Stereoselective synthesis of CF3-substituted trans- and cis-enediynes via carbocupration or hydrostannation reactions of CF 3-containing diyne

Article abstract of DOI:10.1016/j.tet.2014.02.015

CF₃-containing diyne, readily prepared from (Z)-2,3,3,3- tetrafluoro-1-iodoprop-1-ene in two steps, was smoothly subjected to carbocupration reaction with various organocuprates, followed by treatment of the resultant carbocupration adducts with iodine, the corresponding vinyl iodides being formed in good yields in a cis-addition manner. Thus obtained iodide could be successfully converted into CF₃-substituted trans-enediynes in high yields. Also, hydrostannation reaction of the diyne proceeded well in a trans-addition manner to give the corresponding vinylstannane in high yield. The vinylstannane was also found to be effectively convertible to CF₃-substituted cis-enediynes in high yields.

Full text of DOI:10.1016/j.tet.2014.02.015

Tetrahedron 70 (2014) 2455e2463
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective synthesis of CF3-substituted trans- and cis-enediynes
via carbocupration or hydrostannation reactions of CF3-containing
diyne
,
a
a
b
Tsutomu Konno a , Misato Kishi , Takashi Ishihara , Shigeyuki Yamada
*
a Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
b Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei 184-
8588, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 January 2014
Received in revised form 6 February 2014
Accepted 7 February 2014
Available online 14 February 2014
CF3-containing diyne, readily prepared from (Z)-2,3,3,3-tetrafluoro-1-iodoprop-1-ene in two steps, was
smoothly subjected to carbocupration reaction with various organocuprates, followed by treatment of
the resultant carbocupration adducts with iodine, the corresponding vinyl iodides being formed in good
yields in a cis-addition manner. Thus obtained iodide could be successfully converted into CF3-
substituted trans-enediynes in high yields. Also, hydrostannation reaction of the diyne proceeded well in
a trans-addition manner to give the corresponding vinylstannane in high yield. The vinylstannane was
also found to be effectively convertible to CF3-substituted cis-enediynes in high yields.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Fluoroalkylated enediynes
Fluoroalkylated diynes
Fluoroalkylated enynes
Carbocupration
Hydrostannation
1. Introduction
In the last several years, we have focused on the chemistry of
CF3-containing alkynes and developed highly regio- and stereo-
Both stereoisomers of trans- or cis-enediyne have recently been
attracting much attention in various fields due to their wide ap-
plications. For example, the trans-enediynes have been well-
recognized as important building blocks for the construction of
selective synthetic methods for the preparation of CF3-substituted
alkenes via carbo- or hydrometallation reaction toward the al-
kynes.8 In the course of our studies, we envisioned that their regio-
and stereo-controlled approaches via the carbo- or hydro-
metallation could be employed to realize synthetic achievements
of both stereoisomers of CF3-substituted enediynes. Herein are
described an effective preparation procedure of CF3-containing
diynes from readily available (Z)-2,3,3,3-tetrafluoro-1-iodoprop-1-
ene. Moreover, it would be disclosed that carbocupration or
hydrostannation reactions toward the CF3-containing diynes pro-
ceed to furnish regio- and stereoselective vinylmetal in-
termediates, which can be successfully converted into the stereo-
defined CF3-substituted trans- and cis-enediyne derivatives
(Scheme 1).
p
-conjugated polymers and designed nanoarchitectures,1 while the
cis-enediynes represent important synthetic units for the prepa-
ration of potent antitumor active compounds like Esperamicin A1
and Dynemicin A.2 The cis-isomers are, in addition, considered as
useful precursors for the construction of aromatic ring by an elec-
trocyclization, so-called Bergman cycloaromatization,3 which has
been frequently employed for the synthesis of polyaromatic hy-
drocarbons (PAHs).4 Accordingly, it is not surprising that numerous
synthetic approaches to non-fluorinated enediyne compounds
have been reported so far. On the other hand, there have been quite
limited studies on the synthesis of fluoroalkyl-substituted enediyne
molecules,5,6 though introduction of fluorine atom(s) into organic
molecules quite often changes their physical as well as chemical
characteristics significantly, resulting in the discovery of new ma-
terials with unique physical properties.7
2. Results and discussion
Initial studies toward enediynes began with CF3-containing
diynes. These diynes were prepared by utilizing the following two
steps procedure: Sonogashira cross-coupling reaction of (Z)-
2,3,3,3-tetrafluoro-1-iodoprop-1-ene (1a)9 with terminal alkynes,
followed by elimination of HF (Scheme 2).
* Corresponding author. Tel.: þ81 75 724 7517; fax: þ81 75 724 7580; e-mail
address: konno@kit.ac.jp (T. Konno).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.015

2456
T. Konno et al. / Tetrahedron 70 (2014) 2455e2463
Table 1
1) Sonogashira
F3C
1) cross-coupling
Preparation of Rf-containing diynes 3 via elimination of HF from the precursors 2
F3C
R1
2) Elimination of
2) HF
F
I
Carbocupration
Hydrostannation
R1
R1
F3C
H
H
Entry
Rf
R1
Yielda/%of 3
Recoverya/% of 2
F3C
F3C
H
F3C
Sn
1
CF3
CF3
CF3
CF3
CF3
HCF2
HCF2CF2CF2
Ph (3a)
4-MeOC6H4 (3b)
n-C6H13 (3c)
BnOCH2 (3d)
BnOC(Me)2 (3e)
BnOC(Me)2 (3f)
BnOC(Me)2 (3g)
74
Quant
48
0
0
35
13
0
R2
Cu
R2
2
R1
3b
4
3
R3
trans-endiynes
R3
R1
5
6
7
Quant (95)
Quant (76)
Quant (89)
cis-endiynes
R1
F3C
0
0
I
F3C
a
Determined by 19F NMR. Values in parentheses are of isolated yield.
Carried out for 24 h.
Sonogashira
cross-coupling
Sonogashira
cross-coupling
b
R1
I
R2
Scheme 1. Synthetic strategy for stereoselective approaches to CF3-substituted trans-
and cis-enediyne compounds.
observed even when 3a was kept in a freezer. Elimination of HF
from enyne 2b having an electron-rich aromatic ring as R1 took
place effectively to give the corresponding diyne 3b in a quantita-
tive yield (entry 2), which led to a slight increase of the thermal
stability compared to that of 3a, though it could not be isolated in
a pure form. In the case of enyne 2c having an alkyl group as R1, on
the other hand, the diyne 3c was obtained as inseparable mixture
with the unreacted 2c regardless of the reaction carried out for 24 h
(entry 3). In addition, the reaction proceeded very sluggishly in the
case of enyne 2d having BnOCH2 as R1, and neither 2d nor 3d was
obtained in high yield (entry 4). In sharp contrast, the enyne 2e
having BnOC(Me)2 group as R1, which can be potentially convertible
to other functional substituents, underwent quite effectively the
elimination of HF to afford the desired diyne 3e in a quantitative
yield. Since 3e was found to be thermally stable, it could be isolated
as a pure product by silica-gel column chromatography (95% iso-
lated yield) (entry 5). Enynes 2f and 2g bearing other fluoroalkyl
groups, such as HCF2 and HCF2CF2CF2, could also participate well in
the HF elimination reaction, giving the corresponding diynes 3f and
3g in 76% and 89% isolated yields, respectively (entries 6 and 7).
Next our attempts were directed toward stereoselective carbo-
cupration to CF3-containing diyne 3e with organocuprates. The
results are tabulated in Table 2.
Scheme 2. Retrosynthesis of CF3-containing diynes 3.
Thus, treatment of 1a (Rf¼CF3) with 1.2 equiv of terminal al-
kynes and 1.5 equiv of Et3N in the presence of 5 mol % of Pd(OAc)2
and 10 mol % each of PPh3 and CuI in DMF at room temperature for
24 h, gave rise to the corresponding Sonogashira cross-coupling
products 2aee in good to excellent isolated yields (Scheme 3). In
addition, the use of other fluoroalkylated vinyl iodides, such as 1b
(Rf¼HCF2) and 1c (Rf¼HCF2CF2CF2), as a substrate did not influence
on the reaction efficacy at all, the desired enynes 2f and 2g being
afforded in excellent yields.
Thus, treatment of 3e with 1.2 equiv of organocuprate [n-
Bu2Cu(CN)Li2], derived from CuCN and 2.0 equiv of n-BuLi, at
ꢀ78 ꢁC for 2 h, followed by quenching with satd aq NH4Cl solution,
provided the corresponding carbocupration product 4eA in 46%
yield as a sole stereoisomer, together with a trace recovery of the
starting 3e (entry 1).10 Since it is well known that the carbocup-
ration reaction of fluoroalkylated internal alkynes with organo-
cuprates proceeded in a highly regio and a cis-stereoselective
manner,8q,8l the present carbocupration may take place in a similar
manner as well. It was especially noteworthy that only the triple
bond possessing
a CF3 group, not the triple bond carrying
a BnOC(Me)2 group, was exclusively subjected to the carbocupra-
tion reaction. As shown in entry 2, the carbocupration reaction with
n-Bu2Cu(CN)Li2 at higher temperature (ꢀ45 ꢁC) smoothly brought
about the product 4eA in 61% yield. We also examined the carbo-
cupration reaction using organocuprate prepared from the combi-
nation of CuCN and Grignard reagent like n-Bu2Cu(CN)(MgBr)2
instead of Li-counterpart. Unfortunately, the carbocupration re-
action was found to be sluggish, a significant decrease of the yield of
4eA was observed when the reaction was performed by using
1.2 equiv of organocuprate (entries 3e5). However, the use of
1.5 equiv of the n-Bu2Cu(CN)(MgBr)2 realized the most satisfactory
results, the desired 4eA being obtained in 85% yield (entry 6),
though the yield was somewhat eroded in the reaction for 2 h
(entry 7). As shown in entries 8e14 in Table 2, we next investigated
Scheme 3. Preparation of Rf-containing diyne precursors 2.
Subsequently, elimination of HF from 2a was examined by
treating with various types of bases, such as potassium tert-but-
oxide, aq KOH solution, lithium diisopropylamide, and lithium
hexamethyldisilazide (LHMDS). After intensive investigations, it
was found that the best yield of 3a (74% NMR yield) was obtained
when 2a was treated with 1.5 equiv of LHMDS in THF at ꢀ78 ꢁC for
1 h (entry 1, Table 1).
Unfortunately, the isolation of CF3-containing diyne 3a by silica-
gel column chromatography failed due to the low thermal stability.
It was found, additionally that the partial decomposition was

T. Konno et al. / Tetrahedron 70 (2014) 2455e2463
2457
Table 2
Carbocupration of CF3-substituted diyne 3e with organocuprates
F3C
R1
R22Cu(CN)M2
F3C
R1
F3C
R1
CuI
CuI
R2
Int-A
R2
R2
R2
Int-B
Entry Organocupratea ½R22CuðCNÞM2ꢂ/
E
Temp/ꢁC Time/h
Yieldb/%
(4eA) 46
equiv
1c
2
n-Bu2Cu(CN)Li2/1.2
n-Bu2Cu(CN)Li2/1.2
H
H
H
H
H
H
H
I
I
I
I
I
ꢀ78
ꢀ45
ꢀ45
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ45
ꢀ45
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
2
1
1
1
2
1
2
1
1
1
1
1
1
1
61
38
44
44
85
α
β
3
n-Bu2Cu(CN)(MgBr)2/1.2
n-Bu2Cu(CN)(MgBr)2/1.2
n-Bu2Cu(CN)(MgBr)2/1.2
n-Bu2Cu(CN)(MgBr)2/1.5
n-Bu2Cu(CN)(MgBr)2/1.5
n-Bu2Cu(CN)Li2/1.2
F3C
R1
F3C
R1
4c
5
CuIII
R2
R2
Int-C
CuIII
R2
6
7
8
R2
Int-D
57
(5eA) (54)
(5eB) (55)
(5eA) (60)
(5eB) (59)
(5eC) (44)
(5eD) (55)
(5eE) (49)
9
Me2Cu(CN)Li2/1.2
10
11
12
13
14d
n-Bu2Cu(CN)(MgBr)2/1.5
Me2Cu(CN)(MgBr)2/1.5
Cy2Cu(CN)(MgBr)2/1.5
Ph2Cu(CN)(MgBr)2/1.5
Ar2Cu(CN)(MgBr)2/1.5
R1
R1
R1
I
I
F3C
F3C
I2
F3C
R2
a
Organocuprates were prepared from CuCN (1.0 equiv) and R2Li or R2MgBr
R2 CuI R2
CuI R2
I
R2
(2.0 equiv).
5
Int-E
Int-F
b
c
Determined by 19F NMR. Values in parentheses are of isolated yield.
A trace amount of recovery of 3e was detected.
4-MeOC6H4MgBr was used to prepare organocuprate.
Scheme 4. A proposed reaction mechanism for the carbocupration with CF3-con-
d
taining diyne.
the carbocupration reaction of 3e with various organocuprate de-
rived from not only organolithium but also Grignard reagent under
the optimum reaction conditions (entry 2 for organolithium; entry
6 for Grignard reagent), whose vinylcopper intermediate in situ
generated was converted directly to vinyl iodide 5e by treating with
iodine as an electrophile. Organocuprate derived from butyllithium
or methyllithium could participate nicely in the successive carbo-
cupration/coupling reactions to give the corresponding vinyl io-
dides 5eA and 5eB in good yields (entries 8 and 9). Furthermore,
the carbocupration/coupling sequence using alkyl Grignard re-
agents, such as butyl, methyl, and cyclohexylmagnesium bromide,
also proceeded well under the optimized reaction conditions (en-
tries 10e12). Switching the dialkylcuprate to diarylcuprate did not
cause any significant influence on the yield at all, giving rise to the
coupling product 5eD and 5eE in 55% and 49% yields, respectively
(entries 13 and 14).
(Scheme 5). It was found that, in all cases, other stereoisomers were
not detected at all and the enediyne 6e8eA were generated as
a sole product.
Achievement of the stereoselective construction of CF3-
substituted trans-enediyne structure next prompted us to establish
A proposed reaction mechanism for the regio- and stereo-
selective carbocupration reaction is illustrated in Scheme 4. Based
on the accumulated studies on the chemistry of fluoroalkylated
alkynes, it appears possible that the copper reagent coordinates to
the triple bond proximate to the CF3 group (Int-A), rather than the
alternative one (Int-B), due to high reactivity of the CF3-substituted
alkyne moiety. Then, oxidative addition of CuI to the alkyne con-
nected with CF3 group occurs preferentially to form the in-
Scheme 5. Synthesis of stereo-defined CF3-substituted trans-enediyne compounds.
synthetic procedure for another isomer, i.e., CF3-substituted cis-
enediyne compounds. In our group was developed hydro-
stannation reaction to CF3-containing internal alkyne with an ex-
cellent trans-addition manner.8s This preliminary finding led us to
conceive a stereoselective three step-approach to CF3-substituted
cis-enediyne compounds by using CF3-containing diyne 3 as
a substrate (Scheme 6).
Initially, we attempted the radical hydrostannation reaction of
above prepared CF3-containing diyne 3e according to our reported
procedure.8s Thus, on treating 3e with 1.2 equiv of n-Bu3SnH in the
presence of 20 mol% of Et3B in toluene at ꢀ78 ꢁC for 1 h, fortunately,
the hydrostannation reaction proceeded quite smoothly to afford
the corresponding vinylstannane 9e in 75% isolated yield as a sole
product. Assignment of the stereochemistry of the vinylstannane
9e was carried out by NMR analysis after 9e being transformed to
10e (Scheme 7).
termediate Int-C. The CF3C
due to the strong electron-withdrawing effect of a CF3 group.
a
-CuIII bond may be stronger than CuIII-
C
b
Accordingly, a migration of the R2 group on CuIII to the olefinic
carbon distal to a CF3 group may take place exclusively to furnish
vinylcopper intermediate Int-E, not Int-F. As a result, vinyl iodide 5
can be yielded in a highly regio- and stereoselective manner.
To expand the usefulness of the regio- and stereoselective car-
bocupration reaction, our next challenge was directed to the syn-
thesis
of
stereo-defined
CF3-substituted
trans-enediyne
compounds. Thus, treatment of vinyl iodide 5eA with 1.2 equiv of
terminal alkynes and 40 equiv of Et3N in the presence of 10 mol %
each of Pd(PPh3)4 and CuI in THF at 70 ꢁC for 2e5 h gave the desired
CF3-substituted trans-enediynes 6e8eA in high to excellent yields

2458
T. Konno et al. / Tetrahedron 70 (2014) 2455e2463
SnBu3
H
F3C
R1
F3C
H
Int-B
F3C
Sn
Sn
R1
Sn
Int-A
9
R1
H
C
α attack
SnBu3
Et3B
O2
Scheme 6. Synthetic approach to stereo-defined CF3-substituted cis-enediyne
compounds.
SnH
Sn
F3C
Sn
R1
F3C
F3C
Cβ attack
R1
Sn
α
β
γ
δ
F3C
R1
F3C
4
R1
Sn = Bu3Sn
Cγ attack
Sn
R1
Sn
Scheme 7. Radical hydrostannation reaction of 3e and the assignment of the stereo-
chemistry of 9e by chemical transformation.
F3C
F3C
Sn
R1
Thus, the vinylstannane 9e was converted effectively into the
corresponding di-substituted alkene 10e by treating with an excess
amount of p-toluenesulfonic acid in CH2Cl2 at room temperature
for 3 h. 1H NMR analysis revealed that the vicinal coupling constant
(3JHa-Hb) of 10e was 16.2 Hz, which clearly indicates that the 10e has
E configuration at the olefinic bond. Also, comparison of spinespin
splitting pattern of 19F signal in 9e and 10e gave us information on
the position of Bu3Sn group in 9e. Thus, the spinespin splitting
pattern of 19F signal in 9e was singlet, while that in 10e was doublet.
These two observations explicitly suggest that the stereochemistry
of 9e is Z configuration. On the basis of these findings, a proposed
reaction mechanism for the radical hydrostannation reaction is
figured in Scheme 8.
R1
Sn
C
δ attack
Scheme 8. A proposed reaction mechanism for radical hydrostannation reaction with
CF3-containing diyne.
A radical reaction initiates by attack of tributyltin radical, gen-
erated from Bu3SnH and Et3B in the presence of O2, to the triple
bond in CF3-containing diyne. In this case, eight types of in-
termediates may be possible since the diyne consists of two triple
bonds carrying different substituents in the terminus. Among them,
intermediates formed by attack of tributyltin radical toward b and g
carbon on diyne could be excluded due to the lack of a resonance
stabilization in a generated vinyl radical. In addition, a nucleophilic
tributyltin radical may attack more electrophilic
than carbon because a strongly electron-withdrawing CF3 group is
attached with carbon. Consequently, Int-A and Int-B may be
a carbon rather
d
a
formed exclusively. Furthermore, it is highly possible that the n-
Bu3SnH comes to the side occupied by a CF3 group, avoiding
a bulkier tributylstannyl group owing to a large steric repulsion.
Thereby, the vinylstannane 9 was preferentially produced with
a highly regio- and stereoselective manner.
Finally, stereoselective synthesis of CF3-substituted cis-enediyne
compounds was conducted as a synthetic application for the regio-
and stereoselective hydrostannation of diyne 3e (Scheme 9).
Thus, the stereoselectively obtained CF3-substituted vinyl-
stannane 9e was converted to the corresponding vinyl iodide 11e by
treating 9e with iodine in CH2Cl2 at room temperature, which un-
derwent quite smoothly Sonogashira cross-coupling reaction with
terminal alkynes, giving rise to the corresponding stereo-defined
CF3-substituted cis-enediyne compounds 12e14e in 74e97%
Scheme 9. Synthesis of stereo-defined CF3-substituted cis-enediyne compounds.
isolated yields. It was found, moreover that the terminal functional
group, i.e., BnOC(Me)2, in enediyne like 12e was easily convertible
to the corresponding enediyne 15 through the deprotection and the
subsequent Sonogashira cross-coupling reaction.

T. Konno et al. / Tetrahedron 70 (2014) 2455e2463
2459
3. Conclusion
known compounds, which was reported in the previous
publication.5a,6a
We have demonstrated an effective preparation of CF3-con-
taining diynes, which should be quite interesting building blocks
for constructing fluorine-containing organic molecules, from easily
prepared 2,3,3,3-tetrafluoro-1-iodoprop-1-ene with facile two
steps. The two types of alkyne moieties could be easily distin-
guished due to the strong electron-withdrawing CF3 group, the CF3-
containing diyne undergoing regio- and stereoselectively carbo-
cupration with organocuprates or hydrostannation with tributyltin
hydride. Thus obtained stereo-defined vinylmetal intermediates
were transformed quite smoothly into the CF3-substituted trans-
enediyne (via carbocupration) as well as cis-enediyne compounds
(via hydrostannation) up to 97% isolated yield. Further synthetic
applications using the present CF3-containing diynes as well as
enediyne compounds are currently under investigation in our
laboratory.
4.3.1. (Z)-1,1,1,2-Tetrafluoro-5-phenyl-2-en-4-yne
compound. Yield: 76%; Oil; Solvent for chromatography: Hexane
only; 1H NMR (CDCl3)
5.93 (1H, d, J¼28.8 Hz, vinylic CH),
7.36e7.40 (3H, m, AreH), 7.49e7.51 (2H, m, AreH); 19F NMR (CDCl3)
(2a). Known
d
d
ꢀ120.82 (1F, dq, J¼28.8, 9.8 Hz, vinylic CF), ꢀ72.99 (3F, d, J¼9.8 Hz,
CF3).
4.3.2. (Z)-1,1,1,2-Tetrafluoro-5-(4-methoxyphenyl)-2-en-4-yne
(2b). Known compound. Yield: 62%; Oil; Solvent for chromatog-
raphy: Hexane/EtOAc¼100/0/20/1/10/1; 1H NMR (CDCl3)
d 3.83
(3H, s, CH3O), 5.91 (1H, d, J¼29.2 Hz, vinylic CH), 6.85e6.90 (2H, m,
AreH), 7.40e7.46 (2H, m, AreH); 19F NMR (CDCl3)
d
ꢀ122.18 (1F, dq,
J¼29.2, 12.0 Hz, vinylic CF), ꢀ72.89 (3F, d, J¼12.0 Hz, CF3).
4.3.3. (Z)-1,1,1,2-Tetrafluoroundec-2-en-4-yne (2c). Known com-
pound. Yield: 51%; Oil; Solvent for chromatography : Hexane only;
4. Experimental
4.1. General
1H NMR (CDCl3)
d
0.90 (3H, t, J¼6.80 Hz, CH3), 1.24e1.44 and
1.52e1.60 (6H and 2H, m, CH3(CH2)4CH2), 2.38 (2H, t, J¼7.2 Hz,
CH3(CH2)4CH2), 5.68 (1H, d, J¼29.2 Hz, vinylic CH); 19F NMR (CDCl3)
d
ꢀ123.76 (1F, dq, J¼29.2, 9.8 Hz, vinylic CF), ꢀ73.08 (3F, d, J¼9.8 Hz,
Infrared spectra (IR) were determined in a liquid film on a NaCl
plate or KBr disk method with a JASCO FT/IR-4100 typeA spec-
trometer. 1H and 13C NMR spectra were measured with a JEOL JNM-
AL 400 NMR spectrometer in a chloroform-d (CDCl3) solution with
tetramethylsilane (Me4Si) as an internal reference. A JEOL JNM-
EX90A (84.21 MHz) FT-NMR spectrometer and a JEOL JNM-AL
400 NMR spectrometer were used for determining the yield of
the products with hexafluorobenzene (C6F6). 19F NMR (376.05 MHz)
spectra were measured with a JEOL JNM-AL 400 NMR spectrometer
in a chloroform-d (CDCl3) solution with trichlorofluoromethane
(CFCl3) as an internal standard. High-resolution mass spectra
(HRMS) were taken on a JEOL JMS-700MS spectrometer by electron
impact (EI), chemical ionization (CI), and fast atom bombardment
(FAB) methods. All reactions were routinely monitored by 19F NMR
spectroscopy or TLC, and carried out under an atmosphere of argon.
CF3).
4.3.4. (Z)-6-Benzyloxy-1,1,1,2-tetrafluoro-2-hexen-4-yne
(2d). Known compound. Yield: 84%; Oil; Solvent for chromatog-
raphy : Hexane/EtOAc¼10/1; 1H NMR (CDCl3)
d 4.36 (2H, s,
PhCH2OCH2), 4.63 (2H, s, PhCH2OCH2), 5.77 (1H, dq, J¼29.6, 1.10 Hz,
vinylic CH), 7.30e7.40 (5H, m, AreH); 19F NMR (CDCl3)
(1F, dq, J¼29.6, 9.8 Hz, vinylic CF), ꢀ73.21 (3F, d, J¼9.8 Hz, CF3).
d
ꢀ120.08
4.3.5. (Z)-6-Benzyloxy-1,1,1,2-tetrafluoro-6-methyl-2-hepten-4-yne
(2e). Yield: 94%; Oil; Solvent for chromatography: Hexane/
EtOAc¼10/1; 1H NMR (CDCl3)
d 1.59 (6H, s, CH3), 4.63 (2H, s, CH2),
5.76 (1H, d, J¼28.8 Hz, vinylic CH), 7.27e7.36 (5H, m, AreH); 13C
NMR (CDCl3)
d 28.5, 66.8, 71.0, 81.7, 94.47e94.64 (m), 103.0 (d,
J¼5.7 Hz), 118.2 (qd, J¼271.2, 39.7 Hz), 127.4, 127.7, 128.3, 138.5,
152.5 (dq, J¼272.6, 39.3 Hz); 19F NMR (CDCl3)
d
ꢀ120.71 (1F, dq,
4.2. Materials
J¼28.96, 9.78 Hz, vinylic CF), ꢀ73.19 (3F, d, J¼9.78 Hz, CF3); IR (neat)
n
3069, 2988, 2868, 2229, 1684, 1455, 1301, 1111, 929, 846, 697,
661 cmꢀ1; HRMS calcd for C15H14F4O (Mþ) 286.0981, Found
Ethanol was fleshly distilled from magnesium (Mg). DMF were
fleshly distilled from calcium hydride (CaH2). All chemicals were of
reagent grade and, if necessary, were purified in the usual manner
prior to use. Thin-layer chromatography (TLC) was done with
Merck silica gel 60 F254 plates, and column chromatography was
carried out with Wako gel C-200. All reactions were carried out
under an atmosphere of argon.
286.0977.
4.3.6. (Z)-6-Benzyloxy-1,1,2-trifluoro-6-methyl-2-hepten-4-yne
(2f). Yield: quant; Oil; Solvent for chromatography: Hexane/
Benzene¼1/1; 1H NMR (CDCl3)
d 1.59 (6H, s, CH3), 4.63 (2H, s, CH2),
5.53 (1H, d, J¼30.4 Hz, vinylic CH), 6.08 (1H, td, J¼53.6, 4.9 Hz,
HCF2), 7.28e7.39 (5H, m, AreH); 13C NMR (CDCl3)
d 28.5, 66.7, 71.0,
4.3. Typical procedure for the preparation of CF3-containing
enynes
73.6 (m, 1C), 93.2e93.4 (m, 1C), 101.1 (dt, J¼6.6, 2.1 Hz), 108.6 (td,
J¼239.7, 38.1 Hz), 127.4, 127.7, 128.3, 138.7, 157.4 (dt, J¼272.5,
25.4 Hz); 19F NMR (CDCl3)
d
ꢀ124.28 (2F, dd, J¼53.55,19.55 Hz, CF2),
To a solution of Pd(OAc)2 (224 mg, 1.0 mmol) in DMF (133 mL)
was added triphenyl phosphine (525 mg, 2.0 mmol) at 25 ꢁC. After
the mixture was stirred for 20 min, 3,3,3,4-tetrafluoro-1-iodo-1-
propene (4.80 g, 20 mmol) was added into the reaction mixture,
then stirred for 20 min. After that, ethynylbenzene (4.18 g,
24 mmol), triethylamine (4.2 mL, 3.07 g, 30 mmol), and copper
iodide (381 mg, 2 mmol) was added in this order into the above
mixture. The whole was stirred for 24 h, then quenched with satd
NH4Cl aq. The mixture was extracted with ether three time, and the
combined organic layers were dried over anhydrous Na2SO4, then
filtered. The filtrate was evaporated to give the corresponding
crude materials, which was purified by silica gel column chroma-
tography, affording the 1,1,1,2-tetrafluoro-5-phenyl-2-penten-4-
yne (2e) (5.38 g, 18.8 mmol, 94% yield). Compounds 2aed was
ꢀ117.90 to ꢀ117.71 (1F, m, vinylic CF); IR (neat)
n 3033, 2987, 2869,
1685, 1403, 1191, 1054, 891, 767 cmꢀ1; HRMS calcd for C15H15F3NaO
(MþNa) 291.0973, Found 291.0967.
4.3.7. (Z)-8-Benzyloxy-1,1,2,2,3,3,4-heptafluoro-8-methyl-4-nonen-
6-yne (2g). Yield: 82%; Oil; Solvent for chromatography: Hexane/
Benzene¼1/1; 1H NMR (CDCl3)
d 1.61 (6H, s, CH3), 4.64 (2H, s, CH2),
5.77 (1H, d, J¼19.2 Hz, vinylic CH), 6.03 (1H, tt, J¼52.0, 5.1 Hz,
HCF2CF2), 7.27e7.39 (5H, m, AreH); 13C NMR (CDCl3)
d 28.4, 66.8
(m, 1C), 71.1, 73.0, 96.6e96.8 (m), 103.2 (d, J¼7.4 Hz), 107.8 (tt,
J¼252.1, 31.8 Hz), 109.5e113.5 (m, 2C), 127.5, 127.7, 128.3, 138.7,
153.3 (dt, J¼273.6, 29.1 Hz); 19F NMR (CDCl3)
ꢀ137.35 (2F, dquint.,
d
J¼51.9, 7.1 Hz, HCF2), ꢀ130.68 (2F, dquint., J¼4.9, 7.1 Hz, CF2),
ꢀ119.79 (2F, dt, J¼15.8, 7.3 Hz, CF2), ꢀ116.12 to ꢀ115.92 (1F, m,

2460
T. Konno et al. / Tetrahedron 70 (2014) 2455e2463
vinylic CF); IR (neat)
n
3032, 2988, 2869, 2229, 1677, 1497, 1348,
afford (Z)-6-benzyloxy-3-butyl-1,1,1-trifluoro-6-methyl-2-hepten-
4-yne (4eA, 98 mg, 0.30 mmol, 60%).
1222, 1162, 1051, 924, 778 cmꢀ1; HRMS calcd for C17H15F7 (Mþ)
368.1011, Found 368.1004.
4.5.1. (Z)-6-Benzyloxy-3-butyl-1,1,1-trifluoro-6-methyl-2-hepten-4-
yne (4eA). Yield: 60%; Oil; Solvent for chromatography: Hexane/
4.4. Typical procedure for the preparation of CF3-containing
diyne
Benzene¼1/1; 1H NMR (CDCl3)
d 0.80e2.15 (15H, m, C4H9 and CH3),
4.54 (2H, s, CH2), 5.67 (1H, q, J¼7.6 Hz, vinylic CH), 7.17e7.28 (5H, m,
To a solution of hexamethyldisilazane (1.6 mL, 7.5 mmol) in THF
(50 mL) was slowly added 1.6 M hexane solution of n-BuLi (4.7 mL,
7.5 mmol) at ꢀ78 ꢁC and the whole was stirred for 15 min. To the
resultant solution was added 6-benzyloxy-1,1,1,2-tetrafluoro-6-
methyl-2-hepten-4-yne (2e, 1.43 g, 5.0 mmol) at ꢀ78 ꢁC, followed
by continuous stirring at the temperature for 1 h. After being stirred
for 1 h, the reaction mixture was poured into satd aq NH4Cl solu-
tion, followed by extraction with Et2O (three times). The combined
organic layers were dried over anhydrous Na2SO4, filtered, and
concentrated with a rotary evaporator. Column chromatography of
the residue yielded pure 6-benzyloxy-1,1,1-trifluoro-6-methyl-2,4-
heptadiyne (3e, 1.26 g, 4.74 mmol, 95%).
AreH); 19F NMR (CDCl3)
(CDCl3)
d
ꢀ60.37 (3F, d, J¼7.6 Hz, CF3); 13C NMR
d
13.8, 21.8, 28.52, 28.54, 29.8, 37.5, 66.8, 71.0, 79.7 (q,
J¼1.7 Hz), 101.7 (q, J¼1.7 Hz), 122.1 (q, J¼34.4 Hz), 122.4 (q,
J¼270.0 Hz), 127.4, 127.8, 128.3, 134.2 (q, J¼5.8 Hz), 138.8; IR (neat)
n
3066, 2934, 2864, 2224, 1642, 1497, 1455, 1379, 1123, 1056,
915 cmꢀ1; HRMS (FAB) Calcd for (MþNa) C19H23F3NaO: 347.1599,
found 347.1601.
4.6. Typical procedure for the preparation of (E)-6-benzyloxy-
3-n-butyl-1,1,1-trifluoro-2-iodo-6-methyl-2-hepten-4-yne
(5eA)
To a suspension of CuCN (54 mg, 0.6 mmol) in THF (2.0 mL) was
added dropwise 1.6 M hexane solution of n-BuLi (0.75 mL,
1.2 mmol) at ꢀ45 ꢁC and the solution was stirred for 10 min, then
allowed to warm up to ꢀ20 ꢁC and stirred for another 30 min. To the
resultant solution was added dropwise diyne 3e (133 mg,
0.5 mmol). Followed by continuous stirring at ꢀ45 ꢁC for 1 h. After
stirring for 1 h, iodine (609 mg, 2.4 mmol) was added to the re-
action mixture. After stirring for 1 h, the reaction was quenched
with NH3 aq/MeOH (v/v¼1/5), followed by extraction with Et2O
three times. The combined organic layers were washed with
Na2S2O3 aq, then dried over anhydrous Na2SO4, and concentrated in
vacuo. The residue was chromatographed on silica gel to afford (E)-
6-benzyloxy-3-n-butyl-1,1,1-trifluoro-2-iodo-6-methyl-2-hepten-
4-yne 5eA (0.121 g, 0.27 mmol, 54% yield).
4.4.1. 6-Benzyloxy-1,1,1-trifluoro-6-methyl-2,4-heptadiyne
(3e). Yield: 95%; Oil; Solvent for chromatography: Hexane/
Benzene¼1/1; 1H NMR (CDCl3)
d 1.59 (6H, s, CH3), 4.62 (2H, s, CH2),
7.28e7.36 (5H, m, AreH); 19F NMR (CDCl3)
d
ꢀ50.38 (s, CF3); 13C
NMR (CDCl3)
d
28.2, 64.0 (q, J¼53.7 Hz), 66.1 (q, J¼3.3 Hz), 67.2, 70.7
(q, J¼6.6 Hz), 70.9, 87.2, 113.8 (q, J¼257.4), 127.67, 127.71, 128.4,
138.0; IR (neat)
n 3033, 2989, 2868, 2266, 2171, 1467, 1383, 1321,
1149, 1054, 930 cmꢀ1; HRMS (FAB) Calcd for (Mþ) C15H13F3O:
266.0918, found 266.0915.
4.4.2. 6-Benzyloxy-1,1-difluoro-6-methyl-2,4-heptadiyne (3f). Yield:
76%; Oil; Solvent for chromatography: Hexane/Benzene¼1/1; 1H
NMR (CDCl3)
d 1.60 (6H, s, CH3), 4.63 (2H, s, CH2), 6.24 (1H, t,
J¼53.9 Hz, HCF2), 7.30e7.37 (5H, m, AreH); 13C NMR (CDCl3)
d 28.3,
66.8 (t, J¼5.7 Hz), 67.1, 68.6 (t, J¼34.3 Hz), 70.9, 72.5 (t, J¼7.8 Hz),
4.6.1. (E)-6-Bezyloxy-3-n-butyl-1,1,1-trifluoro-2-iodo-6-methyl-2-
hepten-4-yne (5eA). Yield: 54%; Oil; Solvent for chromatography:
85.9 (t, J¼2.5 Hz), 103.4 (t, J¼233.5 Hz), 127.6, 127.7, 128.4, 138.2; 19
F
NMR (CDCl3)
d
ꢀ106.46 (2F, d, J¼53.88 Hz, HCF2); IR (neat)
n
3033,
Hexane/Benzene¼1/1; 1H NMR (CDCl3)
0.94 (3H, t, J¼7.3 Hz, CH3),
d
2988, 2869, 2259, 2170, 1455, 1373, 1154, 1053, 891, 698 cmꢀ1
;
1.39 (2H, sex., J¼7.3 Hz, CH2), 1.52e1.62 (2H, m, CH2), 1.58 (6H, s,
CH3), 2.44e2.54 (2H, m, CH2), 4.61 (2H, s, CH2), 7.26e7.36 (5H, m,
HRMS calcd for C15H14F2O (Mþ) 248.1013, Found 248.1004.
AreH); 13C NMR (CDCl3)
d 13.9, 22.1, 28.38, 28.39, 29.4, 43.08, 66.8
4.4.3. 2-Benzyloxy-7,7,8,8,9,9-hexafluoro-1-methyl-3,5-nonadiyne
(3g). Yield: 89%; Oil; Solvent for chromatography: Hexane/
(t, J¼2.1 Hz), 71.1, 79.2, 93.8 (q, J¼34.4 Hz), 102.7 (q, J¼2.2 Hz), 120.8
(q, J¼273.3 Hz), 127.5, 127.7, 128.3, 138.1 (q, J¼3.6 Hz), 138.7; 19F
Benzene¼1/1; 1H NMR (CDCl3)
d
1.62 (6H, s, CH3), 4.64 (2H, s, CH2),
NMR (CDCl3)
d
ꢀ57.12 (3F, s, CF3); IR (neat)
n 3090, 3032, 2960,
6.04 (1H, tt, J¼52.1, 5.4 Hz, HCF2CF2), 7.29e7.38 (5H, m, AreH); 13
C
2933, 2864, 2220, 1947, 1806, 1710, 1643, 1577, 1455, 1380, 1240,
1159, 1057, 904, 697 cmꢀ1; HRMS calcd for C19H22F3INaO (MþNa)
473.0565, Found 473.0568.
NMR (CDCl3)
d
28.2, 63.6 (t, J¼36.8 Hz), 66.2 (t, J¼5.0 Hz), 67.2, 70.9,
75.5 (t, J¼6.6 Hz), 87.8 (t, J¼2.1 Hz), 95e110 (m, 2C), 107.7 (tt,
J¼253.3, 31.6 Hz), 127.67, 127.71, 128.4, 138.0; 19F NMR (CDCl3)
d
ꢀ137.1 to ꢀ136.8 (2F, m, HCF2), ꢀ130.4 to ꢀ130.2 (2F, m, CF2),
4.6.2. (E)-6-Benzyloxy-1,1,1-trifluoro-2-iodo-3,6-dimethyl-2-hepten-
4-yne (5eB). Yield: 59%; Oil; Solvent for chromatography: Hexane/
ꢀ99.4 to ꢀ99.2 (2F, m, CF2); IR (neat)
n 3033, 2991, 2939, 2260,
2166, 1498, 1384, 1274, 1163, 969, 919, 809, 737, 698 cmꢀ1; HRMS
EtOAc¼10/1; 1H NMR (CDCl3)
d
1.57 (6H, s, CH3), 2.22 (3H, s, CH3),
calcd for C17H14F6O (Mþ) 348.0949, Found 348.0955.
4.60 (2H, s, CH2), 7.25e7.36 (5H, m, AreH); 13C NMR (CDCl3)
d 28.4,
31.0 (q, J¼1.6 Hz), 66.8 (t, J¼2.1 Hz), 71.1, 80.1, 94.5 (q, J¼34.7 Hz),
102.2, 120.8 (q, J¼273.0 Hz), 127.5, 127.7, 128.3, 133.7 (q, J¼3.6 Hz),
4.5. Typical procedure for carbocupration of 3e with Bu2
-
Cu(CN)Li2
138.7; 19F NMR (CDCl3)
d
ꢀ57.50 (3F, s, CF3); IR (neat)
n 3033, 2986,
1703, 1454, 1296, 1241, 1131, 1056, 908, 697 cmꢀ1; HRMS calcd for
16H16F3INaO (MþNa) 431.0096, Found 431.0087.
To a suspension of CuCN (54 mg, 0.6 mmol) in THF (2.0 mL) was
added dropwise 1.6 M hexane solution of n-BuLi (0.75 mL,
1.2 mmol) at ꢀ45 ꢁC and the solution was stirred at the temperature
for 10 min, then allowed to warm up to ꢀ20 ꢁC and stirred for
another 30 min. To the resultant solution was added dropwise
diyne 3e (133 mg, 0.5 mmol), followed by continuous stirring at
ꢀ45 ꢁC for 1 h. After stirring for 1 h, the reaction mixture was
quenched with a mixed solution of NH3 aq/MeOH (v/v¼1/5), fol-
lowed by extraction with Et2O (three times). The combined organic
layers were dried over anhydrous Na2S2O4, filtered, and concen-
trated in vacuo. The residue was chromatographed on silica gel to
C
4.6.3. (E)-6-Benzyloxy-3-cyclohexyl-1,1,1-trifluoro-2-iodo-6-methyl-
2-hepten-4-yne (5eC). Yield: 44%; Oil; Solvent for chromatogra-
phy: Hexane/Benzene¼1/1; 1H NMR (CDCl3)
d 1.00e1.85 (10H, m,
CH2 in c-Hex), 1.61 (6H, s, CH3), 2.60e2.75 (1H, m, CH in c-Hex),
4.65 (2H, s, CH2), 7.26e7.40 (5H, m, AreH); 13C NMR (CDCl3)
d 25.7,
28.5, 28.6, 30.2, 50.9, 67.0 (t, J¼2.5 Hz), 71.2, 92.7 (q, J¼34.2 Hz),
103.7 (q, J¼2.5 Hz), 120.8 (q, J¼273.59 Hz), 127.5, 127.8, 128.3, 138.7,
142.3 (q, J¼3.3 Hz); 19F NMR (CDCl3)
ꢀ56.45 (3F, s, CF3); IR (neat)
d
n
3584, 3032, 2932, 2856, 1569, 1451, 1288, 1129, 1056, 846,

T. Konno et al. / Tetrahedron 70 (2014) 2455e2463
2461
697 cmꢀ1; HRMS calcd for C21H24F3INaO (MþNa) 499.0722, Found
128.3, 133.8, 136.2 (q, J¼2.5 Hz); 19F NMR (CDCl3)
d
ꢀ61.58 (3F, s,
499.0723.
CF3); IR (neat) n 3032, 2958, 2932, 2861, 2222,1585,1347,1160,1131,
1057, 914, 696 cmꢀ1; HRMS calcd for C27H35F3NaO (MþNa)
4.6.4. (E)-6-Benzyloxy-1,1,1-trifluoro-2-iodo-6-methyl-3-phenyl-2-
hepten-4-yne (5eD). Yield: 55%; Oil; Solvent for chromatography:
455.2538, Found 455.2542.
Hexane/EtOAc¼10/1; 1H NMR (CDCl3)
d
1.56 (6H, s, CH3), 4.56 (2H,
28.3, 66.9 (t,
4.7.3. (Z)-7-Benzyloxy-4-n-butyl-7-methyl-3-trifluoromethyl-1-
trimethylsilyl-3-octen-1,5-diyne (8eA). Yield: 84%; Oil; Solvent for
s, CH2), 7.26e7.43 (10H, m, AreH); 13C NMR (CDCl3)
d
J¼1.7 Hz), 71.2, 80.1, 94.9 (q, J¼34.4 Hz), 104.7 (q, J¼2.2 Hz), 121.1 (q,
chromatography: Hexane/Benzene¼1/1; 1H NMR (CDCl3)
d 0.25
J¼273.3 Hz), 127.5, 127.8 (2C), 128.3, 128.5, 129.0, 138.01 (q,
(9H, s, TMS-H), 0.95 (3H, t, J¼7.4 Hz, CH3 in n-Bu), 1.39 (2H, sex.,
J¼7.4 Hz, CH2 in n-Bu), 1.55e1.65 (2H, m, CH2 in n-Bu), 1.60 (6H, s,
CH3), 2.50e2.60 (2H, m, CH2 in n-Bu), 4.63 (2H, s, CH2), 7.25e7.40
J¼3.9 Hz), 138.6, 141.7; 19F NMR (CDCl3)
d
ꢀ57.74 (3F, s, CF3); IR
(neat)
n 3584, 2985, 1563, 1454, 1299, 1248, 1132, 1053, 906,
698 cmꢀ1; HRMS calcd for C21H18F3INaO (MþNa) 493.0252, found
(5H, m, AreH); 13C NMR (CDCl3)
d
ꢀ0.40, 13.8, 22.0, 28.4, 29.7, 36.1,
493.0251.
66.9, 71.3, 80.9, 96.6 (q, J¼2.5 Hz), 107.2 (q, J¼1.7 Hz), 108.2, 119.0 (q,
J¼33.6 Hz), 121.2 (q, J¼274.2 Hz), 127.5, 127.8, 128.3, 138.7, 139.1 (q,
4.6.5. (E)-6-Benzyloxy-1,1,1-trifluoro-2-iodo-6-methyl-3-p-methox-
yphenyl-2-hepten-4-yne (5eE). Yield: 49%; Oil; Solvent for chro-
J¼2.7 Hz); 19F NMR (CDCl3)
d
ꢀ61.38 (3F, s, CF3); IR (neat)
n 3033,
2960, 2933, 2863, 2144, 1578, 1455, 1339, 1253, 1134, 1057, 847,
696 cmꢀ1; HRMS calcd for C24H31F3NaOSi (MþNa) 443.1994, Found
443.1992.
matography: Hexane/Benzene¼1/1; 1H NMR (CDCl3)
d 1.59 (6H, s,
CH3), 3.86 (3H, s, OCH3), 4.59 (2H, s, CH2), 6.93e7.52 (9H, m,
AreH); 13C NMR (CDCl3)
d
28.3, 55.3 (q, J¼2.5 Hz), 66.9, 71.2, 80.3,
93.7 (q, J¼34.2 Hz), 104.2 (q, J¼2.5 Hz), 113.7, 114.1, 121.2 (q,
4.8. Typical procedure for hydrostannation of 3e with Bu3SnH
in the presence of a catalytic amount of Et3B
J¼273.6 Hz), 127.8, 128.3, 129.6, 133.7, 137.6 (q, J¼3.6 Hz), 138.2,
160.07; 19F NMR (CDCl3)
d
ꢀ57.35 (3F, s, CF3); IR (neat)
n 3584,
3033, 2985, 2936, 2839, 2212, 1888, 1606, 1508, 1249, 1130, 1041,
906, 825, 698 cmꢀ1; HRMS calcd for C22H20F3IO2 (Mþ) 500.0460,
Found 500.0463.
To a solution of diyne 3e (53 mg, 0.20 mmol) and Bu3SnH
(70 mg, 0.24 mmol) in toluene (4.0 mL) was added 1.0 M hexane
solution of Et3B (0.04 mL, 0.04 mmol) at ꢀ78 ꢁC and the whole
was stirred for 1 h. The reaction mixture was quenched by the
addition of 2,6-di-tert-butyl-4-methylphenol (BHT), followed by
extraction with Et2O (three times). The organic layer was dried over
anhydrous Na2S2O4 and concentrated in vacuo. Silica-gel column
chromatography of the residue by using Hexane/Benzene (5/1)
as an eluent yielded (Z)-6-benzyloxy-1,1,1-trifluoro-7-methyl-2-
tributylstannyl-2-hepten-4-yne (9e, 83 mg, 0.15 mmol, 75%),
whose silica-gel was treated in advance with the basic solution.
4.7. Typical procedure for Sonogashira cross-coupling re-
action of 5eA with 1-octyne
To a solution of (E)-6-bezyloxy-3-n-butyl-1,1,1-trifluoro-2-iodo-
6-methyl-2-hepten-4-yne (5eA) (0.450 g, 1.0 mmol), 1-octyne
(0.220 g, 2.0 mmol), CuI (0.019 g. 0.10 mmol) in THF (10 mL) was
added Pd(PPh3)4 (0.116 mg, 0.10 mmol) followed by Et3N (5.6 mL,
40 mmol) at 25 ꢁC. The whole was allowed to warm to 70 ꢁC, then
stirred for additional 2 h. After quenching the reaction with satd
NH4Cl aq, the reaction mixture was extracted with Et2O three
times, and the combined organic layers were dried over anhydrous
Na2SO4, then filtered. The filtrate was evaporated to give the cor-
responding crude materials, which was purified by silica gel col-
umn chromatography, affording the (Z)-2-benzyloxy-6-n-butyl-2-
methyl-6-trifluoromethyl-5-pentadecen-3,7-diyne (7eA) (0.301 g,
0.70 mmol, 70% yield.)
4.8.1. (Z)-6-Benzyloxy-1,1,1-trifluoro-7-methyl-2-tributylstannyl-2-
hepten-4-yne (9e). Yield: 75%; Oil; Solvent for chromatography:
Hexane/Benzene¼5/1; 1H NMR (CDCl3)
d 0.87e1.57 (27H, m, pro-
tons in Bu3Sn group), 1.56 (6H, s, CH3), 4.62 (2H, s, CH2), 6.83 (1H, q,
J¼2.7 Hz, vinylic CH), 7.26e7.35 (5H, m, AreH); 19F NMR (CDCl3)
d
ꢀ61.49 (3F, s, CF3); 13C NMR (CDCl3)
d 10.6, 13.6, 28.6, 28.7 (2C),
66.7, 70.9, 82.2 (q, J¼1.6 Hz), 98.7 (q, J¼1.7 Hz), 126.0 (q, J¼12.1 Hz),
126.6 (q, J¼272.0 Hz), 127.47, 127.52, 128.3, 138.7, 146.8 (q,
J¼34.2 Hz); IR (neat)
695 cmꢀ1
n 2957, 2855, 1592, 1465, 1379, 1242, 1112,
4.7.1. (Z)-7-Benzyloxy-4-n-butyl-7-methyl-1-phenyl-3-
;
HRMS (FAB) Calcd for (MþNa) C27H41F3NaOSn:
trifluoromethyl-3-octen-1,5-diyne (6eA). Yield: 94%; Oil; Solvent for
581.2029, found 581.2037.
chromatography: Hexane/EtOAc¼10/1; 1H NMR (CDCl3)
d 0.97 (3H,
t, J¼7.4 Hz, CH3 in n-Bu), 1.44 (2H, sex., J¼7.4 Hz, CH2 in n-Bu),
1.60e1.70 (2H, m, CH2 in n-Bu), 1.63 (6H, s, CH3), 2.60e2.70 (2H, m,
CH2 in n-Bu), 4.64 (2H, s, CH2), 7.26e7.48 (10H, m, AreH); 13C NMR
4.9. Hydrodestannylation of 9e
(Z)-6-Benzyloxy-1,1,1-trifluoro-7-methyl-2-tributyl-stannyl-2-
hepten-4-yne (9e) (0.112 g, 0.20 mmol) was added to p-TsOH$H2O
(0.380 g, 2.0 mmol) in CH2Cl2 (4 mL) at room temperature and the
whole solution was stirred for 3 h. The reaction mixture was
quenched with NaHCO3 aq and extracted with CH2Cl2 three times.
The combined organic layers were dried over anhydrous Na2SO4
and concentrated in vacuo. The residue was chromatographed on
silica gel to afford (E)-6-benzyloxy-1,1,1-trifluoro-6-methyl-2-
hepten-4-yne (10e) (0.048 g, 0.18 mmol, 90% yield).
(CDCl3)
d
13.9, 22.1, 28.5, 29.9, 36.2, 66.9 (t, J¼2.5 Hz), 71.3, 81.1, 82.1
(q, J¼2.5 Hz), 101.4, 106.8 (q, J¼1.9 Hz), 119.0 (q, J¼33.6 Hz), 121.4 (q,
J¼274.4 Hz), 122.3, 127.5, 127.8, 128.3, 128.5, 129.1, 131.5, 137.6 (q,
J¼2.48 Hz), 138.8; 19F NMR (CDCl3)
d
ꢀ61.27 (3F, s, CF3); IR (neat)
n
3033, 2959, 2932, 2862, 2214, 1576, 1491, 1355, 1235, 1133, 1058,
1000, 755, 735, 689 cmꢀ1; HRMS calcd for C27H27F3NaO (MþNa)
447.1912, Found 447.1909.
4.7.2. (Z)-2-Benzyloxy-6-n-butyl-2-methyl-6-trifluoromethyl-5-
pentadecen-3,7-diyne (7eA). Yield: 70%; Oil; Solvent for chroma-
4.9.1. (E)-6-Benzyloxy-1,1,1-trifluoro-6-methyl-2-hepten-4-yne
(10e). Yield: 90%; Oil; Solvent for chromatography: Hexane/
tography: Hexane/EtOAc¼10/1; 1H NMR (CDCl3)
d 0.85e0.95 (6H,
m, CH3 in alkyl chains), 1.25e1.45 (8H, m, CH2 in alkyl chains),
1.50e1.65 (5H, m, CH2 in alkyl chains), 1.59 (6H, s, CH3), 2.35e2.60
(3H, m, CH2 in alkyl chains), 4.62 (2H, s, CH2), 7.29e7.38 (5H, m,
EtOAc¼10/1; 1H NMR (CDCl3)
d 1.58 (6H, s, CH3), 4.61 (2H, s, CH2),
6.04 (1H, dq, J¼16.2, 6.7 Hz, CF3CH]CH), 6.32 (1H, dq, J¼16.2,
2.3 Hz, CF3CH]CH), 7.27e7.36 (5H, m, AreH); 13C NMR (CDCl3)
AreH); 13C NMR (CDCl3)
d
13.8, 14.0, 19.8, 22.1, 22.5, 28.3, 28.4, 28.5,
d
28.6, 66.7, 70.9, 72.09, 79.2 (q, J¼1.7 Hz), 99.0 (q, J¼1.7 Hz), 118.5
(q, J¼7.7 Hz), 122.4 (q, J¼269.4 Hz), 127.5, 127.6, 127.8 (q, J¼35.5 Hz),
128.4, 138.7; 19F NMR (CDCl3)
ꢀ65.41 (3F, d, J¼6.7 Hz, CF3); IR
29.8, 31.2, 35.9, 66.8, 71.2, 73.6 (q, J¼2.5 Hz), 81.0, 103.5, 105.5 (q,
J¼1.6 Hz), 119.2 (q, J¼33.0 Hz), 121.5 (q, J¼274.4 Hz), 127.4, 127.8,
d

2462
T. Konno et al. / Tetrahedron 70 (2014) 2455e2463
(neat)
n
2987, 2265, 1649, 1454, 1313, 1243, 1143, 1059, 953, 878,
1249, 1181, 1140, 1057, 925, 865, 735, 697 cmꢀ1; HRMS calcd for
696 cmꢀ1; HRMS calcd for C15H15F3O (Mþ) 268.1075, Found
C23H27F3NaO (MþNa) 399.1912, Found 399.1905.
268.1083.
4.11.3. (E)-7-Benzyloxy-7-methyl-3-trifluoromethyl-1-trimethylsilyl-
3-octen-1,5-diyne (14e). Yield: 84%; Oil; Solvent for chromatogra-
4.10. Iododestannylation of 9e
phy: Hexane/EtOAc¼10/1; 1H NMR (CDCl3)
d 0.22 (9H, s, protons in
TMS group),1.64 (6H, s, CH3), 4.67 (2H, s, CH2), 6.45 (1H, q, J¼1.2 Hz,
(Z)-6-Benzyloxy-1,1,1-trifluoro-7-methyl-2-tributylstannyl-2-
hepten-4-yne (9e) (0.558 g, 1 mmol) was added to I2 (0.305 g,
1.2 mmol) in CH2Cl2 (10 mL) at 0 ꢁC and the whole solution was
warmed to 25 ꢁC, then stirred overnight at that temperature. The
reaction mixture was quenched with NaHCO3 aq and extracted
with CH2Cl2 three times and the organic layer was dried over an-
hydrous Na2SO4 and concentrated. The residue was chromato-
graphed on silica gel to afford 6-benzyloxy-1,1,1-trifluoro-2-iodo-6-
methyl-2-hepten-4-yne (11e) (0.38 g, 0.98 mmol, 98% yield).
vinylic CH), 7.31e7.38 (5H, m, AreH); 13C NMR (CDCl3)
d
ꢀ0.5, 28.7,
66.9, 71.2, 79.8, 95.5 (q, J¼1.6 Hz), 105.2 (q, J¼2.4 Hz), 106.9, 121.1 (q,
J¼5.5 Hz), 121.3 (q, J¼273.2 Hz), 123.6 (q, J¼33.8 Hz), 127.5, 127.8,
128.3, 138.60; 19F NMR (CDCl3)
3033, 2986, 2211, 1594, 1362, 1293, 1252, 1142, 1042, 928, 846, 761,
697 cmꢀ1; HRMS calcd for C20H23F3NaOSi (MþNa) 387.1368, Found
387.1368.
d
ꢀ66.96 (3F, s, CF3); IR (neat)
n
4.12. Oxidative deprotection of benzyl group from 12e
4.10.1. (Z)-6-Benzyloxy-1,1,1-trifluoro-2-iodo-6-methyl-2-hepten-4-
yne (11e). Yield: 98%; Oil; Solvent for chromatography: Hexane/
To
a solution of (E)-7-benzyloxy-7-methyl-1-phenyl-3-tri-
fluoromethyl-3-octen-1,5-diyne (12e, 0.37 g, 1.0 mmol) in
ClCH2CH2Cl/buffer (9/1) (10 mL) was added DDQ (0.68 g, 3.0 mmol)
at room temperature. The whole was allowed to heat at the reflux
temperature (110 ꢁC), then stirred overnight. The reaction mixture
was cooled to room temperature and the whole was extracted with
CH2Cl2 three times. The combined organic layers were dried over
anhydrous Na2SO4, then filtered. The filtrate was evaporated to give
the crude materials, which was purified by silica gel column chro-
matography, affording the 1-methyl-8-phenyl-6-trifluoromethyl-5-
octen-3,7-diyn-2-ol (0.24 g, 0.86 mmol, 86% yield).
EtOAc¼10/1; 1H NMR (CDCl3)
d 1.63 (6H, s, CH3), 4.71 (2H, s, CH2),
6.96 (1H, q, J¼1.6 Hz, vinylic CH), 7.28e7.40 (5H, m, AreH); 13C NMR
(CDCl3)
d
28.5, 67.0, 71.2, 82.3, 97.2 (q, J¼36.3 Hz), 104.5 (q,
J¼1.7 Hz), 121.1 (q, J¼271.7 Hz), 125.7 (q, J¼6.6 Hz), 127.5, 127.8,
128.4, 138.6; 19F NMR (CDCl3)
d
ꢀ65.28 (3F, s, CF3); IR (neat)
n
3031,
2986, 2866, 2221, 1605, 1454, 1382, 1276, 1243, 1141, 1088, 923, 789,
729, 656 cmꢀ1; HRMS calcd for C15H14F3INaO (MþNa) 416.9939,
Found 416.9946.
4.11. Typical procedure for Sonogashira cross-coupling re-
action of 11e with 1-octyne
4.12.1. (E)-2-Methyl-8-phenyl-6-trifluoromethyl-5-octen-3,7-diyn-2-
ol. Yield: 86%; Oil; Solvent for chromatography: Hexane/EtOAc¼3/
To a solution of 6-benzyloxy-1,1,1-trifluoro-2-iodo-6-methyl-2-
hepten-4-yne (11e) (0.118 g, 0.3 mmol), 1-octyne (0.066 g,
0.6 mmol), CuI (0.006 g. 0.03 mmol) in THF (6 mL) was added
Pd(PPh3)4 (0.035 mg, 0.03 mmol) followed by Et3N (1.7 mL,
12 mmol) at room temperature. The whole was allowed to warm to
50 ꢁC, and stirred overnight, then quenched with satd NH4Cl aq.
The mixture was extracted with Et2O three times, and the com-
bined organic layers were dried over anhydrous Na2SO4, then fil-
tered. The filtrate was evaporated to give the corresponding crude
materials, which was purified by silica gel column chromatography,
affording 2-benzyloxy-2-methyl-6-trifluoromethyl-5-tetradecen-
3,7-diyne (13e) (0.110 g, 0.29 mmol, 97% yield.)
1; 1H NMR (CDCl3)
d
1.61 (6H, s, CH3), 6.42 (1H, q, J¼1.6 Hz, vinylic
CH), 7.35e7.54 (5H, m, AreH); 13C NMR (CDCl3)
d 31.1, 65.8, 77.8,
99.8, 107.2, 120.0 (q, J¼5.5 Hz), 121.4 (q, J¼273.6 Hz), 121.7, 123.8 (q,
J¼34.7 Hz), 128.50, 129.52, 131.93; 19F NMR (CDCl3)
ꢀ66.75 (3F, s,
d
CF3); IR (neat) n 3359, 2984, 2201, 1588, 1390, 1290, 1139, 952, 865,
756, 688 cmꢀ1; HRMS calcd for C16H13F3O (Mþ) 278.0918, Found
278.0914.
4.13. Preparation of the corresponding terminal alkyne
To a solution of KOH (0.49 g, 8.6 mmol) in toluene (5 mL) was
added 2-methyl-8-phenyl-6-trifluoromethyl-5-octen-3,7-diyn-2-
ol (0.24 g, 0.86 mmol) above prepared at room temperature. The
whole was allowed to heat at the reflux temperature (60 ꢁC), then
stirred overnight. The reaction mixture was cooled to room tem-
perature, quenched with NH4Cl aq, and the whole was extracted
with Et2O three times. The combined organic layers were dried over
anhydrous Na2SO4, then filtered. The filtrate was evaporated to give
the crude materials, which were used for the next reaction without
further purification.
4.11.1. (E)-7-Benzyloxy-7-methyl-1-phenyl-3-trifluoromethyl-3-
octen-1,5-diyne (12e). Yield: 74%; Oil; Solvent for chromatography:
Hexane/Benzene¼1/1; 1H NMR (CDCl3)
d 1.65 (6H, s, CH3), 4.69
(2H, s, CH2), 6.49 (1H, q, J¼1.6 Hz, vinylic CH), 7.26e7.47 (10H, m,
AreH); 13C NMR (CDCl3)
d
28.7, 66.9, 71.2, 80.1, 81.2 (q, J¼2.2 Hz),
99.8,105.3, 120.0 (q, J¼5.5 Hz), 121.5 (q, J¼273.3 Hz), 121.6, 123.7 (q,
J¼34.7 Hz), 127.4, 127.7, 128.3, 128.4, 129.4, 131.9, 138.6; 19F NMR
(CDCl3)
d
ꢀ66.83 (3F, s, CF3); IR (neat)
n 3034, 2986, 2935, 2201,
1589, 1491, 1389, 1292, 1183, 1139, 1030, 867, 756, 689 cmꢀ1; HRMS
4.13.1. (E)-1-Phenyl-3-trifluoromethyl-3-hexen-1,5-diyne. 1H NMR
calcd for C23H18F3O (Mþ) 367.1310, Found 367.1312.
(CDCl3)
d
3.67 (1H, m, C^CH), 6.41 (1H, m, vinylic CH), 7.34e7.56
78.6, 80.8 (d, J¼2.5 Hz), 90.2 (t,
(5H, m, AreH); 13C NMR (CDCl3)
d
4.11.2. (Z)-2-Benzyloxy-2-methyl-6-trifluoromethyl-5-tetradecen-
3,7-diyne (13e). Yield: 97%; Oil; Solvent for chromatography:
J¼1.6 Hz), 100.5, 119.2 (q, J¼5.5 Hz), 121.3 (q, J¼275.0 Hz), 121.5,
125.6 (q, J¼34.7 Hz), 128.4, 129.7, 132.1; 19F NMR (CDCl3)
d
ꢀ67.15
Hexane/EtOAc¼10/1; 1H NMR (CDCl3)
d
0.87 (3H, t, J¼7.0 Hz, CH3 in
(3F, s, CF3); IR (neat) n 3303, 3059, 2989, 2937, 2203, 2105, 1734,
alkyl chain), 1.20e1.40 (6H, m, CH2 in alkyl chain), 1.45e1.65 (2H, m,
CH2 in alkyl chain), 1.60 (6H, s, CH3), 2.30 (2H, t, J¼7.0 Hz, CH2 in
alkyl chain), 4.62 (2H, s, CH2), 6.34 (1H, q, J¼1.6 Hz, vinylic CH),
1641, 1492, 1443, 1388, 1287, 1135, 1015, 905, 756, 689, 645 cmꢀ1
;
HRMS calcd for C13H7F3 (Mþ) 220.0500, Found 220.0501.
7.28e7.38 (5H, m, AreH); 13C NMR (CDCl3)
d
14.0, 19.6, 22.4, 28.2,
4.14. Sonogashira cross-coupling of the above terminal al-
kyne with iodobenzene
28.5, 28.6, 31.2, 66.8, 71.2, 72.8 (q, J¼1.6 Hz), 80.1, 102.3, 103.7 (q,
J¼1.4 Hz), 118.9 (q, J¼5.5 Hz), 121.5 (q, J¼273.2 Hz), 124.0 (q,
J¼33.9 Hz), 127.5, 127.7, 128.3, 138.72; 19F NMR (CDCl3)
d
ꢀ67.39 (3F,
To a solution of the above-obtained (E)-1-phenyl-3-trifluoro
methyl-3-hexen-1,5-diyne, PhI (0.35 g, 1.72 mmol), CuI (17 mg,
s, CF3); IR (neat)
n
2985, 2933, 2861, 2211, 1600, 1455, 1382, 1292,

T. Konno et al. / Tetrahedron 70 (2014) 2455e2463
2463
5. For the synthesis of fluoroalkyl-substituted cis-enediynes, see: (a) Konno, T.;
Kishi, M.; Ishihara, T.; Yamada, S. J. Fluorine Chem. 2013, 156, 144e151; (b) Ya-
mada, S.; Konno, T.; Ishihara, T.; Yamanaka, H. J. Fluorine Chem. 2005, 126,
125e133; (c) Hong, F.; Hu, C. M. Chin. Chem. Lett. 1995, 6, 279e280.
0.086 mmol) in THF (20 mL) was added Pd(PPh3)4 (100 mg,
0.086 mmol) followed by Et3N (4.9 mL, 34 mmol) at room tem-
perature. The whole was stirred overnight, then quenched with
satd NH4Cl aq. The mixture was extracted with Et2O three times,
and the combined organic layers were dried over anhydrous
Na2SO4, then filtered. The filtrate was evaporated to give the cor-
responding crude materials, which were purified by silica gel col-
6. For the synthesis of fluoroalkyl-substituted trans-enediynes, see: (a) Konno, T.;
Kishi, M.; Ishihara, T. Beilstein J. Org. Chem. 2012, 8, 2207e2213; (b) Jeon, H. H.;
Son, J. B.; Choi, J. H.; Jeong, I. H. Tetrahedron Lett. 2007, 48, 627e631; (c) Shi-
mizu, M.; Fujimoto, T.; Liu, X.; Minezaki, H.; Hata, T.; Hiyama, T. Tetrahedron
2003, 59, 9811e9823; (d) Shimizu, M.; Fujimoto, T.; Minezaki, H.; Hata, T.;
Hiyama, T. J. Am. Chem. Soc. 2001, 123, 6947e6948.
umn
chromatography,
affording
the
(E)-1,6-diphenyl-3-
ꢀ
ꢀ
7. (a) O’Hagen, D. Chem. Soc. Rev. 2008, 37, 308e319; (b) Begue, J.-P.; Bonnet-
Delpon, D. J. Fluorine Chem. 2006, 127, 992e1012; (c) Yamamoto, S.; Matsuda, K.;
Irie, M. Org. Lett. 2003, 5, 1769e1772; (d) Kaieda, T.; Kobatake, S.; Miyasaka, H.;
Murakami, M.; Iwai, N.; Nagata, Y.; Itaya, A.; Irie, M. J. Am. Chem. Soc. 2002, 124,
2015e2024; (e) Irie, M. Chem. Rev. 2000, 100, 1685e1716; (f) Hiyama, T. Orga-
nofluorine Compounds. Chemistry and Applications; Springer: New York, NY,
2000.
trifluoromethyl-3-hexen-1,5-diyne (15) (0.22 g, 0.75 mmol, 87%
for two steps).
4.14.1. (E)-1,6-Diphenyl-3-trifluoromethyl-3-hexen-1,5-diyne
(15). Yield: 87% (for two steps); Oil; Solvent for chromatography:
Hexane/Benzene¼1/1; 1H NMR (CDCl3)
d 6.60e6.64 (1H, m, vinylic
8. (a) Konno, T.; Kida, T.; Tani, A.; Ishihara, T. J. Fluorine Chem. 2012, 144, 147e156;
(b) Konno, T.; Moriyasu, K.; Kinugawa, R.; Ishihara, T. Org. Biomol. Chem. 2010, 8,
1718e1724; (c) Konno, T.; Kinugawa, R.; Morigaki, A.; Ishihara, T. J. Org. Chem.
2009, 74, 8456e8459; (d) Konno, T.; Moriyasu, K.; Ishihara, T. Synthesis 2009,
1087e1094; (e) Konno, T.; Taku, K.; Yamada, S.; Moriyasu, K.; Ishihara, T. Org.
Biomol. Chem. 2009, 7, 1167e1170; (f) Konno, T.; Taku, K.; Ishihara, T. J. Fluorine
Chem. 2006, 127, 966e972; (g) Ishihara, T.; Mantani, T.; Konno, T.; Yamanaka, H.
Tetrahedron 2006, 62, 3783e3793; (h) Konno, T.; Nagai, G.; Ishihara, T. J. Fluorine
Chem. 2006, 127, 510e518; (i) Konno, T.; Chae, J.; Tanaka, T.; Ishihara, T.; Ya-
manaka, H. J. Fluorine Chem. 2006, 127, 36e43; (j) Konno, T.; Ishihara, T. In
Fluorine-containing Synthons; Soloshonok, V. A., Ed.; ACS: Washington, DC,
2005; pp 190e203; (k) Konno, T.; Chae, J.; Miyabe, T.; Ishihara, T. J. Org. Chem.
2005, 70, 10172e10174; (l) Konno, T.; Daitoh, T.; Noiri, A.; Chae, J.; Ishihara, T.;
Yamanaka, H. Tetrahedron 2005, 61, 9391e9404; (m) Konno, T.; Chae, J.; Ishi-
hara, T.; Yamanaka, H. Tetrahedron 2004, 60, 11695e11700; (n) Konno, T.; Chae,
J.; Ishihara, T.; Yamanaka, H. J. Org. Chem. 2004, 69, 8258e8265; (o) Chae, J.;
Konno, T.; Ishihara, T.; Yamanaka, H. Chem. Lett. 2004, 33, 314e315; (p) Konno,
T.; Chae, J.; Tanaka, T.; Ishihara, T.; Yamanaka, H. Chem. Commun. 2004,
690e691; (q) Konno, T.; Daitoh, T.; Noiri, A.; Chae, J.; Ishihara, T.; Yamanaka, H.
Org. Lett. 2004, 6, 933e936; (r) Konno, T.; Takeana, T.; Chae, J.; Ishihara, T.;
Yamanaka, H. J. Org. Chem. 2004, 69, 2188e2190; (s) Chae, J.; Konno, T.; Kanda,
M.; Ishihara, T.; Yamanaka, H. J. Fluorine Chem. 2003, 120, 185e193.
CH), 7.35e7.42 (6H, m, AreH), 7.52e7.57 (4H, m, AreH); 13C NMR
(CDCl3)
121.9, 122.9 (q, J¼34.7 Hz), 121.6 (q, J¼273.1 Hz), 122.1, 128.5, 128.6,
129.5, 129.6, 131.9, 132.0; 19F NMR (CDCl3)
ꢀ66.55 (3F, s, CF3); IR
d
81.7 (q, J¼2.2 Hz), 85.2, 100.2, 102.8, 120.4 (q, J¼5.5 Hz),
d
(neat)
n 3054, 2926, 2244, 2209, 2189, 1952, 1729, 1490, 1391, 916,
864, 754, 687 cmꢀ1; HRMS calcd for C19H11F3 (Mþ) 296.0813,
Found 296.0807.
References and notes
1. (a) Liu, Y.; Gao, H. Org. Lett. 2006, 8, 309e311; (b) Nielsen, M. B.; Diederich, F.
Chem. Rev. 2005, 105, 1837e1868; (c) Martin, R. E.; Diederich, F. Angew. Chem.,
Int. Ed. 1999, 38, 1350e1377.
2. (a) Joshi, M. C.; Rawat, D. S. Chem. Biodiversity 2012, 9, 459e498; (b) Galm, U.;
Hager, M. H.; Van Lanen, S. G.; Ju, J.; Thorson, J. S.; Shen, B. Chem. Rev. 2005, 105,
739e758; (c) Nicolaou, K. C.; Smith, A. L.; Yue, E. W. Proc. Natl. Acad. Sci. U.S.A.
1993, 90, 5881e5888.
3. (a) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25e31; (b) Jone, R. R.; Bergman, R. G.
J. Am. Chem. Soc. 1972, 94, 660e661.
9. 2,3,3,3-Tetrafluoro-1-iodoprop-1-ene (1) was easily prepared from commer-
cially available 2,2,3,3,3-pentafluoropropanol in three steps, see: Konno, T.;
Chae, J.; Kanda, M.; Nagai, G.; Tamura, K.; Ishihara, T.; Yamanaka, H. Tetrahedron
2003, 59, 7571e7580.
10. It has been reported that the stereoselectivity as well as regioselectivity is not
so high in the reaction of nonfluorinated diyne with the copper reagent. See:
Kong, K.; Moussa, Z.; Lee, C.; Romo, D. J. Org. Chem. 2011, 133, 19844e19856.
4. (a) Landis, C. A.; Payne, M. M.; Eaton, D. L.; Anthony, J. E. J. Am. Chem. Soc. 2004,
126, 1338e1339; (b) Scott, J. L.; Parkin, S. R.; Anthony, J. E. Synlett 2004,
161e165; (c) Bowles, D. M.; Palmer, G. J.; Landis, C. A.; Scott, J. L.; Anthony, J. E.
Tetrahedron 2001, 57, 3753e3760; (d) Chow, S.-Y.; Palmer, G. J.; Bowles, D. M.;
Anthony, J. E. Org. Lett. 2000, 2, 961e963; (e) Bowles, D. M.; Anthony, J. E. Org.
Lett. 2000, 2, 85e87.