, 126.1
(q, J = 276 Hz, CF3), 113.8, 83.3, 71.7, 55.4, 32.4, 31.3, 18.4, 17.7.
19F NMR (376 MHz, CDCl3): δ = –47.5 (s, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C28H30F3GeO2: 529.1363;
A microwave tube was successively charged with (E)-30a (50 mg, 0.09
mmol), dioxane (0.3 mL), and concd HCl (37%, 0.3 mL), and the mix-
ture was stirred under MW irradiation at 160 °C (internal pressure:
13 bar), for 1 h. The mixture was cooled to r.t., CH2Cl2 (10 mL) and
water (10 mL) were added, and the two resulting phases were sepa-
rated. The aqueous layer was extracted with CH2Cl2 (10 mL) and the
combined organic layers were washed with brine and dried (MgSO4).
After filtration and evaporation of the solvents under reduced pres-
sure, the crude material (E)-33a-Cl was obtained with 100% conver-
sion as a brown oil. This compound was not fully characterized due to
its extreme moisture sensitivity; the corresponding hydroxy-germa-
nium derivative is very easily obtained upon exposure to ambient at-
mosphere (see the Supporting Information for details).
1H NMR (300 MHz, CDCl3): δ = 7.62–7.57 (m, 3 H), 7.50–7.41 (m, 7 H),
6.65 (t, J = 7.6 Hz, 1 H), 2.49–2.2.41 (m, 2 H), 1.48–1.23 (m, 16 H), 0.87
(t, J = 6.9 Hz, 3 H).
found: 529.1362.
19F NMR (282 MHz, CDCl3): δ = –52.0 (t, J = 2.7 Hz, CF3).
Triphenyl[(E)-trans-1,1,1-trifluoro-3-(2-phenylcyclopropyl)prop-
2-en-2-yl]germane [(E)-30e]
Bromodiphenyl[(E)-1,1,1-trifluorotridec-2-en-2-yl]germane [(E)-
Obtained from the corresponding α-CF3-alkyne (19 mg, 0.09 mmol)
following TP D. The mixture was stirred at 50 °C for 2 h. After purifi-
cation of the crude material by preparative TLC chromatography (cy-
clohexane/CH2Cl2 8:2), (E)-30e (30 mg, 65%) was isolated as a color-
less oil.
1H NMR (400 MHz, CDCl3): δ = 7.54–7.52 (m, 6 H), 7.45–7.37 (m, 9 H),
7.28 (t, J = 7.3 Hz, 2 H), 7.19 (t, J = 7.3 Hz, 1 H), 7.10 (d, J = 7.3 Hz, 2 H),
5.56 (d, J = 10.8 Hz, 1 H), 2.40–2.32 (m, 1 H), 2.01–1.96 (m, 1 H), 1.41–
1.36 (m, 1 H), 1.10–1.05 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 157.9 (q, J = 6.4 Hz, CH), 140.5, 135.3,
135.1, 129.5, 128.6, 128.5, 126.5 (q, J = 276 Hz, CF3), 126.4, 126.4 (q, J =
31 Hz, C), 27.0, 25.0, 18.4.
19F NMR (376 MHz, CDCl3): δ = –47.1 (d, J = 1.3 Hz, CF3).
HRMS-APCI: m/z [M – C6H5]+ calcd for C24H20F3Ge: 439.0728; found:
33a-Br]
A microwave tube was successively charged with (E)-30a (50 mg, 0.09
mmol), dioxane (0.3 mL), and concd HBr (48%, 0.3 mL), and the mix-
ture was stirred under MW at 160 °C (internal pressure: 13 bar), for 1
h. The mixture was cooled to r.t., CH2Cl2 (10 mL) and water (10 mL)
were added, and the two resulting phases were separated. The aque-
ous layer was extracted with CH2Cl2 (10 mL) and the combined organ-
ic layers were washed with brine and dried (MgSO4). After filtration
and evaporation of the solvents under reduced pressure, the crude
material (E)-33a-Br was obtained with 100% conversion as a brown
oil. This compound was not fully characterized due to its extreme
moisture sensitivity; the corresponding hydroxy-germanium deriva-
tive is very easily obtained upon exposure to ambient atmosphere
(see the Supporting Information for details).
1H NMR (300 MHz, CDCl3): δ = 7.63–7.59 (m, 3 H), 7.51–7.42 (m, 7 H),
6.66 (t, J = 7.7 Hz, 1 H), 2.50–2.41 (m, 2 H), 1.50–1.23 (m, 16 H), 0.88
(t, J = 6.7 Hz, 3 H).
439.0726.
19F NMR (282 MHz, CDCl3): δ = –52.0 (t, J = 2.1 Hz, CF3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

L
C. Tresse et al.
Paper
Synthesis
Dichlorophenyl[(E)-1,1,1-trifluorotridec-2-en-2-yl]germane [(E)-
19F NMR (376 MHz, CDCl3): δ = –54.7 (d, J = 1.8 Hz, CF3).
35a]
In a two-necked round-bottom flask equipped with a condenser and
dry N2 inlet, a solution of ICl (301 mg, 1.85 mmol) in CHCl3 (3.5 mL)
was added at 0 °C to a solution of (E)-30a (200 mg, 0.37 mmol) in
CHCl3 (4 mL). The red mixture was stirred at 50 °C for 4 h to provide
100% conversion of (E)-30a (as monitored by 19F NMR). The mixture
was cooled, the solvent was removed under reduced pressure, and the
crude material was purified by distillation of PhI and excess ICl under
reduced pressure (60 °C, 0.133 mbar) to provide (E)-35a (166 mg,
98%) as a colorless residual oil. This compound was not fully charac-
terized due to its extreme moisture sensitivity; the corresponding hy-
droxy-germanium derivative is very easily obtained upon exposure to
ambient atmosphere.
Trichloro[(E)-1,1,1-trifluorotridec-2-en-2-yl]germane [(E)-37a]
A round-bottom flask equipped with a magnetic stirring bar, dry N2
inlet and a septum was charged with (E)-30a (1.5 g, 2.78 mmol). At
0 °C, ICl (3.6 g, 22.2 mmol) was added in one portion, and the result-
ing dark red mixture was stirred under N2 at 85 °C for 2 h to provide
100% conversion of the (E)-30a (as monitored by 19F NMR). The crude
material was then purified by distillation of byproducts (PhI and 1,4-
diiodobenzene) under reduced pressure (90 °C, 0.133 mbar) to pro-
vide (E)-37a (830 mg, 72%) as a brown residual oil. This compound
was not fully characterized due to its extreme moisture sensitivity;
the corresponding hydroxy-germanium derivative is very easily ob-
tained upon exposure to ambient atmosphere.
1H NMR (400 MHz, CDCl3): δ = 7.71–7.67 (m, 2 H), 7.58–7.49 (m, 3 H),
6.90 (t, J = 7.7 Hz, 1 H), 2.53–2.46 (m, 2 H), 1.56–1.48 (m, 2 H), 1.35–
1.24 (m, 14 H), 0.88 (t, J = 6.7 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 6.94 (t, J = 7.7 Hz, 1 H), 2.55–2.48 (m, 2
H), 1.58–1.50 (m, 2 H), 1.38–1.23 (m, 14 H), 0.88 (t, J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.8 (q, J = 5.0 Hz, CH), 128.7 (q, J =
35 Hz, C), 123.0 (q, J = 275 Hz, CF3), 32.0, 31.0, 29.7, 29.5, 29.4, 29.3,
29.3, 28.4, 22.8, 14.2.
19F NMR (376 MHz, CDCl3): δ = –47.9 (m, CF3).
Dichlorophenyl[(Z)-1,1,1-trifluorotridec-2-en-2-yl]germane [(Z)-
34a]
19F NMR (376 MHz, CDCl3): δ = –48.2 (s, CF3).
In a two-necked round-bottom flask equipped with a condenser and
dry N2 inlet, a solution of ICl (226 mg, 1.40 mmol) in CHCl3 (2.5 mL)
was added at 0 °C to a solution of (Z)-29a (150 mg, 0.28 mmol) in
CHCl3 (3 mL). The red mixture was stirred at 55 °C for 12 h to provide
100% conversion of (Z)-29a (as monitored by 19F NMR). The mixture
was cooled, the solvent was removed under reduced pressure, and the
crude material was purified by distillation of PhI and excess ICl under
reduced pressure (60 °C, 0.133 mbar) to provide (Z)-34a (112 mg,
88%) as a colorless residual oil. This compound was not fully charac-
terized due to its extreme moisture sensitivity; the corresponding hy-
droxy-germanium derivative is very easily obtained upon exposure to
ambient atmosphere.
Synthesis of α-Trifluoromethylated Styrenes 40a and 43a; General
Coupling Procedure
A round-bottom flask equipped with a magnetic stirring bar, a dry N2
inlet and a septum was successively charged with (Z)-36a or (E)-37a
(100 mg, 0.24 mmol) and dioxane (1.5 mL). 2 M aq NaOH solution
(960 μL, 1.92 mmol) and H2O (540 μL) were then successively added
and the solution was stirred at r.t. for 10 min. After addition of aryl
halide (0.12 mmol) and Pd(OAc)2 (2.7 mg, 5 mol%), the mixture was
stirred under N2 at 80 °C for 1 h. The mixture was cooled and H2O was
added, and the mixture was extracted with EtOAc (2 ×). The com-
bined organic layers were washed with brine, dried (MgSO4) and fil-
tered, and the solvents were removed under reduced pressure. The
crude material was purified by chromatography to provide the de-
sired α-trifluoromethylated styrene.
1H NMR (400 MHz, CDCl3): δ = 7.74–7.70 (m, 2 H), 7.57–7.49 (m, 3 H),
6.90 (tq, J = 7.9, 2.0 Hz, 1 H), 2.38–2.30 (m, 2 H), 1.43–1.36 (m, 2 H),
1.30–1.16 (m, 14 H), 0.88 (t, J = 7.7 Hz, 3 H).
19F NMR (376 MHz, CDCl3): δ = –54.5 (q, J = 2.1 Hz, CF3).
(Z)-1,1,1-Trifluoro-2-(4-nitrophenyl)tridec-2-ene [(Z)-40a]
From (E)-37a: obtained from the reaction of (E)-37a (100 mg, 0.24
mmol) with 1-iodo-4-nitrobenzene (30 mg, 0.12 mmol) following the
general coupling procedure. After purification of the crude material
by preparative TLC chromatography (cyclohexane/EtOAc 95:5), (Z)-
40a (41 mg, 95%) was isolated as a colorless oil.
Trichloro[(Z)-1,1,1-trifluorotridec-2-en-2-yl]germane [(Z)-36a]
A round-bottom flask equipped with a magnetic stirring bar, dry N2
inlet and a septum was charged with (Z)-29a (1.6 g, 2.97 mmol). At
0 °C, ICl (4.8 g, 29.7 mmol) was added in one portion, and the result-
ing dark red mixture was stirred under N2 at 85 °C for 4 h to provide
100% conversion of the (Z)-29a (as monitored by 19F NMR). The crude
material was then purified by distillation of byproducts (PhI and 1,4-
diiodobenzene) under reduced pressure (90 °C, 0.133 mbar ) to pro-
vide (Z)-36a (950 mg, 77%) as a brown residual oil. This compound
was not fully characterized due to its extreme moisture sensitivity;
the corresponding hydroxy-germanium derivative is very easily ob-
tained upon exposure to ambient atmosphere.
1H NMR (400 MHz, CDCl3): δ = 7.19 (tq app. td, J = 7.8, 1.8 Hz, 1 H),
2.59–2.52 (m, 2 H), 1.58–1.51 (m, 2 H), 1.39–1.26 (m, 14 H), 0.88 (t, J =
6.5 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.1 (q, J = 7.1 Hz, CH), 128.4 (q, J =
33 Hz, C), 122.6 (q, J = 274 Hz, CF3), 32.0, 31.7, 29.6, 29.5, 29.4, 29.3,
29.2, 28.3, 22.8, 14.2.
From (E)-38a: Obtained from the reaction of (E)-38a (40 mg, 0.06
mmol) with 1-iodo-4-nitrobenzene (30 mg, 0.12 mmol) following the
general coupling procedure and heating at 80 °C for 15 h. After purifi-
cation of the crude material by preparative TLC chromatography (cy-
clohexane/EtOAc 95:5), (Z)-40a (27 mg, 62%) was isolated as a color-
less oil.
1H NMR (400 MHz, CDCl3): δ = 8.21 (d, J = 8.5 Hz, 2 H), 7.46 (d, J = 8.5
Hz, 2 H), 6.16 (t, J = 7.7 Hz, 1 H), 2.51–2.44 (m, 2 H), 1.55–1.48 (m, 2
H), 1.38–1.23 (m, 14 H), 0.88 (t, J = 6.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 147.6, 145.3 (q, J = 3.0 Hz, CH), 143.2 (q,
J = 1.5 Hz, CAr), 130.2 (q, J = 30 Hz, C), 129.2, 123.7, 123.6 (q, J = 276
Hz, CF3), 32.0, 29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 29.2, 29.1, 22.8, 14.2.
19F NMR (376 MHz, CDCl3): δ = –52.5 (s, CF3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

M
C. Tresse et al.
Paper
Synthesis
(Z)-1,1,1-Trifluoro-2-(4-methoxyphenyl)tridec-2-ene [(Z)-43a]
7971. (c) Vulpetti, A.; Dalvit, C. Drug Discovery Today 2012, 17,
890. (d) Cobb, S. L.; Murphy, C. D. J. Fluorine Chem. 2009, 130,
132. (e) Yu, L.; Hajduk, P.; Mack, J.; Olejniczak, E. J. Biomol. NMR
2006, 34, 221. (f) Dalvit, C.; Ardini, E.; Flocco, M.; Fogliatto, G. P.;
Mongelli, N.; Veronesi, M. J. Am. Chem. Soc. 2003, 125, 14620.
(g) Meyer, B.; Peters, T. Angew. Chem. Int. Ed. 2003, 42, 864.
(4) Tsuchikawa, H.; Matsushita, N.; Matsumori, N.; Murata, M.;
Oishi, T. Tetrahedron Lett. 2006, 47, 6187.
(5) Woods, J. R.; Mo, H.; Bieberich, A. A.; Alavanja, T.; Colby, D. A.
J. Med. Chem. 2011, 54, 7934.
(6) Shibata, H.; Tsuchikawa, H.; Hayashi, T.; Matsumori, N.; Murata,
M.; Usui, T. Chem. Asian J. 2015, 10, 915.
Obtained from the reaction of (E)-37a (100 mg, 0.24 mmol) with 4-
iodoanisole (28 mg, 0.12 mmol) following the general coupling proce-
dure. After purification of the crude material by preparative TLC chro-
matography (cyclohexane/EtOAc 95:5), (Z)-43a (26 mg, 60%) was iso-
lated as a colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.22 (d, J = 8.7 Hz, 2 H), 6.87 (d, J = 8.7
Hz, 2 H), 5.96 (t, J = 7.7 Hz, 1 H), 3.81 (s, 3 H), 2.44–2.37 (m, 2 H),
1.51–1.46 (m, 2 H), 1.32–1.24 (m, 14 H), 0.88 (t, J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.5, 141.6 (q, J = 3.1 Hz, CH), 131.0
(q, J = 30 Hz, C), 129.6, 128.0, 124.3 (q, J = 275 Hz, CF3), 113.7, 55.4,
32.0, 29.7, 29.7, 29.5, 29.5, 29.4, 29.3, 22.8, 14.2.
(7) Chany, A. C.; Tresse, C.; Casarotto, V.; Blanchard, N. Nat. Prod.
Rep. 2013, 30, 1527.
19F NMR (376 MHz, CDCl3): δ = –52.8 (s, CF3).
(8) (a) Blanchard, N.; Chany, A.-C.; Tresse, C.; Casarotto, V.;
Bréthous, L.; Saint-Auret, S. In Strategies and Tactics in Organic
Synthesis; Vol. 11; Michael, H., Ed.; Academic Press 2015, 85.
(b) Chany, A.-C.; Veyron-Churlet, R.; Tresse, C.; Mayau, V.;
Casarotto, V.; Le Chevalier, F.; Guenin-Macé, L.; Demangel, C.;
Blanchard, N. J. Med. Chem. 2014, 57, 7382. (c) Chany, A.-C.;
Casarotto, V.; Schmitt, M.; Tarnus, C.; Guenin-Macé, L.;
Demangel, C.; Mirguet, O.; Eustache, J.; Blanchard, N. Chem. Eur.
J. 2011, 17, 14413.
(9) For other efforts in this area, see: (a) Scherr, N.; Gersbach, P.;
Dangy, J.-P.; Bomio, C.; Li, J.; Altmann, K.-H.; Pluschke, G. Plos
Neglected Trop. Dis. 2013, 7, e2143. (b) Gersbach, P.; Jantsch, A.;
Feyen, F.; Scherr, N.; Dangy, J.-P.; Pluschke, G.; Altmann, K.-H.
Chem. Eur. J. 2011, 17, 13017. (c) Kishi, Y. Proc. Natl. Acad. Sci.
U.S.A. 2011, 108, 6703.
HRMS-APCI: m/z [M – H]+ calcd for C20H30F3O: 343.2243; found:
343.2247.
Acknowledgment
This work was supported by the Fondation Raoul Follereau, the CNRS,
the ANR, the Université de Strasbourg, the Université de Haute-Alsace
and the Université libre de Bruxelles. CT acknowledges the Université
de Haute-Alsace for a graduate fellowship. Mr. Didier Le Nouen (UHA)
is gratefully acknowledged for his precious assistance with 19F NMR.
Supporting Information
(10) Guenin-Macé, L.; Veyron-Churlet, R.; Thoulouze, M. I.; Romet-
Lemonne, G.; Hong, H.; Leadlay, P. F.; Danckaert, A.; Ruf, M. T.;
Mostowy, S.; Zurzolo, C.; Bousso, P.; Chretien, F.; Carlier, M. F.;
Demangel, C. J. Clin. Invest. 2013, 123, 1501.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561487.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(11) (a) Ayeni, D. O.; Mandal, S. K.; Zajc, B. Tetrahedron Lett. 2013, 54,
6008. (b) Landge, S. M.; Borkin, D. A.; Török, B. Lett. Org. Chem.
2009, 6, 439. (c) Kimura, M.; Yamazaki, T.; Kitazume, T.; Kubota,
T. Org. Lett. 2004, 6, 4651. (d) Hanamoto, T.; Morita, N.; Shindo,
K. Eur. J. Org. Chem. 2003, 4279. (e) Kobayashi, T.; Eda, T.;
Tamura, O.; Ishibashi, H. J. Org. Chem. 2002, 67, 3156.
(12) (a) Charpentier, J.; Früh, N.; Togni, A. Chem. Rev. 2015, 115, 650.
(b) Feng, Z.; Min, Q.-Q.; Zhao, H.-Y.; Gu, J.-W.; Zhang, X. Angew.
Chem. Int. Ed. 2015, 54, 1270. (c) Choi, W. J.; Choi, S.; Ohkubo,
K.; Fukuzumi, S.; Cho, E. J.; You, Y. Chem. Sci. 2015, 6, 1454.
(d) Arimori, S.; Shibata, N. Org. Lett. 2015, 17, 1632. (e) Wang,
X.; Xu, Y.; Deng, Y.; Zhou, Y.; Feng, J.; Ji, G.; Zhang, Y.; Wang, J.
Chem. Eur. J. 2014, 20, 961. (f) Koike, T.; Akita, M. J. Fluorine
Chem. 2014, 167, 30. (g) Xiong, Y. P.; Wu, M. Y.; Zhang, X. Y.; Ma,
C. L.; Huang, L.; Zhao, L. J.; Tan, B.; Liu, X. Y. Org. Lett. 2014, 16,
1000. (h) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem. Int.
Ed. 2013, 52, 8214. (i) Morimoto, H.; Tsubogo, T.; Litvinas, N. D.;
Hartwig, J. F. Angew. Chem. Int. Ed. 2011, 50, 3793. (j) Cho, E. J.;
Buchwald, S. L. Org. Lett. 2011, 13, 6552. (k) De-Bao, S.; Jian-
Xiang, D.; Qing-Yun, C. Tetrahedron Lett. 1991, 32, 7689.
(l) Chen, Q.-Y.; Wu, S.-W. J. Chem. Soc., Chem. Commun. 1989,
705.
References
(1) (a) Bégué, J.-P.; Bonnet-Delpon, D. Bioorganic and Medicinal
Chemistry of Fluorine; John Wiley & Sons: Hoboken, 2008.
(b) MacBean, C. The Pesticide Manual: A World Compendium,
17th ed.; British Crop Protection Council: Alton, 2014. (c) Zhou,
Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Acena, J. L.; Soloshonok,
V. A.; Izawa, K.; Liu, H. Chem. Rev. 2016, 116, 422.
(d) Gouverneur, V.; Seppelt, K. Chem. Rev. 2015, 115, 563.
(e) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.;
Meanwell, N. A. J. Med. Chem. 2015, 58, 8315. (f) Boday, D. J. In
Advances in Fluorine-Containing Polymers, ACS Symposium Series
No. 1106; Smith, D. W. Jr.; Iacono, S. T.; Boday, D. J.; Kettwich, S.
C., Eds.; American Chemical Society: Washington, 2012, 1–7.
(2) (a) Zhang, N.; Fu, J.-N.; Chou, T.-C. Am. J. Cancer Res. 2016, 6, 97.
(b) Chou, T. C.; Zhang, X.; Zhong, Z. Y.; Li, Y.; Feng, L.; Eng, S.;
Myles, D. R.; Johnson, R. Jr.; Wu, N.; Yin, Y. I.; Wilson, R. M.;
Danishefsky, S. J. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 13157.
(c) Altmann, K.-H.; Pfeiffer, B.; Arseniyadis, S.; Pratt, B. A.;
Nicolaou, K.-C. ChemMedChem 2007, 2, 396. (d) Danishefsky, S.
J. Drugs Future 2005, 30, 737. (e) Rivkin, A.; Chou, T.-C.;
Danishefsky, S. J. Angew. Chem. Int. Ed. 2005, 44, 2838. (f) Rivkin,
A.; Yoshimura, F.; Gabarda, A. E.; Cho, Y. S.; Chou, T.-C.; Dong,
H.; Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126, 10913.
(g) Rivkin, A.; Biswas, K.; Chou, T.-C.; Danishefsky, S. J. Org. Lett.
2002, 4, 4081.
(13) (a) Li, Y.; Wu, L.; Neumann, H.; Beller, M. Chem. Commun. 2013,
49, 2628. (b) Yasu, Y.; Koike, T.; Akita, M. Chem. Commun. 2013,
49, 2037. (c) Iqbal, N.; Choi, S.; Kim, E.; Cho, E. J. J. Am. Chem. Soc.
2012, 77, 11383.
(3) (a) Veronesi, M.; Giacomina, F.; Romeo, E.; Castellani, B.;
Ottonello, G.; Lambruschini, C.; Garau, G.; Scarpelli, R.;
Bandiera, T.; Piomelli, D.; Dalvit, C. Anal. Biochem. 2016, 495, 52.
(b) Chen, H.; Viel, S.; Ziarelli, F.; Peng, L. Chem. Soc. Rev. 2013, 42,
(14) Besset, T.; Poisson, T.; Pannecoucke, X. Chem. Eur. J. 2014, 20,
16830.
(15) Konno, T. Synlett 2014, 25, 1350.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N

N
C. Tresse et al.
Paper
Synthesis
(16) For the corresponding hydrotrifluoromethylation of terminal
alkynes, see: Jacquet, J.; Blanchard, S.; Derat, E.; Desage-El Murr,
M.; Fensterbank, L. Chem. Sci. 2016, 7, 2030.
(17) Konno, T.; Chae, J.; Tanaka, T.; Ishihara, T.; Yamanaka, H. Chem.
Commun. 2004, 690.
(18) Konno, T.; Taku, K.-i.; Yamada, S.; Moriyasu, K.; Ishihara, T. Org.
Biomol. Chem. 2009, 7, 1167.
(19) Konno, T.; Chae, J.; Tanaka, T.; Ishihara, T.; Yamanaka, H. J. Fluo-
rine Chem. 2006, 127, 36.
(20) Cullen, W. R.; Styan, G. E. J. Organomet. Chem. 1966, 6, 117.
(21) Hanzawa, Y.; Kawagoe, K.-i.; Tanahashi, N.; Kobayashi, Y. Tetra-
hedron Lett. 1984, 25, 4749.
(22) (a) Konno, T.; Kishi, M.; Ishihara, T.; Yamada, S. Tetrahedron
2014, 70, 2455. (b) Chae, J.; Konno, T.; Kanda, M.; Ishihara, T.;
Yamanaka, H. J. Fluorine Chem. 2003, 120, 185. (c) For related
silylstannylation, see: Konno, T.; Kinugawa, R.; Ishihara, T.;
Yamada, S. Org. Biomol. Chem. 2014, 12, 1611.
Gevorgyan, V.; Chatgilialoglu, C. J. Org. Chem. 1997, 62, 8009.
(d) Taniguchi, M.; Oshima, K.; Utimoto, K. Chem. Lett. 1993, 22,
1751. (e) Nozaki, K.; Ichinose, Y.; Wakamatsu, K.; Oshima, K.;
Utimoto, K. Bull. Chem. Soc. Jpn. 1990, 63, 2268. (f) Ichinose, Y.;
Nozaki, K.; Wakamatsu, K.; Oshima, K.; Utimoto, K. Tetrahedron
Lett. 1987, 28, 3709.
(28) Schweizer, S.; Tresse, C.; Bisseret, P.; Lalevée, J.; Evano, G.;
Blanchard, N. Org. Lett. 2015, 17, 1794.
(29) (a) Tresse, C.; Guissart, C.; Schweizer, S.; Bouhoute, Y.; Chany,
A.-C.; Goddard, M.-L.; Blanchard, N.; Evano, G. Adv. Synth. Catal.
2014, 356, 2051. (b) For our recent investigation on the base-
promoted isomerization of trifluoromethylated alkynes to γ-
trifluoromethylated allenamides, see: Guissart, C.; Dolbois, A.;
Tresse, C.; Saint-Auret, S.; Evano, G.; Blanchard, N. Synlett 2016,
in press. (c) For a closely related method, see: He, L.; Tsui, G. C.
Org. Lett. 2016, 18, 2800. (d) For a review, see: Gao, P.; Song, X.
R.; Liu, X. Y.; Liang, Y. M. Chem. Eur. J. 2015, 21, 7648.
(23) (a) Zine, K.; Petrignet, J.; Thibonnet, J.; Abarbri, M. Synlett 2012,
23, 755. (b) Carcenac, Y.; Zine, K.; Kizirian, J.-C.; Thibonnet, J.;
Duchêne, A.; Parrain, J.-L.; Abarbri, M. Adv. Synth. Catal. 2010,
352, 949.
(30) Tsipis, C. A. J. Organomet. Chem. 1980, 187, 427.
(31) (a) Rooke, D. A.; Menard, Z. A.; Ferreira, E. M. Tetrahedron 2014,
70, 4232. (b) Rooke, D. A.; Ferreira, E. M. Angew. Chem. Int. Ed.
2012, 51, 3225.
(24) (a) Wolfsberger, W. J. Prakt. Chem. 1992, 334, 453.
(b) Organometallic Compounds of Low-Coordinate Si, Ge, Sn and
Pb: From Phantom Species to Stable Compounds; Lee, V. Y.;
Sekiguchi, A., Eds.; John Wiley & Sons: Chichester, 2010, 45–88.
(c) Akiyama, T. In Main Group Metals in Organic Synthesis;
Yamamoto, H.; Oshima, K., Eds.; Wiley-VCH: Weinheim, 2004,
593–619. (d) Fuchs, R.; Gilman, H. J. Org. Chem. 1957, 22, 1009.
(25) (a) Wada, F.; Abe, S.; Yonemaru, N.; Kikukawa, N.; Matsuda, T.
Bull. Chem. Soc. Jpn. 1991, 64, 1701. (b) Piers, E.; Lemieux, R.
J. Chem. Soc., Perkin Trans. 1 1995, 3. (c) Widenhoefer, R. A.;
Vadehra, A.; Cheruvu, P. K. Organometallics 1999, 18, 4614.
(d) Corriu, R. J. P.; Moreau, J. J. E. J. Organomet. Chem. 1972, 40,
97. (e) Lesbre, M.; Satgé, J. C. R. Hebd. Seances Acad. Sci. 1960,
250, 2220. (f) Ichinose, Y.; Oda, H.; Oshima, K.; Utimoto, K. Bull.
Chem. Soc. Jpn. 1987, 60, 3468. (g) Matsuda, T.; Kadowaki, S.;
Yamaguchi, Y.; Murakami, M. Org. Lett. 2010, 12, 1056.
(h) Itazaki, M.; Kamitani, M.; Nakazawa, H. Chem. Commun.
2011, 47, 7854.
(32) Savall, B. M.; Powell, N. A.; Roush, W. R. Org. Lett. 2001, 3, 3057.
(33) Russell Bowman, W.; Krintel, S. L.; Schilling, M. B. Org. Biomol.
Chem. 2004, 2, 585.
(34) (a) For a review, see: Spivey, A. C. Curr. Org. Synth. 2004, 1, 211.
(b) Matsumoto, K.; Shindo, M. Adv. Synth. Catal. 2012, 354, 642.
(c) Tseng, C.-C.; Li, M.; Mo, B.; Warren, S. A.; Spivey, A. C. Chem.
Lett. 2011, 40, 995. (d) Zhang, Z.-T.; Pitteloud, J.-P.; Cabrera, L.;
Liang, Y.; Toribio, M.; Wnuk, S. F. Org. Lett. 2010, 12, 816.
(e) Pitteloud, J.-P.; Zhang, Z.-T.; Liang, Y.; Cabrera, L.; Wnuk, S. F.
J. Org. Chem. 2010, 75, 8199. (f) Spivey, A. C.; Gripton, C. J. G.;
Hannah, J. P.; Tseng, C.-C.; de Fraine, P.; Parr, N. J.; Scicinski, J. J.
Appl. Organomet. Chem. 2007, 21, 572. (g) Endo, M.; Fugami, K.;
Enokido, T.; Sano, H.; Kosugi, M. Adv. Synth. Catal. 2007, 349,
1025. (h) Enokido, T.; Fugami, K.; Endo, M.; Kameyama, M.;
Kosugi, M. Adv. Synth. Catal. 2004, 346, 1685. (i) Faller, J. W.;
Kultyshev, R. G. Organometallics 2002, 21, 5911. (j) Kosugi, M.;
Tanji, T.; Tanaka, Y.; Yoshida, A.; Fugami, K.; Kameyama, M.;
Migita, T. J. Organomet. Chem. 1996, 508, 255. (k) Ikenaga, K.;
Matsumoto, S.; Kikukawa, K.; Matsuda, T. Chem. Lett. 1990, 19,
185.
(26) Schwier, T.; Gevorgyan, V. Org. Lett. 2005, 7, 5191.
(27) (a) Yorimitsu, H.; Oshima, K. Inorg. Chem. Commun. 2005, 8, 131.
(b) Kinoshita, H.; Nakamura, T.; Kakiya, H.; Shinokubo, H.;
Matsubara, S.; Oshima, K. Org. Lett. 2001, 3, 2521.
(c) Bernardoni, S.; Lucarini, M.; Pedulli, G. F.; Valgimigli, L.;
(35) Minisci, F.; Citterio, A.; Giordano, C. Acc. Chem. Res. 1983, 16, 27.
(36) Anderson, H. H. J. Am. Chem. Soc. 1960, 82, 3016.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–N