Efficient SN2 fluorination of primary and secondary alkyl bromides by copper(I) fluoride complexes

Article abstract of DOI:10.1021/om4008967

Copper(I) fluoride complexes ligated by phenanthroline derivatives have been synthesized and structurally characterized by X-ray crystallography. These complexes adopt as either ionic or neutral forms in the solid state, depending on the steric bulkiness of the substituent groups on the phenanthroline ligands. These complexes react with primary and secondary alkyl bromides to produce the corresponding alkyl fluorides in modest to good yields. This new method is compatible with a variety of important functional groups such as ether, thioether, amide, nitrile, methoxyl, hydroxyl, ketone, ester, and heterocycle moieties.

Full text of DOI:10.1021/om4008967

Article
pubs.acs.org/Organometallics
Efficient SN2 Fluorination of Primary and Secondary Alkyl Bromides
by Copper(I) Fluoride Complexes
Yanpin Liu,† Chaohuang Chen,† Huaifeng Li,‡ Kuo-Wei Huang,*,‡ Jianwei Tan,† and Zhiqiang Weng*,†
†Department of Chemistry, Fuzhou University, Fujian 350108, China
‡Division of Physical Sciences and Engineering and KAUST Catalysis Center, King Abdullah University of Science and Technology
(KAUST), Thuwal 23955-6900, Saudi Arabia
S
* Supporting Information
ABSTRACT: Copper(I) fluoride complexes ligated by
phenanthroline derivatives have been synthesized and
structurally characterized by X-ray crystallography. These
complexes adopt as either ionic or neutral forms in the solid
state, depending on the steric bulkiness of the substituent
groups on the phenanthroline ligands. These complexes react
with primary and secondary alkyl bromides to produce the corresponding alkyl fluorides in modest to good yields. This new
method is compatible with a variety of important functional groups such as ether, thioether, amide, nitrile, methoxyl, hydroxyl,
ketone, ester, and heterocycle moieties.
formation reductive elimination from palladium(IV) com-
plexes.41 Lectka and co-workers published a polycomponent
copper-catalyzed fluorination of aliphatic, benzylic, and allylic
substrates with Selectfluor, the putative radical precursor N-
hydroxyphthalimide (NHPI), and an anionic phase-transfer
catalyst (KB(C6F5)4).42 Kim and co-workers demonstrated
facile nucleophilic fluorination of some halo- and mesylalkanes
to the corresponding fluoroalkanes using alkali metal fluorides
in the presence of an ionic liquid and water or tert-alcohol.43−47
Most recently, Li and co-workers reported an efficient silver-
catalyzed decarboxylative fluorination of aliphatic carboxylic
acids with Selectfluor in aqueous solution.48 Groves and co-
workers reported oxidative aliphatic and benzylic C−H
fluorination with fluoride ion catalyzed by manganese.49 Even
though the development of fluorination reactions has been
greatly advanced, these approaches still suffer from limited
substrate scopes and reaction conditions. The direct and
convenient synthetic route for the fluorination of alkyl halides,
especially secondary alkyl halides or mesylate,43,45 which could
easily be eliminated to the corresponding alkene, is still
challenging.
INTRODUCTION
■
A large number of known biologically active molecules,
including pharmaceuticals, agrochemicals, and positron-emis-
sion tomography (PET) imaging agents contain fluorine
atoms.1−5 Conventionally, protocols for the incorporation of
the fluorine atom into organic molecules include fluorination of
aryl diazonium salts with HBF4 (Balz−Schiemann reaction),6
the direct fluorination of aromatic compounds, and the Halex
exchange reaction of activated aryl halides with metal fluorides.7
More recently, the transition-metal-mediated C−F bond
construction has emerged as an area of extensive research.8−10
Although a number of remarkable examples of such
transformations incorporating Pd,11−19 Ni,20 Cu,21−23 and
Ag24,25 as catalysts or mediators have been developed for the
formation of aromatic C(sp2)−F bonds, the methods for
general and site-specific formation of C(sp3)−F bonds still
remain rather limited.26,27
Current efforts mainly focused on developing transition-
metal-catalyzed allylic fluorination28−31 and on the ring-
opening of epoxides.32 The existing methods for the synthesis
of alkyl fluorides involve nucleophilic33,34 or electrophilic35
substitution reactions or radical fluorination.27,36,37 However,
there are drawbacks with the use of fluoride ions with weak
nucleophilicity such as KF or CsF for C(sp3)−F bond
formation through direct nucleophilic substitution reactions.
Relatively few examples have been reported involving metal-
mediated nucleophilic fluorination of benzyl and alkyl halides.
Togni and co-workers reported the nucleophilic fluorination
of benzylic and tert-butyl alkyl halides catalyzed by a
ruthenium(II) complex using thallium fluoride.38 Sanford and
co-workers reported a Pd-catalyzed method for the formation
of aromatic and benzylic C−F bonds using electrophilic39 and
then nucleophilic fluorinating reagents.40 The same group also
reported the first example of highly selective C(sp3)−F bond
Our continued efforts in the synthesis of a copper reagent for
trifluoromethylation51−55 and trifluoromethylthiolation56−59
prompted us to develop a convenient and general method
that would allow the preparation of alkyl fluorides from a
common starting material. Herein, we report the synthesis of
copper(I) fluoride complexes for efficient fluorination of
primary and secondary alkyl bromides.
Received: September 6, 2013
© XXXX American Chemical Society
A
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RESULTS AND DISCUSSION
■
Synthesis of Copper(I) Fluoride Complexes. Formation
of copper(I) complexes was achieved by the reaction of CuOt-
Bu with the phenanthroline ligand in THF at rt, followed by the
addition of (HF)3·NEt3, i.e., (Me2phen)2Cu(FHF) (1) and (t-
Bu2Phen)Cu(F) (2) (Me2phen = neocuproine, t-Bu2Phen =
2,9-di-tert-butyl-1,10-phenanthroline), in 92% and 38% yields
based on Cu, respectively.
Scheme 1. Synthesis of Cu(l) Fluoride Complexes
Figure 2. ORTEP drawing of 2 showing 40% probability thermal
ellipsoids. The (HF)3·NEt3 and hydrogen atoms are omitted for
clarity.
adopts a trigonal planar geometry with one bidentate sp2 phen
ligand and one fluoride coordinated to the copper(I) center.
Notably, the two Cu−N bonds are not symmetrical, the bond
distance of Cu(1)−N(1) (2.071(4) Å) being slightly longer
than that of Cu(1)−N(2) (2.014(4) Å). In addition, the angle
of N−Cu−N in 2 (84.1°) is larger than that found in 1. The
Cu−F bond length (1.870(8) Å) in 2 is comparable to that of
the (IPr)CuFHF (1.872 Å),60 but is slightly longer than that of
(IMes)CuF (1.820 Å)63 and significantly shorter than that of
(PPh3)3CuF (2.062(6) Å).62
These complexes exist as either ionic or neutral forms in the
solid state, depending on the steric bulkiness of the substituent
groups of the phenanthroline, similar to the observations by
Leyssens and Riant et al. in (NHC)-copper(I) bifluoride
complexes.60 Complex 1 was obtained as an orange-red solid,
which is stable in air for several hours. Complex 2 was isolated
as an orange, air- and moisture-sensitive solid.
X-ray Structures of Complexes 1 and 2. The structures
of 1 and 2 have been determined by single-crystal X-ray
diffraction analysis. Their molecular structures are shown in
Figures 1 and 2. The solid-state structure shows that 1 contains
Table 1. Selected Bond Lengths and Angles of Complex 1
Bond Lengths (Å)
Cu(1)−N(1)
Cu(1)−N(1A)
2.0418(7)
2.0418(7)
Cu(1)−N(2)
Cu(1)-N(2A)
2.0565(6)
2.0564(6)
Bond Angles (deg)
N(1)−Cu(1)−N(2)
N(1)−Cu(1)−N(1A) 122.69(4) N(2)−Cu(1)−N(2A)
N(1)−Cu(1)−N(2A) 133.23(3) N(2)−Cu(1)−N(1A)
82.12(3) N(1A)−Cu(1)−N(2A)
82.12(3)
110.33(3)
133.23(3)
Table 2. Selected Bond Lengths and Angles of Complex 2
Bond Lengths (Å)
Cu(1)−F(1)
Cu(1)−N(2)
1.870(8)
2.014(4)
Cu(1)−N(1)
2.071(4)
Bond Angles (deg)
N(1)−Cu(1)−N(2)
N(2)−Cu(1)−F(1)
Cu(1)−N(2)−C(11)
Cu(1)−N(2)−C(10)
84.07(16)
139.8(9)
109.4(3)
130.6(3)
N(1)−Cu(1)−F(1)
Cu(1)−N(1)−C(12)
Cu(1)−N(1)−C(1)
135.8(9)
108.0(3)
131.6(4)
Figure 1. ORTEP drawing of 1 showing 40% probability thermal
ellipsoids. The hydrogen atoms are omitted for clarity.
Reactivity of Complexes 1 and 2 with Alkyl Halides.
Having established these solid-state structures, we sought to
examine the reactivity of copper(I) complexes with alkyl
bromides toward C(sp3)−F bond formation. Gratifyingly,
treatment of 1 with 5 equiv of 3-phenylpropyl bromide (3a)
in CH3CN at 110 °C for 15 h afforded (3-fluoropropyl)-
benzene (4a) in 92% yield (19F NMR, Table 3, entry 1) and
allylbenzene as major side products.
To our surprise, the neutral form of complex 2 led to poorer
results in fluorination (Table 3, entry 2). Five control
experiments were further carried out for the comparison of
reactivity. KF alone showed very little activity (Table 3, entry
3), and alkyl bromide 3a was fully recovered when only (HF)3·
one cationic tetrahedral copper center ligated by two of the
dative neocuproine ligands and one anionic [HF2]−, with the
anion that carries the fluorine atoms not directly bonded with
the Cu(I) center.
Crystals of 2 (cocrystallizes with adventitious (HF)3·NEt3)
suitable for X-ray diffraction were grown by recrystallization
from its toluene solution layered with n-hexane. Complex 2
belongs to the rare examples of Cu(I) fluoride compounds
containing a Cu−F bond,61 with the claim of the synthesis of
several copper(I) fluoride being denied several times over the
past hundred years.62 The solid-state structure of 2 shows a
three-coordinate neutral [(phen)CuF] species. The complex
B
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a
Table 3. Optimization of Fluorination of 4a
Table 4. Substrate Scope of the Fluorination of Alkyl
a
Bromides
temp
(°C)
time
(h)
yield
b
entry
[F−] source
solvent
(%)
1
1
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
110
110
110
110
110
110
110
110
110
110
110
110
40
15
15
15
15
15
15
15
15
15
15
15
15
15
15
8
92
21
6
2
2
3
KF
4
(HF)3·NEt3
TBAF
0
5
27
1
6
KF+(HF)3·NEt3
TBAF+(HF)3·NEt3
7
25
9
8
1
1
1
1
1
1
1
1
9
diglyme
DMF
33
46
5
10
11
12
13
14
15
DMSO
toluene
CH2Cl2
MeOH
CH3CN
trace
1
80
0.5
110
76
a
Reaction conditions: 1 (0.375 mmol), alkyl bromides 3 (0.250
mmol), 15 h, N2, 110 °C. Yields shown are of isolated products.
a
Conditions: [F−] sources (0.025 mmol), 3a (0.125 mmol), solvent
b
(1.0 mL), under N2 atmosphere. Yields were determined by 19F
NMR spectroscopy with PhOCF3 as internal standard.
a
Table 5. Fluorination of Secondary Alkyl Bromides
NEt3 was used (Table 3, entry 4). On the other hand,
tetrabutylammonium fluoride (TBAF) was found to mediate
the fluorination but in low yield (Table 3, entry 5). Using a
mixture of KF or TBAF with (HF)3·NEt3 did not improve the
reaction yields (Table 3, entries 6, 7). The results are consistent
with previous observations made by Chi and co-workers for
fluorinations of mesylate with metal fluoride in polar aprotic
solvents.44 It is important to note that changing the solvent has
a profound effect on the reaction outcome. CH3CN was
identified to be the most efficient. Replacement of CH3CN with
THF, diglyme, or DMF led to lower conversions, as did the use
of DMSO (Table 3, entries 8−11). The use of toluene, CH2Cl2,
and MeOH suppresses the fluorination (Table 3, entries 12−
14). When the reaction time was shortened from 15 h to 8 h, a
lower yield (76%) of 4a was observed (Table 3, entry 15).
The substrate scope of this fluorination was then expanded
with a series of examples (Table 4). Under the above optimized
reaction conditions, the yields of the desired, isolated alkyl
fluorides were obtained in a range of 50% to 90%, and many
potentially reactive functional groups, such as phenoxide (4b),
benzyl ether (4c), thioether (4d), amide (4e), nitrile (4h),
hydroxyl (4i), and ester (4j, 4k), were well tolerated. The cases
of 4i−4k were particularly noteworthy, as these results suggest
that the base-sensitive groups do not influence the bromide
substitution reaction. Unfunctionalized alkyl bromides also
served as suitable substrates in this protocol (4f and 4g).
Moreover, this method is compatible with more reactive
electrophiles such as benzyl bromides, which can be readily
fluorinated in good yields (4l−4o).
a
Reaction conditions: 1 (0.375 mmol), secondary alkyl bromides 5
(0.25 mmol), 15 h, N2, 110 °C. Yields shown are of isolated products.
and chromene) secondary alkyl bromides, which could be
converted to the desired products (6b, 6c, and 6i) with
synthetically useful yields (85%, 74%, and 89% yields,
respectively). Notably, the fluorination is chemoselective. A
variety of functional groups, including methoxyl (6d), ester
(6e), ketone (6f), hydroxyl (6g), and amido groups (6h), were
well tolerated to afford the desired products in 63−91% yields.
It was worthwhile to note that sensitive functionalities such as a
ketone (6f) or a hydroxyl (6g) group remained untouched
under the same conditions, allowing further transformations. Of
additional note, these moieties cannot survive in the presence
of other fluorinating reagents, i.e., diethylaminosulfur trifluoride
(DAST).64
Subsequently, we explored the reaction with the unactivated
secondary alkyl bromides (Table 5). Under similar conditions,
the reactions also proceeded successfully and gave the products
in good to excellent yields (with alkenes as major byproducts;
see Supporting Information). Fluorination of a secondary
bromoalkane afforded the corresponding product in 74% yield
(6a). This new protocol also provides good access to
pharmaceutically important heterocycle-containing (e.g., indole
To fully demonstrate the excellent chemoselectivity of our
approach, substrates with aryl and alkyl sites were used for this
reaction. Indeed, 5j smoothly underwent chemoselective
fluorination with 1 at the C(sp3)−Br bond, leaving the
C
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C(sp2)−Br bond available for further functionalization
Scheme 6. Inversion of Configuration
(Scheme 2).
Scheme 2. Selective Fluorination of Alkyl over Aryl
Bromides
yield with the complete inversion of configuration.33 This
finding strongly suggests that the fluorination proceeds through
an SN2-type displacement of the bromide leaving group with
the copper fluoride reagent.
Having established the fluorination procedure, we turned our
attention to explore this application to a more complex
substrate. The vitamin E derivative 7 underwent fluorination
with 1 smoothly to give the desired fluorinated product 8 in
86% yield (Scheme 3).
CONCLUSION
■
In conclusion, we have developed an efficient and effective
methodology to prepare alkyl fluorides directly from corre-
sponding primary and secondary alkyl bromides by a copper(I)
fluoride complex ligated by neocuproine. This ionic form of
Cu(I) fluoride can be readily prepared, and it shows superior
reactivity to those of neutral Cu(I) fluoride complexes. The
reaction condition is mild, and a variety of useful functional
groups including those not compatible with other existing
methods, such as thioether, amide, nitrile, hydroxyl, and ester,
can all be well tolerated. Our reagent should provide a
convenient access to various alkyl fluorides that may find
important applications in pharmaceutical and agrochemical
industries.
Scheme 3. Fluorination of Vitamin E Derivative by Complex
1
EXPERIMENTAL SECTION
■
General Experimental Procedure and Reagent Availability.
All manipulations were carried out using a nitrogen-filled glovebox or
standard Schlenk techniques under an inert atmosphere of nitrogen
(purity ≥99.99%). All glassware was dried immediately prior to use.
Solvents were freshly dried and degassed according to the procedures
in Purification of Laboratory Chemicals prior to use. Deuterated
solvents were purchased from Cambridge Isotope Laboratories, Inc.,
and were stored over activated 4 Å molecular sieves. 2,9-Di-tert-butyl-
1,10-phenanthroline50 was synthesized by a literature procedure.
Unless otherwise noted, all other reagents and starting materials were
purchased from commercial sources and used without further
purification. The 1H, 19F, and 13C NMR spectra were obtained at
293 K on a Bruker Avance 400 spectrometer, and chemical shifts were
recorded relative to the solvent resonance. GC-MS measurements
were conducted on a Shimadzu QP2010SE. Elemental analyses were
performed at Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences.
Additional experiments were conducted in an effort to gain
insights for the plausible mechanism. To test the possibility that
the fluorination may proceed via radical intermediates, the
reaction of 1 and 3i was carried out in the presence of
cyclohexa-1,4-diene (CHD), a radical scavenger. It was found
that the addition of CHD did not have any pronounced effect
on the reaction, and 4i was formed in the same yield both in
the absence and in the presence (65%) of CHD (Scheme 4).
Scheme 4. Radical Scavenger Experiments
Synthesis of [Cu(2,9-Dimethyl-1,10-phenanthroline)2]+-
[HF2]− (1). A solution of NaOt-Bu (20 mg, 0.21 mmol) in 2 mL of
THF was added to a suspension of CuCl (20 mg, 0.20 mmol) in 6 mL
of THF, and the resulting mixture was stirred at room temperature for
1 h. The resulting light yellow mixture was filtered through a layer of
Celite. To this filtrate was added a solution of 2,9-dimethyl-1,10-
phenanthroline (42 mg, 0.20 mmol) in 4 mL of THF. The resulting
solution turned reddish-brown immediately and was stirred at room
temperature for an additional 5 min. A THF solution (1 mL) of
(HF)3·NEt3 (32 mg, 0.20 mmol) was added dropwise, and the mixture
was further stirred at room temperature for 5 min. The solution was
filtered, and the filtrate was dried under vacuum to yield an orange
solid. The resulting orange solid was washed with 2 × 2 mL of hexanes
and dried under vacuum to obtain 48 mg (0.092 mmol, 92%) of 1. 1H
NMR (400 MHz, DMSO-d6): δ 13.59 (s, 1H), 8.77 (d, J = 7.1 Hz,
4H), 8.23 (s, 4H), 7.98 (d, J = 7.2 Hz, 4H), 2.40 (s, 12H). 19F NMR
(376 MHz, DMSO-d6): δ −158.4. 13C NMR (101 MHz, DMSO-d6): δ
158.2, 142.8, 138.0, 127.7, 126.5, 126.2, 25.7. MS (ESI): m/z = 479.1
When 1 reacted with 6-bromo-1-hexene in CD3CN at 110 °C
for 15 h, 6-fluoro-1-hexene 9 was the only product in 99% yield
detected by 19F NMR spectroscopy (Scheme 5). No cyclization
Scheme 5. Fluorination of 6-Bromo-1-hexene
product, (fluoromethyl)cyclopentane 10, was observed. This
absence of product 10 and the lack of any influence on the
reactivity with the addition of a radical scavenger suggest that a
radical mechanism is unlikely.
Finally, the stereochemistry of the reaction with an
enantiopure secondary tosylate (Scheme 6) was studied to
probe the nature of the reaction mechanism. The reaction of 1
with 12, prepared from the corresponding chiral secondary
alcohol 11, furnished the corresponding product 13 in 85%
+
+
[63CuL2 ], 481.1 [65CuL2 ]. Anal. Calcd for C28H27CuF2N4O: C 62.62,
H 5.07, N 10.43. Found: C 62.05, H 4.83, N 10.37.
Synthesis of (2,9-Di-tert-butyl-1,10-phenanthroline)CuF·
((HF)3NEt3) (2). A solution of NaOt-Bu (20 mg, 0.21 mmol) in 2
D
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mL of THF was added to a suspension of CuCl (20 mg, 0.20 mmol) in
6 mL of THF, and the resulting mixture was stirred at room
temperature for 1 h. The resulting light yellow mixture was filtered
through a layer of Celite. To this filtrate was added a solution of 2,9-di-
tert-butyl-1,10-phenanthroline (58 mg, 0.20 mmol) in 1 mL of THF.
The resulting solution turned reddish-brown immediately and was
stirred at room temperature for an additional 5 min. A THF solution
(1 mL) of (HF)3·NEt3 (32 mg, 0.20 mmol) was added dropwise, and
the mixture was further stirred at room temperature for 5 min. The
solution was filtered, and the filtrate was dried under vacuum to yield
an orange solid. The solid was dissolved in 5 mL of toluene, layered
with 10 mL of hexanes. The resulting solution was then cooled at −10
°C for 48 h. The resulting orange crystals were separated from the
supernatant, washed with 2 × 2 mL of hexanes, and dried under
to a dried 100 mL test tube with Teflon screw cap equipped with
magnetic stir bar. The tube was sealed, and the solution was placed
into a preheated 110 °C oil bath for 15 h. The tube was removed from
the oil bath and allowed to cool. The reaction mixture was filtered
through Celite to remove metal salts. Water (50 mL) was added to the
mixture at 0 °C. The resulting mixture was extracted with CH2Cl2 (3 ×
10 mL). The combined organic layers were washed with H2O (20 mL)
and brine (20 mL) and dried over magnesium sulfate. The solvent was
removed by rotary evaporation, and the resulting crude product was
purified by column chromatography on silica gel with pentane/AcOEt,
4:1 (v/v).
Crystal Structure Analyses. Suitable crystal of 1 and 2 were
mounted on quartz fibers, and X-ray data collected on a Bruker AXS
APEX diffractometer, equipped with a CCD detector at −50 °C, using
Mo Kα radiation (λ 0.71073 Å). The data were corrected for Lorentz
and polarization effects with the SMART suite of programs65 and for
absorption effects with SADABS.66 Structure solution and refinement
were carried out with the SHELXTL suite of programs.67 The
structure was solved by direct methods to locate the heavy atoms,
followed by difference maps for the light non-hydrogen atoms. In
crystal 1, the asymmetric unit contains half a molecule of the cation
C28H24N4Cu and one-half of the anion and solvent pair of HF2 and
H2O. HF2 and H2O are disordered around the 2-fold axis. For the
disordered HF2 and H2O, the H atoms were put at calculated
positions, and restraints in anisotropic thermal parameters of the O
were applied. In crystal 2, the asymmetric unit contains one molecule
of C20H26N2CuF and one (HF)3·(NEt3). H atoms of the F were not
located. One of the F atoms was disordered into two positions with an
occupancy ratio of 80:20. In crystal 2′, CuHF2 was disordered into two
positions with an occupancy ratio of 58:42.
1
vacuum to obtain 29 mg (0.078 mmol, 38%) of 2. H NMR (400
MHz, DMSO-d6): δ 11.63 (s, 2H), 8.47 (s, 2H), 7.96 (s, 4H), 1.60 (s,
18H). 19F NMR (376 MHz, DMSO-d6): δ −148.2, −148.3. 13C NMR
(101 MHz, DMSO-d6): δ 168.5, 129.3, 128.7, 127.1, 126.1, 119.9,
38.7, 30.6. MS (EI): m/z = 355 [M − F]. Anal. Calcd for
C26H42CuF4N3: C 58.24, H 7.90, N 7.84. Found: C 58.65, H 7.56,
N 7.75.
General Procedure for Fluorination of Primary and
Secondary Alkyl Bromides by Complex [Cu(2,9-dimethyl-
1,10-phenanthroline)2]+[HF2]− (1). Complex 1 (195 mg, 0.375
mmol), 0.25 mmol of primary or secondary alkyl bromides, and 10 mL
of CH3CN were added to a dried 100 mL test tube with a Teflon
screw cap equipped with magnetic stir bar. The tube was sealed, and
the solution was placed into a preheated 110 °C oil bath for 15 h. The
tube was removed from the oil bath and allowed to cool. The reaction
mixture was filtered through Celite to remove metal salts. Water (20
mL) was added to the mixture at 0 °C. The resulting mixture was
extracted with diethyl ether (3 × 10 mL). The combined organic layers
were washed with H2O (1 × 20 mL) and brine (1 × 20 mL), and dried
over magnesium sulfate. The solvent was removed by rotary
evaporation in an ice bath, and the resulting crude product was
purified by column chromatography on silica gel with pentane and
diethyl ether.
Procedure for the Reaction of 1 with 6-Bromohexan-1-ol
(3i) without Cyclohexa-1,4-diene. 1 (13 mg, 0.025 mmol), 3i (22.6
mg, 0.125 mmol), and 1 mL of CH3CN were added to a dried 5 mL
test tube with a Teflon screw cap equipped with a magnetic stir bar.
The tube was sealed, and the solution was placed into a preheated 110
°C oil bath for 15 h. The tube was removed from the oil bath and
allowed to cool; then 10 μL of (trifluoromethoxy)benzene was added
as an internal standard. The resulting mixture was filtered through a
layer of Celite, and the filtrate was analyzed by 19F NMR and GC-MS.
The yield of 6-fluorohexan-1-ol (4i) was calculated to be 64%.
Procedure for the Reaction of 1 with 6-Bromohexan-1-ol
(3i) in the Presence of 1.0 equiv of CHD. 1 (13 mg, 0.025 mmol),
3i (22.6 mg, 0.125 mmol), CHD (2 mg, 0.025 mmol), and 1 mL of
CH3CN were added to a dried 5 mL test tube with a Teflon screw cap
equipped with a magnetic stir bar. The tube was sealed, and the
solution was placed into a preheated 110 °C oil bath for 15 h. The
tube was removed from the oil bath and allowed to cool; then 10 μL of
(trifluoromethoxy)benzene was added as an internal standard. The
resulting mixture was filtered through a layer of Celite, and the filtrate
was analyzed by 19F NMR and GC-MS. The yield of 6-fluorohexan-1-
ol (4i) was calculated to be 65%.
ASSOCIATED CONTENT
* Supporting Information
Spectra and crystallographic data (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Authors
*E-mail: zweng@fzu.edu.cn (Z.W.).
*E-mail: hkw@kaust.edu.sa (K.-W.H.).
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge the financial support from National Natural
Science Foundation of China (21072030), Research Fund for
the Doctoral Program of Higher Education of China (No.
20123514110003), SRF for ROCS, SEM (J20121707), the
Science Foundation of the Fujian Province, China
(2013J01040), and Fuzhou University (022318, 022494) to
Z.W. and King Abdullah University of Science and Technology
to K.-W.H.
REFERENCES
■
Procedure for Fluorination of 6-Bromo-1-hexene by 1. 1 (44
mg, 0.080 mmol), 6-bromohex-1-ene (8.2 mg, 0.050 mmol), and 1 mL
of CD3CN were added to a dried 5 mL test tube with a Teflon screw
cap equipped with a magnetic stir bar. The tube was sealed, and the
solution was placed into a preheated 110 °C oil bath for 15 h. The
tube was removed from the oil bath and allowed to cool. Then 10 μL
(trifluoromethoxy)benzene was added as an internal standard. The
resulting mixture was analyzed by 19F NMR and GC-MS. The yield of
6-fluorohex-1-ene (9) was calculated to be 99%. Formation of
(fluoromethyl)cyclopentane product was not detected from 1H NMR.
Procedure for Inversion of Configuration. 1 (390 mg, 0.75
mmol), 12 (200 mg, 0.50 mmol), and 25 mL of CH3CN were added
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dx.doi.org/10.1021/om4008967 | Organometallics XXXX, XXX, XXX−XXX