Catalytic halodefluorination of aliphatic carbon-fluorine bonds

Article abstract of DOI:10.1039/c6ra09429e

A variety of halosilanes, in conjunction with aluminum catalysts, convert fluorocarbons into higher halocarbons. Bromination and iodination of fluorocarbons are more effective than chlorination in terms of yield and activity. The mechanism for the reaction is investigated utilizing experimental and computational evidence and preliminary results suggest an alternate mechanism to that reported for the related hydrodefluorination reaction.

Full text of DOI:10.1039/c6ra09429e

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Catalytic halodefluorination of aliphatic carbon–
fluorine bonds†
Cite this: RSC Adv., 2016, 6, 42708
*
Kelvin K. K. Goh, Arup Sinha, Craig Fraser and Rowan D. Young
Received 12th April 2016
Accepted 21st April 2016
DOI: 10.1039/c6ra09429e
www.rsc.org/advances
A variety of halosilanes, in conjunction with aluminum catalysts, carbon–uorine bonds into other halogen–carbon bonds offers
convert fluorocarbons into higher halocarbons. Bromination and novel access to the ability to further functionalise substrates
iodination of fluorocarbons are more effective than chlorination in with well-developed synthetic methods that are effective in the
terms of yield and activity. The mechanism for the reaction is inves- presence of chloro-, bromo- and iodo-organic substrates, but
tigated utilizing experimental and computational evidence and largely ineffective with organouorides. Additionally, the
preliminary results suggest an alternate mechanism to that reported incorporation of higher halides into many materials is of
for the related hydrodefluorination reaction.
intrinsic value. For example, the ability to access novel bromi-
nated ame retardant additives to supersede the current
controversially employed additives is of commercial interest.5
Indeed, the conversion of uorine to other halogens has been
achieved previously in stoichiometric reactions using group 13
trihalides. Such reactivity was rst reported by Henne and
Newman as early as 1938 using excess aluminum trichloride,6
Fluorine–carbon chemistry has established a ‘foot-hold’ as one
of the most utilized areas of modern chemistry.1 Fluorine–
carbon bonds have found their way into refrigerants, agro-
chemicals, pharmaceutical drugs and plastics, while the incor-
poration of uorine into organic substrates can be very useful
given its chemical inertness, electron withdrawing power and
ability to act as an NMR spectator.2 As such, a variety of powerful
methods for the introduction of uorine or uorine-containing
groups into organic molecules have recently been developed.
However, the late-stage modication of C–F bonds suffers
greatly from the inherent chemical stability of the carbon–
uorine bond and catalytic transformation of these bonds to
other functional groups remains challenging, especially for sp3
hybridised carbon–uorine bonds.3
Recent reports have shown the use of silylium, phospho-
nium and aluminium intermediates as effective hydro-
deuorination (HDF) catalysts for aliphatic C–F bonds
(Scheme 1).4 Despite the importance of efficient HDF protocols
to counter the release of CFCs, HCFCs and HFCs, the substi-
tution of uorine by hydrogen offers little potential for further
functionalization and/or recycling of uorine compounds. In
addition, the conditions for HDF are conducive to Friedel–
Cras alkylations, preventing the clean conversion to product in
the presence of aromatic systems. Conversely, the conversion of
Scheme 1 Metal-free hydrodefluorination (HDF) has recently been
achieved using (inter alia) catalyst systems A, B and C ([anion] ¼
[B(C6F5)4]ꢀ or [HCB11H5Cl6]ꢀ).4a,b,c,f Aluminum reagents for stoichio-
metric halodefluorination (HaloDF), also previously reported, include D
and E.7b,c
Department of Chemistry, National University of Singapore, 117543, Singapore.
E-mail: rowan.young@nus.edu.sg
† Electronic supplementary information (ESI) available: Details of experimental
procedures, calculated structures and free energy calculations. See DOI:
10.1039/c6ra09429e
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and has since been utilized using boron or aluminum chlorides, halide catalyst resting state being much less efficient at Frie-
bromides, iodides and even alkanides (Scheme 1).7 This protocol del–Cras reactivity.10 As such, the use of stoichiometric, or
has also been extended to the formation of C–C bonds from slightly decient, halosilane resulted in complete consumption
trihydrocarbyl aluminum reagents and the scrambling of C–X/C– of 1 and high yields of 1-Cl (Table 1-3 and 1-4).
F bonds in mixed halouorocarbons.7b,8 Such reactions suffer
Employing silicon chloride as a halogen source further
from Friedel–Cras side-reactivity and are thus typically carried improved the reaction efficiency. In this case, delivery of
out under controlled conditions (e.g. low temperature). In all of multiple chloride atoms resulted in mono, di, tri and tetrau-
these cases, the formation of a very stable group 13 element– orides of silicon as by-products – thus complete conversion of 1
uorine bond has driven reactivity. Silicon is also known to be to 1-Cl could be accomplished using only 0.75 equiv. of SiCl4.
extremely uorophilic, with many reported HDF studies using Notably, the loss of silicon uoride gas by-product from the
silicon–uoride bond formation as a thermodynamic sink. As reaction together with precipitation of hydrolysed aluminum
such, we decided to explore the opportunity of driving halode- catalyst (i.e. exposure to atmosphere) facilitated the isolation of
uorination (HaloDF) using cheap and readily available pure product in high yield (Table 1-6).
halosilanes.
Control reactions in the absence of aluminum halide
Herein, we describe a catalytic process that converts carbon– between 1 and TMSCl or SiCl4 showed no evidence of silicon
uorine bonds into carbon–chloride, bromide and iodide uorides or 1-Cl formation (Table 1-9 and 1-10).
bonds in moderate to high yields. Our process utilizes a variety
of halosilanes and catalytic quantities of aluminum halide.
A solvent screen revealed chlorinated alkanes and arenes to
be effective solvents, while the reaction tolerated electron rich
Attempted chlorodeuorination (ChloroDF) of our test arenes to a large extent (Table 1-11 to 1-15). Although GC-MS
substrate, benzotriuoride (1), using a catalytic amount of identied Friedel–Cras products as by-products when
aluminum chloride (20 mol%) in combination with excess tri- benzene, toluene and benzene-d6 were employed as solvents,
methylsilyl chloride, TMSCl (5 equiv.), resulted in complete moderate yields of 1-Cl could still be achieved. The low solu-
consumption of 1, but only trace amounts of the desired bility of aluminum chloride in n-octane solvent resulted in slow
product, benzotrichloride (1-Cl) (Table 1-1). Running the reac- conversion, with only 32% HFC conversion aer 65 h, however,
tion with decient TMSCl resulted in quantitative conversion of little by-product was observed with almost quantitative gener-
1 to 1-Cl based on TMSCl,9 likely due to a uoro-aluminum ation of 1-Cl based on HFC conversion.
When aluminum uoride was employed as a catalyst,
negligible reactivity was observed, with a conversion of only
19% aer 63 hours (Table 1-17). Aluminum uoride is less able
Table 1 Optimization of conditions for ChloroDF of substrate 1a
to act as a molecular Lewis acid as compared to its higher
homologues due to its high lattice energy and very low solu-
bility,11 but may become activated by halogen exchange with
halosilane. Bromodeuorination (BromoDF) and iodode-
uorination (IodoDF) were achieved using the homohalogen
systems TMSBr/AlBr3 and TMSI/AlI3. BromoDF reactions pro-
ceeded to provide comparable, or higher, conversions/yields to
ChloroDF reactions. IodoDF provided high C–F conversion of 1,
but benzotriiodide was found to be light- and temperature-
sensitive, compromising product yield. Running the reaction
at room temperature alleviated the decomposition of 1-I, but
large quantities of decomposition were still observed (Table 2).
Reaction scope was tested using substrates 1–15. High Hal-
oDF conversion was observed in primary uoroalkanes, tri-
phenylmethyl uoride and benzylic C–F bonds, even with
electron-decient arenes. Bis(triuoro)arenes proved excep-
tions, likely due to the larger number of sp3 C–F bonds to
convert. HaloDF of phenyl ether 6 proceeded to low C–F
conversions and yields. This result correlates to the reduced
HaloDF activity observed in the presence of ether (Table 1-16),
and may reect competing oxygen coordination to the catalyst
as opposed to an increased C–F bond strength in 6.
Halogen
reagent
Temp./
C–F
Yield
Entry Catalyst
Solvent time (ꢁC/h) conv. (%) (%)
1
2
3
4
5
6
7
8
AlCl3 (0.2) Et3SiCl (5)
AlCl3 (0.2) TMSCl (0.66) PhCl
AlCl3 (0.2) TMSCl (3) PhCl
AlCl3 (0.2) TMSCl (2.8) PhCl
AlCl3 (0.2) Et3SiCl (3) PhCl
AlCl3 (0.2) SiCl4 (0.75) Neat
AlCl3 (0.05) SiCl4 (0.75) Neat
AlCl3 (0.05) TMSCl (2.8) Neat
TMSCl (3)
SiCl4 (0.75) PhCl
AlCl3 (0.2) TMSCl (2.8) C6H4Cl2 80/42
AlCl3 (0.2) TMSCl (2.8) DCE
AlCl3 (0.2) TMSCl (2.8) PhH
AlCl3 (0.2) TMSCl (2.8) PhMe
AlCl3 (0.2) TMSCl (2.8) n-C8H18 80/65
AlCl3 (0.2) TMSCl (2.8) PhCl
AlF3 (0.2) TMSCl (2.8) PhCl
PhCl
80/20
80/20
80/20
80/20
80/42
80/20
80/20
80/60
80/20
80/42
100
24
97
98
94
100
100
87
0
Trace
24
80
78
65
94b
84
80
0
9
—
PhCl
10
11
12
13
14
15
16
17
—
0
0
99
96
96
88
32
34
19
71
83
60
62
30
29c
10
80/42
80/42
80/42
80/48
80/63
Reaction conversion correlated well with product yield with
the exception of alkane 2-Br (100% conversion, 48% yield) and
a
General conditions: 1 (ca. 1 M); reaction volume 1 mL; C6D6 (0.1 mL) alkane 2-Cl (100 conversion, 9% yield). In these reactions, it was
added for locking purposes; CF conversion based on C6F6 internal
found that the remainder of the 1-uorooctane was converted
into 2-, 3- and 4-halooctanes. In the case of alkyl uoride 4,
rearrangement products were signicantly reduced.
b
standard; yield determined by GC-MS except where isolated. Isolated
yield in absence of C6D6. c 0.2 equiv. of Et2O added.
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Table 2 Reaction scope of HaloDF reaction exploring the ChloroDF,
BromoDF and IodoDF of various substrates employing aluminum
halide catalystsn
Scheme 2 HaloDF is postulated to occur in one of two distinct cycles.
Mechanism A: aluminum halide acts as a HaloDF agent that is regen-
erated by halosilane (see ESI for computational details†), mechanism
B: aluminum halide, acting as a Lewis acid, activates halosilane towards
HaloDF.
acids acting as catalysts for HDF via the formation of
aluminum–hydrosilane adducts.14a,16
Conversely, aluminum halides are known to facilitate Hal-
oDF in a stoichiometric manner in the absence of halosilane.
Regeneration of aluminum halides from silicon halides war-
ranted investigation, given that the generation of aluminum
halides from the reaction of alumina and silicon halides is
a well-known industrial process.17 However, reports also exist
for the chlorination of uorosilanes facilitated by aluminum
chloride.18
a
General conditions: substrate (ca. 1 M); reaction volume 1 mL, PhCl
solvent; C6D6 (0.2 mL) added for locking purposes 80 ꢁC, 21 hours.
b
General conditions: substrate (ca. 1 M); reaction volume 1 mL, PhCl
solvent; C6D6 (0.2 mL) added for locking purposes room temperature,
c
1 hour. General conditions: substrate (ca. 1 M); reaction volume 1
mL, PhCl solvent; C6D6 (0.2 mL) added for locking purposes 80 ꢁC, 42
d
hours. General conditions: substrate (ca. 1 M); reaction volume 1
mL, PhCl solvent; C6D6 (0.2 mL) added for locking purposes 80 ꢁC, 90
The formation of halosilane–aluminum halide Lewis
adducts is pivotal to both postulated mechanisms (A and B).
Such adducts were spectroscopically observed by us to form
prior to addition of HFC substrate and have been studied
previously by NMR in solution, and typically result in
deshielding of the silicon nucleus.15b,15c,19 However, it is unclear
as to whether such adducts act as pre-catalysts, catalyst resting
states or as active intermediates in the catalytic cycle.
Few data are available on calculated or experimentally
observed geometries of aluminum–silicon halide bridged
e
f
hours. In the absence of C6D6. Product was found to be thermally
and photolytically unstable and product decomposed during reaction
at room temperature. Yield determined by 1H NMR. Other bromo-
g
h
i
octane isomers account for 52%. Reaction proceeded prior to
j
addition of catalyst. Product yield could not be accurately
determined using 1H NMR or GC-MS. Single product detected by
k
GC-MS. Major product is 1-(CBr3)-4-(CF3)-C6H4 (26% yield). m sp2 C–F
l
n
bond did not react. CF conversion based on C6F6 internal standard,
yield determined by GC-MS except where isolated.
Plausible mechanisms of the above described HaloDF reac- adducts, and none on simple homoleptic aluminum systems.20
tion were explored through a series of control reactions sup- As such geometries and bond energies of TMS–X–AlX3 adducts
ported with calculated free energy changes.
Two pathways for the substitution of uoride with halide energy determined the overall HaloDF reaction to be exergonic
present themselves as plausible mechanisms. Aluminum halide (Table S2, ESI†).
were calculated (X ¼ F, Cl, Br, I) (Table S1, ESI†). Calculated free
acts as a HaloDF agent that is regenerated by halosilane
(Scheme 2 mechanism A), or that the halosilane and aluminum Cl, Br) was observed to generate TMSF. Heating samples of
Halide exchange between aluminum uoride and TMSX (X ¼
halide form an ‘encounter complex’ that activates the silane aluminum uoride with 1.05 equivalents of either TMSCl or
towards attack of the uoride (Scheme 2 mechanism B).
TMSBr in benzene-d6 for 48 hours produced small amounts of
The formation of hydrosilane-borane adducts has been TMSF (<10% conversion). Although these reactions were
postulated to occur in hydrosilylation reactions of carbonyls observed to occur slowly in respect to HaloDF reaction times,
and olens, and may play a role in specic HDF reactions.12,13 the strong lattice network of solid AlF3, restricting its ability to
Recently crystallographic evidence of both a borane–silane act as a molecular species, and the relative insolubility of AlF3 as
adduct and an alane–silane adduct were reported supporting compared to AlFX2 may account for the slow observed
the ability of Lewis acids to activate hydrosilanes.14 Strong Lewis exchange.12 Indeed, when aluminum uoride was employed as
acids and halosilanes have also been reported to form such a catalyst, slow reactivity was observed, with a conversion of
adducts.15 Recently, there have been reports of aluminum Lewis only 19% aer 63 hours (Table 1-17).
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We were not able to obtain TMSF to establish the exchange
equilibrium constant between TMSF and higher aluminum
halides, however, reported syntheses relying upon this
exchange would seem to indicate the presence of an equilib-
rium with relatively little free energy.18
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aluminum halide exchanges were calculated. In agreement
with the exchanges observed by NMR, the change in free ener-
gies supports the favorable regeneration of TMSX from AlX3 and
TMSF (Table S3, ESI†). HaloDF is likely to be kinetically assisted
using TMSX and SiCl4 reagents, given that both TMSF and SiF4
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The nature of the reaction invokes comparison with the
related SN2 Finkelstein reaction, however, the generation of an
intermediate carbocation species, pertinent to both mecha-
nisms A and B, is supported by a number of observations. (1)
The use of Et3SiCl or Et3SiBr as HaloDF agents in the HaloDF of
benzotriuoride also generates small amounts of benzyl halide
and dihalide, presumably via hydride abstraction from the alkyl
silane; (2) benzylic uorides prove to be better substrates than
aliphatic uorides; (3) the HaloDF of primary alkyluorides
results in rearrangement products. To account for the low
amounts of Friedel–Cras by-products, we propose that
aluminum tetrahalide-carbocation ‘ion pairs’ are formed that
are able to combine at a faster rate than arene attack of carbo-
cation intermediates.
In HDF, the hydride is presumed to be delivered to the car-
bocation intermediate directly by the hydrosilane. To determine
whether a similar mechanism may operate in HaloDF, we added
an equivalent of TMSCl to [CPh3][B(C6F5)4], aer which no
evidence of trityl chloride formation was observed by NMR
spectroscopy or GC-MS spectrometry. Indeed, reaction of [Et3Si]
[B(C6F5)4] (generated in situ from Et3SiH and [CPh3][B(C6F5)4])
with 5 equivalents of benzotriuoride and 15 equivalents of either
Et3SiCl or TMSCl produced one equivalent of Et3SiF or TMSF,21
but no benzotrichloride. These reactions imply that in catalysis,
halosilane does not quench the carbocation intermediate directly.
It was also found that the strong Lewis acid, B(C6F5)3 devoid
of higher halogen substituents, did not promote HaloDF, even
though uoride abstraction by B(C6F5)3 has been reported.12
In conclusion, we have developed a catalytic method to
effectively convert aliphatic uorocarbons into higher halocar-
bons in high yield using cheap and accessible aluminum cata-
lysts and silicon halide reagents under mild, practical
conditions. Such conversions may have potential applications in
the processing of HFCs, the production of brominated ame
retardants and the late-stage-functionalization of carbon–uo-
rine bonds. Preliminary mechanistic studies suggest an alternate
mechanism as compared to those reported for HDF reactions.
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Acknowledgements
We thank the National University of Singapore and the Singa-
pore Ministry of Education for nancial support (WBS R-143-
000-586-112).
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