Straightforward Synthesis of Fluorinated Enals via Photocatalytic α-Perfluoroalkenylation of Aldehydes

Article abstract of DOI:10.1021/acs.joc.1c00383

(Per)fluorinated substances represent an important compound class with regard to drug design and material chemistry. We found a mild, operationally simple, and inexpensive photocatalytic perfluoroalkenylation reaction giving tetrasubstituted, highly electron-deficient enals straight from aldehydes. This one-step reaction tolerates various functional groups and can be applied to a wide range of substrates giving the products in yields of 52-84%.

Full text of DOI:10.1021/acs.joc.1c00383

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Article
Straightforward Synthesis of Fluorinated Enals via Photocatalytic
α‑Perfluoroalkenylation of Aldehydes
Christian Wulkesch and Constantin Czekelius*
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ABSTRACT: (Per)fluorinated substances represent an important
compound class with regard to drug design and material chemistry.
We found a mild, operationally simple, and inexpensive photo-
catalytic perfluoroalkenylation reaction giving tetrasubstituted,
highly electron-deficient enals straight from aldehydes. This one-
step reaction tolerates various functional groups and can be applied
to a wide range of substrates giving the products in yields of 52−
84%.
temperatures, the addition of an excess of both pyrrolidine
and substrate results in the formation of the fluorinated α,β-
unsaturated ketones. For aldehydes, there are even fewer
known protocols that require the intermediate generation of
the corresponding silyl enol ether.40
Given the interesting potential of (per)fluorinated enals as
synthesis intermediates, an efficient preparation protocol
would be desirable, especially with regard to their application
in the synthesis of heteroaromatics.47−49 In this work, we
present a straightforward protocol for the photocatalytic
transformation of aldehydes into the corresponding β-fluoro-
β-fluoroalkylated enals in one step using a simple organo-
catalyst and triphenylphosphine.
INTRODUCTION
■
Fluorinated organic compounds show unique characteristics in
lipophilicity, solubility, binding ability, metabolic stability, and
chemical reactivity.1−6 Therefore, the occurrence of fluorinated
compounds in pharmaceuticals,7−11 anesthetics,12,13 agro-
chemicals,14,15 and new materials16−19 is increasing continu-
ously. Although the process of introducing fluorine into
organic compounds has been known for a long time,20−23
practical and selective fluorination methods have attracted
great interest in the literature during the past few decades.24−27
In particular, perfluoroalkylations as C−C-bond forming
transformations were investigated in different ways.28−30
A
versatile methodology for perfluoroalkylations is found in
photo(redox) catalysis, where the generation and subsequent
addition of perfluoroalkyl radicals to double bonds is promoted
by visible light.31−33
RESULTS AND DISCUSSION
■
Initial investigations on the stereoselective α-perfluoroalkyla-
tion of aldehydes, based on the procedure of MacMillan et al.36
(Scheme 1a), showed that a replacement of the iridium
complex by triphenylphosphine and applying reaction
conditions developed earlier for phosphine EDA complex
catalysis33 (Scheme 1b) lead to the concomitant double bond
formation by hydrogen fluoride (HF)-elimination. β-Fluoro-β-
fluoroalkyl-α,β-unsaturated aldehydes were detected as main
products. Given the rapid degradation of the original
organocatalyst 1a, more suitable derivatives were investigated
Using chiral catalysts, even stereoselective perfluoroalkyla-
tions can be achieved, providing a powerful tool for the
synthesis of complex fluorinated molecules (Scheme 1a).34−36
However, the predominantly employed ruthenium or iridium
complexes are expensive as photocatalysts and their use is
sometimes synthetically sophisticated. Therefore, a more
straightforward methodology is desirable. As an alternative
for the formation of perfluoroalkyl radicals, a photocatalyst
system based on electron donor−acceptor (EDA) complexes
with phosphines has been developed for perfluoroalkylations
(Scheme 1b).33,37,38
During our research, by aiming at perfluoroalkylations of
enamines with phosphine EDA complexes, we observed the
formation of tetrasubstituted, fluorinated α,β-unsaturated
aldehydes. This structural motif is only rarely reported in the
literature,39−42 involving mostly the transformation of ketone
derivatives.43−45 The recent work by Beller et al. provides the
first generally applicable method for the synthesis of
perfluoroalkenylated ketones (Scheme 1c).46 At elevated
1
and the conversion was determined by H NMR spectroscopy
(Table 1, entries 1−5). Among these, only 1b led to complete
conversion of octanal (2a) as a reference. This imidazolidinone
Received: February 16, 2021
Published: May 19, 2021
© 2021 The Authors. Published by
American Chemical Society
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Scheme 1. Previous Work on Perfluoroalk(en)ylation Reactions33,36,46 and Photocatalytic Synthesis of Perfluoroalkenylated
Enals
has an additional advantage in that it can be isolated in solid
form as a free base and does not require the formation of the
trifluoroacetic acid (TFA) salt. In the absence of any
organocatalyst, no reaction of octanal (2a) was found (entry
6). We further found that the reaction protocol does not
require the exclusion of air or moisture.
amines (3j) are compatible with this reaction as well, providing
the desired products in good yields.
The described perfluoroalkenylation protocol is chemo-
selective for aldehydes. As already seen in substrate 3h, also
ketones such as acetophenone or butyrophenone were not
transformed at all, even after up to 23 h of irradiation time.
This may be explained by the low propensity of 1b to form
enamines from ketones, which is in line with the earlier
observations using this type of catalyst.51−53 Halogen
substituents are tolerated as well, as it is exemplified in the
successful transformation of 6-iodohexanal (giving 3k). In the
case of the 6-bromohexanal analogue, a partial nucleophilic
displacement of the bromo substituent by released iodide was
observed and a mixture of bromine- and iodine-substituted
products was obtained. Olefinic substrates are not surprisingly
forming the doubly perfluorinated products (3l). Herein, the
iodoperfluoroalkylation of the alkene is a similarly fast
process,33 which competes with the perfluoroalkenylation of
the aldehyde. Using only 1 equiv of nonafluoro-1-iodobutane
results in the transformation of both moieties with preferential
functionalization of alkene.
In all cases, the products were isolated as double bond
isomer mixtures in comparable ratios of 69:31−85:15, which is
predominantly influenced by the residue of aldehyde 2. In
comparison to the perfluoroalkenylation experiments of Beller
et al.,46 a heteronuclear Overhauser enhancement spectroscopy
(HOESY) NMR experiment revealed that the main product
exhibits a complementary E-configuration (see the Supporting
Information (SI)) in lower selectivity. This can be explained by
the increased allylic strain for ketone derivatives. For 3d, the
highest excess of the E-isomer was observed, which is likely due
to the sterically demanding substituent in proximity to the
reaction center. Mechanistic studies showed that isomer
equilibration under the photocatalytic reaction conditions is
very slow (6% after 17 h). Therefore, we assume the
configuration to be set during the elimination process
following either an E2- or ECB-mechanism. Alternatively, the
The screening showed that the combination of organo-
catalyst 1b and blue light (461 nm) results in full conversion.
In contrast, in the dark, no reaction was apparent even after
18.5 h and all starting materials were found unchanged in the
corresponding NMR spectra (entry 7). Red light did not
promote the reaction substantially and irradiation of green
light resulted in only very slow conversion (entries 8−11). In
comparison, blue light shows complete conversion after already
3 h (entry 12), and also longer exposure of the reaction
mixture to light has no negative impact with respect to side
product formation or product degradation. For purification
purposes, a longer reaction time is even beneficial due to easy
chromatographic removal of phosphine degradation products.
The presence of a base is substantial for product formation
(entry 15). Otherwise, conversion of octanal is incomplete and
side product formation is observed. Noteworthily, the study
showed that even without PPh3, a slower background reaction
occurs, which may be explained by the potential formation of
an EDA complex between the organocatalyst or dimethylfor-
mamide (DMF) and C4F9I (entries 16 and 17), as seen in
earlier studies on amine activation of perfluoroalkyliodides.32,50
However, in comparison, the use of PPh3 is preferable due to
the significantly higher catalytic activity and reaction rate.
To test for functional group tolerance, different aldehydes
were applied to the reaction (Table 2a). In all cases, the
corresponding perfluoroalkenylation products were success-
fully isolated in yields up to 84%. Ethers (3e) as well as
alcohols (3f) are well-suited for the applied photoredox
conditions. Esters (3g) and ketones (3h) showed no aldol
reaction or enamine interference. Nitriles (3i) and protected
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observed. The isolated compounds also provided additional
proof of identity since the enals were surprisingly reluctant in
some cases to be ionized in high-resolution mass spectrometry
(HRMS).
Table 1. Screening of Reaction Parameters for the
Photocatalytic Perfluoroalkenylation of Octanal (2a)
As a result of earlier mechanistic studies addressing the
photochemical activation of phosphine EDA complexes by
visible light,38,55 we propose the intermediate formation of an
EDA complex by the interaction of the lone pair of the
phosphine and the σ*C-I-orbital of the perfluoroalkyl iodide
(Scheme 4, I). Irradiation of blue light leads to the excitation
and formation of a radical-ion pair (II), which forms the
perfluoroalkyl radical (III). By the release of iodide (IV), a
radical-cationic phosphorous species remains, which may act as
an oxidant via a single electron transfer (SET). Closely related
to mechanistic considerations by MacMillan et al.,36 the
parallel organocatalytic cycle starts with the formation of an
enamine by condensation of aldehyde 2 and organocatalyst 1b
(V). Its electron-rich double bond is attacked by the
perfluoroalkyl radical, leading to an N-stabilized radical (VI).
This species may then be oxidized to generate the
corresponding iminium ion (VII), which can finally be
hydrolyzed to release the α-perfluoroalkylated aldehyde
(VIII). This intermediate that can be isolated in the case of
Rf is CF3. For longer perfluoroalkyl homologues, fast
elimination of hydrogen fluoride (IX) generates the tetrasub-
stituted, fluorinated double bond of the enal under the reaction
conditions.
LED
reaction time
(h)
conversion
(%)
E/Z-
a
entry organocatalyst
color
ratio
1
2
1a
1a
blue
blue
blue
blue
blue
blue
no light
red
16
16
16
16
16
16
18.5
3
18.5
3
18.5
1
85
78
>99
62
36
0
0
1
2
39
92
79
>99
>99
6
69:31
68:32
70:30
63:37
79:21
b
3
1b
4
1c
5
pyrrolidine
6
7
none
1b
e
8
1b
n.d.
9
1b
red
72:28
70:30
71:29
69:31
70:30
70:30
79:21
71:29
77:23
10
11
12
13
14
15
16
17
1b
1b
1b
1b
1b
1b
1b
1b
green
green
blue
blue
blue
blue
blue
blue
CONCLUSIONS
■
The results show that tetrasubstituted, highly electron-deficient
(per)fluorinated enals are accessible in an operationally simple,
straightforward, and efficient way by photocatalysis. Examples
for such functionalizations are rare in the literature, and
perfluoroalkenylations have only been efficiently demonstrated
for ketones.46 No transition metal complexes or large excess of
reagents have to be employed. Furthermore, there is no need
for heating, UV light irradiation, or inert reaction conditions.
The reaction is chemoselective for aldehydes and a broad
range of functional groups is tolerated, rendering this
methodology also applicable to complex substrates or for
late-stage modifications. In addition, the upscaling can be
exploited for the preparation of interesting building blocks in
the synthesis of heteroaromatics. The possibility of facile
derivatization of the aldehyde functionality increases the
applicability of the developed methodology further providing
access to a plethora of new functionalized fluorinated
compounds.
3
18.5
16
3
c
d
53
54
d
18.5
a
b
d
Wavelengths: red: 630 nm, green: 513 nm, and blue: 461 nm.
Reaction with 2.4 equiv 2,6-lutidine. Reaction without 2,6-lutidine.
c
Reaction without PPh3, E/Z-ratios were determined by integrating
e
1
the aldehyde signals in H NMR spectra. n.d. = not determined.
outcome could also be explained by an intramolecular six-
membered ring rearrangement of the corresponding enol form,
as reported in related cases.42,44,54
Further investigations showed that the reaction is not only
limited to the perfluorobutyl iodide but also longer chain
analogues as well as difluoroiodoacetates were successfully
employed (Table 2b). In the case of CF3I, no elimination was
observed, but instead, the α-trifluoromethylated product was
isolated in 53% yield.
In a large-scale experiment using 10 mmol of octanal (2a), a
yield of 84% was found matching the small-scale setup
(Scheme 2). Therefore, this reaction can be applied in a
preparative way. It is mandatory for reactions on a large scale,
however, that irradiated light can pass through as much volume
of the reaction solution as possible by ensuring good stirring
and suitable vessel design.
The isolated enals 3 are extremely electron-deficient
intermediates. Therefore, we evaluated their reactivity profile
toward incoming nucleophiles and the regioselectivity of such
an attack. We found that the enals were cleanly converted to
the 2,4-dinitrophenyl hydrazone derivatives (Scheme 3a) or
reduced to the corresponding alcohols using NaBH4,
respectively (Scheme 3b). No 1,4-addition product was
EXPERIMENTAL SECTION
■
General Information. All reactions were performed in oven-dried
glassware equipped with a magnetic stirring bar, heated using an oil
bath if necessary. All commercially available aldehydes were
purchased from Sigma-Aldrich, distilled, and stored under N2.
Noncommercially available aldehydes were prepared by literature-
known procedures to be used immediately. Solvents were distilled
before use. Nonafluoro-1-iodobutane was purchased from TCI and
was filtered through an oven-dried plug, packed with aluminum oxide
90 basic 0.063−0.200 mm (Brockmann I) and molecular sieves (4 Å)
to receive a colorless liquid, which was stored in a brown glass bottle
under a N2 atmosphere. All photoreactions were performed in a self-
built photoreactor.33 Irradiation was performed using a high-density
XUNATA RGB light-emitting diode (LED) strip (120 LEDs/m, 12
V, size: L 120 cm × W 1 cm × T 0.2 cm). The emission maximum
was at 461 nm. The reaction vessels were made of borosilicate glass
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a
Table 2. Photocatalytic Perfluoroalkenylation of Aldehydes
a
Reaction conditions: 2 (0.80 mmol), RfI (1.6 mmol), 1b (0.16 mmol), PPh3 (0.080 mmol), 2,6-lutidine (1.0 mmol), in 0.5 mL DMF at r.t., 14−
1
16 h under irradiation of blue light (461 nm). Isolated yields given. E/Z-ratios were determined by integrating the aldehyde signals in H NMR
spectra.
and were placed at a distance of 1−2 cm from the LEDs (reaction
setup shown in the Supporting Information). Flash chromatography
separations were performed using silica gel 40−63 μm from
Macherey-Nagel. Mixtures of distilled n-pentane and diethyl ether
or dichloromethane and methanol were used as eluents. Note: We
found that most perfluoroalkylated enals are surprisingly volatile and
evaporation should be performed with appropriate care. Thin-layer
chromatography (TLC) was performed using precoated TLC sheets
ALUGRAM Xtra SIL G/UV254 from Macherey-Nagel. Mixtures of
distilled solvents were used as eluents. The substances were detected
by UV light (254 nm) or KMnO4 stain.
Scheme 2. Large-Scale Perfluoroalkenylation of Octanal
(2a)
1H, 13C, and 19F NMR spectra were recorded on a Bruker Avance
III spectrometer 300, 500, or 600 MHz at 298 K. Chemical shifts are
reported in parts per million (ppm) with respect to tetramethylsilane.
As a reference, the residual solvent signal was used. The citations of
Scheme 3. Derivatives of Tetrasubstituted, Perfluoroalkenylated Enals
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Scheme 4. Proposed Reaction Mechanism for the Formation of Perfluoroalkenylated Aldehydes
signals include the following information in parentheses: (a)
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, p =
pentet, m = multiplet, and combinations of those), (b) coupling
constant (in hertz), and (c) number of protons or fluorine atoms. In
the case of a product mixture of diastereomers, the number of protons
or fluorine atoms is given as decimals. In some 13C NMR spectra,
fluorinated carbon atoms could not be detected due to their extensive
coupling to fluorine. Some signals of the different diastereomers
coincide into one signal. The diastereomeric ratios (d.r.) were
determined by the integrals of distinguishable proton signals in the 1H
NMR spectrum. IR spectra were recorded on a JASCO FT/IR-6200
spectrometer as a thin film on a KBr crystal. HRMS-electrospray
ionization (ESI) spectra were recorded using a Bruker Daltonics
UHR-QTOF maXis 4G spectrometer. HRMS-atmospheric pressure
chemical ionization (APCI) spectra were detected using an Orbitrap
XL spectrometer.
CD3OD): δ 3.90 (q, 1H, J = 7.0 Hz), 2.79 (s, 3H), 2.55 (s, 0.36H,
methylamine), 1.48 (d, 3H, J = 7.0 Hz). The NMR spectroscopic data
is consistent with the literature.57
The crude mixture of L-alanine-N-methylamide hydrochloride (1b-
2) (2.00 g mixture, containing 11.7 mmol L-alanine-N-methylamide
hydrochloride, 1.00 equiv) was dissolved in MeOH (0.25 M). After
acetone (4.40 mL, 59.4 mmol, 5.08 equiv) and diisopropylethylamine
(DIPEA) (3.70 mL, 21.2 mmol, 1.81 equiv) were added, the reaction
mixture was heated to reflux for 6 h. The solvent was removed under
reduced pressure and the residue was purified by flash chromatog-
raphy (CH2Cl2/MeOH 20:1) to give (S)-2,2,3,5-tetramethylimidazo-
lidin-4-one (1b) as slightly beige crystals (1.54 g, 10.9 mmol, 93%).
1H NMR (600 MHz, CDCl3) δ 3.52 (q, J = 6.8 Hz, 1H), 2.76 (s, 3H),
1.62 (s, 1H), 1.40 (s, 3H), 1.33 (d, J = 6.9 Hz, 3H), 1.28 (s, 3H). The
NMR spectroscopic data are consistent with the literature,58 mp 86−
87 °C.
Synthesis of Organocatalyst 1b. Dry MeOH (60 mL) was
cooled to −10 °C before thionyl chloride (12.2 mL, 168 mmol, 2.99
equiv) was added dropwise. L-Alanine (5.00 g, 56.1 mmol, 1.00 equiv)
was added and the reaction mixture was stirred at 40 °C for 17 h. The
solvent was removed under reduced pressure and the solid residue
was washed with Et2O (100 mL) twice. The solvent was removed
using a pipette and the remaining solid was dried in vacuo to give L-
alanine-methyl ester hydrochloride (1b-1) as a colorless solid (7.85 g,
Organocatalysts 1a and 1c have been synthesized according to the
literature.57,58
Synthesis of Starting Materials. 4-Phenylbutanal (2c).
Following a related procedure by Jones et al.,59 4-phenylbutanol
(0.79 mL, 5.0 mmol, 1.0 equiv) was added to a stirred suspension of
Dess−Martin periodinane (2.5 g, 5.9 mmol, 1.2 equiv) in dry CH2Cl2
(20 mL). After 2 h of stirring at r.t., the reaction mixture was diluted
with Et2O (50 mL) and quenched with sat. NaHCO3 solution (30
mL). The phases were separated, and the aqueous phase was extracted
with Et2O (3 × 25 mL). The combined organic phases were washed
with saturated NaHCO3 solution (40 mL), water (40 mL), and brine
(40 mL). The solvent was removed in vacuo. Purification by flash
chromatography (n-hexane/EtOAc 90:10) gave 4-phenylbutanal (2c)
1
56.1 mmol, 99%). H NMR (300 MHz, CD3OD): δ 4.12 (q, J = 7.2
Hz, 1H), 3.85 (s, 3H), 1.55 (d, J = 7.2 Hz, 3H). The NMR
spectroscopic data are consistent with the literature,56 mp 103−105
°C.
L-Alanine-methyl ester hydrochloride (1b-1) (2.00 g, 14.4 mmol,
1.00 equiv) was dissolved in EtOH (20 mL) and methylamine
solution (40 wt % in H2O, 24.5 mL, 286 mmol, 19.9 equiv) was
added. The reaction mixture was stirred at 80 °C for 20 h. The solvent
was removed under reduced pressure. The residue was diluted with
toluene (4 mL) and stirred for 10 min, whereupon a solid
precipitated. The liquid was removed using a pipette and the washing
procedure was repeated four times. The remaining solid was dried in
vacuo. The product was isolated as a yellowish solid, which is a
mixture of L-alanine-N-methylamide hydrochloride (1b-2) and
methylamine. The yield of L-alanine-N-methylamide hydrochloride
1
as a colorless liquid (0.64 g, 4.3 mmol, 86%). H NMR (300 MHz,
CDCl3) δ 9.76 (t, J = 1.6 Hz, 1H), 7.34−7.24 (m, 2H), 7.24−7.15
(m, 3H), 2.67 (dd, J = 8.3, 6.9 Hz, 2H), 2.46 (td, J = 7.3, 1.6 Hz, 2H),
2.03−1.92 (m, 2H). NMR data is in accordance with the literature.60
2-Cyclohexylacetaldehyde (2d). Following a related procedure by
O’Connor et al.,61 2-cyclohexylethanol (0.98 mL, 7.0 mmol, 1.0
equiv) was added to a stirred suspension of Dess−Martin periodinane
(3.6 g, 8.4 mmol, 1.2 equiv) in dry CH2Cl2 (20 mL). After 1 h of
stirring at r.t., the reaction mixture was diluted with Et2O (50 mL)
and quenched with saturated NaHCO3 solution (30 mL). The phases
were separated, and the aqueous phase was extracted with Et2O (3 ×
20 mL). The combined organic phases were washed with sat.
NaHCO3 solution (40 mL), water (40 mL), and brine (40 mL). The
1
can be calculated by the ratio of integrals of CH3-signals in the H
NMR spectrum (1.83 g, 13.2 mmol, 92%). The mixture was directly
used in the next step without purification. 1H NMR (300 MHz,
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solvent was removed in vacuo. Purification by flash chromatography
(n-pentane/Et2O 95:5) gave 2-cyclohexyl-acetaldehyde (2d) as a
colorless liquid (0.63 g, 5.0 mmol, 71%). 1H NMR (300 MHz,
CDCl3) δ 9.75 (t, J = 2.4 Hz, 1H), 2.28 (dd, J = 6.8, 2.4 Hz, 2H), 1.88
(dddt, J = 14.8, 8.1, 6.8, 3.4 Hz, 1H), 1.69 (ddddd, J = 13.7, 8.8, 7.1,
3.5, 1.5 Hz, 5H), 1.41−0.85 (m, 5H). NMR data is in accordance
with the literature.61
4-Methoxybutanal (2e). Following a related procedure by Lindsey
et al.,62 oxalyl chloride (2.50 mL, 28.8 mmol, 1.47 equiv) was
dissolved in dry CH2Cl2 (60 mL) under a N2 atmosphere and cooled
to −78 °C. Dimethyl sulfoxide (DMSO) (3.80 mL, 53.8 mmol, 2.74
equiv) was added dropwise within 10 min and the mixture was stirred
for 15 min at −78 °C. A solution of 4-methoxybutan-1-ol (2.20 mL,
19.6 mmol, 1.00 equiv) in dry CH2Cl2 (10 mL) was added dropwise
within 10 min. The solution was stirred for 1 h at −78 °C before
triethylamine (13.0 mL, 93.2 mmol, 4.76 equiv) was added. The
mixture was warmed to r.t. and water (40 mL) was added. The phases
were separated, and the aqueous phase was extracted with CH2Cl2 (2
× 20 mL). The combined organic phases were washed with water (50
mL) and dried over MgSO4. The solvent was removed in vacuo.
Purification by flash chromatography (n-pentane/Et2O 85:15) gave 4-
methoxybutanal (2e) as a slightly yellow liquid (666 mg, 6.52 mmol,
33%). NMR data is in accordance with the literature.63
9-Hydroxynonanal (2f). Following a related procedure by Jin et
al.,64 KOsO4·2H2O (37 mg, 0.10 mmol, 2.0 mol %), tert-butanol (1
mL), NaIO4 (4.30 g, 20.1 mmol, 4.03 equiv), and 2,6-lutidine (1.2
mL, 10 mmol, 2.1 equiv) were added to a stirred solution of 9-decenol
(0.89 mL, 5.0 mmol, 1.0 equiv) in dioxane/water (3:1, 50 mL). The
suspension was stirred for 1 h at r.t. The reaction was quenched with
water (60 mL) and diluted with CH2Cl2 (100 mL). The phases were
separated, and the aqueous phase was extracted with CH2Cl2 (3 × 30
mL). The combined organic phases were washed with 0.1 M aqueous
HCl (60 mL) and water (50 mL) and were dried over MgSO4. The
solvent was removed in vacuo. Purification by flash chromatography
(CH2Cl2/MeOH 97:3) gave 9-hydroxynonanal (2f) as a slightly
brown solid (0.64 g, 4.0 mmol, 80%). NMR data is in accordance with
the literature.65
solvent was removed in vacuo. Purification by flash chromatography
(n-hexane/EtOAc 1:1) gave 1-methylcyclohexane-1,2-diol as colorless
crystals (1.02 g, 7.83 mmol, 78%). NMR data is in accordance with
the literature.70
71
́
Following a related procedure by Lopez et al., a solution of
NaIO4 (1.11 g, 5.19 mmol, 1.30 equiv) in water (8 mL) was added
dropwise to a well-stirred suspension of silica gel (8.00 g) in CH2Cl2
(40 mL). 1-Methylcyclohexane-1,2-diol (519 mg, 3.99 mmol, 1.00
equiv) was added and the reaction mixture was stirred for 24 h at r.t.
After filtration and washing the solid with CH2Cl2, the solvent was
removed in vacuo. Purification by flash chromatography (n-pentane/
Et2O 1:1) gave 6-oxoheptanal (2h) as a colorless liquid (437 mg, 3.41
mmol, 85%). NMR data is in accordance with the literature.72
7-Oxoheptanitrile (2i). Following a related procedure by Ragoussis
et al.,73 6-bromohexanol (1.05 mL, 8.00 mmol, 1.00 equiv) was added
to a well-stirred solution of NaOH (22 mg, 0.55 mmol, 6.9 mol %),
KCN (789 mg, 12.1 mmol, 1.51 equiv), and Bu4N(HSO4) (82 mg,
0.24 mmol, 0.30 equiv) in water (5 mL). The reaction mixture was
stirred for 4.5 h at 60 °C. After dilution with CH2Cl2 (20 mL), the
phases were separated. The organic phase was washed with water (10
mL) and brine (10 mL) and was dried over Na2SO4. The solvent was
removed in vacuo. Purification by flash chromatography (n-pentane/
Et2O 1:1) gave 7-hydroxyheptanitrile as a colorless liquid (766 mg,
6.02 mmol, 75%). NMR data is in accordance with the literature.74
Following a related procedure by Jones et al.,59 7-hydroxyheptani-
trile (760 mg, 5.97 mmol, 1.00 equiv) was added to a stirred
suspension of Dess−Martin periodinane (3.05 g, 7.19 mmol, 1.20
equiv) in dry CH2Cl2 (20 mL). After 1.5 h of stirring at r.t., the
reaction mixture was diluted with Et2O (50 mL) and quenched with
sat. NaHCO3-solution (30 mL). The phases were separated, and the
aqueous phase was extracted with Et2O (3 × 25 mL). The combined
organic phases were washed with saturated NaHCO3 solution (40
mL), water (40 mL), and brine (40 mL). The solvent was removed in
vacuo. Purification by flash chromatography (n-hexane/EtOAc 1:1)
gave 7-oxoheptanitrile (2i) as a colorless liquid (560 mg, 4.47 mmol,
75%). NMR data is in accordance with the literature.74
tert-Butyl-(6-oxohexyl)-carbamate (2j). Following a related
procedure by Mattingly,75 a solution of di-tert-butyl-dicarbonate
(4.00 mL, 19.0 mmol, 1.10 equiv) in CH2Cl2 (10 mL) was added
dropwise to a stirred solution of 6-aminohexanol (2.01 g, 17.2 mmol,
1.00 equiv) in CH2Cl2 (10 mL) and stirred for 17 h at r.t. The
reaction mixture was diluted with Et2O (20 mL), washed with
aqueous phosphate buffer (0.5 M, pH = 5.4, 2 × 20 mL), saturated
NaHCO3 solution (20 mL), and brine (20 mL), and dried over
MgSO4. Removing the solvent in vacuo gave crude tert-butyl-(6-
hydroxyhexyl)-carbamate as a colorless solid, which was used without
further purification. NMR data is in accordance with the literature.75
Following a related procedure by Cushman et al.,76 DMSO (1.20
mL, 18.4 mmol, 4.00 equiv) was dissolved in dry CH2Cl2 (60 mL)
and cooled to −78 °C under a N2 atmosphere. Oxalyl chloride (0.790
mL, 9.21 mmol, 2.00 equiv) was added dropwise within 20 min and
the mixture was stirred for 1 h at −78 °C. A solution of tert-butyl-(6-
hydroxyhexyl)-carbamate (1.00 g, 4.60 mmol, 1.00 equiv) in dry
CH2Cl2 (10 mL) was added dropwise within 20 min. The solution
was stirred for 1 h at −78 °C before DIPEA (4.00 mL, 22.9 mmol,
4.98 equiv) was added. The mixture was warmed to r.t. before water
(20 mL) and Et2O (150 mL) were added. The phases were separated,
the organic phase was washed with water (2 × 30 mL) and brine (2 ×
30 mL), and dried over Na2SO4. The solvent was removed in vacuo.
Purification by flash chromatography (n-pentane/Et2O 1:1) gave tert-
butyl-(6-oxohexyl)-carbamate (2j) as a slightly yellow oil (512 mg,
2.38 mmol, 52%). NMR data is in accordance with the literature.76
6-Iodohexanal (2k). Following a related procedure by Mo et al.,77
NaI (6.01 g, 40.1 mmol, 4.05 equiv) was added to a stirred solution of
6-bromohexanol (1.30 mL, 9.91 mmol, 1.00 equiv) in acetone (30
mL). The reaction mixture was refluxed for 15 h. After cooling to r.t.,
CH2Cl2 (70 mL) was added. The precipitated solid was removed by
filtration and the solvent was removed in vacuo. The residue was
diluted with EtOAc (30 mL) and washed with aqueous Na2S2O3
solution (0.1 M, 10 mL). The solvent was removed in vacuo.
Ethyl-6-oxo-hexanoate (2g). 6-Bromohexanoic acid (5.03 g, 25.8
mmol, 1.00 equiv) was dissolved in EtOH (170 mL). After the
addition of aqueous HCl (37%, 1.10 mL), the reaction mixture was
stirred for 6 h at r.t. The solvent volume was reduced in vacuo and
diluted with Et2O (50 mL). The organic layer was washed with water
(2 × 100 mL) and saturated NaHCO3 solution (50 mL) and dried
over Na2SO4. The solvent was removed in vacuo giving ethyl-6-
bromohexanoate as a slightly yellow liquid (5.51 g, 24.7 mmol, 96%).
1H NMR (300 MHz, CDCl3) δ 4.12 (q, J = 7.1 Hz, 2H), 3.40 (t, J =
6.7 Hz, 2H), 2.31 (t, J = 7.4 Hz, 2H), 2.02−1.79 (m, 2H), 1.76−1.56
(m, 2H), 1.55−1.39 (m, 2H), 1.25 (t, J = 7.2 Hz, 3H). NMR data is
in accordance with the literature.66
Following a related procedure by Manolikakes et al.,67 ethyl-6-
bromohexanoate (1.04 g, 4.66 mmol, 1.00 equiv), Na2CO3 (494 mg,
4.66 mmol, 1.00 equiv), and KI (779 mg, 4.69 mmol, 1.05 equiv)
were suspended in DMSO (23 mL) and stirred for 24 h at 85 °C.
After cooling to 0 °C, Et2O (40 mL) was added. The organic layer
was washed with saturated Na2CO3 solution (30 mL), water (30 mL),
and brine (30 mL). The solvent was removed in vacuo. Purification by
flash chromatography (n-hexane/EtOAc 90:10) gave ethyl-6-
bromohexanoate (2g) as a colorless liquid (307 mg, 1.94 mmol,
1
42%). H NMR (300 MHz, CDCl3) δ 9.77 (t, J = 1.6 Hz, 1H), 4.12
(q, J = 7.1 Hz, 2H), 2.53−2.24 (m, 4H), 1.75−1.57 (m, 4H), 1.25 (t,
J = 7.2 Hz, 3H). NMR data is in accordance with the literature.68
6-Oxoheptanal (2h). Following a related procedure by Zimmer-
man et al.,69 1-methylcyclohex-1-ene (1.20 mL, 10.1 mmol, 1.00
equiv) was dissolved in a mixture of acetone/water/tert-butanol
(5:3:1, 17 mL). After adding N-methylmorpholine N-oxide (50 wt %
in H2O, 1.30 g, 11.1 mmol, 1.10 equiv) and KOsO4·2H2O (74 mg,
0.20 mmol, 2.0 mol %), the mixture was stirred for 3 h at r.t. Then,
Et2O (30 mL) and water (10 mL) were added and the phases were
separated. The aqueous phase was extracted with Et2O (3 × 20 mL).
The combined organic phases were washed with brine (30 mL). The
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Purification by flash chromatography (n-hexane/EtOAc 4:1) gave 6-
iodohexanol as an orange liquid (2.05 g, 8.99 mmol, 91%). NMR data
is in accordance with the literature.78
mL) were added and the mixture was stirred at 0 °C for 1 h. The
reaction was quenched with aqueous HCl solution (0.1 M, 10 mL),
and the phases were separated. The aqueous phase was extracted with
Et2O (10 mL) three times and the combined organic layers were
washed with brine (10 mL). The solvent was removed in vacuo, and
the crude product was purified by flash chromatography (n-pentane/
Et2O).
General Procedure 4: Derivatization of Allylic Alcohols to 4-
Methoxy Benzoates. The corresponding alcohol was dissolved in
pyridine (0.25 M) and cooled to 0 °C. At this temperature, 4-
methoxybenzoyl chloride (1.1 equiv) was added and the mixture was
stirred at 0 °C for 30 min. The cooling bath was removed and the
reaction was stirred at r.t. overnight. After transferring to a separatory
funnel, the mixture was diluted with Et2O (10 mL) and washed with
sat. NaHCO3 solution (10 mL). The phases were separated, and the
aqueous phase was extracted with Et2O (10 mL) three times. The
solvent was removed in vacuo, and the crude product was purified by
flash chromatography (n-pentane/Et2O).
Perfluoroalkenylation Products. 2-(Perfluorobutylidene)-octa-
nal (3a). Following general procedure 1, octanal (2a) (98 mg, 0.76
mmol, 1.0 equiv), (S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (25
mg, 0.18 mmol 0.24 equiv), triphenylphosphine (22 mg, 0.084 mmol,
0.11 equiv), nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 2.1 equiv),
and 2,6-lutidine (0.12 mL, 1.0 mmol, 1.3 equiv) were mixed and
irradiated for 16 h. Purification by flash chromatography (n-pentane/
Et2O 95:5) gave a mixture of (E)- and (Z)-2-(perfluorobutylidene)-
octanal (3a) (E/Z: 78:22) as a colorless liquid (0.21 g, 0.64 mmol,
84%). 1H NMR (600 MHz, CDCl3) δ 10.21 (s, 0.2H), 9.98 (s, 0.7H),
2.45 (td, J = 7.9, 4.2 Hz, 1.5H), 2.30 (ddt, J = 7.7, 4.9, 2.4 Hz, 0.5H),
1.45−1.36 (m, 2H), 1.35−1.21 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H).
13C{1H} NMR (75 MHz, CDCl3) δ 187.8 (d, J = 18.0 Hz), 187.5 (q,
Following a related procedure by Jones et al.,59 6-iodohexanol
(1.17 g, 5.13 mmol, 1.00 equiv) was added to a stirred suspension of
Dess−Martin periodinane (2.64 g, 6.23 mmol, 1.21 equiv) in dry
CH2Cl2 (20 mL). After 2 h of stirring at r.t., the reaction mixture was
diluted with Et2O (50 mL) and quenched with sat. NaHCO3 solution
(30 mL). The phases were separated, and the aqueous phase was
extracted with Et2O (3 × 25 mL). The combined organic phases were
washed with saturated NaHCO3 solution (40 mL), water (40 mL),
and brine (40 mL). The solvent was removed in vacuo. Purification by
flash chromatography (n-pentane/Et2O 90:10) gave 6-iodohexanal
(2k) as an orange oil (816 mg, 3.61 mmol, 70%). NMR data is in
accordance with the literature.79
Dec-9-enal (2l). Following a related procedure by Banwell et al.,80
oxalyl chloride (1.03 mL, 12.0 mmol, 2.00 equiv) was dissolved in dry
CH2Cl2 (30 mL) and cooled to −78 °C under a N2 atmosphere.
DMSO (1.70 mL, 23.9 mmol, 3.98 equiv) was added dropwise within
15 min and the mixture was stirred for 1 h at −78 °C. A solution of
dec-9-enol (1.07 mL, 6.00 mmol, 1.0 equiv) in dry CH2Cl2 (10 mL)
was added dropwise within 15 min. The solution was stirred for 1 h at
−78 °C before DIPEA (5.20 mL, 29.8 mmol, 4.97 equiv) was added.
The mixture was warmed to 0 °C and CH2Cl2 (40 mL) and saturated
NaHCO3 solution (30 mL) was added. The phases were separated.
The organic phase was washed with water (30 mL) and saturated
NaHCO3 solution (30 mL) and dried over Na2SO4. The solvent was
removed in vacuo. Purification by flash chromatography (n-pentane/
Et2O 95:5) gave dec-9-enal (2l) as a slightly yellow liquid (768 mg,
4.98 mmol, 83%). NMR data is in accordance with the literature.80
Optimization of Reaction Conditions. In a 2.5 mL reaction
vessel, the corresponding organocatalyst (0.20 equiv) and triphenyl-
phosphine (10 mol %) were dissolved in DMF (0.5 mL). Nonafluoro-
1-iodobutane (2.0 equiv), octanal (2a) (1.0 equiv), and 2,6-lutidine
were added and the reaction mixture was stirred at r.t. under
irradiation of light. The conversion was determined by integrating the
J = 9.6 Hz), 155.5 (dt, J = 277.7, 31.4 Hz), 155.5 (dt, J = 277.7, 31.4
Hz), 132.5 (d, J = 9.6 Hz), 129.4, 120.7−106.0 (CF signals, m), 31.5,
31.5, 29.7, 29.6−29.3 (m), 29.1, 28.2, 23.5 (d, J = 3.9 Hz), 22.8, 22.6,
22.3 (d, J = 3.8 Hz), 14.2, 14.1. 19F NMR (282 MHz, CDCl3) δ
−80.55 (q, J = 8.4 Hz, 1.9F), −80.69 (q, J = 8.5 Hz, 0.9F), −106.93
(q, J = 9.1 Hz, 0.7F), −112.29 (q, J = 9.8, 9.2 Hz, 1.4F), −116.34 (dt,
J = 16.7, 8.6 Hz, 0.6F), −125.97 (q, J = 9.4 Hz, 0.4F), −127.27 (t, J =
1
product’s aldehyde signals in the corresponding H NMR spectrum.
General Procedures for Photoreactions and Derivatiza-
tions. General Procedure 1: Photocatalytic Perfluoroalkenylation
of Aldehydes. In a 2.5 mL reaction vessel, (S)-2,2,3,5-tetramethyli-
midazolidin-4-one (1b) (0.20 equiv) and triphenylphosphine (10 mol
%) were dissolved in DMF (0.5 mL). The corresponding
perfluoroiodoalkane (2.0 equiv), aldehyde (1.0 equiv), and 2,6-
lutidine (1.2 equiv) were added and the reaction mixture was stirred
at r.t. under irradiation of blue LEDs (461 nm). After dilution with
Et2O (10 mL), the organic phase was washed with the aqueous HCl
solution (0.1 M, 10 mL). The resulting phases were separated, and
the aqueous phase was extracted with Et2O (10 mL) five times. The
solvent was removed at 50 °C without vacuum, and the crude product
was purified by flash chromatography (silica gel, n-pentane/Et2O).
The solvent was removed at 50 °C without vacuum again, and the
product was dried by slow evaporation overnight. Both diastereomers
show a minor difference in the Rf-value, leading to E/Z-ratio
differences in different fractions. Only pure fractions were collected,
and the reported yield is representative for this isomer mixture.
General Procedure 2: Derivatization of Enals to 2,4-Dinitro-
phenyl hydrazone Derivatives. 2,4-Dinitrophenyl-hydrazine (3
equiv) was dissolved in H2O (3 mL), H2SO4 (conc., 2 mL), and
EtOH (10 mL). The corresponding enal (1 equiv) was dissolved in
EtOH (2 mL) and added dropwise to the stirred solution. After 10
min, precipitation was observed and the reaction mixture was diluted
with CH2Cl2 (10 mL) to redissolve the precipitate. The reaction
mixture was transferred into a separatory funnel and was washed with
H2O (10 mL). The aqueous phase was extracted with CH2Cl2 (10
mL) three times and the combined organic phases were washed with
brine (15 mL). The solvent was removed in vacuo, and the crude
product was purified by flash chromatography (n-pentane/Et2O).
General Procedure 3: Reduction of Enals to Allylic Alcohols. The
corresponding enal was dissolved in dry CH2Cl2 (10 mL) and cooled
to 0 °C. At this temperature, sodium borohydride and dry MeOH (10
6.6 Hz, 0.6F), −127.57 (d, J = 6.0 Hz, 1.3F). IR (ν
̃
in cm−1): 2933,
1697, 1660, 1354, 1233, 966, 745. HRMS-ESI: The compound could
not be ionized by HRMS-ESI. Therefore, this compound was
characterized as its 2,4-dinitrophenyl hydrazone derivative (see 4a).
2-(Perfluorobutylidene)-octanal (3a): Large-Scale Experiment. In
a 25 mL round bottom flask, octanal (2a) (1.30 g, 10.1 mmol, 1.00
equiv), (S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (286 mg, 2.01
mmol, 0.199 equiv), triphenylphosphine (268 mg, 1.02 mmol, 0.101
equiv), nonafluoro-1-iodobutane (3.40 mL, 20.2 mmol, 2.00 equiv),
and 2,6-lutidine (1.3 mL, 11.2 mmol, 1.11 equiv) were mixed in DMF
(6.2 mL) and irradiated for 16 h. After dilution with Et2O (30 mL),
the organic phase was washed with aqueous HCl solution (0.1 M, 30
mL). The resulting phases were separated, and the aqueous phase was
extracted with Et2O (30 mL) five times. The solvent was removed at
50 °C without vacuum, and the crude product was purified by flash
chromatography (silica gel, n-pentane/Et2O 97:3). Removing the
solvent at 50 °C without vacuum again and drying by slow
evaporation overnight gave a mixture of (E)- and (Z)-2-(perfluor-
obutylidene)-octanal (3a) (E/Z: 70:30) as a colorless liquid (2.77 g,
8.49 mmol, 84%).
2-(Perfluorobutylidene)-3-phenylpropanal (3b). Following gen-
eral procedure 1, 3-phenylpropanal (2b) (114 mg, 0.850 mmol, 1.00
equiv), (S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (23 mg, 0.16
mmol, 0.19 equiv), triphenylphosphine (22 mg, 0.084 mmol, 0.099
equiv), nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 1.9 equiv), and
2,6-lutidin (0.12 mL, 1.0 mmol, 1.2 equiv) were mixed and irradiated
for 16 h. Purification by flash chromatography (n-pentane/Et2O 95:5)
gave a mixture of (E)- and (Z)-2-(perfluorobutylidene)-3-phenyl-
propanal (3b) (E/Z: 78:22) as a colorless liquid (167 mg, 0.503
1
mmol, 59%). H NMR (300 MHz, CDCl3) δ 10.25 (d, J = 0.7 Hz,
0.2H), 9.99 (q, J = 1.1 Hz, 0.8H), 7.33−7.12 (m, 5H), 3.80 (d, J = 4.2
Hz, 1.6H), 3.72 (d, J = 2.4 Hz, 0.5H). 13C{1H} NMR (151 MHz,
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CDCl3) δ 187.5 (d, J = 17.9 Hz), 187.1 (q, J = 9.0 Hz), 155.9 (J =
279.7 Hz), 155.9 (J = 279.7 Hz), 136.6, 136.5, 131.2 (d, J = 9.2 Hz),
128.9, 128.9, 128.8, 128.5, 127.7, 127.2, 127.1, 121.4−102.3 (CF
signals, m), 29.1 (d, J = 4.1 Hz), 27.7. 19F NMR (282 MHz, CDCl3) δ
−80.34 (td, J = 8.9, 2.5 Hz, 2.2F), −80.44 (td, J = 9.1, 2.6 Hz, 0.8F),
−104.93 to −105.10 (m, 0.8F), −112.23 to −112.46 (m, 1.6F),
−115.23 (p, J = 8.9 Hz, 0.5F), −123.75 (tdd, J = 11.2, 5.6, 2.6 Hz,
0.2F), −126.83 (d, J = 8.6 Hz, 0.5F), −127.19 to −127.33 (m, 1.5F).
Hz, 0.7H), 3.28 (s, 3H), 2.75 (tdt, J = 6.4, 3.9, 1.3 Hz, 1.6H), 2.68−
2.59 (m, 0.7H). 13C{1H} NMR (75 MHz, CDCl3) δ 187.6 (d, J = 4.8
Hz), 187.5−187.1 (m), 156.1 (dt, J = 279.5, 31.2 Hz), 156.1 (dt, J =
279.5, 31.2 Hz), 129.3 (d, J = 9.3 Hz), 126.1, 123.0−104.4 (CF
signals, m), 70.5, 69.7 (d, J = 2.5 Hz), 58.8, 58.7, 24.1 (d, J = 3.6 Hz),
22.7 (t, J = 3.7 Hz). 19F NMR (282 MHz, CDCl3) δ −80.54 (t, J = 9.0
Hz, 2.1F), −80.67 (t, J = 9.1 Hz, 0.9F), −105.43 (ttd, J = 10.1, 6.5, 3.0
Hz, 0.7F), −112.24 to −112.75 (m, 1.6F), −115.80 (p, J = 8.9 Hz,
0.7F), −122.72 (tdd, J = 11.7, 9.1, 4.9 Hz, 0.3F), −127.03 (d, J = 9.0
IR (ν
̃
in cm−1): 3034, 2927, 1696, 1660, 1353, 1233, 1127, 1127, 698.
HRMS-ESI: The compound could not be ionized by HRMS-ESI.
Therefore, this compound was characterized as its 2,4-dinitrophenyl
hydrazone derivative (see 4b).
Hz, 0.6F), −127.57 (d, J = 7.0 Hz, 1.4F). IR (ν
̃
in cm−1): 2933, 2898,
2366, 1698, 1665, 1355, 1231, 1122, 933, 729. HRMS-ESI: calcd for
C9H9F8O2 [M + H+] m/z 301.0469, found 301.0468.
2-(Perfluorobutylidene)-4-phenylbutanal (3c). Following general
procedure 1, 4-phenylbutanal (2c) (126 mg, 0.850 mmol, 1.00 equiv),
(S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (23 mg, 0.16 mmol,
0.19 equiv), triphenylphosphine (21 mg, 0.080 mmol, 0.094 equiv),
nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 1.9 equiv), and 2,6-
lutidine (0.12 mL, 1.0 mmol, 1.2 equiv) were mixed and irradiated for
14 h. Purification by flash chromatography (n-pentane/Et2O 95:5)
gave a mixture of (E)- and (Z)-2-(perfluorobutylidene)-4-phenyl-
butanal (3c) (E/Z: 72:28) as a colorless liquid (216 mg, 0.624 mmol,
73%). 1H NMR (300 MHz, CDCl3) δ 10.24 (s, 0.3H), 9.99−9.93 (m,
0.7H), 7.37−7.27 (m, 2H), 7.27−7.15 (m, 3H), 2.77 (h, J = 2.8, 2.3
Hz, 3H), 2.70−2.60 (m, 1H). 13C{1H} NMR (75 MHz, CDCl3) δ
187.5 (d, J = 12.4 Hz), 187.4−187.0 (m), 158.4−153.4 (m), 158.4−
153.4 (m), 140.3, 140.0, 132.3, 131.3 (d, J = 9.3 Hz), 128.8, 128.7,
128.6, 128.5, 126.7, 126.7, 125.5−104.8 (CF signals, m), 35.7 (d, J =
3.4 Hz), 34.1 (q, J = 1.5 Hz), 25.6 (d, J = 3.3 Hz), 24.8 (t, J = 3.7 Hz).
19F NMR (282 MHz, CDCl3) δ −80.35 (td, J = 9.1, 2.5 Hz, 2.1F),
−80.47 (td, J = 9.0, 2.6 Hz, 0.9F), −105.57 (ttd, J = 9.8, 6.5, 2.6 Hz,
0.7F), −112.04 to −112.28 (m, 1.5F), −116.20 to −116.36 (m, 0.6F),
−124.28 (dddt, J = 11.3, 8.7, 5.9, 2.7 Hz, 0.3F), −127.06 (d, J = 8.4
9-Hydroxy-2-(perfluorobutylidene)-nonanal (3f). Following gen-
eral procedure 1, 9-hydroxynonanal (2f) (128 mg, 0.809 mmol, 1.00
equiv), (S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (25 mg, 0.18
mmol, 0.22 equiv), triphenylphosphine (21 mg, 0.080 mmol, 0.099
equiv), nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 2.0 equiv), and
2,6-lutidine (0.12 mL, 1.0 mmol, 1.2 equiv) were mixed and irradiated
for 14 h. Purification by flash chromatography (n-pentane/Et2O 1:1)
gave a mixture of (E)- and (Z)-9-hydroxy-2-(perfluorobutylidene)-
nonanal (3f) (E/Z: 71:29) as a colorless oil (173 mg, 0.486 mmol,
60%). 1H NMR (300 MHz, CDCl3) δ 10.21 (s, 0.3H), 9.97 (s, 0.7H),
3.64 (t, J = 6.5 Hz, 2H), 2.45 (td, J = 7.4, 4.1 Hz, 1.4H), 2.30 (s,
0.6H), 1.55 (q, J = 6.6 Hz, 2H), 1.47−1.27 (m, 8H). 13C{1H} NMR
(75 MHz, CDCl3) δ 187.8 (d, J = 18.5 Hz), 187.5 (q, J = 10.0 Hz),
158.1−152.7 (m), 158.1−152.7 (m), 132.3 (d, J = 9.7 Hz), 129.3,
124.2−106.8 (CF signals, m), 63.0, 32.8, 29.6, 29.5, 29.4, 29.0, 29.0,
28.1, 25.6 (d, J = 2.1 Hz), 23.4 (d, J = 3.9 Hz), 22.2. 19F NMR (282
MHz, CDCl3) δ −80.36 (td, J = 9.1, 2.6 Hz, 2.1F), −80.51 (td, J =
9.2, 2.6 Hz, 0.9F), −106.59 (dqt, J = 13.2, 6.5, 3.0 Hz, 0.7F), −111.96
to −112.35 (m, 1.5F), −116.20 (p, J = 8.8 Hz, 0.6F), −125.56 (tdd, J
= 11.3, 8.7, 6.0 Hz, 0.3F), −127.12 (d, J = 8.2 Hz, 0.6F), −127.40
(dd, J = 6.7, 2.4 Hz, 1.5F). IR (ν
̃
in cm−1): 2931, 2359, 1716, 1697,
Hz, 0.6F), −127.26 to −127.43 (m, 1.4F). IR (ν
̃
in cm−1): 3031,
1653, 1353, 1234, 913. HRMS-ESI: calcd for C13H20F8O2N [M +
2932, 1695, 1660, 1354, 1233, 961, 748. HRMS-ESI: The compound
could not be ionized by HRMS-ESI. Therefore, this compound was
characterized as its 2,4-dinitrophenyl hydrazone derivative (see 4c).
2-(Perfluorobutylidene)-2-cyclohexylethanal (3d). Following gen-
eral procedure 1, 2-cyclohexylacetaldehyde (2d) (144 mg, 1.14 mmol,
1.00 equiv), (S)-2,2,3,5-tetramethyl-imidazolidin-4-one (1b) (24 mg,
0.17 mmol, 0.15 equiv), triphenylphosphine (21 mg, 0.080 mmol,
0.070 equiv), nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 1.4
equiv), and 2,6-lutidine (0.12 mL, 1.0 mmol, 0.88 equiv) were mixed
and irradiated for 16 h. Purification by flash chromatography (n-
pentane/Et2O 95:5) gave a mixture of (E)- and (Z)-2-(perfluor-
obutylidene)-2-cyclohexylethanal (3d) (E/Z: 85:15) as a colorless
+
NH4 ] m/z 374.1361, found 374.1361; calcd for C13H16F8O2Na [M +
Na+] m/z 379.0915, found 379.0915.
Ethyl-2-(perfluorobutylidene)-6-oxo-hexanoate (3g). Following
general procedure 1, ethyl-6-oxo-hexanoate (2g) (125 mg, 0.790
mmol, 1.00 equiv), (S)-2,2,3,5-tetramethyl-imidazolidin-4-one (1b)
(23 mg, 0.16 mmol, 0.20 equiv), triphenylphosphine (22 mg, 0.084
mmol, 0.11 equiv), nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 2.0
equiv), and 2,6-lutidine (0.12 mL, 1.0 mmol, 1.3 equiv) were mixed
and irradiated for 18 h. Purification by flash chromatography (n-
pentane/Et2O 95:5) gave a mixture of (E)- and (Z)-ethyl-2-
(perfluorobutylidene)-6-oxo-hexanoate (3g) (E/Z: 68:32) as a
1
1
colorless liquid (153 mg, 0.430 mmol, 54%). H NMR (600 MHz,
liquid (202 mg, 0.623 mmol, 55%). H NMR (300 MHz, CDCl3) δ
CDCl3) δ 10.19 (s, 0.3H), 9.95 (s, 0.7H), 4.12 (qd, J = 7.2, 4.6 Hz,
2H), 2.53−2.46 (m, 1.5H), 2.36 (ddq, J = 10.5, 5.0, 2.4 Hz, 0.7H),
2.31 (dt, J = 9.4, 7.3 Hz, 2H), 1.74 (p, J = 7.4 Hz, 1.5H), 1.71−1.66
(m, 0.8H), 1.24 (td, J = 7.1, 3.0 Hz, 3H). 13C{1H} NMR (151 MHz,
CDCl3) δ 187.5 (d, J = 18.2 Hz), 187.2 (q, J = 9.5 Hz), 172.7, 172.7,
157.2−154.8 (m), 157.2−154.8 (m), 131.4 (d, J = 9.2 Hz), 128.5,
122.0−102.4 (CF signals, m), 60.6 (2 signals), 34.0, 33.6, 24.5 (d, J =
3.9 Hz), 23.2, 22.8 (d, J = 4.3 Hz), 21.7 (t, J = 3.8 Hz), 14.3, 14.2. 19F
NMR (282 MHz, CDCl3) δ −80.35 (td, J = 9.0, 2.5 Hz, 2.1F),
−80.49 (td, J = 9.1, 2.5 Hz, 0.9F), −105.53 (dqt, J = 9.9, 6.5, 2.8 Hz,
0.7F), −112.26 (tt, J = 10.5, 8.5 Hz, 1.5F), −116.14 (p, J = 8.8 Hz,
0.7F), −124.11 (tddd, J = 11.1, 8.5, 5.5, 2.5 Hz, 0.3F), −127.06 to
10.15 (d, J = 2.4 Hz, 0.15H), 9.98−9.84 (m, 0.85H), 2.84 (tt, J = 11.4,
4.2 Hz, 0.87H), 2.48 (t, J = 12.3 Hz, 0.15H), 1.85−1.54 (m, 7H),
1.40−1.17 (m, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 188.9 (d, J =
19.0 Hz), 188.3 (dt, J = 10.5, 8.7 Hz), 155.0 (dt, J = 279.0, 30.9 Hz),
155.0 (dt, J = 279.0, 30.9 Hz), 135.7 (d, J = 7.5 Hz), 133.0, 123.2−
106.0 (CF signals, m), 36.4, 30.0, 29.8 (d, J = 3.5 Hz), 26.6, 26.6,
25.7, 25.5. 19F NMR (282 MHz, CDCl3) δ −80.52 (td, J = 8.9, 2.6
Hz, 3F), −108.72 (ttd, J = 9.9, 6.7, 3.2 Hz, 0.9F), −111.80 (pd, J =
9.5, 3.1 Hz, 1.8F), −114.18 to −116.18 (m, 0.3F), −123.59 (qt, J =
9.1, 4.8 Hz, 0.15F), −126.37 to −128.65 (m, 2F). IR (ν
̃
in cm−1):
2934, 1698, 1652, 1354, 1231, 972, 873. HRMS-ESI: The compound
could not be ionized by HRMS-ESI. Therefore, this compound was
characterized as its 2,4-dinitrophenyl hydrazone derivative (see 4d).
2-(Perfluorobutylidene)-4-methoxybutanal (3e). Following gen-
eral procedure 1, 4-methoxybutanal (2e) (52 mg, 0.51 mmol, 1.0
equiv), (S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (24 mg, 0.17
mmol, 0.33 equiv), triphenylphosphine (21 mg, 0.080 mmol, 0.16
equiv), nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 3.1 equiv), and
2,6-lutidine (0.12 mL, 1.0 mmol, 2.0 equiv) were mixed and irradiated
for 18 h. Purification by flash chromatography (n-pentane/Et2O 95:5)
gave a mixture of (E)- and (Z)-2-(perfluorobutylidene)-4-methox-
ybutanal (3e) (E/Z: 70:30) as a colorless liquid (90 mg, 0.30 mmol,
−127.21 (m, 0.7F), −127.25 to −127.42 (m, 1.4F). IR (ν
̃
in cm−1):
2985, 1739, 1696, 1660, 1354, 1234, 966, 747. HRMS-ESI: calcd for
C12H13F8O3 [M + H+] m/z 357.0731, found 357.0733.
6-Oxo-2-(perfluorobutylidene)-heptanal (3h). Following general
procedure 1, 6-oxoheptanal (2h) (122 mg, 0.951 mmol, 1.00 equiv),
(S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (23 mg, 0.16 mmol,
0.17 equiv), triphenylphosphine (21 mg, 0.080 mmol, 0.084 equiv),
nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 1.7 equiv), and 2,6-
lutidine (0.12 mL, 1.0 mmol, 1.1 equiv) were mixed and irradiated for
17 h. Purification by flash chromatography (n-pentane/Et2O 3:1)
gave a mixture of (E)- and (Z)-6-oxo-2-(perfluorobutylidene)-
heptanal (3h) (E/Z: 71:29) as a colorless liquid (223 mg, 0.684
1
59%). H NMR (300 MHz, CDCl3) δ 10.19 (d, J = 0.8 Hz, 0.3H),
9.99−9.91 (m, 0.7H), 3.44 (td, J = 6.4, 0.6 Hz, 1.6H), 3.38 (t, J = 6.7
7432
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1
mmol, 72%). H NMR (300 MHz, CDCl3) δ 10.20 (d, J = 0.8 Hz,
gave a mixture of (E)- and (Z)-6-iodo-2-(perfluorobutylidene)-
hexanal (3k) (E/Z: 69:31) as a colorless liquid (213 mg, 0.502
mmol, 62%). H NMR (300 MHz, CDCl3) δ 10.21 (d, J = 0.8 Hz,
0.3H), 9.99−9.93 (m, 0.7H), 2.46 (td, J = 7.2, 5.2 Hz, 3.5H), 2.32
(ddt, J = 7.8, 5.2, 2.3 Hz, 0.6H), 2.14 (d, J = 0.8 Hz, 3H), 1.70 (dq, J
= 15.1, 7.5 Hz, 2H). 13C{1H} NMR (75 MHz, CDCl3) δ 207.7, 187.6
(d, J = 18.5 Hz), 187.5−187.1 (m), 155.9 (dt, J = 279.1, 31.5 Hz),
155.9 (d, J = 279.1, Hz), 131.6 (d, J = 9.4 Hz), 128.6, 120.2−106.7
(CF signals, m), 43.0, 42.7, 29.9, 29.8, 23.3, 22.7 (d, J = 4.1 Hz), 21.9,
21.5. 19F NMR (282 MHz, CDCl3) δ −80.49 (q, J = 9.2 Hz, 2.2F),
−80.63 (q, J = 9.2 Hz, 0.9F), −105.81 to −106.02 (m, 0.8F), −112.34
(h, J = 8.9 Hz, 1.7F), −116.21 (hept, J = 8.0 Hz, 0.7F), −124.35 to
−124.47 (m, 0.3F), −127.23 (t, J = 7.6 Hz, 0.6F), −127.45 (d, J = 6.5
1
0.3H), 9.97 (q, J = 1.2 Hz, 0.7H), 3.16 (td, J = 6.9, 4.8 Hz, 2H), 2.48
(dddd, J = 9.1, 7.6, 4.7, 2.6 Hz, 1.4H), 2.33 (ddt, J = 10.5, 4.9, 2.4 Hz,
0.6H), 1.83 (dt, J = 14.9, 6.8 Hz, 2H), 1.61−1.46 (m, 2H). 13C{1H}
NMR (75 MHz, CDCl3) δ 187.5 (d, J = 18.2 Hz), 187.2 (q), 158.6−
153.5 (m), 158.6−153.5 (m), 131.6 (d, J = 9.2 Hz), 128.6, 122.6−
105.9 (CF signals, m), 33.4, 33.0, 30.4, 29.0, 22.4 (d, J = 4.1 Hz),
21.3, 5.4, 5.2. 19F NMR (282 MHz, CDCl3) δ −80.33 to −80.47 (m,
2.1F), −80.54 (td, J = 9.2, 2.3 Hz, 0.9F), −105.68 (th, J = 9.8, 2.8 Hz,
0.7F), −112.28 (p, J = 9.6 Hz, 1.5F), −116.23 (p, J = 8.8 Hz, 0.7F),
−124.32 to −124.54 (m, 0.3F), −127.16 (d, J = 8.1 Hz, 0.6F),
Hz, 1.5F). IR (ν
̃
in cm−1): 2943, 1715, 1696, 1660, 1354, 1232, 977.
HRMS-ESI: calcd for C11H11F8O2 [M + H+] m/z 327.0626, found
327.0630.
−127.40 (d, J = 6.5 Hz, 1.4F). IR (ν
̃
in cm−1): 2939, 1695, 1660,
7-Oxo-2-(perfluorobutylidene)-heptanitrile (3i). Following gen-
eral procedure 1, 7-oxoheptanitrile (2i) (101 mg, 0.807 mmol, 1.00
equiv), (S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (24 mg, 0.17
mmol, 0.21 equiv), triphenylphosphine (22 mg, 0.080 mmol, 0.10
equiv), nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 2.0 equiv), and
2,6-lutidine (0.12 mL, 1.0 mmol, 1.2 equiv) were mixed and irradiated
for 16 h. Purification by flash chromatography (n-pentane/Et2O 3:1)
gave a mixture of (E)- and (Z)-7-oxo-2-(perfluorobutylidene)-
heptanitrile (3i) (E/Z: 69:31) as a colorless liquid (206 mg, 0.638
1456, 1354, 1231, 968, 741. HRMS-ESI: The compound could not be
ionized by HRMS-ESI. Therefore, this compound was characterized
as its 2,4-dinitrophenyl hydrazone derivative (see 4k).
9-Iodo-10-(perfluorobutyl)-2-(perfluorobutylidene)-decanal (3l).
Following general procedure 1, dec-9-enal (2l) (123 mg, 0.797 mmol,
1.00 equiv), (S)-2,2,3,5-tetramethyl-imidazolidin-4-one (1b) (23 mg,
0.16 mmol, 0.20 equiv), triphenylphosphine (21 mg, 0.080 mmol,
0.10 equiv), nonafluoro-1-iodobutane (0.40 mL, 2.4 mmol, 3.0 equiv),
and 2,6-lutidine (0.12 mL, 1.0 mmol, 1.3 equiv) were mixed and
irradiated for 16 h. Purification by flash chromatography (n-pentane/
Et2O 95:5) gave a mixture of (E)- and (Z)-9-iodo-10-(perfluor-
obutyl)-2-(perfluorobutylidene)-decanal (3l) (E/Z: 70:30) as a
1
mmol, 79%). H NMR (300 MHz, CDCl3) δ 10.21 (d, J = 0.8 Hz,
0.3H), 9.98 (d, J = 1.7 Hz, 0.7H), 2.50 (td, J = 7.3, 4.0 Hz, 1.4H),
2.37 (td, J = 6.9, 4.4 Hz, 2.7H), 1.68 (dddd, J = 12.7, 8.9, 6.9, 2.7 Hz,
2H), 1.63−1.49 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3) δ 187.4
(d, J = 18.4 Hz), 187.2 (dd, J = 11.1, 9.3 Hz), 156.1 (dt, J = 279.6,
31.6 Hz), 156.1 (dt, J = 279.6, 31.6 Hz), 131.2 (d, J = 9.2 Hz), 128.2,
119.2, 119.2, 117.4−106.7 (CF signals, m), 28.5, 27.1, 25.3, 25.1, 22.5
(d, J = 4.1 Hz), 21.4, 16.9. 19F NMR (282 MHz, CDCl3) δ −80.33
(td, J = 8.9, 3.3 Hz, 2.1F), −80.45 (td, J = 9.2, 3.3 Hz, 0.9F), −105.08
(th, J = 9.7, 3.5 Hz, 0.7F), −112.27 (pd, J = 9.9, 3.6 Hz, 1.5F),
−116.21 (p, J = 9.0 Hz, 0.7F), −123.67 (ddt, J = 11.4, 8.5, 4.5 Hz,
1
colorless liquid (372 mg, 0.533 mmol, 74%). H NMR (300 MHz,
CDCl3) δ 10.21 (s, 1H, 0.3H), 9.98 (s, 0.7H), 4.32 (tt, J = 8.3, 5.0 Hz,
1H), 3.03−2.65 (m, 2H), 2.46 (td, J = 7.9, 7.4, 4.0 Hz, 1.6H), 2.31
(tt, J = 6.2, 3.0 Hz, 0.7H), 1.79 (dqt, J = 14.9, 9.6, 4.4 Hz, 2H), 1.50−
1.24 (m, 8H). 13C{1H} NMR (75 MHz, CDCl3) δ 187.7 (d, J = 18.3
Hz), 187.5−187.3 (m), 155.7 (d, J = 278.4 Hz), 155.7 (d, J = 278.4
Hz), 132.2 (d, J = 9.5 Hz), 129.2, 122.5−102.7 (CF signals, m), 41.8
(t, J = 20.8 Hz), 40.3, 29.5, 29.4, 29.1, 28.2, 28.1, 28.0, 23.4 (d, J = 3.9
Hz), 22.2, 20.6. 19F NMR (282 MHz, CDCl3) δ −80.50 (t, J = 9.2 Hz,
2.1F), −80.64 (t, J = 9.3 Hz, 0.9F), −81.16 (dt, J = 9.6, 6.0 Hz, 3F),
−106.59 (0.7F), −111.48 (dd, J = 29.1, 13.4 Hz, 0.35F), −112.26 (p,
J = 9.3 Hz, 1.5F), −112.43 (d, J = 35.4 Hz, 0.6F), −114.49 (dq, J =
22.8, 10.9 Hz, 0.7F), −115.45 (dq, J = 22.7, 11.4, 10.8 Hz, 0.34F),
−116.27 (p, J = 9.3 Hz, 0.7F), −124.63 (q, J = 10.1 Hz, 2F), −125.50
(t, J = 9.3 Hz), −125.99 (dq, J = 13.1, 7.0, 6.5 Hz, 1.9F), −127.20 (d,
0.3F), −127.11 (d, J = 8.2 Hz, 0.7F), −127.33 (d, J = 6.5 Hz). IR (ν
̃
in cm−1): 2943, 2355, 2249, 1695, 1353, 1232, 742. HRMS-ESI: calcd
+
for C11H13F8N2O [M + NH4 ] m/z 341.0895, found 341.0890; calcd
for C11H9F8NONa [M + Na+] m/z 346.0449, found 346.0443.
tert-Butyl-5-(perfluorobutylidene)-(6-oxohexyl)-carbamate (3j).
Following general procedure 1, tert-butyl-(6-oxohexyl)-carbamate
(2j) (172 mg, 0.799 mmol, 1.00 equiv), (S)-2,2,3,5-tetramethylimi-
dazolidin-4-one (1b) (23 mg, 0.16 mmol, 0.20 equiv), triphenyl-
phosphine (22 mg, 0.084 mmol, 0.10 equiv), nonafluoro-1-
iodobutane (0.27 mL, 1.6 mmol, 2.0 equiv), and 2,6-lutidine (0.12
mL, 1.0 mmol, 1.3 equiv) were mixed and irradiated for 15 h.
Washing with H2O instead of aqueous HCl and purification by flash
chromatography (n-pentane/Et2O 1:1) gave a mixture of (E)- and
(Z)-tert-butyl-5-(perfluorobutylidene)-(6-oxohexyl)-carbamate (3j)
(E/Z: 72:28) as a yellowish oil (270 mg, 0.653 mmol, 82%). 1H
NMR (300 MHz, CDCl3) δ 10.18 (d, J = 1.7 Hz, 0.3H), 9.95 (s,
0.7H), 4.57 (s, 1H), 3.10 (dq, J = 11.6, 5.7 Hz, 2H), 2.44 (q, J = 6.6,
5.9 Hz, 1.4H), 2.35−2.23 (m, 0.6H), 1.45 (s, 4H), 1.41 (d, J = 1.9 Hz,
9H). 13C{1H} NMR (75 MHz, CDCl3) δ 187.6 (d, J = 18.7 Hz),
187.3 (q, J = 9.4 Hz), 156.1, 158.2−153.0 (m), 158.2−153.0 (m),
131.9 (d, J = 9.4 Hz), 128.9, 122.7−105.1 (CF signals, m), 79.3, 40.1,
30.1, 29.9, 28.5, 26.8, 25.3, 23.1 (d, J = 4.1 Hz), 21.9. 19F NMR (282
MHz, CDCl3) δ −80.35 (td, J = 9.0, 2.5 Hz, 2.1F), −80.48 (td, J =
J = 8.3 Hz, 0.6F), −127.48 (d, J = 6.7 Hz, 1.4F). IR (ν
̃
in cm−1):
2935, 2359, 1697, 1660, 1456, 1233, 742. HRMS-ESI: The compound
could not be ionized by HRMS-ESI. Therefore, this compound was
characterized as its 2,4-dinitrophenyl hydrazone derivative (see 4l).
2-(Perfluorohexylidene)-octanal (3m). Following general proce-
dure 1, octanal (2a) (102 mg, 0.796 mmol, 1.0 equiv), (S)-2,2,3,5-
tetramethylimidazolidin-4-one (1b) (24 mg, 0.17 mmol, 0.21 equiv),
triphenylphosphine (21 mg, 0.080 mmol, 0.10 equiv), tridecafluoro-1-
iodohexane (0.35 mL, 1.6 mmol, 2.0 equiv), and 2,6-lutidine (0.12
mL, 1.0 mmol, 1.3 equiv) were mixed and irradiated for 16 h.
Purification by flash chromatography (n-pentane/Et2O 50:1) gave a
mixture of (E)- and (Z)-2-(perfluorohexylidene)-octanal (3m) (E/Z:
1
69:31) as a colorless liquid (226 mg, 0.530 mmol, 67%). H NMR
(600 MHz, CDCl3) δ 10.2 (s, 0.7H), 10.0 (s, 0.7H), 2.4 (td, J = 7.9,
4.2 Hz, 1.4H), 2.3−2.3 (m, 0.6H), 1.4 (ddd, J = 15.3, 9.1, 7.2 Hz,
2H), 1.4−1.2 (m, 8H), 0.9 (t, J = 6.7 Hz, 3H). 13C{1H} NMR (126
MHz, CDCl3) δ 187.7 (d, J = 24.5 Hz), 187.7−187.4 (m), 157.1−
154.0 (m), 157.1−154.0 (m), 132.5 (d, J = 9.6 Hz), 129.5, 121.0−
106.1 (CF signals, m), 31.5, 31.5, 29.6, 29.4, 29.1, 28.2, 23.6 (d, J =
3.8 Hz), 22.6, 22.4 (t, J = 3.7 Hz), 14.0. 19F NMR (565 MHz, CDCl3)
δ −80.8 (q, J = 10.4 Hz, 3F), −106.6 (tq, J = 11.0, 6.1, 4.8 Hz, 0.7F),
−111.3 (q, J = 14.1, 12.3 Hz, 1.6F), −115.3 (dd, J = 15.5, 8.7 Hz,
0.7F), −122.6 to −122.8 (m, 2F), −122.9 to −123.0 (m, 0.7F),
−123.1 to −123.2 (m, 1.3F), −125.6 (dtd, J = 17.3, 8.7, 5.6 Hz, 0.3F),
9.1, 2.6 Hz, 0.9F), −105.93 (dqt, J = 10.3, 6.6, 3.0 Hz, 0.7F), −112.06
to −112.56 (m, 1.6F), −115.97 to −116.41 (m, 0.6F), −124.80 (s,
0.3F) −127.13 (d, J = 8.2 Hz, 0.6F), −127.38 (dt, J = 6.7, 3.1 Hz,
1.4F). IR (ν
̃
in cm−1): 3359, 2936, 1693, 1514, 1354, 1233, 974, 742.
HRMS-ESI: calcd for C15H20F8NO3 [M + H+] m/z 414.1310, found
414.1306.
6-Iodo-2-(perfluorobutylidene)-hexanal (3k). Following general
procedure 1, 6-iodohexanal (2k) (183 mg, 0.810 mmol, 1.00 equiv),
(S)-2,2,3,5-tetramethylimidazolidin-4-one (1b) (24 mg, 0.17 mmol,
0.21 equiv), triphenylphosphine (23 mg, 0.080 mmol, 0.11 equiv),
nonafluoro-1-iodobutane (0.27 mL, 1.6 mmol, 2.0 equiv), and 2,6-
lutidine (0.12 mL, 1.0 mmol, 1.2 equiv) were mixed and irradiated for
16 h. Purification by flash chromatography (n-pentane/Et2O 9:1)
−126.2 (ddd, J = 17.9, 12.2, 5.2 Hz, 2F). IR (ν
̃
in cm−1): 2934, 2864,
1697, 1659, 1463, 1362, 1241, 726. HRMS-APCI: calcd for
C14H13F12O [M − H]+ m/z 425.0769, found 425.0761.
2-(Perfluorooctylidene)-octanal (3n). Following general proce-
dure 1, octanal (2a) (96 mg, 0.75 mmol, 1.0 equiv), (S)-2,2,3,5-
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tetramethylimidazolidin-4-one (1b) (23 mg, 0.16 mmol, 0.21 equiv),
triphenylphosphine (21 mg, 0.080 mmol, 0.11 equiv), heptadeca-
fluoro-1-iodooctane (894 mg, 1.64 mmol, 2.19 equiv), and 2,6-
lutidine (0.12 mL, 1.0 mmol, 1.3 equiv) were mixed and irradiated for
16 h. Purification by flash chromatography (n-pentane to n-pentane/
Et2O 200:1) gave a mixture of (E)- and (Z)-2-(perfluorooctylidene)-
octanal (3n) (E/Z: 72:28) as a colorless liquid (0.24 g, 0.45 mmol,
60%). 1H NMR (300 MHz, CDCl3) δ 10.21 (s, 0.2H), 9.98 (d, J = 1.6
Hz, 0.8H), 2.51−2.39 (m, 1.5H), 2.37−2.23 (m, 0.6H), 1.42−1.20
(m, 8H), 0.86 (d, J = 6.9 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3)
δ 187.8 (d, J = 17.9 Hz), 178.8−187.3 (m), 158.1−153.3 (m), 158.1−
153.3 (m), 132.5 (d, J = 9.7 Hz), 129.5, 123.8−102.6 (CF signals, m),
31.5, 31.5, 29.7 (d, J = 2.6 Hz), 29.5, 29.1, 28.2, 23.5 (d, J = 3.9 Hz),
22.6, 22.4, 14.0. 19F NMR (282 MHz, CDCl3) δ −80.7 (tt, J = 9.8, 2.5
Hz, 3F), −106.4 (ttt, J = 10.9, 7.4, 4.0 Hz, 0.8F), −111.1 (dtd, J =
14.0, 10.8, 5.7 Hz, 1.5F), −114.6 to −115.8 (m 0.6F), −121.6 to
−122.1 (m, 3.9F), −122.5 to −122.8 (m, 0.6F), −122.8 to −123.1
(m, 1.4F), −125.5 (td, J = 8.8, 4.5 Hz, 0.3F), −126.1 (ddq, J = 18.5,
J = 13.0, 10.6, 8.0, 2.8 Hz, 0.4F), −127.24 (h, J = 5.3 Hz, 0.7F),
in cm−1): 3291, 2930, 2857,
1617, 1507, 1334, 1230, 911, 741. HRMS-ESI: calcd for
C18H19F8O4N4 [M + H+] m/z 507.1273, found 507.1274, mp:
137−138 °C.
−127.48 (dd, J = 6.6, 3.1 Hz, 1.4F). IR (ν
̃
1-(2,4-Dinitrophenyl)-(2-(perfluorobutylidene)-3-phenylpropyli-
dene)-hydrazone (4b). Following general procedure 2, 2-(perfluor-
obutylidene)-3-phenylpropanal (3b) (99 mg, 0.30 mmol, 1.0 equiv)
and 2,4-dinitrophenylhydrazine (179 mg, 0.902 mmol, 3.01 equiv)
were reacted. Purification by flash chromatography (n-pentane/Et2O
4:1) gave a mixture of (E)- and (Z)-1-(2,4-dinitrophenyl)-(2-
(perfluorobutylidene)-3-phenylpropylidene)-hydrazone (4b) (E/Z:
1
69:31) as a yellow solid (0.14 g, 0.27 mmol, 90%). H NMR (300
MHz, CDCl3) δ 11.29 (s, 1H), 9.12 (d, J = 2.5 Hz, 0.8H), 9.10 (d, J =
2.6 Hz, 0.2H), 8.36 (ddd, J = 9.6, 2.5, 0.7 Hz, 0.2H), 8.32−8.26 (m,
0.2H), 8.20 (s, 0.2H), 8.01 (s, 0.8H), 7.79 (d, J = 9.5 Hz, 0.8H), 7.59
(d, J = 9.5 Hz, 0.2H), 7.35−7.26 (m, 3H), 7.26−7.20 (m, 2H), 4.07
(d, J = 4.5 Hz, 1.6H), 3.99 (s, 0.4H). 13C{1H} NMR (75 MHz,
CDCl3) δ 147.5 (dt, J = 262.8, 28.9 Hz), 147.5 (dt, J = 262.8, 28.9
Hz), 144.4, 144.3, 140.3 (d, J = 12.0 Hz), 139.8 (t, J = 6.6 Hz), 139.4,
139.3, 137.7, 137.4 (d, J = 2.0 Hz), 130.3 (d, J = 2.9 Hz), 130.2,
128.9, 128.8, 128.3 (d, J = 1.2 Hz), 127.9, 127.7, 127.5, 127.0, 126.9,
123.3, 123.2, 116.9, 116.8, 116.4−105.8 (CF signals, m), 31.0 (d, J =
5.6 Hz), 29.8. 19F NMR (282 MHz, CDCl3) δ −80.30 (td, J = 8.9, 2.6
Hz, 2.3F), −80.44 (td, J = 9.0, 2.6 Hz, 0.7F), −113.06 to −113.25 (m,
1.6F), −113.60 (qd, J = 9.3, 6.9 Hz, 0.5F), −113.72 to −113.93 (m,
0.8F), −121.29 (ddt, J = 12.3, 7.0, 3.5 Hz, 0.3F), −126.95 (d, J = 7.6
10.8, 3.7 Hz, 2F). IR (ν
̃
in cm−1): 2934, 2864, 1697, 1659, 1458,
1366, 1243, 1024, 710, HRMS-APCI: calcd for C16H13F16O [M −
H]+ m/z 525.0705, found 525.0694.
Ethyl-2-fluoro-3-formyl-non-2-enoate (3o). Following general
procedure 1, octanal (2a) (97 mg, 0.76 mmol, 1.0 equiv), (S)-
2,2,3,5-tetramethylimidazolidin-4-one (1b) (23 mg, 0.16 mmol, 0.21
equiv), triphenylphosphine (22 mg, 0.084 mmol, 0.11 equiv), ethyl
iododifluoroacetate (0.24 mL, 1.6 mmol, 2.1 equiv), and 2,6-lutidine
(0.12 mL, 1.0 mmol, 1.3 equiv) were mixed and irradiated for 16 h.
Purification by flash chromatography (n-pentane/Et2O 98.5:1.5) gave
isolated (E)-ethyl-2-fluoro-3-formyl-non-2-enoate ((E)-3o) (0.10 mg,
0.45 mmol, 59%) and (Z)-ethyl-2-fluoro-3-formyl-non-2-enoate ((Z)-
3o) (23 mg, 0.10 mmol, 13%) as colorless liquids. (E)-Ethyl-2-fluoro-
3-formyl-non-2-enoate ((E)-3o) (major product): 1H NMR (300
MHz, CDCl3) δ 10.49 (d, J = 1.2 Hz, 1H), 4.37 (qd, J = 7.1, 0.8 Hz,
2H), 2.37 (td, J = 7.4, 3.6 Hz, 2H), 1.37 (td, J = 7.1, 0.8 Hz, 5H), 1.26
(qd, J = 7.7, 2.4 Hz, 6H), 0.88−0.77 (m, 3H). 13C{1H} NMR (126
MHz, CDCl3) δ 191.4 (d, J = 10.7 Hz), 159.6 (d, J = 35.4 Hz), 157.2
(d, J = 283.2 Hz), 133.3 (d, J = 9.7 Hz), 62.8, 31.6, 29.3, 28.2, 28.2,
23.5 (d, J = 3.7 Hz), 22.6, 14.1, 14.1. 19F NMR (282 MHz, CDCl3) δ
Hz, 0.5F), −127.11 to −127.26 (m, 1.5F). IR (ν
̃
in cm−1): 3291,
3108, 3032, 1618, 1507, 1335, 1231, 1140, 876, 742. HRMS-ESI:
calcd for C19H13F8O4N4 [M + H+] m/z 513.0804, found 513.0809,
mp: 142−144 °C.
1-(2,4-Dinitrophenyl)-(2-(perfluorobutylidene)-4-phenylbutyli-
dene)-hydrazone (4c). Following general procedure 2, 2-(perfluor-
obutylidene)-4-phenyl-butanal (3c) (0.10 g, 0.30 mmol, 1.0 equiv)
and 2,4-dinitrophenylhydrazine (178 mg, 0.897 mmol, 3.00 equiv)
were reacted. Purification by flash chromatography (n-pentane/Et2O
9:1) gave a mixture of (E)- and (Z)-1-(2,4-dinitrophenyl)-(2-
(perfluorobutylidene)-4-phenylbutylidene)-hydrazone (4c) (E/Z:
1
−104.66 (d, J = 3.0 Hz). IR (ν
̃
in cm−1): 2932, 2861, 1732, 1684,
80:20) as a yellow solid (81 mg, 0.15 mmol, 51%). H NMR (600
MHz, CDCl3) δ 11.39 (s, 0.8H), 11.30 (s, 0.2H), 9.16 (dd, J = 6.8,
2.6 Hz, 1H), 8.40 (dd, J = 9.6, 2.7 Hz, 1H), 8.20 (s, 0.8H), 7.96 (s,
0.2H), 7.91 (d, J = 9.5 Hz, 0.8H), 7.88 (d, J = 9.5 Hz, 0.2H), 7.32 (dt,
J = 21.2, 7.4 Hz, 2H), 7.23 (dt, J = 20.4, 6.7 Hz, 3H), 3.07−3.01 (m,
0.4H), 2.90 (d, J = 5.4 Hz, 3.6H). 13C{1H} NMR (151 MHz, CDCl3)
δ 147.0 (d, J = 269.1 Hz), 144.4, 140.7, 140.5 (d, J = 12.4 Hz), 139.9,
139.5, 139.4, 130.5, 130.4, 130.37, 128.9, 128.7, 128.5, 128.4, 126.8,
126.7, 126.1, 123.5, 123.5, 116.8, 116.7, 36.2, 34.7, 27.4, 26.3. 19F
NMR (282 MHz, CDCl3) δ −80.35 (td, J = 9.0, 2.7 Hz, 0.6F),
−80.48 (td, J = 9.1, 2.7 Hz, 2.4F), −113.05 to −113.31 (m, 0.4F),
−114.27 to −114.46 (m, 0.2F), −114.62 (qdt, J = 10.7, 6.8, 3.5 Hz,
1.7F), −122.96 (dddq, J = 13.0, 7.9, 5.3, 2.6 Hz, 0.8F), −127.12 (qd, J
1467, 1370, 1296, 1102, 1032, 862. HRMS-ESI: calcd for C12H20FO3
[M + H+] m/z 231.1391, found 231.1389. (Z)-Ethyl-2-fluoro-3-
formyl-non-2-enoate ((Z)-3o) (minor product): 1H NMR (300
MHz, CDCl3) δ 10.28 (t, J = 0.7 Hz, 1H), 4.38 (q, J = 7.2 Hz, 2H),
2.66−2.43 (m, 2H), 1.39 (t, J = 7.1 Hz, 5H), 1.35−1.23 (m, 6H),
0.91−0.82 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 189.8 (d, J
= 18.2 Hz), 160.6 (d, J = 35.2 Hz), 156.5 (d, J = 280.5 Hz), 130.3,
62.6, 31.6, 29.5, 29.3 (d, J = 3.2 Hz), 23.1, 22.7, 14.2, 14.1. 19F NMR
(282 MHz, CDCl3) δ −123.79. IR (ν
̃
in cm−1): 2930, 2859, 1737,
1691, 1466, 1320, 1221, 1106, 1027, 862. HRMS-ESI: calcd for
C12H20FO3 [M + H+] m/z 231.1391, found 231.1388.
1-(2,4-Dinitrophenyl)-2-(2-(perfluorobutylidene)-octylidene)-hy-
drazone (4a). Following general procedure 2, 2-(perfluorobutyli-
dene)-octanal (3a) (104 mg, 0.319 mmol, 1.00 equiv) and 2,4-
dinitrophenylhydrazine (401 mg, 2.02 mmol, 6.28 equiv) were
reacted. Purification by flash chromatography (n-pentane/Et2O 9:1)
gave a mixture of (E)- and (Z)-1-(2,4-dinitrophenyl)-2-(2-(perfluor-
obutylidene)-octylidene)-hydrazone (4a) (E/Z: 70:30) as a yellow
= 7.2, 2.4 Hz, 1.6F), −127.36 (dd, J = 7.2, 2.5 Hz, 0.4F). IR (ν in
̃
cm−1): 3289, 3108, 2928, 1619, 1512, 1335, 1234, 1124, 912, 741.
HRMS-ESI: calcd for C20H15F8O4N4 [M + H+] m/z 527.0960, found
527.0961, mp: 159−161 °C.
1-(2,4-Dinitrophenyl)-(2-(perfluorobutylidene)-2-cyclohexylethy-
lidene)-hydrazone (4d). Following general procedure 2, 2-(perfluor-
obutylidene)-2-cyclohexyl-ethanal (3d) (96 mg, 0.30 mmol, 1.00
equiv) and 2,4-dinitrophenylhydrazine (178 mg, 0.900 mmol, 3.00
equiv) were reacted. Purification by flash chromatography (n-
pentane/Et2O 3:1) gave a mixture of (E)- and (Z)-1-(2,4-
dinitrophenyl)-(2-(perfluorobutylidene)-2-cyclohexylethylidene)-hy-
drazone (4d) (E/Z: 92:8) as a yellow solid (0.13 g, 0.26 mmol, 88%).
1H NMR (300 MHz, CDCl3) δ 11.27 (s, 1H), 9.15 (d, J = 2.6 Hz,
1H), 8.42 (ddd, J = 9.5, 2.6, 0.7 Hz, 1H), 8.06 (s, 0.1H), 7.90 (d, J =
9.5 Hz, 1.9H), 3.14 (td, J = 11.6, 5.7 Hz, 1H), 1.84 (dd, J = 26.7, 13.9
Hz, 7H), 1.48−1.19 (m, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ
147.2 (dt, J = 265.3, 28.5 Hz), 144.5, 144.5, 140.8 (d, J = 12.5 Hz),
140.5 (q, J = 6.4 Hz), 139.2, 139.2, 132.1 (d, J = 16.2 Hz), 130.6,
130.5, 130.4, 130.3, 130.2, 123.5, 123.4, 116.8, 116.7, 115.5−107.5
1
solid (121 mg, 0.239 mmol, 75%). H NMR (300 MHz, CDCl3) δ
11.37 (s, 0.3H), 11.32 (s, 0.7H), 9.16 (dd, J = 2.6, 1.6 Hz, 1H), 8.39
(dd, J = 9.5, 2.6 Hz, 1H), 8.16 (s, 0.3H), 7.98 (s, 0.7H), 7.92 (d, J =
9.6 Hz, 1H), 2.72 (q, J = 6.6 Hz, 1.4H), 2.58 (s, 0.6H), 1.59 (t, J = 6.8
Hz, 2H), 1.35 (ddt, J = 11.4, 7.7, 4.7 Hz, 6H), 0.91 (dq, J = 7.1, 4.7,
3.5 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 146.9 (d, J = 262.2
Hz), 144.5, 140.9 (d, J = 12.7 Hz), 140.3 (d, J = 6.9 Hz), 139.3, 139.3,
130.4, 130.2, 129.0 (d, J = 18.9 Hz), 127.0, 123.4, 116.7, 116.7,
116.2−104.2 (CF signals, m), 31.6, 31.5, 29.9 (d, J = 4.8 Hz), 29.6,
29.2, 28.4, 25.3 (d, J = 5.0 Hz), 24.1, 22.6, 14.1. 19F NMR (282 MHz,
CDCl3) δ −80.47 (td, J = 9.0, 2.8 Hz, 2F), −80.61 (td, J = 9.0, 2.6 Hz,
1F), −113.13 (pq, J = 9.1, 3.0 Hz, 1.5F), −114.52 (pd, J = 9.4, 2.9 Hz,
0.7F), −115.29 (ddtt, J = 12.5, 9.6, 6.1, 3.4 Hz, 0.7F), −124.10 (dddd,
7434
https://doi.org/10.1021/acs.joc.1c00383
J. Org. Chem. 2021, 86, 7425−7438

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(CF signals, m), 38.4, 37.2, 31.1 (d, J = 2.2 Hz), 30.1 (d, J = 3.7 Hz),
26.9, 26.7, 26.3, 26.0. 19F NMR (565 MHz, CDCl3) δ −80.48 (t, J =
8.8 Hz, 3F), −112.46 (pd, J = 8.9, 4.1 Hz, 1.8F), −112.94 (p, J = 7.3,
6.6 Hz, 0.3F), −114.66 (q, J = 11.2, 9.8 Hz, 0.9F), −120.09 (d, J = 9.2
Hz, 0.16F), −127.44 (t, J = 5.6 Hz, 1.6F), −127.63 (d, J = 6.1 Hz,
1.41−1.24 (m, 7H), 0.94−0.78 (m, 3H). 13C{1H} NMR (75 MHz,
CDCl3) δ 144.8−139.7 (m), 131.2, 131.1, 123.3−102.6 (CF signals,
m), 58.4 (d, J = 11.7 Hz), 57.8 (d, J = 6.5 Hz), 31.6 (d, J = 1.6 Hz),
29.4, 29.2, 28.6 (d, J = 2.9 Hz), 27.5, 27.4, 26.0, 22.7, 14.1. 19F NMR
(282 MHz, CDCl3) δ −80.58 to −80.78 (m, 3F), −113.67 (dddd, J =
15.1, 12.8, 7.5, 3.8 Hz, 1.5F), −114.23 to −114.45 (m, 0.6F), −126.31
(tp, J = 10.2, 3.3 Hz, 0.7F), −127.66 (dd, J = 8.2, 2.4 Hz, 0.6F),
−127.95 (dtt, J = 10.8, 8.1, 2.8 Hz, 0.3F), −128.07 (dt, J = 7.7, 3.9
0.3F). IR (ν
̃
in cm−1): 3286, 2931, 2860, 1615, 1506, 1335, 1233,
1122, 737. HRMS-ESI: calcd for C18H17F8O4N4 [M + H+] m/z
505.1117, found 505.1117, mp: 168−170 °C.
1-(2,4-Dinitrophenyl)-6-iodo-(2-(perfluorobutylidene)-hexyli-
dene)-hydrazone (4k). Following general procedure 2, 6-iodo-2-
(perfluorobutylidene)-hexanal (3k) (128 mg, 0.302 mmol, 1.00
equiv) and 2,4-dinitrophenylhydrazine (178 mg, 0.897 mmol, 2.97
equiv) were reacted. Purification by flash chromatography (n-
pentane/Et2O 85:15) gave a mixture of (E)- and (Z)-1-(2,4-
dinitrophenyl)-6-iodo-(2-(perfluorobutylidene)-hexylidene)-hydra-
zone (4k) (E/Z: 60:40) as a yellow solid (175 mg, 0.290 mmol, 96%).
1H NMR (300 MHz, CDCl3) δ 11.40 (s, 0.4H), 11.35 (s, 0.6H), 9.15
Hz, 1.4F). IR (ν
̃
in cm−1): 3339, 2934, 1690, 1354, 1232, 1020, 746.
HRMS-ESI: The compound could not be ionized by HRMS-ESI.
Therefore, this compound was characterized as its 4-methoxybenzoate
derivative (6a).
Following general procedure 4, 2-(perfluorobutylidene)-octan-1-ol
(5a) (89 mg, 0.27 mmol, 1.0 equiv) and 4-methoxybenzoyl chloride
(0.050 mL, 0.37 mmol, 1.4 equiv) were reacted. Purification by flash
chromatography (n-pentane/Et2O 9:1) gave a mixture of (E)- and
(Z)-(2-(perfluorobutylidene)-octyl)-4-methoxy-benzoate (6a) (E/Z:
1
67:33) as a colorless oil (0.12 g, 0.25 mmol, 94%). H NMR (300
(dd, J = 2.6, 1.2 Hz, 1H), 8.40 (dd, J = 9.4, 2.6 Hz, 1H), 8.18 (s,
0.4H), 8.05−7.96 (m, 1.6H), 3.25 (td, J = 6.6, 1.6 Hz, 2H), 2.76 (td, J
= 7.8, 4.7 Hz, 1.2H), 2.66−2.56 (m, 0.8H), 2.02−1.86 (m, 2H),
1.86−1.66 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3) δ 149.4−145.2
(m), 145.4, 144.3, 140.5 (d, J = 12.4 Hz), 139.9 (d, J = 7.0 Hz), 139.5,
139.4, 130.4, 130.3, 128.2 (d, J = 18.7 Hz), 126.3, 123.4, 117.1, 117.0,
120.4−105.3 (CF signals, m), 33.4, 33.0, 30.4, 29.1, 24.3 (d, J = 5.4
Hz), 23.2, 6.2, 6.2. 19F NMR (282 MHz, CDCl3) δ −80.35 (td, J =
8.9, 2.6 Hz, 1.8F), −80.48 (td, J = 9.1, 2.7 Hz, 1.2F), −113.13 (qdd, J
= 8.8, 6.1, 3.0 Hz, 1.3F), −114.36 (pd, J = 9.2, 2.6 Hz, 0.8F), −114.53
(tdq, J = 11.9, 6.8, 3.3 Hz, 0.7F), −122.90 (tt, J = 13.0, 5.4 Hz, 0.4F),
−127.19 (dt, J = 7.8, 3.9 Hz, 0.8F), −127.34 (dd, J = 7.1, 3.0 Hz,
MHz, CDCl3) δ 8.20−7.73 (m, 2H), 7.06−6.78 (m, 2H), 5.02 (dt, J =
3.5, 1.7 Hz, 0.6H), 4.93 (q, J = 2.1 Hz, 1.3H), 3.87 (s, 3H), 2.44−2.33
(m, 1.3H), 2.33−2.24 (m, 0.7H), 1.51 (dd, J = 14.0, 6.1 Hz, 2H),
1.40−1.18 (m, 6H), 0.98−0.75 (m, 3H). 13C{1H} NMR (151 MHz,
CDCl3) δ 165.9, 165.9, 163.9, 131.9, 127.5 (d, J = 14.3 Hz), 127.3,
122.0, 121.9, 113.9, 113.9, 59.6 (d, J = 12.3 Hz), 59.2 (d, J = 7.2 Hz)
55.6, 31.6, 31.5, 29.3, 29.0, 28.5, 28.0 (d, J = 5.8 Hz), 27.3, 26.4, 22.6,
22.6, 14.1. CF signals could not be detected due to complex C−F
coupling. 19F NMR (282 MHz, CDCl3) δ −80.60 (td, J = 9.0, 2.7 Hz,
2.1F), −80.68 (td, J = 9.0, 2.8 Hz, 0.9F), −113.89 to −114.18 (m,
1.5F), −114.35 (pd, J = 10.0, 9.5, 3.4 Hz, 0.7F), −122.86 to −123.04
(m, 0.7F), −123.98 (dqt, J = 10.4, 7.8, 2.8 Hz, 0.3F), −127.62 (h, J =
1.2F). IR (ν
̃
in cm−1): 3289, 3110, 2945, 1616, 1507, 1333, 1230,
4.7 Hz, 0.6F), −127.76 (dd, J = 7.1, 2.4 Hz, 1.4F). IR (ν
̃
in cm−1):
1122, 1089, 835. HRMS-ESI: calcd for C16H14F8IO4N4 [M + H+] m/
z 604.9927, found 604.9924, mp: 160−162 °C.
2934, 2861, 1724, 1607, 1513, 1464, 1354, 1258, 1033, 847. HRMS-
ESI: calcd for C20H23F8O3 [M + H+] m/z 463.1514, found 463.1520.
2-(Perfluorobutylidene)-3-phenylpropan-1-ol (5b). Following
general procedure 3, 2-(perfluorobutylidene)-3-phenylpropanal (3b)
(0.12 g, 0.35 mmol, 1.0 equiv) and sodium borohydride (68 mg, 1.8
mmol, 5.2 equiv) were reacted. Purification by flash chromatography
(n-pentane/Et2O 4:1) gave a mixture of (E)- and (Z)-2-(perfluor-
obutylidene)-3-phenylpropan-1-ol (5b) (E/Z: 72:28) as a colorless
1-(2,4-Dinitrophenyl)-9-iodo-10-(perfluorobutyl)-2-(perfluorobu-
tylidene)-decylidene-hydrazone (4l). Following general procedure 2,
10-(perfluorobutyl)-9-iodo-2-(perfluorobutylidene)-decanal (3l) (200
mg, 0.286 mmol, 1.00 equiv) and 2,4-dinitrophenylhydrazine (170
mg, 0.859 mmol, 3.00 equiv) were reacted. Purification by flash
chromatography (n-pentane/Et2O 3:1) gave a mixture of (E)- and
(Z)-1-(2,4-dinitrophenyl)-9-iodo-10-(perfluorobutyl)-2-(perfluorobu-
tylidene)-decylidene-hydrazone (4l) (E/Z: 73:27) as a yellow grease
1
oil (89 mg, 0.27 mmol, 76%). H NMR (600 MHz, CDCl3) δ 7.36−
1
(242 mg, 0.276 mmol, 96%). H NMR (300 MHz, CDCl3) δ 11.38
7.29 (m, 2H,), 7.29−7.23 (m, 1H), 7.24−7.20 (m, 2H), 4.26 (ddd, J
= 6.9, 3.7, 1.8 Hz, 0.6H), 4.18 (dq, J = 6.5, 2.2 Hz, 1.5H), 3.76 (dt, J =
3.6, 1.6 Hz, 1.5H), 3.70 (t, J = 2.0 Hz, 0.5H), 1.42 (td, J = 6.6, 1.3 Hz,
0.3H), 1.36 (td, J = 6.4, 1.2 Hz, 0.7H). 13C{1H} NMR (151 MHz,
CDCl3) δ 143.5−140.8 (m), 143.5−140.8 (m), 136.9, 136.6 (d, J =
3.0 Hz), 129.9 (d, J = 9.9 Hz), 129.4 (d, J = 8.5 Hz), 129.0, 129.0,
128.9, 127.2, 127.2, 122.2−105.3 (CF signals, m), 57.6 (d, J = 11.1
Hz), 56.9 (q, J = 6.3 Hz), 32.7 (d, J = 6.6 Hz), 31.3. 19F NMR (565
MHz, CDCl3) δ −80.57 (t, J = 9.2 Hz, 3F), −113.22 (p, J = 8.4 Hz,
0.6F), −113.70 (t, J = 9.4 Hz, 1.5F), −125.38 (t, J = 9.9 Hz, 0.7F),
(s, 0.3H), 11.33 (s, 0.7H), 9.16 (dd, J = 2.6, 1.7 Hz, 1H), 8.44−8.37
(m, 1H), 8.17 (s, 0.3H), 7.98 (s, 0.7H), 7.91 (d, J = 9.5 Hz, 1H), 4.32
(ddd, J = 13.3, 8.4, 4.9 Hz, 1H), 3.06−2.53 (m, 4H), 1.86−1.72 (m,
2H), 1.61 (s, 2H), 1.42 (s, 6H). 13C{1H} NMR (75 MHz, CDCl3) δ
149.4−144.9 (m), 144.5, 140.9 (d, J = 12.6 Hz), 140.2 (d, J = 6.9
Hz), 139.3, 139.3, 130.4 (d, J = 1.9 Hz, 2 x), 130.3, 128.80 (d, J = 18.8
Hz), 126.82, 123.39, 116.7, 116.7, 122.3−104.4 (CF signals, m), 41.7
(t, J = 20.8 Hz), 40.2 (d, J = 2.2 Hz), 29.8, 29.6, 29.5, 29.2, 28.3, 28.2,
25.2 (d, J = 5.2 Hz), 24.0, 20.7. 19F NMR (282 MHz, CDCl3) δ
−80.59 (td, J = 9.0, 2.7 Hz, 2.1F), −80.72 (td, J = 9.1, 2.6 Hz, 0.9F),
−81.21 (tt, J = 9.7, 3.3 Hz, 3F), −111.25 to −111.69 (m, 0.3F),
−112.42 (tt, J = 24.1, 12.7 Hz, 0.6F), −113.21 (p, J = 9.6 Hz, 1.4F),
−114.56 (ddddq, J = 18.9, 15.4, 11.7, 7.4, 3.8 Hz, 1.2F), −115.16
(tdd, J = 15.8, 7.3, 3.6 Hz, 0.7F), −115.53 (dq, J = 22.7, 11.5, 10.9 Hz,
0.3F), −123.89 (p, J = 9.8 Hz, 0.3F), −124.68 (qd, J = 9.5, 4.8 Hz,
2F), −126.04 (tdd, J = 12.8, 10.9, 9.0, 5.8 Hz, 2F), −127.32 (dd, J =
−125.56 (t, J = 8.5 Hz, 0.3F), −127.39 (d, J = 7.2 Hz, 0.5F), −127.85
−1
(d, J = 6.9 Hz, 1.4F). IR (ν in cm ): 3365, 3033, 2935, 1692, 1604,
̃
1455, 1353, 1233, 1122, 1031, 850, 746. HRMS-ESI: calcd for
+
C13H14F8ON [M + NH4 ] m/z 352.0942, found 352.0943.
2-(Perfluorobutylidene)-4-phenylbutan-1-ol (5c). Following gen-
eral procedure 3, 2-(perfluorobutylidene)-4-phenylbutanal (3c) (0.12
g, 0.33 mmol, 1.0 equiv) and sodium borohydride (78 mg, 2.0 mmol,
6.0 equiv) were reacted. Purification by flash chromatography (n-
pentane/Et2O 4:1) gave a mixture of (E)- and (Z)-2-(perfluor-
obutylidene)-4-phenylbutan-1-ol (5c) (E/Z: 72:28) as a colorless oil
(88 mg, 0.25 mmol, 76%). 1H NMR (300 MHz, CDCl3) δ 7.32
(dddd, J = 7.7, 6.0, 3.0, 1.3 Hz, 2H), 7.23 (tt, J = 7.2, 1.6 Hz, 3H),
4.37 (ddt, J = 5.8, 3.7, 1.8 Hz, 0.6H), 4.20 (dq, J = 6.5, 2.3 Hz, 1.4H),
2.83 (qd, J = 8.0, 3.3 Hz, 2H), 2.71 (dddd, J = 10.6, 5.0, 2.7, 1.3 Hz,
1.5H), 2.66−2.57 (m, 0.6H), 1.63−1.52 (m, 0.4H), 1.39 (h, J = 5.6,
5.1 Hz, 0.7H). 13C{1H} NMR (75 MHz, CDCl3) δ 142.6 (d, J =
254.3 Hz), 140.8, 140.7, 130.4, 130.3, 128.78, 128.7, 128.5, 128.5,
126.6, 126.6, 123.2−97.8 (CF signals, m), 58.6 (d, J = 11.7 Hz), 58.0
(d, J = 6.5 Hz), 35.3, 33.9 (d, J = 2.2 Hz), 29.4 (d, J = 5.5 Hz), 28.0.
19F NMR (282 MHz, CDCl3) δ −80.66 (dtd, J = 16.2, 9.0, 2.5 Hz,
8.2, 6.0 Hz, 0.6F), −127.53 (dd, J = 7.1, 2.9 Hz, 1.4F). IR (ν in
̃
cm−1): 3293, 3108, 2935, 2861, 1619, 1514, 1435, 1336, 1233, 1136,
+
835, 741. HRMS-ESI: calcd for C24H24F8IO4N5 [M + NH4 ] m/z
896.0596, found 896.0606.
2-(Perfluorobutylidene)-octan-1-ol (5a). Following general pro-
cedure 3, 2-(perfluorobutylidene)-octan-1-al (3a) (191 mg, 0.585
mmol, 1.00 equiv) and sodium borohydride (133 mg, 3.41 mmol,
5.82 equiv) were reacted. Purification by flash chromatography (n-
pentane/Et2O 95:5) gave a mixture of (E)- and (Z)-2-(perfluor-
obutylidene)-octan-1-ol (5a) (E/Z: 70:30) as a colorless oil (166 mg,
0.506 mmol, 86%). 1H NMR (300 MHz, CDCl3) δ 4.36 (ddt, J = 6.8,
3.6, 1.7 Hz, 0.6H), 4.25 (dq, J = 6.5, 2.2 Hz, 1.6H), 2.43−2.34 (m,
1.4H), 2.28 (ddq, J = 10.5, 4.6, 2.5 Hz, 0.6H), 1.57−1.41 (m, 2H),
7435
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J. Org. Chem. 2021, 86, 7425−7438

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
3F), −113.86 (qd, J = 9.2, 6.5 Hz, 1.5F), −114.54 (pd, J = 9.8, 2.8 Hz,
0.6F), −125.23 (tdp, J = 10.1, 6.8, 2.9 Hz, 0.7F), −126.76 (ddp, J =
10.7, 8.2, 3.3, 2.9 Hz, 0.3F), −127.58 (d, J = 7.7 Hz, 0.6F), −127.94
AUTHOR INFORMATION
■
Corresponding Author
to −128.05 (m, 1.4F). IR (ν
̃
in cm−1): 3364, 2936, 1691, 1354, 1232,
Constantin Czekelius − Department of Organic Chemistry
and Macromolecular Chemistry, Heinrich-Heine-Universität
̈ ̈
Dusseldorf, 40225 Dusseldorf, Germany; orcid.org/0000-
0002-2814-8686; Email: constantin.czekelius@hhu.de;
Fax: +49-211-8115362
+
1016, 746. HRMS-ESI: calcd for C14H16F8ON [M + NH4 ] m/z
366.1099, found 366.1101.
2-(Perfluorobutylidene)-2-cyclohexylethan-1-ol (5d). Following
general procedure 3, 2-(perfluorobutylidene)-2-cyclohexylethanal
(3d) (80 mg, 0.25 mmol, 1.00 equiv) and sodium borohydride (87
mg, 2.2 mmol, 9 equiv) were reacted. Purification by flash
chromatography (n-pentane/Et2O 4:1) gave a mixture of (E)- and
(Z)-2-(perfluorobutylidene)-2-cyclohexylethan-1-ol (5d) (E/Z:
Author
Christian Wulkesch − Department of Organic Chemistry and
Macromolecular Chemistry, Heinrich-Heine-Universität
1
85:15) as a colorless oil (73 mg, 0.22 mmol, 90%). H NMR (300
Dusseldorf, 40225 Dusseldorf, Germany
̈ ̈
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00383
MHz, CDCl3) δ 4.31 (ddt, J = 6.5, 3.8, 1.1 Hz, 0.3H), 4.21 (dq, J =
6.5, 2.1 Hz, 1.7H), 2.69 (tt, J = 11.8, 3.5 Hz, 0.85H), 2.57 (t, J = 11.7
Hz, 0.15H), 1.87−1.64 (m, 5H), 1.60−1.10 (m, 6H). 13C{1H} NMR
(75 MHz, CDCl3) δ 143.1 (dt, J = 255.3, 28.2 Hz), 135.2, 134.5 (d, J
= 8.2 Hz), 123.5−103.8 (CF signals, m), 58.0−54.3 (m), 39,0 (d, J =
4.5 Hz), 37.0, 30.8 (d, J = 2.8 Hz), 30.4 (d, J = 2.4 Hz), 26.5, 26.1,
25.9, 25.8. 19F NMR (282 MHz, CDCl3) δ −80.75 (qd, J = 8.6, 2.8
Hz, 3F), −113.29 to −113.53 (m, 1.8F), −113.78 to −113.98 (m,
0.3F), −125.28 (qdt, J = 10.1, 6.6, 3.0 Hz, 0.9F), −127.64 (tdd, J =
11.6, 6.6, 3.3 Hz, 0.1F), −128.08 (dt, J = 8.1, 4.3 Hz, 1.7F), −128.12
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
to −128.21 (m, 0.3F). IR (ν
̃
in cm−1): 3364, 2936, 1691, 1456, 1354,
This research was funded by the Deutsche Forschungsgemein-
1232, 1016, 746. HRMS-ESI: The compound could not be ionized by
HRMS-ESI. Therefore, this compound was characterized as its 4-
methoxybenzoate derivative (see 6d).
schaft (DFG, German Research Foundation)396890929/
GRK 2482. We thank Gulin Kurt for initial experimental
̈
studies on organocatalyst design.
Following general procedure 4, 2-(perfluorobutylidene)-2-cyclo-
hexylethan-1-ol (5d) (27 mg, 0.083 mmol, 1.0 equiv) and 4-
methoxybenzoyl chloride (0.020 mL, 0.15 mmol, 1.8 equiv) were
reacted. Purification by flash chromatography (n-pentane/Et2O 9:1)
gave a mixture of (E)- and (Z)-(2-(perfluorobutylidene)-4-phenyl-
butyl)-4-methoxy-benzoate (6d) (E/Z: 85:15) as a colorless oil (30
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* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00383.
Reaction setup with a photoreactor; NMR spectra of
organocatalyst 1b and intermediates; and NMR spectra
of new compounds (PDF)
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