Phosphine-Relayed Aldehyde-Olefination and Aza-Wittig Reaction with 2,2,2-Trifluorodiazoethane

Article abstract of DOI:10.1002/cjoc.201800158

Phosphine-relayed olefination and aza-Wittig reactions of readily available aldehydes with 2,2,2-trifluorodiazoethane (CF₃CHN₂) have been realized. This protocol enables the facile construction of a series of trifluoromethylated alkenes and hydrazones in good to high yield under mild conditions.

Full text of DOI:10.1002/cjoc.201800158

Phosphine-Relayed Aldehyde-Olefination and Aza-Wittig Reaction with
2,2,2-Trifluorodiazoethane
Fa-Guang Zhang,*,† Ning Lv,† Yan Zheng, and Jun-An Ma*
ABSTRACT Phosphine-relayed olefination and aza-Wittig reaction of readily available aldehydes with 2,2,2-trifluorodiazoethane (CF3CHN2) have been
realized. This protocol enables the facile construction of a series of trifluoromethylated alkenes and hydrazones in good to high yield under mild
conditions.
KEYWORDS diazo compounds, olefination, Wittig reactions, 2,2,2-trifluorodiazoethane, phosphine
Introduction
Scheme
1 Different products from the reactions of CF3CHN2 with
The incorporation of trifluoromethyl group into organic
molecules would impart significant alterations to parent
compounds such as improved bioavailability, lipophilicity, or
metabolic stability.[1] Thus, trifluoromethyl-containing compounds
have played an increasingly important role in the area of
pharmaceuticals, agrochemicals, and materials.[2] With the
demand to prepare various trifluoromethylated compounds in
efficient ways, great efforts have been devoted and a number of
trifluoromethyl building blocks have been developed over the
past decades.[3] In this context, 2,2,2-trifluorodiazoethane
(CF3CHN2) has emerged as a versatile synthon in the construction
of different trifluoromethyl-containing frameworks.[4] Among
these studies, Carreira and co-workers developed an elegant
protocol for the in situ generation of CF3CHN2 and its subsequent
utilization in various chemical transformations.[5] For example, the
homologation reaction of aldehydes with CF3CHN2 employing
ZrCl4 as a suitable Lewis acid was reported by Carreira group in
2011 (Scheme 1a).[6] This method allows the straightforward
conversion of aldehydes into trifluoromethyl substituted ketones.
Very recently, Kappe and co-workers described a convenient
generation of CF3CHN2 and subsequent aldol-type reaction with
aldehydes utilizing continuous flow technology (Scheme 1b).[7]
With our continuous interest in the utilization of CF3CHN2 in
synthetic chemistry,[8] we envisioned that an olefination reaction
of aldehydes would be achieved by employing phosphine in
carbene relay process with CF3CHN2.[9] On the other hand,
aza-Wittig process of aldehydes with trifluorodiazoethane to
aldehydes
Results and Discussion
We commenced our study by evaluating the olefination of
aldehyde 1a with CF3CHN2 in the presence of different metal
catalysts (Table1, entries 1–4). It has been found that only
Fe(TPP)Cl could deliver the desired product 2a in the presence of
PPh3 at 40 °C in toluene, albeit with low yield (entry 3).
Subsequently, by increasing the amount of PPh3 and Fe(TPP)Cl
(entries 5–7), the yield of 2a could be dramatically improved to 94%
with 2.0:1 of E/Z ratio (entry 7). Encouraged by this result, a
survey of the reaction parameters, such as solvents and reaction
temperature, was conducted. Unfortunately, no improvement of
the reaction efficiency was observed (entries 8–12). Nevertheless,
a stream of gas generation was observed when CF3CHN2 was
added quickly to the reaction mixture. We speculated that the
amount of Fe catalyst could be further reduced if the reaction
could be controlled in a slower manner. Indeed, with a syringe
pump equipment to add CF3CHN2 in one hour, only 1 mol % of
Fe(TPP)Cl could still deliver the target product in 93% yield
(entries 13–15). Moreover, the amount of PPh3 could also be
reduced to 1.8 equivalents while keeping the high yield of 2a
(entries 16–17). However, it should also be mentioned that
further improving the E/Z ratio of trifluoromethylated alkene
appeared to be challenging (entries 18–24). Of note is that when
MePPh2 was employed, 2a was generated with 4.5:1 of the E/Z
ratio, but in dramatically decreasing yield (35%, entry 24). Taken
together, optimal conditions for the formation of alkene 2a from
aldehyde with CF3CHN2 was established to be performed in
toluene at 80 °C with the combination of Fe(TPP)Cl (1 mol %) and
PPh3 (1.8 equiv.).
CF3-hydrazones
would
also
be
accomplished
when
carbene-generating catalyst is absent in reaction media. To realize
this proposal, two main challenges need to be addressed: i) to
identify a suitable metal catalyst for carbene generation and
transferring; ii) to carefully deal with the high reactivity of
CF3CHN2 toward phosphines. To our delight, the
phosphine-relayed olefination of aldehydes has been achieved by
employing iron(III) porphyrin complex (Fe(TPP)Cl) as the catalyst
(Scheme 1c). This transformation proceeds under mild conditions
in
a one pot manner, thus providing rapid access to
trifluoromethylated olefins from readily available aldehydes.[10]
Meanwhile, in the absence of iron catalyst, a wide range of
trifluoromethylated
hydrazones
were
afforded
via
phosphine-relayed aza-Wittig process with CF3CHN2 and
aldehydes.[11] It should be noted that hydrazones not only serve
as useful building block in organic chemistry,[12] but also are
considered as important structural motif for their presence in a
number of bio-active compounds, natural products, molecular
switches and metalo-assemblies.[13] Herein we wish to report our
detailed investigation on this subject.
Department of Chemistry, Tianjin Key Laboratory of Molecular Optoelectronic
Sciences, and Tianjin Collaborative Innovation Center of Chemical Science &
Engineering, Tianjin University, Tianjin 300072, P. R. China
*E-mail: zhangfg1987@tju.edu.cn
*E-mail: majun_an68@tju.edu.cn
†These authors contribute equally to this work.
This article has been accepted for publication and undergone full peer review but has not
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may lead to differences between this version and the Version of Record. Please cite this
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Table 1 Optimization of the reaction conditions for aldehyde olefination a
Catalyst
(mol %)
Phosphine
(equiv.)
Temp
(°C) / time (h)
40 / 12
Yield
Entry
Solvent
(%)b (E/Z)
1
2
toluene
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
CH3CN
Cu(TPP) (2)
Co(TPP) (2)
PPh3 (1.5)
PPh3 (1.5)
nd
40 / 12
40 / 12
40 / 12
80 / 8
80 / 8
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
80 / 4
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
80 / 2
nd
3
Fe(TPP)Cl (2)
Fe(salen)Cl (10)
Fe(TPP)Cl (2)
Fe(TPP)Cl (2)
Fe(TPP)Cl (5)
Fe(TPP)Cl (5)
Fe(TPP)Cl (5)
Fe(TPP)Cl (5)
Fe(TPP)Cl (5)
Fe(TPP)Cl (5)
Fe(TPP)Cl (2)
Fe(TPP)Cl (1)
Fe(TPP)Cl (0.5)
Fe(TPP)Cl (1)
Fe(TPP)Cl (1)
Fe(TPP)Cl (2)
Fe(TPP)Cl (2)
Fe(TPP)Cl (2)
Fe(TPP)Cl (2)
Fe(TPP)Cl (2)
Fe(TPP)Cl (2)
Fe(TPP)Cl (2)
PPh3 (1.5)
25 (1.8:1)
nd
4
PPh3 (1.5)
5
PPh3 (1.5)
33 (2.0:1)
61 (2.3:1)
94 (2.0:1)
41 (2.7:1)
8
6
PPh3 (2.4)
7
PPh3 (2.4)
8
PPh3 (2.4)
9
PPh3 (2.4)
10
11
12
13
14c
15c
16c
17c
18c
19c
20c, d
21c
22c
23c
24c
DMF
PPh3 (2.4)
nd
DCE
PPh3 (2.4)
35 (2.3:1)
85 (1.3:1)
96 (2.1:1)
93 (2.5:1)
81 (2.7:1)
94 (2.5:1)
82 (2.3:1)
nd
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
PPh3 (2.4)
PPh3 (2.4)
PPh3 (2.4)
PPh3 (2.4)
PPh3 (1.8)
PPh3 (1.5)
PtBu3 (2.4)
P(OEt)3 (2.4)
PPh3 (2.4)
nd
95 (2.0:1)
90 (3.5:1)
90 (2.3:1)
55 (3.5:1)
35 (4.5:1)
P(4-F-C6H4)3 (2.4)
P(4-Me-C6H4)3 (2.4)
P(4-MeO-C6H4)3 (2.4)
MePPh2 (2.4)
a
General reaction conditions: 2-naphthaldehyde (0.2 mmol, 1.0 equiv.), phosphine and catalyst under Ar atmosphere, then added CF3CHN2
b
(corresponding solution, 2.5 equiv., 0.5 mmol) slowly and reacted at indicated temperature for appropriate time unless otherwise noted; NMR yields
with PhCF3 as the standard reagent; c CF3CHN2 was added via syringe pump in one hour; d 2 equiv. of LiBr was added.
With the optimized reaction conditions in hand (Table 1, entry
16), we then set out to probe the scope of phosphine-relayed
olefination with a variety of aldehydes. As depicted in Table 2,
various aromatic aldehydes proved to be compatible substrates
including the ones with electron-neutral, electron-withdrawing or
electron-donating substituents, thus providing corresponding
trifluoromethylated olefins in good to high chemical yields. Of
note is that aldehydes bearing a strong electron-withdrawing
group on the aromatic ring, were transformed to target olefins at
room temperature in high yield as a single E isomer (Table 2,
products 2f–h). In addition to NO2, CN, CO2Me, and halogen
functionalities, the olefination could also tolerate amino groups
as exemplified with the formation of 2l in 78% yield. Besides,
several alkyl aldehydes and aromatic ketones were also tested in
this reaction, however, the conversion was poor even with high
loadings of Fe(TPP)Cl or at elevated temperature.
(see the proposed mechanism in Scheme 3).[14] With this
hypothesis in mind, 1a was then treated with CF3CHN2 and
phosphine in the absence of iron catalyst. Pleasingly,
trifluoromethylated hydrazone 3a could be smoothly obtained as
a single isomer in 90% yield. This method could provide a mild,
operationally simple and efficient access to trifluoromethylated
hydrazones, thus a series of aldehydes were subjected to this
transformation to demonstrate the substrate scope. These results
are summarized in Table 3. A wide range of aromatic aldehydes
could be smoothly transformed into trifluoromethylated
hydrazones in good to high yield (Table 3, 3a–n). It is found that
the electronic nature and steric hindrance of substitutents play a
crucial role on the reactivity. For instance, for substrate with a
strong electron-withdrawing group, the reaction underwent
Table 2 Substrate scope of the trifluoromethylated olefins a, b
Notably, trifluoromethylated hydrazone 3a was observed in
several cases during afore-mentioned optimization process (Table
1). This hydrazone was assumed to be produced from aza-Wittig
reaction of phosphazine intermediate with 2-naphthaldehyde
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Ph
Br
CF3
NO2
CF3
Me
N
N
N
F3C
N
F3C
N
CF3
CF3
2c, 75%, E/Z = 2.2:1
F3C
N
3c, 85%
3b, 93%
3a
, 90%
2b, 81%, E/Z = 3.5:1
2a, 92%, E/Z = 2.5:1
MeO
CO2Me
CN
Me
O2N
N
N
N
F3C
F3C
N
F3C
N
F3C
F3C
N
3f, 51%
3e, 95%
3d
, 91%
CF3
2e, 62%, E/Z = 5:1
CF3
2f, 90%, E/Z > 20:1
CF3
2d, 75%, E/Z = 2.5:1
N
N
N
N
NO2
N
OMe F3C
N
OPh
3i, 91%
3g, 93%
3h, 91%
MeO2C
Cl
Cl
NC
O2N
HO
O
CF3
2h, 83%, E/Z > 20:1
CF3
N
N
N
CF3
2g, 80%, E/Z > 20:1
N
N
F3C
F3C
F3C
N
F3C
2i, 80%, E/Z = 2.7:1
3l
, 82%
3k, 73%
3j, 78%
Bn
N
N
CF3
N
N
N
N
N
F3C
N
O2N
CF3 MeO
CF3 Bn2N
CF3
3m, 75%
3p, 50%
3n
, 53%
2k, 86%, E/Z = 2.3:1
2l, 78%, E/Z = 4.3:1
2j, 86%, E/Z = 3.5:1
N
CF3
N
CF3
N
Me
N
a General reaction conditions: aldehyde (0.4 mmol, 1.0 equiv.), PPh3 (0.72
mmol, 1.8 equiv.), and Fe(TPP)Cl (1–2 mol %) under Ar atmosphere, then
added CF3CHN2 (2.5 equiv., 0.2 mol/L in toluene) via syringe pump in one
hour at indicated temperature and reacted for one hour unless otherwise
noted; for compound 2f–h, reaction was run at rt; Isolated yields, E/Z
ratio was determined by F-NMR.
3q
3r
, 62%
OMOM
OMOM
Me
Me
Me
F3C
N
N
N
, 82%
N
CF3
3o
, 80%
b
a General reaction conditions: PPh3 (0.45 mmol, 1.5 equiv.), CF3CHN2 (1.5
equiv., 0.15 mol/L in toluene), rt for 5 minutes under Ar atmosphere, then
added aldehyde 1 (0.3 mmol, 1.0 equiv.) in one pot and reacted at 40–
60 °C for 24–48 h unless otherwise noted; b Isolated yield.
at 40–50 °C leading to corresponding product in high yield (3b–e).
In contrast, for aldehyde bearing an electron-donating group, the
desired alkene could still be afforded, but dramatic decrease in
yield was observed even at elevated temperature (3f). In the light
of steric effect, it explains the observation that the yield of 3j is
inferior to that of 3b and 3g. To our surprise, despite steric
hindrance and free O-H bond, salicylaldehyde is still a compatible
substrate in this reaction, thus affording 3k in 73% yield. The
substrate scope could also be expanded to 2-furaldehyde and
pyridine-2-aldehyde, along with the generation of 3l and 3m in
good yield. Notably, we succeeded in obtaining indole derivate 3n
in moderate yield, which was subjected to single crystal X-ray
analysis to confirm the molecular structure unambiguously.[15]
Moreover, BINOL derivate 3o was obtained in 82% yield by using
this simple aza-Wittig reaction. In addition, alkyl aldehydes,
including cyclohexanal, n-decanal and citral, could also participate
in the transformation with moderate outcome, highlighting the
robustness of current protocol.
Scheme 2 Aza-Wittig reaction of α-ketoesters with CF3CHN2 and reduction
of trifluoromethylated hydrazone
Furthermore, with these promising results in hand, we
attempted to extend this reaction to ketone substrates. However,
no conversion was observed in the case of 4-nitroacetophenone
even under harsh conditions, indicating the inert nature of
ketones in this reaction. Nevertheless, we speculated that a
strong electron-withdrawing group adjacent to the C=O bond
would facilitate the reaction to occur. Indeed, aza-Wittig reaction
of α-keto esters proceed smoothly under optimized conditions,
leading to corresponding products in 76–91% yield (Scheme 2a,
5a–e). Compounds with hydrazone functional groups are
potential useful building blocks in organic synthesis. As illustrated
in Scheme 2b, the aza-Wittig product 3 was treated with LiAlH4
and Pd/C respectively in a one-pot procedure. Interestingly,
regioselective reduction was observed in both cases, generating
corresponding product 6a and 6b in good yield. These results
displayed the diverse chemical reactivity of the bis-hydrazone
moiety. Furthermore, gram-scale reactions were carried out to
demonstrate the scalability of our newly developed method,
thereby smoothly furnishing 2a (1.36 g, 88% yield) and 3a (1.43 g,
82% yield) respectively (see experimental part for details).
A proposed mechanism is illustrated in Scheme 3 based on
our observations and previous studies.[9] When CF3CHN2 was
added to the reaction mixture (Scheme 3a), Fe(TPP)Cl would be in
situ reduced to Fe(II), followed by the fast formation of
[Fe]=CHCF3 species via release of N2. Subsequently, carbene
transfer from Fe species to PPh3 yields the CF3-Wittig
intermediate and releases iron catalyst, implying that the excess
of PPh3 is beneficial for the efficient trapping of active
[Fe]-carbene intermediate. Then the Wittig intermediate reacted
with aldehyde to furnish the olefin product and
triphenylphosphine oxide (OPPh3). The observed poor
Table 3 Substrate scope of the trifluoromethylated hydrazones from
aldehydes a, b
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stereoselectivity in this transformation contrasts sharply with
previous variant of diazoacetates,[9] which likely can be attributed
to the lack of stabilizing effects on the generated
CF3-oxaphosphetane intermediates in comparison with
CO2Et-substituted ones.[16] On the other hand, in the absence of
iron catalyst (Scheme 3b), phosphazene intermediate P-1 would
be generated while adding CF3CHN2 to PPh3.[14] In this scenario, an
aza-Wittig process of this intermediate with aldehyde will
proceed to yield trifluoromethylated hydrazone. Control
experiments between Fe(TPP)Cl with phosphazene intermediate
P-1 or hydrazone 3a were performed, while no olefination
product 2a was observed in either case (Scheme 3c). These results
not only strongly support the proposed mechanism, but also
explain the essentiality of slow addition of CF3CHN2 in the
procedure.
uncorrected. X-ray structural analysis was conducted on the
XtaLAB mini instrument. All purchased reagents were used
without further purification unless otherwise noted. Analytical
thin layer chromatography was performed on 0.20 mm Qingdao
Haiyang silica gel plates. Silica gel (200-300 mesh) (from Qingdao
Haiyang Chem. Company, Ltd.) was used for flash
chromatography. 2,2,2-Trifluorodiazoethane (CF3CHN2) in
different solutions was prepared and handled as described in the
literature.[8c] α-keto esters were synthesized according to known
procedure.[17]
Typical Procedure 1: To a 25 mL Schlenk tube was aldehyde
(0.4 mmol, 1.0 equiv.), PPh3 (0.72 mmol, 189 mg, 1.8 equiv.) and
Fe(TPP)Cl (0.004 mmol, 3 mg, 0.01 equiv.) under Ar atmosphere,
then CF3CHN2 (1.0 mmol, 5 mL, 0.2 mol/L in toluene) was added
via a syringe pump to the reaction system in about one hour at
80 °C and reacted for 1 h with stirring. After the reaction was
complete detected by TLC, column chromatography on silica gel
Scheme 3 Proposed mechanism
(ethyl acetate/hexane
conducted on the reaction mixture to afford the desired product
2.
= 1:100 as the eluent) was directly
a) Fe-carbene pathway:
CF3CHN2
OPPh3
PPh3
ArCH=CHCF3
ArCHO
[Fe]
Typical Procedure 2: To a 25 mL Schlenk tube was PPh3 (0.45
mmol, 118 mg, 1.5 equiv.) under Ar atmosphere, then CF3CHN2
(0.45 mmol, 3 mL, 0.15 mol/L in toluene) was added and the
mixture was stirred at rt for 5 minutes. Subsequently aldehyde
(0.3 mmol, 1.0 equiv.) was added to the reaction system in one
pot and the reaction was performed at 60 °C for 30 h with stirring.
After the reaction was complete detected by TLC, column
chromatography on silica gel (ethyl acetate/hexane = 1:20 as the
eluent) was directly conducted on the reaction mixture to afford
the desired product 3.
Typical Procedure 3: To a 10 mL Schlenk tube was PPh3 (0.45
mmol, 1.5 equiv.) under Ar atmosphere, then CF3CHN2 (0.45
mmol, 1.5 equiv.) was added and the mixture was stirred at rt for
5 minutes. Subsequently, carbonyl esters (0.3 mmol, 1.0 equiv.)
was added to the reaction system in one pot and the reaction was
performed at 60 °C for 48 h with stirring. After the reaction was
complete detected by TLC, column chromatography on silica gel
(ethyl acetate/petroleum ether = 1:50 as the eluent) was directly
conducted on the reaction mixture to afford the desired product
5.
CF3
Ph3P=CHCF3
N2
[Fe]
b) N-aza-Wittig pathway:
N
R
CF3CHN2
F3C
N
+
RCHO
N
+
PPh3
F3C
N
PPh3
OPPh3
P-1
c) Control experiments:
CHO
CF3
P-1 (1.8 equiv.)
Fe(TPP)Cl (5 mol%)
toluene, 80 C, 2 h
2a, not observed
1a
N
CF3
CF3
Fe(TPP)Cl (5 mol%)
toluene, 80 C, 2 h
N
3a
2a, not observed
2a, Typical Procedure 1, 50 mg, 92% yield, white solid, E/Z =
2.5:1; this compound was also prepared with
7 mmol of
2-naphthaldehyde, 1 mol % of Fe(TPP)Cl, 1.8 equiv. of PPh3, and
1.5 equiv. of CF3CHN2 (0.2 mol/L in toluene) which was added via
syringe pump in 6 hours, thus giving 1.36 g of 2a in 88% yield. H
NMR (E, 600 MHz, CDCl3) δ 7.82 – 7.80 (m, 4H), 7.50 (dt, J = 7.1,
5.4 Hz, 3H), 7.28 (dd, J = 16.1, 1.8 Hz, 1H), 6.29 (dq, J = 13.1, 6.5
Hz, 1H); 19F NMR (565 MHz, CDCl3) δ –57.27 (Z, d, J = 9.1 Hz, 3F), –
63.10 (E, d, J = 6.7 Hz, 3F); 13C NMR (E, 150 MHz, CDCl3) δ 137.9 (q,
3JF-C = 6.6 Hz), 134.2, 133.4, 131.0, 129.2, 128.9, 128.5, 127.9,
127.3, 126.9, 123.9 (q, 1JF-C = 267.3 Hz), 123.2, 116.1 (q, 2JF-C = 33.6
Hz).
Conclusions
1
In conclusion, by judicious tuning reaction conditions,
phosphine-relayed Wittig olefination and aza-Wittig reaction of
aldehydes with CF3CHN2 have been accomplished. In the presence
of Fe(TPP)Cl, a series of aromatic aldehydes were transformed to
trifluoromethylated alkenes in good yields under mild conditions.
Meanwhile, in the absence of iron catalyst, a wide range of
trifluoromethylated hydrazones were readily afforded via
aza-Wittig process. α-Keto esters have also been successfully
employed in this aza-Wittig reaction to provide corresponding
hydrazones in high yield. Further studies including the substrate
scope extension, synthetic applications together with detailed
mechanistic investigation are underway in our laboratory.
2b, Typical Procedure 1, 50 mg, 81% yield, light yellow oil, E/Z
= 3.5:1, 1H NMR (E, 600 MHz, CDCl3) δ 7.59 (t, J = 7.3 Hz, 5H), 7.49
(d, J = 8.3 Hz, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.17 (dd, J = 16.1, 1.9 Hz,
1H), 6.22 (dq, J = 16.1, 6.5 Hz, 1H); 19F NMR (565 MHz, CDCl3) δ –
57.45 (Z, d, J = 9.1 Hz, 3F), –63.13 (E, dd, J = 6.1, 1.4 Hz, 3F); 13
NMR (E, 150 MHz, CDCl3) δ 142.9, 140.2, 137.4 (q, JF-C = 6.7 Hz),
132.5, 129.1, 128.1, 128.0, 127.7, 127.2, 123.8 (q, 1JF-C = 267.1 Hz),
115.8 (q, 2JF-C = 33.4 Hz).
C
3
Experimental
General information
1H, 13C and 19F NMR spectra were recorded on a Bruker
AVANCE III 600 M or 400 M spectrometer. Chemical shifts were
reported in parts per million (ppm) from the solvent resonance as
the internal standard (CDCl3: δH = 7.26 ppm, δC = 77.16 ppm). High
resolution mass spectrometry (HRMS) spectra were obtained on a
Bruker miorOTOF-QII instrument. IR spectra were recorded on an
AVATAR 360 FT-IR spectrometer. Melting points (MP) were
2c, Typical Procedure 1, 50 mg, 75% yield, light yellow oil, E/Z
= 2.2:1, 1H NMR (E, 600 MHz, CDCl3) δ 7.43 (d, J = 8.4 Hz, 2H), 7.22
(d, J = 8.4 Hz, 2H), 7.00 (dd, J = 16.1, 1.9 Hz, 1H), 6.11 (dq, J = 16.1,
6.4 Hz, 1H); 19F NMR (565 MHz, CDCl3) δ –57.62 (Z, d, J = 9.0 Hz,
3F), –63.47 (E, dd, J = 6.3, 1.6 Hz, 3F); 13C NMR (E, 150 MHz, CDCl3)
δ 136.6 (q, 3JF-C = 6.7 Hz), 132.3, 131.7, 129.1, 124.4, 123.6 (q, 1JF-C
= 267.7 Hz), 116.7 (q, 2JF-C = 33.7 Hz).
measured on a WRS-1A digital melting point apparatus and are
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2d, Typical Procedure 1, 50 mg, 75% yield, light yellow oil, E/Z
= 2.5:1, 1H NMR (E, 600 MHz, CDCl3) δ 7.30 (d, J = 8.6 Hz, 2H), 7.00
(dd, J = 16.1, 1.8 Hz, 1H), 6.82 (d, J = 8.6 Hz, 2H), 5.97 (dq, J = 16.0,
6.6 Hz, 1H), 3.74 (s, 3H); 19F NMR (565 MHz, CDCl3) δ –57.54 (Z, d,
J = 9.3 Hz, 3F), –62.84 (E, d, J = 6.9 Hz, 3F); 13C NMR (E, 150 MHz,
CDCl3) δ 161.2, 137.2 (q, 3JF-C = 6.7 Hz), 129.2, 126.2, 124.1 (q, 1JF-C
= 266.9 Hz), 114.5, 113.5 (q, 2JF-C = 33.4 Hz), 55.5.
3a, Typical Procedure 2, 60 °C, 30 h, 68 mg, 90% yield, white
solid, mp 68 °C; this compound was also prepared with 7 mmol of
2-naphthaldehyde, 1.5 equiv. of PPh3, and 1.5 equiv. of CF3CHN2
(0.2 mol/L in toluene), thus giving 1.43 g of 3a in 82% yield. 1H
NMR (600 MHz, CDCl3) δ 8.52 (s, 1H), 7.95 (s, 1H), 7.90 (d, J = 8.6
Hz, 1H), 7.82 (dd, J = 8.0, 3.9 Hz, 1H), 7.75 (dd, J = 17.0, 8.3 Hz, 3H),
7.43 (dt, J = 14.9, 7.0 Hz, 2H); 13C NMR (150 MHz, CDCl3) δ 165.9,
2
2e, Typical Procedure 1, 46 mg, 62% yield, light yellow oil, E/Z
148.6 (q, JF-C = 37 Hz), 135.5, 133.0, 132.6, 130.4, 129.0, 129.0,
= 5:1, 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 7.9 Hz, 3H), 7.19 (dd, 128.3, 128.1, 127.0, 123.5, 119.9 (q, JF-C = 271 Hz); 19F NMR (565
1
J = 30.9, 11.9 Hz, 4H), 6.18 (dq, J = 13.1, 6.5 Hz, 1H), 2.41 (s, 4H).;
19F NMR (377 MHz, CDCl3) δ -57.53 (d, J = 9.2 Hz), -63.11 (d, J = 6.3
Hz).; 13C NMR (101 MHz, CDCl3) δ 140.48, 137.76 (q, J = 6.7 Hz),
130.91, 129.83, 129.26, 127.67, 124.0 (q, J = 270 Hz), 29.91.
2f, Typical Procedure 1, reaction was run at rt with 2 mol% of
MHz, CDCl3) δ –68.59 (d, J = 4.0 Hz, 3F); HRMS (ESI) found: m/z
251.0795 [M+H]+; calcd. for C13H9F3N2+H 251.0791; IR (KBr): ν
3467, 1792, 1751, 1604, 1465, 1345, 1208, 1080, 763, 466 cm-1.
3b, Typical Procedure 2, 40 °C, 24 h, 68 mg, 93% yield, light
yellow solid, mp 102 °C; 1H NMR (600 MHz, CDCl3) δ 8.46 (s, 1H),
Fe(TPP)Cl, 50 mg, 90% yield, light yellow oil, E/Z > 20:1, 1H NMR (E, 8.25 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 3.7 Hz,
600 MHz, CDCl3) δ 8.27 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.6 Hz, 2H),
1H); 13C NMR (150 MHz, CDCl3) δ 161.7, 149.9, 148.9 (q, 2JF-C = 39
7.23 (dd, J = 16.2, 1.6 Hz, 1H), 6.37 (dq, J = 16.1, 6.3 Hz, 1H); 19
F
Hz), 138.3, 129.9, 124.3, 119.6 (q, JF-C = 271 Hz); 19F NMR (565
1
NMR (E, 565 MHz, CDCl3) δ –63.98 (d, J = 6.1 Hz, 3F); 13C NMR (E,
MHz, CDCl3) δ –68.95 (d, J = 3.5 Hz, 3F); HRMS (APCI) found: m/z
246.0490 [M+H]+; calcd. for C9H6F3N3O2+H 246.0485; IR (KBr): ν
3111, 2958, 1588, 1532, 1349, 1276, 1187, 1139, 967, 880, 668,
503 cm-1.
3
150 MHz, CDCl3) δ 148.7, 139.6, 135.6 (q, JF-C = 6.7 Hz), 128.4,
124.3, 123.0 (q, 1JF-C = 267.9 Hz), 120.2 (q, 2JF-C = 34.3 Hz).
2g, Typical Procedure 1, reaction was run at rt with 2 mol% of
Fe(TPP)Cl, 50 mg, 80% yield, light yellow oil, E/Z > 20:1,1H NMR (E,
600 MHz, CDCl3) δ 7.70 (d, J = 8.2 Hz, 2H), 7.56 (d, J = 8.1 Hz, 2H),
7.17 (d, J = 16.2 Hz, 1H), 6.32 (dq, J = 16.1, 6.3 Hz, 1H); 19F NMR (E,
565 MHz, CDCl3) δ –63.89 (d, J = 6.7 Hz, 3F); 13C NMR (E, 150 MHz,
CDCl3) δ 137.8, 136.0 (q, 3JF-C = 6.6 Hz), 132.8, 128.2, 123.1 (q, 1JF-C
= 267.9 Hz), 119.6 (q, 2JF-C = 34.2 Hz), 118.3, 113.6.
3c, Typical Procedure 2, 50 °C, 24 h, 68 mg, 85% yield, oil; 1H
NMR (600 MHz, CDCl3) δ 8.53 (s, 1H), 7.93 (d, J = 8.1 Hz, 2H), 7.88
(q, J = 3.9 Hz, 1H), 7.73 (d, J = 8.2 Hz, 2H); 13C NMR (150 MHz,
2
2
CDCl3) δ 163.2, 148.9 (q, JF-C = 37 Hz), 136.0, 133.9 (q, JF-C = 32
Hz), 129.4, 126.0, 123.8 (q, 1JF-C = 270 Hz), 119.7 (q, 1JF-C = 270 Hz);
19F NMR (565 MHz, CDCl3) δ –63.11 (s, 3F), –68.96 (d, J = 4.0 Hz,
3F); HRMS (APCI) found: m/z 269.0516 [M+H]+; calcd. for
2h, Typical Procedure 1, reaction was run at rt with 2 mol% of
Fe(TPP)Cl, 50 mg, 83% yield, light yellow oil, E/Z > 20:1, 1H NMR (E,
600 MHz, CDCl3) δ 7.97 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 8.3 Hz, 2H),
7.10 (dd, J = 16.2, 1.8 Hz, 1H), 6.22 (dq, J = 16.1, 6.4 Hz, 1H), 3.85
C
10H6F6N2+H 269.0508; IR (KBr): ν 2964, 1571, 1325, 1172, 1065,
839, 713, 597 cm-1.
3d, Typical Procedure 2, 50 °C, 24 h, 61 mg, 91% yield, white
solid, mp 100 °C; 1H NMR (600 MHz, CDCl3) δ 8.48 (s, 1H), 7.92 (d,
J = 8.1 Hz, 2H), 7.85 (dd, J = 7.4, 3.6 Hz, 1H), 7.75 (d, J = 8.1 Hz, 2H);
(s, 3H); 19F NMR (E, 565 MHz, CDCl3) δ –63.70 (dd, J = 6.2, 1.6 Hz,
3
3F); 13C NMR (E, 150 MHz, CDCl3) δ 166.5, 137.7, 136.7 (q, JF-C
=
1
2
6.7 Hz), 131.5, 130.3, 127.6, 123.4 (q, JF-C = 267.4 Hz), 118.3 (q,
13C NMR (150 MHz, CDCl3) δ 162.3, 148.8 (q, JF-C = 37 Hz), 136.6,
2JF-C = 33.9 Hz), 52.4.
132.7, 129.4, 119.5 (q, JF-C = 271 Hz), 118.2, 115.5; 19F NMR (565
1
2i, Typical Procedure 1, 50 mg, 80% yield, light yellow oil, E/Z
= 2.7:1, 1H NMR (E, 600 MHz, CDCl3) δ 7.43 (s, 1H), 7.35 (d, J = 5.7
Hz, 1H), 7.18 (d, J = 7.7 Hz, 1H), 6.96 (d, J = 15.7 Hz, 1H), 6.11 (dq,
J = 22.3, 6.2 Hz, 1H); 19F NMR (565 MHz, CDCl3) δ –57.70 (Z, d, J =
8.8 Hz, 3F), –63.69 (E, d, J = 5.4 Hz, 3F); 13C NMR (E, 150 MHz,
CDCl3) δ 135.5 (q, 3JF-C = 6.7 Hz), 134.2, 133.5, 131.1, 130.5, 129.4,
126.7, 123.3 (q, 1JF-C = 267.7 Hz), 117.9 (q, 2JF-C = 34.0 Hz).
2j, Typical Procedure 1, 50 mg, 86% yield, light yellow oil, E/Z
= 3.5:1, 1H NMR (E, 600 MHz, CDCl3) δ 8.25 (s, 1H), 8.16 (d, J = 8.2
Hz, 1H), 7.70 (d, J = 7.7 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.15 (d, J =
16.2 Hz, 1H), 6.29 (dq, J = 16.1, 6.3 Hz, 1H); 19F NMR (565 MHz,
CDCl3) δ –57.75 (Z, d, J = 8.8 Hz, 3F), –63.88 (E, dd, J = 6.1, 1.4 Hz,
3F); 13C NMR (E, 150 MHz, CDCl3) δ 148.82, 135.5 (q, 3JF-C = 6.7 Hz),
135.25, 133.36, 130.21, 124.62, 123.1 (q, 1JF-C = 267.7 Hz), 122.25,
119.2 (q, 2JF-C = 34.2 Hz).
MHz, CDCl3) δ –68.92 (d, J = 3.7 Hz, 3F); HRMS (APCI) found: m/z
226.0695 [M+H]+; calcd. for C10H6F3N3+H 226.0587; IR (KBr): ν
2960, 2857, 1593, 1351, 1271, 1139, 872, 829, 707, 483 cm-1.
3e, Typical Procedure 2, 50 °C, 24 h, 74 mg, 95% yield, white
solid, mp 90 °C; 1H NMR (600 MHz, CDCl3) δ 8.50 (s, 1H), 8.10 (d, J
= 8.2 Hz, 2H), 7.86 (t, J = 6.7 Hz, 3H), 3.93 (s, 3H); 13C NMR (150
2
MHz, CDCl3) δ 166.4, 163.8, 148.8 (q, JF-C = 37 Hz), 136.6, 134.4,
1
130.2, 129.1, 119.8 (q, JF-C = 271 Hz), 52.6; 19F NMR (565 MHz,
CDCl3) δ –68.90 (d, J = 3.9 Hz, 3F); HRMS (APCI) found: m/z
259.0695 [M+H]+; calcd. for C11H9F3N2O2+H 259.0689; IR (KBr): ν
2923, 1597, 1371, 1278, 1137, 991, 867, 707, 554 cm-1.
3f, Typical Procedure 2, 60 °C, 48 h, 33 mg, 51% yield, light
yellow solid, mp 100 °C; 1H NMR (600 MHz, CDCl3) δ 8.54 (s, 1H),
7.91 (q, J = 4.1 Hz, 1H), 7.72 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 7.9 Hz,
2H), 2.43 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 166.2, 148.4 (q, 2JF-C
= 37 Hz), 136.5, 130.1, 129.9, 129.4, 119.9 (q, 1JF-C = 271 Hz), 21.9;
19F NMR (565 MHz, CDCl3) δ –69.69 (d, J = 4.1 Hz, 3F); HRMS (APCI)
found: m/z 215.0797 [M+H]+; calcd. for C10H9F3N2+H 215.0791; IR
(KBr): ν 2924, 1461, 1375, 1268, 1156, 815, 509 cm-1.
2k, Typical Procedure 1, 50 mg, 86% yield, light yellow oil, E/Z
= 2.3:1, 1H NMR (E, 600 MHz, CDCl3) δ 7.19 (t, J = 7.9 Hz, 1H), 7.01
(dd, J = 16.1, 2.0 Hz, 1H), 6.93 (d, J = 7.6 Hz, 1H), 6.86 (s, 1H), 6.82
(dd, J = 8.2, 2.3 Hz, 1H), 6.09 (dq, J = 16.1, 6.5 Hz, 1H), 3.71 (s, 3H);
19F NMR (565 MHz, CDCl3) δ –57.40 (Z, d, J = 8.9 Hz, 3F), –63.32 (E,
dd, J = 6.9, 1.7 Hz, 3F); 13C NMR (E, 150 MHz, CDCl3) δ 160.1, 137.8
3g, Typical Procedure 2, 50 °C, 24 h, 68 mg, 93% yield, light
yellow solid, mp 62 °C; 1H NMR (600 MHz, CDCl3) δ 8.68 (s, 1H),
8.57 (s, 1H), 8.37 (d, J = 8.1 Hz, 1H), 8.14 (d, J = 7.7 Hz, 1H), 7.90 (d,
J = 3.9 Hz, 1H), 7.69 (t, J = 7.9 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ
3
1
(q, JF-C = 6.6 Hz), 134.9, 130.1, 123.8 (q, JF-C = 267.3 Hz), 120.2,
116.2 (q, 2JF-C = 33.4 Hz), 115.8, 112.9, 55.4.
2
2l, Typical Procedure 1, 50 mg, 78% yield, light yellow oil, E/Z
= 4.3:1, 1H NMR (E, 600 MHz, CDCl3) δ 7.24 (q, J = 7.3 Hz, 5H), 7.15
(d, J = 7.9 Hz, 5H), 7.08 (t, J = 8.1 Hz, 1H), 6.93 (d, J = 16.1 Hz, 1H),
6.73 (d, J = 7.1 Hz, 1H), 6.68 – 6.65 (m, 2H), 6.00 – 5.90 (m, 1H),
4.58 (s, 4H); 19F NMR (565 MHz, CDCl3) δ –57.30 (Z, d, J = 9.0 Hz,
3F), –63.10 (E, d, J = 6.3 Hz, 3F); 13C NMR (E, 150 MHz, CDCl3) δ
162.0, 149.1 (q, JF-C = 37 Hz), 148.7, 134.6, 134.4, 130.2, 126.6,
122.2, 119.6 (q, 1JF-C = 271 Hz); 19F NMR (565 MHz, CDCl3) δ –68.91
(d, J = 3.5 Hz, 3F); HRMS (APCI) found: m/z 246.0490 [M+H]+;
calcd. for C9H6F3N3O2+H 246.0485; IR (KBr): ν 2923, 1534, 1376,
1272, 1173, 991, 880, 735, 527 cm-1.
1
3h, Typical Procedure 2,60 °C, 48 h, 63 mg, 91% yield, oil; H
3
149.7, 138.6 (q, JF-C = 6.6 Hz), 138.2, 134.5, 129.9, 128.9, 127.2,
NMR (600 MHz, CDCl3) δ 8.39 (s, 1H), 7.79 (q, J = 4.0 Hz, 1H), 7.30
(s, 1H), 7.27 (d, J = 7.9 Hz, 1H), 7.23 (d, J = 7.5 Hz, 1H), 6.97 (dd, J =
8.0, 2.4 Hz, 1H), 3.76 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 164.5,
1
2
126.7, 123.8 (q, JF-C = 267.0 Hz), 115.8, 115.5 (q, JF-C = 33.6 Hz),
114.3, 111.8, 54.4.
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2
159.1, 147.5 (q, JF-C = 37 Hz), 133.0, 129.1, 121.7, 118.9 (q, 1JF-C
=
J = 3.9 Hz, 6F); HRMS (ESI) found: m/z 641.1599 [M+Na]+; calcd.
271 Hz), 118.3, 111.4, 54.4; 19F NMR (565 MHz, CDCl3) δ –68.78 (d, for C30H24F6N4O4+Na 641.1594; IR (KBr): ν 2927, 1619, 1457, 1351,
J = 4.0 Hz, 3F); HRMS (APCI) found: m/z 231.0748 [M+H]+; calcd.
for C10H9F3N2O+H 231.0740; IR (KBr): ν 2961, 1603, 1463, 1370,
1267, 1161, 1044, 879, 792, 699 cm-1.
1275, 1156, 969, 921, 753 cm-1.
3p, Typical Procedure 2, 50 °C, 48 h, 31 mg, 50% yield, oil; 1H
NMR (600 MHz, CDCl3) δ 7.78 (d, J = 5.6 Hz, 1H), 7.71 (dd, J = 7.8,
3.8 Hz, 1H), 2.37 (d, J = 3.8 Hz, 1H), 1.86 (d, J = 10.0 Hz, 2H), 1.81 –
1.77 (m, 2H), 1.70 (d, J = 12.6 Hz, 1H), 1.32 (dd, J = 20.2, 11.3 Hz,
3i, Typical Procedure 2, 60 °C, 48 h, 80 mg, 91% yield, oil; 1H
NMR (600 MHz, CDCl3) δ 8.34 (s, 1H), 7.72 (d, J = 4.0 Hz, 1H), 7.40
– 7.35 (m, 2H), 7.29 (t, J = 7.9 Hz, 1H), 7.25 (t, J = 7.1 Hz, 2H), 7.03
(t, J = 7.9 Hz, 2H), 6.92 (d, J = 7.8 Hz, 2H); 13C NMR (150 MHz,
2
5H); 13C NMR (150 MHz, CDCl3) δ 173.4, 147.7 (q, JF-C = 37 Hz),
119.7 (q, 1JF-C = 271 Hz), 41.2, 29.5, 26.0, 25.4; 19F NMR (565 MHz,
CDCl3) δ –69.05 (d, J = 3.9 Hz, 3F); HRMS (APCI) found: m/z
207.1114 [M+H]+; calcd. for C9H13F3N2+H 207.1104; IR (KBr): ν
2
CDCl3) δ 164.7, 158.1, 156.6, 148.6 (q, JF-C = 37 Hz), 134.5, 130.4,
1
130.1, 124.4, 124.0, 122.7, 119.8 (q, JF-C = 270 Hz), 119.4, 118.3;
19F NMR (565 MHz, CDCl3) δ –68.75 (d, J = 3.6 Hz, 3F); HRMS (APCI) 2960, 2927, 1457, 1261, 1097, 1023, 802, 699 cm-1.
found: m/z 293.0902 [M+H]+; calcd. for C15H11F3N2O+H 293.0896;
IR (KBr): ν 2961, 1573, 1488, 1369, 1258, 1168, 882, 800, 690
cm-1.
3q, Typical Procedure 2, 60 °C, 48 h, 46 mg, 62% yield, oil; 1H
NMR (600 MHz, CDCl3) δ 7.93 (t, J = 5.4 Hz, 1H), 7.72 (d, J = 3.9 Hz,
1H), 2.41 (d, J = 6.5 Hz, 2H), 1.60 – 1.57 (m, 2H), 1.26 (s, 11H),
0.87 (t, J = 6.9 Hz, 4H); 13C NMR (150 MHz, CDCl3) δ 170.7, 147.9
3j, Typical Procedure 2, 50 °C, 24 h, 57 mg, 78% yield, light
yellow solid, mp 162 °C; 1H NMR (600 MHz, CDCl3) δ 8.91 (s, 1H),
8.12 (dd, J = 12.5, 8.1 Hz, 2H), 7.82 (d, J = 3.8 Hz, 1H), 7.75 (t, J =
7.5 Hz, 1H), 7.68 (t, J = 7.7 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ
2
1
(q, JF-C = 37 Hz), 110.7 (q, JF-C = 271 Hz), 33.0, 32.0, 29.6, 29.5,
29.4, 29.3, 25.9, 22.8, 14.2; 19F NMR (565 MHz, CDCl3) δ –69.07 (d,
J = 3.6 Hz, 3F); HRMS (APCI) found: m/z 251.1757 [M+H]+; calcd.
for C12H21F3N2+H 251.1730; IR (KBr): ν 2928, 2857, 1463, 1266,
1164, 1022, 804, 701 cm-1.
2
159.4, 149.0, 148.3 (q, JF-C = 37 Hz), 133.9, 132.3, 129.8, 127.8,
125.0, 119.5 (q, 1JF-C = 271 Hz); 19F NMR (565 MHz, CDCl3) δ –68.95
(d, J = 3.7 Hz, 3F); HRMS (APCI) found: m/z 246.0489 [M+H]+;
calcd. for C9H6F3N3O2+H 246.0485; IR (KBr): ν 3082, 1528, 1347,
1276, 1141, 849, 742, 645 cm-1.
3r, Typical Procedure 2,50 °C, 48 h, 59 mg, 80% yield, oil; 1H
NMR (600 MHz, CDCl3) δ 8.53 (dd, J = 32.9, 10.3 Hz, 1H), 7.84 –
7.74 (m, 1H), 6.23 – 6.10 (m, 1H), 5.07 (d, J = 6.2 Hz, 1H), 2.37 (t, J
= 7.5 Hz, 1H), 2.27 – 2.23 (m, 1H), 2.22 – 2.15 (m, 2H), 1.98 (d, J =
3.5 Hz, 3H), 1.67 (d, J = 14.0 Hz, 3H), 1.59 (d, J = 10.7 Hz, 3H); 13C
NMR (150 MHz, CDCl3) δ 164.4, 164.1, 157.5, 157.5, 146.9 (q, 2JF-C
3k, Typical Procedure 2, 60 °C, 48 h, 47 mg, 73% yield, white
solid, mp 70 °C; 1H NMR (600 MHz, CDCl3) δ 10.91 (s, 1H), 8.68 (s,
1H), 7.85 (s, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.27 (d, J = 7.5 Hz, 1H),
6.95 (d, J = 8.3 Hz, 1H), 6.89 (t, J = 7.1 Hz, 1H); 13C NMR (150 MHz,
CDCl3) δ 170.8, 160.5, 149.5 (q, 2JF-C = 37 Hz), 135.0, 133.6, 120.1,
119.7 (q, 1JF-C = 271 Hz), 117.5, 116.5; 19F NMR (565 MHz, CDCl3) δ
= 37 Hz), 132.4, 131.9, 121.9, 121.7, 121.5, 120.5, 119.0 (q, 1JF-C
=
271 Hz), 39.8, 32.3, 26.0, 25.2, 24.8, 24.7, 24.1, 17.0, 16.8, 16.8;
19F NMR (565 MHz, CDCl3) δ –68.69 to –68.70 (m, 3F); HRMS (APCI)
–68.64 (d, J = 3.8 Hz, 3F); HRMS (ESI) found: m/z 217.0588 [M+H]+; found: m/z 247.1425 [M+H]+; calcd. for C12H17F3N2+H 247.1417; IR
calcd. for C9H7F3N2O+H 217.0583; IR (KBr): ν 3087, 2963, 1620,
(KBr): ν 2963, 2926, 1651, 1450, 1264, 1166, 1099, 1022, 803, 705
1561, 1489, 1379, 1264, 1133, 1015, 879, 804, 712 cm-1.
cm-1.
3l, Typical Procedure 2, 40 °C, 48 h, 47 mg, 82% yield, oil; 1H
NMR (600 MHz, CDCl3) δ 8.44 (s, 1H), 7.95 (q, J = 4.1 Hz, 1H), 7.67
(s, 1H), 7.04 (d, J = 3.4 Hz, 1H), 6.60 (dd, J = 3.3, 1.6 Hz, 1H); 13C
5a, Typical Procedure 3, 74 mg, 91% yield, oil; 1H NMR (600
MHz, CDCl3) δ 7.72 (d, J = 7.9 Hz, 2H), 7.43 (t, J = 7.4 Hz, 1H), 7.36
(t, J = 7.7 Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H);
2
2
NMR (150 MHz, CDCl3) δ 154.9, 149.4 (q, JF-C = 37 Hz), 148.3,
13C NMR (150 MHz, CDCl3) δ 163.1, 163.0, 147.1 (q, JF-C = 37 Hz),
1
147.3, 119.8 (q, JF-C = 270 Hz), 119.8, 112.9; 19F NMR (565 MHz,
131.8, 129.4, 128.1, 127.2, 118.5 (q, 1JF-C = 271 Hz), 61.2, 13.2;19
F
CDCl3) δ –68.68 (d, J = 4.1 Hz, 3F); HRMS (APCI) found: m/z
191.0435 [M+H]+; calcd. for C7H5F3N2O+H 191.0427; IR (KBr): ν
2925, 1464, 1262, 1097, 1022, 803, 671 cm-1.
NMR (565 MHz, CDCl3) δ –68.88 (d, J = 3.7 Hz, 3F); HRMS (APCI)
found: m/z 5273.0857 [M+H]+; calcd. for C12H11F3N2O2+H
273.0845; IR (KBr): ν 2965, 1741, 1567, 1449, 1352, 1264, 1143,
1020, 800, 691 cm-1.
3m, Typical Procedure 2, 50 °C, 48 h, 45 mg, 75% yield, oil;1H
NMR (600 MHz, CDCl3) δ 8.71 (d, J = 4.1 Hz, 1H), 8.47 (s, 1H), 8.01
(d, J = 7.8 Hz, 1H), 7.83 (d, J = 3.9 Hz, 1H), 7.80 (t, J = 7.7 Hz, 1H),
7.39 (dd, J = 7.4, 4.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 163.4,
151.7, 150.3, 148.1 (q, 2JF-C = 38 Hz), 136.9, 130.0, 123.0, 119.6 (q,
1JF-C = 271 Hz); 19F NMR (565 MHz, CDCl3) δ –68.95 (d, J = 4.0 Hz,
3F); HRMS (APCI) found: m/z 202.0595 [M+H]+; calcd. for
C8H6F3N3+H 202.0587; IR (KBr): ν 2925, 1587, 1467, 1265, 1153,
803, 692 cm-1.
5b, Typical Procedure 3, 65 mg, 76% yield, oil; 1H NMR (400
MHz, CDCl3) δ 7.73 (q, J = 3.9 Hz, 1H), 7.62 (d, J = 8.1 Hz, 2H), 7.17
(d, J = 7.9 Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H), 2.31 (s, 3H), 1.28 (t, J =
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.4, 164.3, 147.9 (q,
1
2JF-C = 37 Hz), 143.8, 129.9, 128.3, 127.8, 119.6 (q, JF-C = 271 Hz),
62.1, 21.7, 14.2; 19F NMR (376 MHz, CDCl3) δ –68.81 (d, J = 3.9 Hz,
3F); HRMS (ESI) found: m/z 287.1004 [M+H]+; calcd. for
C
13H13F3N2O2+H 287.1002; IR (KBr): ν 2987, 1741, 1589, 1352,
3n, Typical Procedure 2, 60 °C, 48 h, 52 mg, 53% yield, yellow
solid, mp 98 °C; 1H NMR (600 MHz, CDCl3) δ 8.72 (s, 1H), 8.27 (d, J
= 6.0 Hz, 1H), 7.92 (d, J = 4.2 Hz, 1H), 7.45 (s, 1H), 7.22 (t, J = 7.9
Hz, 6H), 7.05 (d, J = 6.8 Hz, 2H), 5.22 (s, 2H); 13C NMR (150 MHz,
CDCl3) δ 162.5, 146.8 (q, 2JF-C = 36 Hz), 137.8, 135.9, 135.8, 129.2,
1275, 1170, 1038, 821, 742, 498 cm-1.
5c, Typical Procedure 3, 80 mg, 87% yield, oil; 1H NMR (600
MHz, CDCl3) δ 7.73 (d, J = 3.8 Hz, 1H), 7.67 (d, J = 8.5 Hz, 2H), 7.36
(d, J = 8.5 Hz, 2H), 4.37 (q, J = 7.1 Hz, 2H), 1.30 (t, J = 7.1 Hz, 3H);
13C NMR (150 MHz, CDCl3) δ 163.7, 162.8, 148.3 (q, JF-C = 38 Hz),
2
1
128.4, 127.1, 125.9, 124.1, 122.9, 122.5, 120.4 (q, JF-C = 270 Hz),
139.2, 129.5, 129.5, 128.9, 119.5 (q, 1JF-C = 271 Hz), 62.5, 14.2;19
F
111.5, 110.5, 50.8; 19F NMR (565 MHz, CDCl3) δ –68.03 (d, J = 4.1
NMR (565 MHz, CDCl3) δ –68.88 (d, J = 3.2 Hz, 3F); HRMS (ESI)
found: m/z 329.0276 [M+Na]+; calcd. for C12H10ClF3N2O2+Na
329.0275; IR (KBr): ν 2987, 1741, 1590, 1352, 1274, 1171, 1035,
834, 690, 501 cm-1.
Hz, 3F); HRMS (ESI) found: m/z 330.1218 [M+H]+; calcd. for
C
18H14F3N3+H 330.1213; IR (KBr): ν 3107, 2930, 1569, 1465, 1343,
1264, 1168, 995, 881, 744, 698 cm-1; CCDC 993954.
3o, Typical Procedure 2,50 °C, 48 h, 101 mg, 82% yield, light
yellow solid, mp 90 °C; 1H NMR (600 MHz, CDCl3) δ 8.97 (s, 2H),
8.70 (s, 2H), 7.95 – 7.88 (m, 4H), 7.38 (t, J = 6.9 Hz, 2H), 7.27 (t, J =
7.0 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 4.54 (s, 4H), 2.76 (s, 6H).; 13C
5d, Typical Procedure 3, 81 mg, 90% yield, oil; 1H NMR (600
MHz, CDCl3) δ 7.75 (d, J = 3.9 Hz, 1H), 7.33 (s, 1H), 7.28 (t, J = 7.9
Hz, 1H), 7.23 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 10.0 Hz, 1H), 4.36 (q, J
= 7.1 Hz, 2H), 3.76 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (150
2
2
NMR (150 MHz, CDCl3) δ 162.5, 153.1, 148.4 (q, JF-C = 37 Hz),
MHz, CDCl3) δ 164.0, 163.8, 160.0, 148.1 (q, JF-C = 37 Hz), 131.7,
1
135.9, 130.4, 130.0, 129.6, 128.8, 126.1, 126.1, 125.8, 119.8 (q,
1JF-C = 270 Hz), 100.3, 57.0; 19F NMR (565 MHz, CDCl3) δ –68.64 (d,
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130.1, 121.2, 119.4 (q, JF-C = 271 Hz), 119.3, 112.2, 62.3, 55.5,
14.2; 19F NMR (565 MHz, CDCl3) δ –68.85 (d, J = 3.8 Hz, 3F); HRMS

(ESI) found: m/z 325.0779 [M+Na]+; calcd. for C13H13F3N2O3+Na
325.0770; IR (KBr): ν 2985, 2841, 1740, 1573, 1464, 1352, 1252,
1171, 1033, 894, 711 cm-1.
Acknowledgement
This work was supported financially by the National Natural
Science Foundation of China (No. 21225208, 21472137, and
21532008), the National Basic Research Program of China (973
Program: 2014CB745100 and 2015CB856500), and Tianjin
Municipal Science & Technology Commission (14JCQNJC06200).
5e, Typical Procedure 3, 84 mg, 86% yield, oil; 1H NMR (600
MHz, CDCl3) δ 8.03 (s, 1H), 7.93 (d, J = 8.6 Hz, 1H), 7.78 (d, J = 8.0
Hz, 3H), 7.74 (d, J = 8.2 Hz, 1H), 7.47 (t, J = 7.4 Hz, 1H), 7.44 – 7.41
(m, 1H), 4.42 (dd, J = 14.2, 7.1 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H); 13
NMR (150 MHz, CDCl3) δ 164.4, 164.3, 148.2 (q, JF-C = 37 Hz),
C
2
References
135.4, 132.8, 130.6, 129.3, 129.1, 128.6, 128.0, 127.9, 127.1,
1
123.2, 119.6 (q, JF-C = 271 Hz), 62.4, 14.2; 19F NMR (565 MHz,
[1] (a) Ojima, I. Fluorine in Medicinal Chemistry and Chemical Biology,
Wiley-Blackwell Publishing, Oxford, 2009; (b) Gouverneur, V.; Müller,
K. Fluorine in Pharmaceutical and Medicinal Chemistry: From
Biophysical Aspects to Clinical Applications, Imperial College Press,
London, 2012.
[2] (a) 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; (b)
Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev.
2008, 37, 320; (c) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, J.
D.; Meanwell, N. A. J. Med. Chem. 2015, 58, 8315; (d) Muller, K.;
Faeh, C.; Diederich, F. Science 2007, 317, 1881; (e) Jeschke, P. Pest
Manag Sci 2017, 73, 1053; (f) Jeschke, P. Pest Manag Sci 2010, 66, 10;
(g) Fujiwara, T.; O’Hagan, D. J. Fluorine Chem. 2014, 167, 16; (h)
Berger, R.; Resnati, G.; Metrangolo, P.; Weberd, E. and Hulliger, J.
Chem. Soc. Rev. 2011, 40, 3496; (i) Zhang, J.; Jin, C.-F.; Zhang, Y.-J.
Chin. J. Org. Chem. 2014, 34, 662.
[3] For selected reviews, see: (a) Ma, J.-A.; Cahard, D. Chem. Rev. 2008,
108, PR1; (b) Tomashenko, O. A. and Grushin, V. V. Chem. Rev. 2011,
111, 4475; (c) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473,
470; (d) Nie, J.; Guo, H.-C.; Cahard, D. and Ma, J.-A. Chem. Rev. 2011,
111, 455; (e) Alonso, C.; de Marigorta, E. M.; Rubiales, G. and
Palacios, F. Chem. Rev. 2015, 115, 1847; (f) Schlosser, M. Angew.
Chem. Int. Ed. 2006, 45, 5432; (g) Shainyan, B. A. and Tolstikova, L. L.
Chem. Rev. 2013, 113, 699; (h) Valentine, G.; Nenajdenko, V. G.;
Muzalevskiy, V. M. and Shastin, A. V. Chem. Rev. 2015, 115, 973; (i)
Liu, X.; Xu, C.; Wang, M. and Liu, Q. Chem. Rev. 2015, 115, 683; (j)
Pan, F.; Shi, Z.-J. Acta Chimica. Sinica 2012, 70, 1679; (k) Qing, F.-L.
Chin. J. Org. Chem. 2012, 32, 815.
[4] For recent reviews, see: (a) Grygorenko, O. O.; Artamonov, O. S.;
Komarov, I. V.; Mykhailiuk, P. K. Tetrahedron 2011, 67, 803; (b) Qiu,
D.; Qiu, M.; Ma, R.; Zhang, Y.; Wang, J. Acta Chim. Sinica 2016, 74,
472; (c) Mertens, L.; Koenigs, R. M. Org. Biomol. Chem. 2016, 14,
10547.
CDCl3) δ –68.85 (d, J = 3.8 Hz, 3F); HRMS (ESI) found: m/z
345.0824 [M+Na]+; calcd. for C16H13F3N2O2+Na 345.0821; IR (KBr):
ν 3061, 2985, 1740, 1585, 1470, 1351, 1272, 1170, 1031, 802, 752,
475 cm-1.
To a 25 mL Schlenk tube was PPh3 (0.75 mmol, 1.5 equiv.)
under Ar atmosphere, then CF3CHN2 (0.45 mmol, 1.5 equiv.) was
added and the mixture was stirred at rt for
5 minutes.
Subsequently benzaldehyde (0.5 mmol, 1.0 equiv.) was added to
the reaction system in one pot and the reaction was performed at
50 °C for 48 h with stirring. After the reaction was complete
detected by TLC, column chromatography on silica gel (ethyl
acetate/ petroleum ether = 1:50 as the eluent) was directly
conducted on the reaction mixture to afford the desired product.
The product from the previous step was then treated with LiAlH4
at 0 °C for 12 h. After the reaction was completed, the mixture
was quenched with aqueous ammonium chloride solution and
extracted with ethyl acetate. The combined organic layers were
washed with brine and dried over MgSO4. Evaporation of the
solvent and purification of the crude mixture by column
chromatography. 6a, 44 mg, 72% yield, oil; 1H NMR (600 MHz,
CDCl3) δ 7.53 (s, 1H), 7.44 (d, J = 7.4 Hz, 2H), 7.24 (t, J = 7.4 Hz, 2H),
7.19 (t, J = 7.2 Hz, 1H), 5.47 (s, 1H), 3.77 – 3.69 (m, 2H); 13C NMR
(150 MHz, CDCl3) δ 140.3, 134.9, 128.9, 128.7, 126.4, 124.8 (q,
1JF-C = 279 Hz), 51.6 (q, 2JF-C = 32 Hz); 19F NMR (565 MHz, CDCl3) δ –
71.79 (t, J = 9.0 Hz, 3F); HRMS (APCI) found: m/z 203.0798 [M+H]+;
calcd. for C9H9F3N2+H 203.0791.
To a 25 mL Schlenk tube was PPh3 (0.75 mmol, 1.5 equiv.)
under Ar atmosphere, then CF3CHN2 (0.45 mmol, 1.5 equiv.) was
added and the mixture was stirred at rt for
5 minutes.
Subsequently benzaldehyde (0.5 mmol, 1.0 equiv.) was added to
the reaction system in one pot and the reaction was performed at
50 °C for 48 h with stirring. After the reaction was complete
detected by TLC, column chromatography on silica gel (ethyl
acetate/ petroleum ether = 1:50 as the eluent) was directly
conducted on the reaction mixture to afford the desired product.
The product from the previous step was transferred to a 50 mL
Schlenk tube, Pd/C (40 mg) and ethyl acetate (10 mL) were added
under Ar atmosphere, then the system was replaced with a
hydrogen atmosphere and maintained at a pressure of 1 atm, and
the reaction was performed at room temperature for 24 h. After
the reaction was complete, the system was suction-filtered, and
the filtrate is concentrated and purified by silica gel column
chromatography (petroleum ether/ethyl acetate = 50:1) to obtain
the product 6b. 60 mg, 60% yield; 1H NMR (600 MHz, CDCl3) δ
7.39 (t, J = 7.2 Hz, 2H), 7.35 (d, J = 7.2 Hz, 1H), 7.32 (d, J = 7.2 Hz,
2H), 6.64 (dd, J = 7.6, 3.7 Hz, 1H), 6.31 (s, 1H), 4.31 (d, J = 4.0 Hz,
2H); 13C NMR (150 MHz, CDCl3) δ 135.1, 129.2, 128.4, 128.2, 121.7
(q, 1JF-C = 267 Hz), 119.4 (q, 2JF-C = 38 Hz), 51.6; 19F NMR (565 MHz,
CDCl3) δ –65.02 (d, J = 3.4 Hz, 3F); HRMS (ESI) found: m/z
225.0618 [M+Na]+; calcd. for C9H9F3N2+Na 225.0610.
[5] (a) Morandi, B.; Carreira, E. M. Angew. Chem. Int. Ed. 2010, 49, 938;
(b) Morandi, B.; Mariampillai, B.; Carreira, E. M. Angew. Chem. Int. Ed.
2011, 50, 1101; (c) Morandi, B.; Cheang, J.; Carreira, E. M. Org. Lett.
2011, 13, 3080; (d) Morandi, B.; Carreira, E. M. Angew. Chem. Int. Ed.
2010, 49, 4294; (e) Morandi, B.; Carreira, E. M. Org. Lett. 2011, 13,
5984; (f) Künzi, S. A.; Morandi, B.; Carreira, E. M. Org. Lett. 2012, 14,
1900.
[6] Morandi, B.; Carreira, E. M. Angew. Chem. Int. Ed. 2011, 50, 9085.
[7] Pieber, B. and Kappe, C. O. Org. Lett. 2016, 18, 1076.
[8] (a) Liu, C.-B.; Meng, W.; Li, F.; Wang, S.; Nie, J.; Ma, J.-A. Angew.
Chem. Int. Ed. 2012, 51, 6227; (b) Li, F.; Nie. J.; Sun, L.; Zheng, Y.; Ma,
J.-A. Angew. Chem. Int. Ed. 2013, 52, 6255; (c) Zhang, F.-G.; Wei, Y.;
Yi, Y.-P.; Nie, J.; Ma, J.-A. Org. Lett. 2014, 16, 3122; (d) Chen, Z.;
Zheng, Y.; Ma, J.-A. Angew. Chem. Int. Ed. 2017, 56, 4569; (e) Qin, S.;
Zheng, Y.; Zhang, F.-G.; Ma, J.-A. Org. Lett. 2017, 19, 3406; (f) Guo, R.;
Zheng, Y.; Ma, J.-A. Org. Lett. 2016, 18, 4170.
[9] (a) Hu, Y.; Zhang, X. P. Top. Curr. Chem. 2012, 327, 147; for selected
examples of olefination with diazoesters, see: (b) Mirafzal, G. A.;
Cheng, G. and Woo, L. K. J. Am. Chem. Soc. 2002, 124, 176; (c) Santos,
A. M.; Romão, C. C. and Kühn, F. E. J. Am. Chem. Soc. 2003, 125, 2414;
(d) Chen, Y.; Huang, L. Ranade, M. A. and Zhang, X. P. J. Org. Chem.
2003, 68, 3714; (e) Aggarwal, V. K.; Fulton, J. R.; Sheldon, C. G.; de
Vicente, J. J. Am. Chem. Soc. 2003, 125, 6034; (f) Murelli, R. P.;
Snapper, M. L. Org. Lett. 2007, 9, 1749; (g) Lu, X.; Fang, H.; Ni, Z. J.
Organometallic Chem. 1989, 373, 77; (h) Li, C.-Y.; Wang, X.-B.; Sun,
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
This article is protected by copyright. All rights reserved.

X.-L.; Tang, Y.; Zeng, J.-C.; Xu, Z.-H.; Zhou, Y.-G.; Dai, L.-X. J. Am. Chem.
Soc. 2007, 129, 1494.
Stegbauer, L.; Savasci, G.; Podjaski, F.; Ochsenfeld, C.; Lotsch, B. V.
Nat. Commun. 2015, 6, 8508.
[10] For selected examples of synthesis of trifluoromethylated olefins: (a)
Kobayashi, T.; Eda, T.; Tamura, O. and Ishibashi, H. J. Org. Chem. 2002,
67, 3156; (b) Patra, T.; Deb, A.; Manna, S.; Sharma, U. and Maiti, D.
Eur. J. Org. Chem. 2013, 5247; (c) Xu, P.; Abdukader, A.; Hu, K.; Cheng,
Y. and Zhu, C. Chem. Commun. 2014, 50, 2308; (d) Parsons, A. T.;
Senecal, T. D. and Buchwald, S. L. Angew. Chem. Int. Ed. 2012, 51,
2947; (e) Kowalskia, M. K.; Obijalskaa, E.; Mlostońa, G.; Heimgartnerb,
H. J. Fluorine Chem. 2017, 200, 102; (f) Gou, B.-Q; Yang, C.; Zhang, L.;
Xia, W.-J. Acta Chimica. Sinica 2017, 75, 66; (g) Wang, Q.; Gao, K.-C.;
Zou, J.-P.; Zeng, R.-S. Chin. J. Org. Chem. 2018, 38, 863.
[11] Byrne, P. A. and Gilheany, D. G. Chem. Soc. Rev. 2013, 42, 6670.
[12] (a) Safari, J. and Gandomi-Ravandi, S. RSC Adv. 2014, 4, 46224; (b)
Xiao, Q.; Zhang, Y. and Wang, J. Acc. Chem. Res. 2013, 46, 236; (c)
Kobayashi, S.; Mori, Y.; Fossey, J. S. and Salter, M. M. Chem. Rev.
2011, 111, 2626; (d) Bauer, J. O.; Leitus, G.; Ben-David, Y. and
Milstein, D. ACS Catal. 2016, 6, 8415; (e) Das, U. K.; Ben-David, Y.;
Diskin-Posner, Y. and Milstein, D. Angew. Chem. Int. Ed. 2018, 57,
2179.
[14] For the reaction of CF3CHN2 with phosphines, see our recent paper:
Zhang, F.-G.; Zeng, J.-L.; Tian, Y.-Q.; Zheng, Y.; Cahard, D.; Ma, J.-A.
Chem. Eur. J. 2018, 10.1002/chem.201801171.
[15] CCDC993954 (3n) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[16] (a) Abell, A. D.; Edmonds, M. K. Modern Carbonyl Olefination,
Wiley-VCH, Weinheim, 2004; (b) Vedejs, E.; Peterson, M. J. Topics in
Stereochemistry, Vol. 21, Wiley-VCH, Weinheim, 1994; (c) Robiette,
R.; Richardson, J.; Agg arwal, V. K. and Harvey, J. N. J. Am. Chem. Soc.
2005, 127, 13468.
[17] Hayashi, M. and Nakamura, S. Angew. Chem. Int. Ed. 2011, 50, 2249.
(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2017
Revised manuscript received: XXXX, 2017
Accepted manuscript online: XXXX, 2017
Version of record online: XXXX, 2017
[13] (a) Goff, G. L.; Ouazzani, J. Bioorg. Med. Chem. 2014, 22, 6529; (b) Su,
X. and Aprahamian, I. Chem. Soc. Rev. 2014, 43, 1963; (c) Blair, L. M.
and Sperry, J. J. Nat. Prod. 2013, 76, 794; (d) Vyas, V. S.; Haase, F.;
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Entry for the Table of Contents
Page No.
Phosphine-Relayed Aldehyde-Olefination
and
Aza-Wittig
Reaction
with
2,2,2-Trifluorodiazoethane
Facile transformations of aldehydes with CF3CHN2 to CF3-alkenes and CF3-hydrazones have been
achieved via phosphine-relay strategy.
Fa-Guang Zhang,*,† Ning Lv,† Yan Zheng,
and Jun-An Ma*
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