Competitive aryl-fluorine and aryl-halogen (Halogen = Cl, Br) bond cleavage with iridium porphyrin complexes

Article abstract of DOI:10.1021/om301196t

Base-promoted competitive Ar-F and Ar-X (X = Cl, Br) bond cleavage with iridium porphyrin complexes was investigated. Mechanistic studies suggested that Ir(ttp)^- (ttp = 5,10,15,20-tetra-p-tolylporphyrinato dianion) cleaves the Ar-F bond via nucleophilic aromatic substitution and Ir ₂(ttp)₂ cleaves the Ar-X (X = Cl, Br) bond via metalloradical ipso substitution. Therefore, a stronger base, polar solvent, lower temperature, and iridium anion precursor favor Ar-F bond cleavage, while a weaker base, nonpolar solvent, higher temperature, and Ir₂(ttp) ₂ precursor favor Ar-X (X = Cl, Br) bond cleavage.

Full text of DOI:10.1021/om301196t

Communication
pubs.acs.org/Organometallics
Competitive Aryl−Fluorine and Aryl−Halogen (Halogen = Cl, Br)
Bond Cleavage with Iridium Porphyrin Complexes
Ying Ying Qian, Bao Zhu Li, and Kin Shing Chan*
Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People’s Republic of China
S
* Supporting Information
ABSTRACT: Base-promoted competitive Ar−F and Ar−X
(X = Cl, Br) bond cleavage with iridium porphyrin complexes
was investigated. Mechanistic studies suggested that Ir(ttp)−
(ttp = 5,10,15,20-tetra-p-tolylporphyrinato dianion) cleaves
the Ar−F bond via nucleophilic aromatic substitution and
Ir2(ttp)2 cleaves the Ar−X (X = Cl, Br) bond via metalloradical
ipso substitution. Therefore, a stronger base, polar solvent,
lower temperature, and iridium anion precursor favor Ar−F
bond cleavage, while a weaker base, nonpolar solvent, higher
temperature, and Ir2(ttp)2 precursor favor Ar−X (X = Cl, Br) bond cleavage.
n Ar−F bond is generally thermally, photochemically,
dibromofluoromethane gave C−F and C−Br bond cleavage
products in a 1.7:1 ratio.13 The second approach employed
carbon or oxygen nucleophiles by taking advantage of the better
leaving ability of fluoride.14 The treatment of 1-bromo-3-
chloro-5-fluorobenzene with 2-(trimethylsilyl)ethanol and
potassium bis(trimethylsilyl)amide gave the Ar−F bond
cleavage product.14a In the third approach, selective Ar−F
bond cleavage has been accomplished by chelation control
using an ortho directing group.15 The coordination of phenol
to Mg facilitated oxidative addition of Ni to the adjacent C−F
bond.15a Recently, it was reported that the Ar−F bond ortho to
an imine directing group was cleaved by a platinum complex
even in the presence of a chlorine group ortho to the imine
group. However, a directing imine group is a must and the
mechanism of this selectivity was not reported.16
For simple fluorohalobenzenes without an ortho directing
group, to our knowledge, few example of selective Ar−F bond
cleavage with transition-metal complexes exist. In our
continuing studies of Ar−X (X = Cl, Br, I) cleavage by
metalloporphyrins,17 we have discovered competitive Ar−F and
Ar−X (X = Cl, Br) bond cleavage with iridium porphyrin
complexes and now report our findings.
Initially, Ir(ttp)(CO)Cl (1a; ttp = 5,10,15,20-tetra-p-
tolylporphyrinato dianion) reacted with p-fluorochlorobenzene
in the presence of K2CO3 in benzene at 150 °C to give a 60%
yield of the Ar−Cl cleavage product, Ir(ttp)(4-fluorophenyl)
(3b) (Table 1, entry 1). Unexpectedly, when the stronger base
KOH was used, competitive Ar−F and Ar−Cl bond cleavage
reactions occurred to give Ir(ttp)(4-chlorophenyl) (3a) and
Ir(ttp)(4-fluorophenyl) (3b) in a 1:1 ratio (Table 1, entry 2).
When THF was used as the solvent, the product ratio further
increased to 3:1 (Table 1, entry 3). When the reaction
A
electrooxidatively, and chemically stable due to its high
bond dissociation energy (BDE), with that of the Ph−F bond
being about 125 kcal/mol.1−3 The activation of carbon−
fluorine bonds has gained increasing attention due to the
challenge in defluorination,4 organic synthesis,3,5 and peptide
sequencing.6 In the presence of Cl, Br, or I substituents,
selective Ar−F bond cleavage is even more difficult.7−11 This is
a consequence of the much lower BDE of Ar−Cl, −Br, and −I
(about 95, 80, and 65 kcal/mol, respectively) in comparison to
that of Ar−F.1 The Ar−F bond is inert toward most
palladium,7,9 nickel,10 and cobalt11 catalysts in cross-coupling,7
dehalogenation,8 and amination9,10 reactions in the presence of
Cl or Br substituents. The Stille cross-coupling reaction of p-
fluorochlorobenzene with ArSnBu3 catalyzed by Pd(OAc)2 and
XPhos (=2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphen-
yl) gave 4-fluorobiaryl in 93% yield.7a The Ar−Cl bond was
cleaved rather than the Ar−F bond at the para or meta position
with the catalyst {Pd(cinnamyl)Cl}2.7b Fluorobenzene was
obtained in the hydrodehalogenation reaction of p-fluorochlor-
obenzene over a supported palladium catalyst.8 The Ar−Cl
bond was aminated in the presence of an Ar−F bond with a
nickel(0) catalyst and NHC ligand.10
Selective cleavage of the stronger Ar−F bond in the presence
of other Ar−X bonds (X = Cl, Br, I) is very difficult, with only a
few examples being reported in the last century. The first
observation of C−F bond cleavage in the presence of a C−Cl
bond was reported by Frank et al. on saturated chlorofluor-
ocarbons with phosphorus in 1965. However, a chlorophilic
process and elimination of fluoride anion rather than direct C−
F bond cleavage account for the observed product.12
In the past 20 years, several approaches have been applied to
achieve selective Ar−F bond cleavage in the presence of other
halogen substituents. In the first approach, a fluorophilic
phosphorus reagent was first used in 1993 to cleave the C−F
bond. The reaction between diisopropyl sodiophosphite and
Received: December 11, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/om301196t | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
Table 1. Competitive Ar−F and Ar−Cl Bond Cleavage with Iridium Porphyrin Complexes
entry
Ir(ttp)X
base
temp/°C
solvent
time/h
yield 3a/%
yield 3b/%
total yield/%
1
2
3
4
5
Ir(ttp)(CO)Cl (1a)
Ir(ttp)(CO)Cl (1a)
Ir(ttp)(CO)Cl (1a)
Ir(ttp)(CO)Cl (1a)
Ir(ttp)SiEt3 (1b)
K2CO3
KOH
KOH
KOH
KOH
150
150
150
120
120
benzene
benzene
THF
48
5
60
60
100
99
50
75
85
90
50
18
24
24
24
THF
13
98
THF
trace
90
temperature was lowered to 120 °C, the reaction became
slower, and the ratio of 3a to 3b increased further (Table 1,
entry 4). To our delight, when Ir(ttp)SiEt3, a known precursor
for Ir(ttp)−,18 was used as the starting material, exclusive Ar−F
bond cleavage occurred to give 3a in 90% yield (Table 1, entry
5).
conditions, and the recovery yields were quantitative (eqs 1 and
2). Thus, the reaction products are not interconvertible and the
product ratios are kinetic.
To find out whether competitive Ar−F and Ar−Br occur, we
then examined the reaction with p-fluorobromobenzene. When
Ir(ttp)(CO)Cl was reacted with p-fluorobromobenzene and
KOH in benzene, only Ar−Br cleavage product 3b was
obtained (Table 2, entry 1). However, in THF solvent, the
Table 2. Competitive Ar−F and Ar−Br Bond Cleavage with
Iridium Porphyrin Complexes
To gain a mechanistic understanding of the competitive Ar−
F and Ar−X (X = Cl, Br) bond cleavages, various iridium
porphyrins were tested as the intermediates of these bond
cleavages. Since we have earlier identified that ipso substitution
addition−elimination of IrII(ttp) is responsible for Ar−Cl and
Ar−Br bond cleavage,17 IrII(ttp) was tested for Ar−F bond
cleavage. However, Ir2(ttp)2 (1e) reacted with fluorobenzene to
give a complex mixture without any Ar−F bond cleavage
product. As it is known that Ir2(ttp)2 equilibrates with Ir(ttp)H
(1d) and Ir(ttp)− (1c) under basic conditions,17,19 Ir(ttp)H
(1d) and Ir(ttp)− (1c) were also tested for the Ar−F bond
cleavage. Without base, Ir(ttp)H (1d) reacted with fluoroben-
zene to give a complex mixture as well. However, Ir(ttp)− (1c),
generated from the Na/Hg reduction of Ir(ttp)(CO)Cl, reacted
with fluorobenzene at 120 °C to give Ir(ttp)Ph (3d) in 40%
yield (eq 3). Therefore, Ir(ttp)− (1c) is the most probable
intermediate for Ar−F bond cleavage.
temp/
yield
yield
total
entry
1
Ir(ttp)X
°C
solvent
time/h 3c/% 3b/% yield/%
Ir(ttp)
(CO)Cl
(1a)
200
200
120
120
benzene
6
6
90
70
66
30
90
70
86
70
2
3
4
Ir(ttp)
(CO)Cl
(1a)
THF
THF
THF
trace
20
Ir(ttp)
(CO)Cl
(1a)
18
24
Ir(ttp)
SiEt3
(1b)
40
reaction gave a trace amount of Ar−F bond cleavage product
(Table 2, entry 2). The same temperature effect was observed,
that the Ar−F bond cleavage product became significant when
the temperature was lowered to 120 °C (Table 2, entry 3).
With Ir(ttp)SiEt3 (1b)/KOH used as the starting materials, the
ratio of 3c to 3b further increased to 4:3 (Table 2, entry 4).
To investigate whether the Ar−F bond cleavage product is
the kinetic product or the thermodynamic product formed
from the Ar−Cl cleavage product, the reactivities of 3a and 3b
were studied. Both 3a and 3b were stable under the reaction
N2, 60 ◦C, 10 min
Ir(ttp)(CO)Cl ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→ Ir(ttp)−Na+
THF, Na/Hg
1a
1c (quantitative)
N2, 60 ◦C, 2 days
⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→⎯ Ir(ttp)C6H5
C6H5F
3d (40%)
(3)
Scheme 1 shows the proposed mechanism for competitive
cleavage of Ar−F and Ar−X bonds (X = Cl, Br). Initially,
Ir(ttp)(CO)Cl (1a) undergoes ligand dissociation and ligand
B
dx.doi.org/10.1021/om301196t | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
ent.17,20,21 At higher temperature, a nonpolar solvent favors the
radical process, while a polar solvent and lower temperature
favor the ionic process. Therefore, Ar−X bonds (X = Cl, Br)
were cleaved at high temperatures in benzene and Ar−F
cleavage was more favored at lower temperatures in THF. As an
Ar−Br bond is much weaker than an Ar−Cl bond, Ar−Br bond
cleavage also occurred competitively at lower temperatures in
THF.
Scheme 1. Proposed Mechanism for Competitive Ar−F and
Ar−X (X = Cl, Br) Bond Cleavage
In summary, selective Ar−F bond cleavage of p-fluorochlor-
obenzene was achieved. The competitive Ar−F and Ar−X (X =
Cl, Br) bond cleavage was investigated. A stronger base, polar
solvent, lower temperature, and iridium anion precursor favor
Ar−F bond cleavage. On the other hand, a weaker base,
nonpolar solvent, higher temperature, and Ir2(ttp)2 precursor
favor Ar−X (X = Cl, Br) bond cleavage. Ir2(ttp)2 is responsible
for the Ar−X (X = Cl, Br) bond cleavage, and Ir(ttp)− is the
intermediate for Ar−F bond cleavage.
ASSOCIATED CONTENT
■
S
* Supporting Information
substitution with OH− to give Ir(ttp)OH, which undergoes
reductive elimination and subsequent dimerization to give
Ir2(ttp)2 (1e) and H2O2.20,21 Ir2(ttp)2 (1e) or, more accurately,
IrII(ttp) monomer then cleaves the Ar−X (X = Cl, Br) bond to
afford Ir(ttp)(4-fluorophenyl) (3b). Ir2(ttp)2 (1e) also reacts
with hydroxide to form Ir(ttp)− (1c),17,20,21 which undergoes
ipso nucleophilic aromatic substitution (SNAr) (addition−
elimination) to give Ir(ttp)Ar.22 On the other hand, when
Ir(ttp)SiEt3 (1b) and KOH are used as the starting materials,
they give Ir(ttp)− (1c) first selectively. The independent
reaction of Ir(ttp)SiEt3 (1b) with KOH gave Ir(ttp)− (1c),
KOSiEt3, and (Et3Si)2O, which formed from condensation of
Et3SiOH,23 thus providing an experimental support (eqs 4 and
5).24
Text, figures, and tables giving a detailed mechanistic study for
1
Ar−F bond cleavage and H, 13C, and 19F NMR spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail for K.S.C.: ksc@cuhk.edu.hk.
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Notes
The authors declare no competing financial interest.
Ir(ttp)SiEt3 + KOH
10 equiv
11%
200 ◦C
ACKNOWLEDGMENTS
⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→ Ir(ttp)−K+ + KOSiEt3 + (Et3Si)2O
■
benzene‐d6
t=5 days
We thank the Research Grants Council (No. 400308) and a
Special Equipment Grant (No. SEG/CUHK09) from the
University Grants Committee of Hong Kong SAR, People’s
Republic of China, for financial support.
11%
20%
6%
(4)
(5)
KOH
2Et3SiOH ⎯⎯⎯⎯→ (Et3Si)2O + H2O
Aryl halides can in principle undergo nucleophilic aromatic
substitution with Ir(ttp)− to form a benzyne intermediate,
which can then be attacked by Ir(ttp)− followed by protonation
to give Ir(ttp)Ar.25 Had the benzyne mechanism indeed
operated, a 1:1 ratio of Ir(ttp)(4-FG-phenyl) and Ir(ttp)(3-FG-
phenyl) would have formed (Scheme 2). However, this
mechanism was excluded, since the regiochemistry of the
starting material was retained.
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dx.doi.org/10.1021/om301196t | Organometallics XXXX, XXX, XXX−XXX