Transition-Metal-Free Decarboxylative Iodination: New Routes for Decarboxylative Oxidative Cross-Couplings

Article abstract of DOI:10.1021/jacs.7b05155

Constructing products of high synthetic value from inexpensive and abundant starting materials is of great importance. Aryl iodides are essential building blocks for the synthesis of functional molecules, and efficient methods for their synthesis from chemical feedstocks are highly sought after. Here we report a low-cost decarboxylative iodination that occurs simply from readily available benzoic acids and I₂. The reaction is scalable and the scope and robustness of the reaction is thoroughly examined. Mechanistic studies suggest that this reaction does not proceed via a radical mechanism, which is in contrast to classical Hunsdiecker-type decarboxylative halogenations. In addition, DFT studies allow comparisons to be made between our procedure and current transition-metal-catalyzed decarboxylations. The utility of this procedure is demonstrated in its application to oxidative cross-couplings of aromatics via decarboxylative/C-H or double decarboxylative activations that use I₂ as the terminal oxidant. This strategy allows the preparation of biaryls previously inaccessible via decarboxylative methods and holds other advantages over existing decarboxylative oxidative couplings, as stoichiometric transition metals are avoided.

Full text of DOI:10.1021/jacs.7b05155

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Article
Transition Metal-Free Decarboxylative Iodination: New
Routes for Decarboxylative Oxidative Cross-Couplings
Gregory J. P. Perry, Jacob M. Quibell, Adyasha Panigrahi, and Igor Larrosa
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 23 Jul 2017
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Transition Metal-Free Decarboxylative Iodination: New Routes for
Decarboxylative Oxidative Cross-Couplings
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Gregory J. P. Perry, Jacob M. Quibell, Adyasha Panigrahi and Igor Larrosa*
School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom
ABSTRACT: Constructing products of high synthetic value from inexpensive and abundant starting materials is of great im-
portance. Aryl iodides are essential building blocks for the synthesis of functional molecules and efficient methods for their synthe-
sis from chemical feedstocks are highly sought after. Here we report a low-cost decarboxylative iodination that occurs simply from
readily available benzoic acids and I2. The reaction is scalable and the scope and robustness of the reaction is thoroughly examined.
Mechanistic studies suggest that this reaction does not proceed via a radical mechanism, which is in contrast to classical
Hunsdiecker-type decarboxylative halogenations. In addition, DFT studies allow comparisons to be made between our procedure
and current transition metal-catalyzed decarboxylations. The utility of this procedure is demonstrated in its application to oxidative
cross-couplings of aromatics via decarboxylative/C–H or double decarboxylative activations that use I2 as the terminal oxidant.
This strategy allows the preparation of biaryls previously inaccessible via decarboxylative methods and holds other advantages over
existing decarboxylative oxidative couplings as stoichiometric transition metals are avoided.
1. INTRODUCTION
Scheme 1. Comparison of traditional cross-couplings, de-
carboxylative oxidative couplings and this report.
The advent of cross-coupling reactions revolutionized the
thought process for C–C bond formation, particularly when
constructing biaryls - common structures in many biologically
active and functional molecules from blockbuster pharmaceu-
ticals to day-to-day electronic devices.1,2 These methods gen-
erally consist of the coupling of an organometallic reagent
with an aryl halide in the presence of a transition metal cata-
lyst (Scheme 1, a). More recently, the areas of C–H and decar-
boxylative activation have looked to develop more efficient
routes for cross-coupling.3,4 In particular, the coupling of ben-
zoic acids with either an arene or a second benzoic acid has
gained great interest as both aryl donors are low-cost and read-
ily-available and, in an ideal scenario, H2O and CO2 are
,
formed as the only waste products (Scheme 1, b). 5 6 Progress
in this area has already begun, however, current procedures
generally yield poor reaction scope and require stoichiometric
transition metals, thus limiting their applicability. Further-
more, the need for stoichiometric transition metals greatly
reduces atom-economy and brings into question the true bene-
fits of these procedures (Scheme 1, b) over traditional cross-
couplings (Scheme 1, a).4i
chances of success are greatly improved as the number of po-
tentially inhibitory side products are reduced.
Using the carboxyl group as a site for selective transfor-
mations is an attractive prospect in synthesis. Benzoic acids
are inexpensive and readily-available, and their conversion
through decarboxylative pathways holds potential in atom-
economical processes. With regard to aryl halide formation,
the Hunsdiecker reaction, is a well-known process for the de-
carboxylative halogenation of anhydrous silver carboxylates
with elemental halogens.10 This reaction affords good reactivi-
ty for aliphatic carboxylic acids, however, aromatic carboxylic
acids have traditionally been poor substrates for this process.
In particular, while some electron-deficient aromatics react
with variable yields, electron-rich aromatics undergo electro-
philic halogenation instead (Scheme 2).11 More recent efforts
towards a decarboxylative halogenation of aromatic acids are
of limited utility as they a) require stoichiometric transition
metal additives; b) show poor substrate scope; and/or c) show
Aryl halides are prolific building blocks in organic synthe-
sis.7 They have proved integral to the development of cross-
coupling reactions and they also undergo a variety of other
transformations such as nucleophilic substitution and meta-
lation amongst many others.8 Due to their undeniable im-
portance, efficient methods for aryl halide formation from
chemical feedstocks are highly sought after.9 When develop-
ing a procedure for aryl halide formation, one should also con-
sider the possibility of directly transforming the aryl halide in
one-pot. This would allow for the streamlined synthesis of
functional molecules from abundant starting materials via aryl
halide intermediates (Scheme 1c). Whether the streamlined
synthesis is successful or not will depend upon the compatibil-
ity of each step (iodination/functionalization) in the synthesis.
By developing simple procedures for aryl halide formation the
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Scheme 2. Current status of the aromatic Hunsdiecker
reaction.
the product in 73 % yield (Entry 8). Finally, control reactions
revealed that a) the reaction is sensitive to water (entry 9);17 b)
no loss of reactivity is observed when conducting the experi-
ment in the dark (entry 10); and c) in the absence of a base the
reaction does not proceed (entry 11). Replacing I2 with Br2 led
to the formation of the brominated acid Br-1a’ and dibromin-
ated product Br-2a’, possibly due to the higher electrophilicity
of Br2 (Entry 12). Efforts towards a selective decarboxylative
bromination are ongoing in our laboratory.
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2
3
4
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8
poor selectivity.12,13 For these reasons, the conversion of aro-
matic benzoic acids into the corresponding aryl halides is gen-
erally carried out via a multistep process.14 Therefore, the de-
velopment of a method for the direct conversion of benzoic
acids to aryl halides via decarboxylation remains an unsolved
challenge.
2.2. Scope of the Transition Metal-Free Decarboxylative
Iodination. The development of such a simple route for the
formation of aryl iodides was highly appealing and we were
keen to examine its applicability to other substrates (Scheme
3). Our first observation was that the system is not limited to
ortho-substituted benzoic acids, in contrast to many transition
metal-catalysed decarboxylations (2b, 2c).4,12 Although both
ortho- and para-anisic acid (2a, 2b) are reactive, meta-anisic
acid (2d) was unreactive suggesting that the position of decar-
boxylation must be sufficiently nucleophilic.18 Increasing the
electron density on the aromatic acid greatly improves the
reactivity of the substrate and allows the temperature to be
reduced, even to room temperature in some cases (2e–2h).
These low temperature decarboxylations are remarkable as
analogous transition metal-catalysed procedures require highly
activated di-ortho-substituted benzoic acids and temperatures
of 160 oC, and we are unaware of any other transition metal-
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We report here a general and cost-effective method for the
decarboxylative iodination of (hetero)aromatic acids simply
using readily-available I2 (Scheme 1c). We detail the first ex-
amples of a transition-metal free decarboxylative iodination of
heteroaromatic acids and the first mechanistic study (through
radical clock, DFT and Hammett plot analysis) of an aromatic
decarboxylative halogenation. The simplicity of the procedure
also allows it to be applied to a streamlined synthesis of biar-
yls. In this process the formed aryl halide can be subsequently
cross-coupled with either an arene or a second benzoic acid
using a copper catalyst in a one-pot process. This streamlined
synthesis holds several advantages over current decarboxyla-
tive oxidative strategies as stoichiometric transition metals are
avoided and normally poorly reactive benzoic acids (e.g. elec-
tron-rich and non-ortho-substituted acids) are efficiently cou-
pled.
Table 1. Optimization of the Transition Metal-Free Decar-
boxylative Iodination
2. RESULTS AND DISCUSSION
2.1. Development of a Transition Metal-Free Decarboxy-
lative Iodination. To begin our study, we investigated a clas-
sical aromatic Hunsdiecker-type decarboxylation -the reaction
of the elemental halogens with the silver salts of benzoic ac-
ids- considering also that silver on its own can promote the
decarboxylation of aromatic acids (Table 1).15 However, simi-
larly to previous reports using Br2 (Scheme 2),11 the mixing of
Ag(I)-2-methoxybenzoate Ag-1a with I2 gave a mixture of the
unwanted iodinated acid 1a’ (74%) and the diiodinated prod-
uct 2a’ (10%), but none of desired aryl iodide 2a (Table 1,
entry 1). Thus, an undesired iodination process appears to be
prevalent under Hunsdiecker-type conditions, preventing the
desired decarboxylative iodination process. To our surprise,
when the reaction was carried out in the absence of silver (us-
ing K-1a) the desired product 2a was formed in excellent yield
and high selectivity (entry 2), revealing a previously unknown
and remarkably simple transition metal-free procedure for the
decarboxylative iodination of aromatic acids. The reasoning
for this switch in chemoselectivity is currently unclear, but our
results suggest that a strong C–H iodinating agent is formed in
the presence of Ag(I) and this is minimized when using the
potassium benzoate K-1a.16 To avoid the preparation of ben-
zoate salts, a screening of carbonate bases revealed that benzo-
ic acids are suitable reagents and that, although all carbonate
bases show some reactivity, the more soluble carbonate bases
show improved reactivity (Table 1, entries 3-6). The screening
of many inorganic bases revealed K3PO4 as the base of choice
for this reaction allowing the product 2a to be isolated in an
excellent yield of 90% without the need for column chroma-
tography (entry 7). A more atom-economic procedure can be
had by decreasing the loading of I2 to 1.5 equivalents and in-
creasing the temperature of the reaction to 170 C to provide
Entry
1
R
Ag
K
H
H
H
H
H
H
H
H
H
H
Base
-
1a
2a
1a’
2a’
14
0
74
10
2
-
9
89
76
64
57
4
90
11
2
trace
trace
trace
trace
1
trace
0
3
Li2CO3
Na2CO3
K2CO3
Cs2CO3
K3PO4
K3PO4
K3PO4
K3PO4
-
4
23
0
5
31
0
6
38
trace
trace
0
7
93 (90)b
73
8c
9d
10e
11
12f
7
2
62
3
34
0
0
94
1
trace
0
94
trace
0
2
K3PO4
0
23
72
a
Reaction conditions: benzoic acid/benzoate (0.2 mmol), I2 (0.6
mmol, 3.0 equiv), base (0.2 mmol, 1.0 equiv), MeCN (1.0 mL),
100 °C, 4 h. b Yield in parenthesis is of isolated material. Isolated
as a mixture with 2a’ (2a:2a’, >100:1). c I2 (0.3 mmol, 1.5 equiv,),
170 °C, 16 h, 1,4-dioxane used as solvent. d 1.0 equiv H2O added.
e
f
Reaction performed in the dark. I2 was replaced with Br2, to
form the corresponding bromides Br-1a’ and Br-2a’.
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however moderate to excellent yields were obtained upon pro-
Scheme 3. The scope of the decarboxylative iodination of
benzoic acids.
1
2
tection of the hydroxyl group (2o, 2p). The system is tolerant
of bearing amide and amino functionality and, in some cases,
the temperature could again be lowered to room temperature
(2q–2t).21 Examining the reactivity of halo-substituted benzoic
acids also clearly revealed that the presence of more electron-
withdrawing substituents, while still producing good yields,
reduce the reactivity of the system (2u–2ab).22 In light of this,
we were surprised to observe that polyfluorinated benzoic
acids showed excellent reactivity under these conditions (2ac–
2ae); we are currently studying the reason for this unexpected
reactivity.23 The procedure was also applied to the meth-
ylestrone-2-carboxylic acid 1af to provide the corresponding
iodide in high yield (2af).24 In accord with the general trend of
reactivity, substrates that do not bear electron-donating sub-
stituents were unreactive under these conditions (2ag–2aj).25
Finally, if a more atom-economical procedure is desired the
equivalents of I2 can be reduced to between 1.0 and 2.0 equiv-
alents by increasing the temperature of the reaction to 170 C.
The results for these atom-efficient couplings are provided in
square brackets in both Schemes 3 and 4.26
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The compatibility of the reaction with various functional
groups was investigated by means of a robustness screen (See
SI, Tables S2a and S2b).27 We screened 30 additives in order
to gain an informed view of the robustness of this reaction.
This study revealed that many important functional groups
such as cyano-, trifluoromethyl-, nitro-, tosylate-, triflate-,
mesylate- and halo functionalities were fully compatible with
the reaction. On the other hand, hydroxyl and amino function-
alities along with other nucleophilic (hetero)arenes were poor-
ly tolerated. Likewise, alkene and alkyne additives were also
detrimental to the reaction, although an internal alkyne addi-
tive was moderately tolerated. Most interesting was that alde-
hyde, ketone and ester functionalities were all compatible with
the reaction conditions.
Scheme 4. Scope of the decarboxylative iodination of het-
erobenzoic acids.
Reactions carried out at a 0.5 mmol scale of 1. a Ratios in brackets
indicate mono:diiodinated material by crude GC-FID analysis.
Asterisk indicates position of diiodination. b I2 (3.0 equiv). c NMR
yield for reactions employing I2 (1.0 - 2.0 equiv) 170 C and 1,4-
d
e
dioxane or o-DCB as solvent. I2 (6.0 equiv), 140 C. I2 (2.0
f
g
equiv). MeCN (5.0 mL). I2 (3.0 equiv), 1,4-dioxane (1.0 M),
170 C. Yields determined by quantitative 19F NMR. I2 (2.5
h
i
equiv).
free decarboxylative transformations of aromatic acids occur-
ring at these low temperatures.12f,19 Polymethylated benzoic
acids have previously proved poorly reactive in decarboxyla-
tive processes,20 however we observed good to excellent reac-
tivity with these substrates (2i–2k) and even orho-toluic acid
(2l) showed some reactivity when increasing both the tempera-
ture and loadings of I2. Likewise, unsubstituted 1-napthoic
acid (1m) was reactive under more forcing conditions, howev-
er, a small amount of diiodination (2m’) was also observed.
The position of diiodination in this and other products is high-
lighted by the position of the asterisks in each scheme. The
reactivity and selectivity of napthoic acid can be improved by
the introduction of a methyl group to this substrate (2n). At-
tempts to decarboxylate salicylic acids were unsuccessful,
Reactions carried out at a 0.5 mmol scale of 1. a Ratios in brackets
indicate mono:diiodinated material by crude GC-FID analysis.
Asterisk indicates position of diiodination. b I2 (2.0 equiv). c NMR
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yield for reactions employing I2 (1.0 - 2.0 equiv), 170 C and 1,4-
mechanism via this route is given in Scheme 6, thus, upon
dioxane or o-DCB as solvent. d MeCN (5.0 mL). e I2 (6.0 equiv).
formation of the benzoyl hypoiodite I(A)3 0 from the corre-
sponding benzoic acid (1a), base and I2, homolytic bond and
breaking of the O–I bond would provide the benzoyl radical II
an iodine radical (Scheme 6, pathway A). A radical decarbox-
ylation event would give the aryl radical III and subsequent
radical recombination would provide aryl iodide (2a). An al-
ternative pathway that does not involve radical intermediates
was also considered (Scheme 6, pathway B). This pathway
may proceed via transition state IV(A) to give the aryl iodide
2a directly from the benzoyl hypoiodite I(A). This form of
concerted decarboxylation-iodination mechanism is reminis-
cent of recently proposed pathways for transition metal-
catalyzed decarboxylations.31 We set out to delineate between
these two pathways by initially conducting a radical clock
experiment with substrate 1A (Scheme 7). Upon formation of
the corresponding aryl radical from 1A, the rate constant for
intramolecular cyclisation to provide products of type 2A’ is
of the order k = 8  109 s–1.32 Upon exposure of substrate 1A to
our conditions we only observed the iodinated product 2A and
none of the cyclized products 2A’. This experiment strongly
suggests that a radical mechanism is not in operation, in con-
trast to the classical Hunsdiecker reaction of aliphatic carbox-
ylic acids and previous mechanistic proposals for transition
metal-free decarboxylative iodinations.10,13h,13i In order to as-
sess the feasibility of our proposed non-radical pathway we
carried out a preliminary DFT study (Scheme 6, pathway B,
see values in parenthesis).33 Decarboxylation via transition
state IV(A) afforded a barrier of 27.6 kcal mol–1 which is rea-
sonable for a reaction that can occur at 100 C. Although fur-
ther investigations are required, our current data supports the
pathway for decarboxylation via transition state IV(A).
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Methods for the decarboxylative iodination of heteroaro-
matic acids are scarce and currently require stoichiometric
o
transition metals and temperatures >160 C,12,13 thus we were
keen to apply our conditions to these substrates (Scheme 4).
Indoles bearing either methyl or tosyl protecting groups (2ak,
2al) showed good reactivity under our conditions as did ben-
zothiophenes and benzofurans (2am–2aq). Conveniently, the
iodination can also be directed to the less nucleophilic C2 po-
sition of these substrates by simply using the C2-carboxyl
substituted substrates (2ao, 2aq). Similarly, thiophenes (2ar),
furans (2as, 2at), pyrazoles (2au) and thiazoles (2av) were all
compatible under these conditions. Once again, the yields pro-
vided in square brackets represent the outcome of the reaction
when using lower equivalents of I2 (1.0 - 2.0 equiv) and higher
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o
temperatures (170 C).26 In agreement with benzoic acids, less
electron-rich heteroaromatic acids require more forcing condi-
tions (2at). Pyridines bearing morpholino- or methoxy-
substituents and chromone-3-carboxylic acid also display good
reactivity (2aw–2ay). Finally, cinnamic acids are also reactive
substrates, however some isomerization of the C–C double
bond was observed (2az-2az’).28
In order to further demonstrate the utility of our procedure
we looked to achieve a multi-gram synthesis of 1-iodo-2,6-
dimethoxybenzene 2f (Scheme 5). Thus, on submitting 10.0 g
of benzoic acid 1f to the standard conditions at room tempera-
ture, the desired product 2f could be isolated with no detriment
to the final yield (97%, 14.1 g)29 and without the requirement
for silica gel chromatography. We believe that the broad avail-
ability of benzoic acid substrates, low-cost and scalability of
this method has potential in large-scale synthesis.
Scheme 7. Radical clock experiment with benzoic acid 1A.
Scheme 5. Multi-gram scale synthesis of 1-iodo-2,6-
dimethoxybenzene 2f
Previous DFT studies by our group and others have proved
highly useful when investigating the mechanism of transition
metal catalyzed decarboxylations.31 In particular, they have
proved essential for delineating why ortho-substituted benzoic
acids are more reactive than non-ortho-substituted benzoic
acids; a phenomenon commonly termed the ortho-effect. Pre-
vious calculations have shown that the energy of the ortho-
2.3. Mechanistic studies on the transition metal-free de-
carboxylative iodination. Our attention then turned to inves-
tigating the mechanism of this reaction. It is largely considered
that the classical Hunsdiecker reaction -the decarboxylative
halogenation of aliphatic silver carboxylates- proceeds via a
radical pathway; therefore, we were interested to determine
whether our system reacts in a similar manner.10 A possible
Scheme 6. Possible pathways for the decarboxylative iodination of aromatic acids. Pathway A: radical decarboxyla-
tion/radical recombination pathway. Pathway B: concerted decarboxylation-iodination pathway.
a Structures and energies calculated by DFT (B97D3/LanL2DZ for I, 6-31G(d) for other atoms); Gibbs free energies (G) are in kcal mol−1.
b Total energy for 2a + CO2.
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Scheme 8. Comparing the ortho-effect of transition metal-
mediated decarboxylations and transition metal-free de-
carboxylative iodination.
substituted substrate is higher than that of its meta- and para-
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2
3
4
5
6
7
8
isomers due to steric clash with the carboxyl group, however,
the energy for the transition state of each isomer is close to
equal. Overall, this causes the decarboxylation barrier to be
lowered for ortho-substituted benzoic acids in transition met-
al-catalyzed procedures. For example, the 2-methoxy-substrate
(I(C)) is destabilised with respect to the 4-methoxy-isomer
(I(D)) by 5.8 kcal mol–1 in palladium-mediated decarboxyla-
tions, however, the transition states (IV(C/D)) only differ by
1.6 kcal mol–1 (Scheme 8, ii). Thus, the overall energy barrier
is 4.2 kcal mol–1 lower for the ortho-substituted benzoic acid in
palladium mediated decarboxylations.31e Similarly, the differ-
ence in the decarboxylation barrier for silver mediated decar-
boxylations is 6.0 kcal mol–1 due to the destabilization of the
ortho-substituted substrate by 6.3 kcal mol–1 (I(E) vs I(F))
(Scheme 84, iii).31d We were keen to establish whether a simi-
lar ortho-effect could be applied to our transition metal-free
system, therefore, we compared the barriers of decarboxyla-
tion for 2-methoxybenzoic acid and 4-methoxybenzoic acid
(Scheme 8, i). From our experimental results (Scheme 3), we
had observed that the corresponding aryl iodides (2a and 2b)
were formed in high yield at 100 C, however, whereas only
3.0 equivalents of I2 were necessary for the reaction with 2-
methoxybenzoic acid, 4.0 equivalents were needed with 4-
methoxybenzoic acid. This shows that, although the reactivity
is similar, 2-methoxybenzoic acid is slightly more susceptible
to decarboxylation under our conditions. Our DFT study sup-
ported this result as we found that the barrier for decarboxyla-
tion with 2-methoxybenzoic acid was slightly lower than that
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‡
for 4-methoxybenzoic acid by 0.9 kcal mol–1 (Scheme 8, ΔGA
= 27.6 kcal mol–1 and ΔGB‡ = 28.5 kcal mol–1 for 2-methoxy-
and 4-methoxybenzoic acid, respectively). Further inspection
of this data revealed that the 2-methoxy-substituted hypoiodite
(I(A)) is 4.5 kcal mol–1 higher in energy than its 4-methoxy
analogue (I(B)). This difference in energy is likely due to a
steric effect when a group is present ortho to the carboxyl
group and is consistent with the ortho-effect that is witnessed
in transition metal-catalyzed procedures. However, whereas
the difference in energy between ortho and para substituted
transition states (IV) is small (< 2.0 kcal mol–1) for transition
metal-catalyzed decarboxylation, we observe a significant
energy difference of 3.6 kcal mol–1 for the decarboxylative
iodination. In light of this, we suggest that an ortho-effect
resulting from steric destabilization is observed in our system,
which causes ortho-substituted benzoic acids (e.g. 2-
methoxybenzoic acid 1a) to be more susceptible to decarboxy-
lation than non-ortho-substituted substrates (e.g. 4-
methoxybenzoic acid 1b). However, this effect is small, espe-
cially when compared to transition metal-catalyzed proce-
dures, therefore, the reactivity difference between ortho- and
non-ortho-substituted benzoic acids is minimized in our sys-
tem. This results somewhat explain why in our system non-
ortho-substituted benzoic acids are suitable substrates and
further display the advantages of our procedure over those that
require transition metals.
i) Investigating the ortho-effect in the transition metal-free decar-
boxylative iodination. Energies measured in kcal mol-1 for DFT
modelling using an acetonitrile solvent correction. Structures and
energies calculated by DFT (LanL2DZ for I, 6-31G(d) for other
atoms); Gibbs free energies (G) are in kcal mol−1. ii) The ortho-
effect in palladium-catalysed decarboxylations as reported by Su
et al.31e iii) The ortho-effect in silver-catalysed decarboxylations
as reported by Su et al.31d
Hammett plot analysis of the initial rates of decarboxylative
iodination of a series of meta- and para-substituted 2-
methoxybenzoic acids provided a rho (ρ) value of –4.6 con-
sistent with a substantial build-up of positive charge in the
transition state IV (Figure 1).22 This value is comparable to
those previously reported for electrophilic aromatic substitu-
tion-type reactions and supports our observation that electron
rich (hetero)aromatic acids are preferred substrates in this
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2B
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2y
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2v
2w
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60
σ
Figure 1. Hammett Plot of the decarboxylative iodination. Equation of fit: y = –4.59x + 0.09. R2 = 0.92. Position (meta/para) of
substituent is with respect to the carboxyl group.
system.22b,34 Our computational study (Scheme 6, Pathway B)
does not suggest a distinct Wheland-type intermediate is
formed. However, the calculated natural bond orbital (NBO)
charges indicate a build-up of positive charge in the transition
state. For example, the carbon atom ipso to the methoxy group
in the pre-transition state VI(A) (see SI) has a value of +0.345,
which rises to +0.416 in the transition state TS-IV(A). There-
fore, the proposed concerted decarboxylation/iodination pro-
cess (Scheme 6, pathway B) is consistent with the experi-
mental Hammett plot. Further studies are necessary to better
understand the mechanism of this reaction.
first undergoes decarboxylative iodination followed by copper
catalyzed cross-coupling using conditions based on those re-
ported by Daugulis and co-workers.Error! Bookmark not defined. Dau-
gulis reported that the presence of iodine inhibits the copper-
catalyzed coupling step,Error! Bookmark not defined.b leading to very
long reaction times of up to 9 days, although dimethylaniline
could be added to quench excess iodine in a multistep process.
In our investigation we found that excess iodine could be more
efficiently eliminated by the addition of Et3N after the decar-
boxylative iodination has concluded, and before the coupling
step is carried out.
2.4. Applying the decarboxylative iodination towards
decarboxylative oxidative couplings. The coupling of a ben-
zoic acid with an arene or a second benzoic acid via a C-C/C-
H or C-C/C-C double activation, respectively, is a highly ap-
pealing transformation. Currently, most procedures to carry
out this transformation require stoichiometric transition metal
additives with only a few exceptions.4i However, these meth-
ods have their own limitations, for example: 1) the copper-
catalyzed coupling of benzoic acids with arenes is restricted to
the coupling of ortho-nitrobenzoic acids with heteroarenes and
requires high loadings of the catalyst;5p and 2) although the
coupling of ortho- and non-ortho-substituted benzoic acids
with arenes is possible under silver- or photoredox-catalysis,
solvent quantities of the arene are required.5o,5q Therefore,
more economical and general methods for oxidative decar-
boxylative couplings are of high importance.
Scheme 9. The scope of the decarboxylative oxidative
cross-coupling between benzoic acids and arenes.
Our simple procedure for decarboxylative iodination does
not require transition metal additives and is applicable to non-
ortho-substituted benzoic acids. Thus, we envisaged that this
new decarboxylative protocol could be used as the cornerstone
to address some of the current limitations in C-C/C-C and C-
C/C-H oxidative couplings. Our approach to these oxidative
couplings would consist of generating the aryl iodide from the
benzoic acid and then cross coupling the aryl iodide with an
arene or a second benzoic acid in a one-pot protocol. This
strategy is reminiscent to that used by Daugulis and co-
workers for the copper-catalyzed cross-coupling of two arenes
via double C-H activations, which proceeds through an aryl
iodide intermediate. In light of this precedent we were confi-
dent that a decarboxylative oxidative cross-coupling should be
possible.
Reactions carried out at a 0.5 mmol scale of 4. All three steps are
conducted between 150 - 190 C. K3PO4 (6.5 - 8.0 equiv) total
across 3 steps. Ratios in brackets indicate ratio of regioisomeric
products by crude GC-FID analysis. Asterisk indicates position of
minor regioisomer.
a
Overall, the biaryl product is formed in a one-pot, three step
process consisting of 1) decarboxylative iodination, 2) iodine
quench, and 3) cross-coupling; with the necessary reagents
We initially investigated the coupling of a benzoic acid
with an arene (Scheme 9). In this procedure the benzoic acid
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being added at each step. Importantly the entire process is The field of decarboxylative activation is highly appealing as
1
2
3
4
5
6
7
8
conducted in one-pot and no work-up or isolation is required
between each step. Our initial results show that many combi-
nations of benzoic acids and arenes can be coupled together.
The reaction tolerates a variety of different functionalities such
as nitro- (5c, 5e), chloro- (5g, 5h), trifluoromethyl (5a), and
cyano-groups (5d, 5f). A range of aromatic acids are applica-
ble in the cross-coupling including methoxy-(e.g. 5b, 5f) and
chloro-substituted (5g) benzoic acids, indole- (5c) and ben-
zothiophene-carboxylic acids (5d). Most notable are the cou-
plings of non-ortho-substituted benzoic acids 5a - 5d as these
substrates are generally unreactive in current decarboxylative
coupling procedures.
it holds potential in efficient and atom-economic synthesis.
We have reported a simple but effective transition metal-free
preparation of aryl iodides from readily-available benzoic
acids and I2. The procedure can be applied to a large range of
electron-rich benzoic acids and to polyfluorinated aromatic
acids. Importantly, this method overcomes some long-standing
problems (e.g. poor selectivity and stoichiometric silver salts)
of the classical aromatic Hunsdiecker decarboxylation. A
combined theoretical and experimental study has shed light on
the mechanism of this reaction which we currently suggest
proceeds via a concerted decarboxylation/halogenation-type
process. To further demonstrate the potential applications of
this procedure we have developed a one-pot decarboxylative
oxidative coupling. This process has several advantages over
current procedures, namely the coupling of non-ortho-
substituted benzoic acids, the removal of stoichiometric transi-
tion metal additives and the coupling of near-identical benzoic
acids. We believe the scalability of the decarboxylative io-
dination holds potential for its application in preparative syn-
thesis. Furthermore, the simplicity of the decarboxylative pro-
tocol, taken together with the breadth of methods for catalytic
transformation of the resulting aryl iodides should allow for
the development of a variety of novel decarboxylative trans-
formations, in addition to the oxidative cross-couplings report-
ed in this manuscript.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Our focus then turned to applying this procedure to the
double decarboxylative cross-coupling of two aromatic acids
(Scheme 10). Our strategy for the cross-coupling of benzoic
acids with arenes could easily be applied to this process to
provide a variety of biaryl products. Whereas current proce-
dures provide high levels of homocoupled product (>9%), our
procedure shows high selectivity for the cross-coupled product
with no homocoupled products, or only traces, being observed.
A range of benzoic acids, including, methoxysubstituted ben-
zoic acids (e.g. 8a, 8b), benzothiophenecarboxylic acids (8c)
and polyfluorinated benzoic acids (8d), could be coupled with
polyfluorobenzoic acids in different combinations. These
Scheme 10. The scope of the double decarboxylative oxida-
tive cross-coupling between two benzoic acids.
ASSOCIATED CONTENT
Supporting Information. Experimental procedures and charac-
terization data are available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* igor.larrosa@manchester.ac.uk
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We gratefully acknowledge the Engineering and Physical Scienc-
es Research Council (EPSRC, EP/I038578/1 and EP/L014017/2)
for funding and the European Research Council for a Starting
Grant (to I.L.).
Reactions carried out at a 0.5 mmol scale of 6. K3PO4 (5.5 - 6.5
REFERENCES
a
equiv) total across 3 steps. The potassium salt of 7 was used in
this case. b Yield determined by quantitative 19F NMR. c Step 3:
No CuI/Phen added, PdCl2/BINAP (9 mol %), Ag2CO3 (3.20
equiv). The potassium salt of 6 was used in this case.
(1) (a) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire,
M. Chem. Rev. 2002, 102, 1359–1470. (b) Johansson Seechurn, C. C.
C.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Angew. Chem. Int.
Ed. 2012, 51, 5062–5085. (c) Bolm, C.; Hildebrand, J. P.; Muniz, K.;
Hermanns, N. Angew. Chem. Int. Ed. 2001, 40, 3284–3308.
(2) (a) Bringmann, G.; Günther, C.; Ochse, M.; Schupp, O.; Tasler,
S. Biaryls in Nature: A Multi-Facetted Class of Stereochemically,
Biosynthetically, and Pharmacologically Intriguing Secondary
Metabolites; In Progress in the Chemistry of Organic Natural
Products; Herz, W., Falk, H., Kirby, G. W., Moore, R. E., Eds.;
Springer Vienna: 2001; Vol. 82, pp 1-249. (b) Horton, D. A.; Bourne,
G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893–930. (c) Grimsdale,
A. C.; Chan, K. L.; Martin, R. E.; Jokisz, P. G.; Holmes, A. B. Chem.
Rev. 2009, 109, 897–1091.
represent the first examples of double decarboxylative cross-
couplings that do not require stoichiometric transition metal
additives. Furthermore, products 8a and 8c represent the first
examples of the coupling of a non-ortho-substituted benzoic
acid in a double decarboxylative coupling. The power of this
procedure can further be seen in the coupling of two electroni-
cally and sterically similar benzoic acids (8d - 8f). Although
the formation of products 8e and 8f require stoichiometric
transition metals and proceeds to moderate yields, we believe
this represents the most efficient route for the coupling of
near-identical benzoic acids to date.
(3) For selected reviews on C–H activation see: (a) Alberico, D.;
Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174–238. (b)
Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem. Int. Ed.
2009, 48, 9792–9826. (c) Boorman, T. C.; Larrosa, I. Chem. Soc. Rev.
3. CONCLUSIONS
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 11
2011, 40, 1910–1925. (d) Wencel-Delord, J.; Dröge, T.; Liu, F.; Glo-
W. P. Synthesis 1987, 665–683. (h) Kim, H.; Lee, C.; Angew. Chem.
rius, F. Chem. Soc. Rev. 2011, 40, 4740–4761. (e) Kuhl, N.; Hopkin-
son, M. N.; Wencel-Delord, J.; Glorius, F. Angew. Chem. Int. Ed.
2012, 51, 10236–10254. (f) Kakiuchi, F.; Kochi, T.; Murai, S. Synlett
2014, 25, 2390–2414. (g) Ahlsten, N.; Cambeiro, X. C.; Perry, G. J.
P.; Larrosa, I. In Topics in Heterocyclic Chemistry; Bandini M., Eds.;
Springer International Publishing, 2016; Vol. 46, pp 175–226. (h)
Font, M.; Quibell, J. M.; Perry, G. J. P.; Larrosa, I. Chem. Commun.
2017, 53, 5584–5597. (i) Simonetti, M.; Cannas, D. M.; Larrosa I.; In
Advances in Organometallic Chemistry; Pérez, P. J., Eds.; Elsevier,
2017; Vol. 67, pp 299–399. (j) Murakami, K.; Perry, G. J. P.; Itami,
K. Org. Biomol. Chem. 2017 doi: 10.1039/C7OB00985B (k) Yi, H.;
Zhang, G.; Wang, H.; Huang, Z.; Wang, J.; Sing, A. K.; Lei, A.
Chem. Rev. 2017, 117, 9016–9085.
(4) For selected reviews on decarboxylative activation see: (a)
Gooßen, L. J.; Gooßen, K.; Rodríguez, N.; Blanchot, M.; Linder, C.;
Zimmermann, B. Pure Appl. Chem. 2008, 80, 1725–1733. (b)
Gooßen, L. J.; Rodríguez, N.; Gooßen, K. Angew. Chem. Int. Ed.
2008, 47, 3100–3120. (c) Gooßen, L. J.; Collet, F.; Gooßen, K. Isr. J.
Chem. 2010, 50, 617–629. (d) Shang, R.; Liu, L. Sci. China Chem.
2011, 54, 1670–1687. (e) Rodríguez, N.; Gooßen, L. J. Chem. Soc.
Rev. 2011, 40, 5030–5048. (f) Dzik, W. I.; Lange, P. P.; Gooßen, L. J.
Chem. Sci. 2012, 3, 2671–2678. (g) Cornella, J.; Larrosa, I. Synthesis
2012, 44, 653–676; (h) Gooßen, L. J.; Gooßen, K. Decarboxylative
Coupling Reactions; In Topics in Organometallic Chemistry; Gooßen,
L. J., Eds.; Springer-Verlag Berlin Heidelberg: 2013; Vol. 44 pp.
121–142. (i) Perry, G. J. P.; Larrosa, I. Eur. J. Org. Chem. 2017,
3517–3527. For a review on deamidative cross-coupling see: (j) Liu,
C.; Szostak, M. Chem. Eur. J, 2017, 23, 7157–7173.
(5) For the coupling of benzoic acids with arenes see (a)
Voutchkova, A.; Coplin, A.; Leadbeater, N. E.; Crabtree, R. H. Chem.
Commun. 2008, 6312–6314. (b) Wang, C.; Piel, I.; Glorius, F. J. Am.
Chem. Soc. 2009, 131, 4194–4195. (c) Cornella, J.; Lu, P.; Larrosa, I.
Org. Lett. 2009, 11, 5506–5509. (d) Zhou, J.; Hu, P.; Zhang, M.;
Huang, S.; Wang, M.; Su, W. Chem. Eur. J. 2010, 16 , 5876–5881. (e)
Xie, K.; Yang, Z.; Zhou, X.; Li, X.; Wang, S.; Tan, Z.; An, X.; Guo,
C.-C. Org. Lett. 2010, 12, 1564–1567. (f) Zhang, F.; Greaney, M. F.
Angew. Chem. Int. Ed. 2010, 49, 2768–2771. (g) Zhao, H.; Wei, Y.;
Xu, J.; Kan, J.; Su, W.; Hong, M. J. Org. Chem. 2011, 76, 882–893.
(h) Hu, P.; Zhang, M.; Jie, X.; Su, W. Angew. Chem. Int. Ed. 2012,
51, 227–231. (i) Luo, H.-Q.; Dong, W.; Loh, T.-P. Tetrahedron Lett.
2013, 54, 2833–2836. (j) Pei, K.; Jie, X.; Zhao, H.; Su, W. Eur. J.
Org. Chem. 2014, 4230–4233. (k) Suresh, R.; Muthusubramanian, S.;
Kumaran, R. S.; Manickam, G. Asian J. Org. Chem. 2014, 3, 604–
608. (l) Yang, K.; Wang, P.; Zhang, C.; Kadi, A. A.; Fun, H.-K.;
Zhang, Y.; Lu, H. Eur. J. Org. Chem. 2014, 7586–7589. (m) Chen,
L.; Ju, L.; Bustin, K. A.; Hoover, J. M. Chem. Commun. 2015, 51,
15059–15062. (n) Zhao, S.; Liu, Y.-J.; Yan, S.-Y.; Chen, F.-J.; Zhang,
Z.-Z.; Shi, B.-F. Org. Lett. 2015, 17, 3338–3341. (o) Kan, J.; Huang,
S.; Lin, J.; Zhang, M.; Su, W. Angew. Chem. Int. Ed. 2015, 54, 2199–
2203. (p) Patra, T.; Nandi, S.; Sahoo, S. K.; Maiti, D. Chem. Com-
mun. 2016, 52, 1432–1435. (q) Candish, L.; Freitag, M.; Gensch T.;
Glorius F. Chem. Sci 2017, 8, 3618−3622.
(6) For the coupling of two benzoic acids see (a) Cornella, J.;
Lahlali, H.; Larrosa, I. Chem. Commun. 2010, 46, 8276–8278. (b)
Xie, K.; Wang, S.; Yang, Z.; Liu, J.; Wang, A.; Li, X.; Tan, Z.; Guo,
C.-C.; Deng, W. Eur. J. Org. Chem. 2011, 5787–5790. (c) Hu, P.;
Shang, Y.; Su, W. Angew. Chem. Int. Ed. 2012, 51, 5945–5949. (d)
Fu, Z.; Li, Z.; Xiong, Q.; Cai, H. RSC Adv. 2015, 5, 52101–52104.
(7) For a comprehensive review on this subject see Iodine chemis-
try and Applications (Ed.: T. Kaiho), Wiley-VCH, Weinheim, 2015.
(8) For the use of aryl iodides: in cross-couplings see ref 1; nucleo-
philic substitution see (a) Burnett, J. F.; Zahler, R. E. Chem. Rev.
1951, 49, 273–412; (b) Hartwig, J. F. Synlett 2006, 1283–1294; in
metalation see (c) Knochel, P.; Dohle, W.; Gommermann, N.;
Kneisel, F. F.; Kopp, F.; Korn, T.; Sapountzis, I.; Vu, V. A. Angew.
Chem. Int. Ed. 2003, 42, 4302–4320. (d) Tilly, D.; Chevallier, F.;
Mongin, F.; Gros, P. C. Chem. Rev. 2014, 114, 1207–1257. (e) Hand-
book of Grignard Reagents; Silverman, G. S., Rakita, P. E., Eds.;
Dekker: New York, NY, 1996. (f) Sotomayor, N.; Lete, E. Curr. Org.
Chem. 2003, 7, 275–300; in aryl radical formation see (g) Neumann,
Int. Ed. 2012, 51, 12303–12306. (i) Nguyen, J. D.; D’Amato, E. M.;
Narayanam, J. M. R.; Stephenson, C. R. J. Nat. Chem. 2012, 4, 854–
859. (j) Ghosh, I.; Ghosh, T.; Bardagi, J. I.; Konig, B. Science 2014,
346, 725–728. (k) Liu, Y. X.; Xue, D.; Wang, J.-D.; Zhao, C.-J.; Zou,
Q.-Z.; Wang, C.; Xiao, J. Synlett 2013, 24, 507–513; in aryne genera-
tion see (l) Pellissier, H.; Santelli, M. Tetrahedron 2003, 59, 701–730.
(m) Moss, R.A.; Platz, M. S.; Jones, Jr, M. In Reactive Intermediate
Chemistry; Winkler, M.; Wenk, H. H.; Sander, W., Eds.; John Wiley
& Sons, Inc.: Hoboken, NJ, USA, 2005; pp 741–794; as hypervalent
iodine species see (n) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008,
108, 5299–5358. (o) Merritt, E. A.; Olofsson, B. Angew. Chem. Int.
Ed. 2009, 48, 9052–9070. (p) Deprez, N. R.; Sanford, M. S.; Inorg.
Chem. 2007, 46, 1924–1935. (q) Cambeiro, X. C.; Boorman, T. C.;
Lu, P.; Larrosa, I. Angew. Chem. Int. Ed. 2013, 52, 1781–1784. (r)
Cambeiro, X. C.; Ahlsten, N.; Larrosa, I. J. Am. Chem. Soc. 2015,
137, 15636–15639; in natural products see (s) Wang, L.; Zhou, X.;
Fredimoses, M.; Liao, S.; Liu, Y. RSC Adv. 2014, 4, 57350–57376. (t)
Markou, K.; Georgopoulos, N.; Kyriazopoulou, V.; Vagenakis, A. G.
Thyroid 2001, 11, 501–510. (u) Hair, P. I.; McCormack, P. L.; Cur-
ran, M. P. Drugs 2008, 68, 1415–1434. (v) Quinn, M. J.; Fitzgerald,
D. J. Circulation 1999, 100, 1667–1672. (w) Boger, D. L. Med. Res.
Rev. 2001, 21, 356–381. (x) DeLeon, A; Patel, N. C.; Crismon, M. L.
Clin. Ther. 2004, 26, 649–666; in medical imaging agents see (y)
Seevers, R. H.; Counsell, R. E. Chem. Rev. 1982, 82, 575–590. (z)
Schlyer, D. J. Ann. Acad. Med. Singapore 2004, 33, 146–154; in or-
ganic materials see (a’) Tang, M. L.; Bao, Z. Chem. Mater. 2011, 23,
446–455.
(9) For the preparation of aryl iodides: via electrophilic aromatic
substitution (SEAr) see (a) Taylor, R. In Electrophilic Aromatic Sub-
stitution; John Wiley: New York, 1990. (b) Barluenga, J.; Gonzalez,
J. M.; Garcia-Martin, M. A.; Campos, P. J.; Asensio, G. J. Org.
Chem. 1993, 58, 2058–2060. (c) Rodriguez, R. A.; Pan, C.-M.; Yabe,
Y.; Kawamata, Y.; Eastgate, M. D.; Baran, P. S. J. Am. Chem. Soc.
2014, 136, 6908–6911; via directed ortho-metalation (DoM) see (d)
Snieckus, V. Chem. Rev. 1990, 90, 879–933; using directing groups
(e) Fahey, D. R. J. Organomet. Chem. 1971, 27, 283–292. (f) Dick, A.
R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 126, 2300–
2301. (g) Giri, R.; Chen, X.; Yu, J.-Q. Angew. Chem. Int. Ed. 2005,
44, 2112–2115. (h) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J.
Am. Chem. Soc. 2006, 128, 6790–6791. (i) Kalyani, D.; Dick, A. R.;
Anani, W. Q.; Sanford, M. S. Tetrahedron 2006, 62, 11483–11498. (j)
Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S. Org. Lett.
2006, 8, 2523–2526. (k) Wan, X.; Ma, Z.; Li, B.; Zhang, K.; Cao, S.;
Zhang, S.; Shi, Z. J. Am. Chem. Soc. 2006, 128, 7416–7417. (l) Whit-
field, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2007, 129, 15142–
15143. (m) Mei, T.-S.; Giri, R.; Maugel, N.; Yu, J.-Q. Angew. Chem.
Int. Ed. 2008, 47, 5215–5219. (n) Li, J.-J.; Mei, T.-S.; Yu, J.-Q. An-
gew. Chem. Int. Ed. 2008, 47, 6452–6455. (o) Whitfield, S. R.; San-
ford, M. S. Organometallics 2008, 27, 1683–1689. (p) Kakiuchi, F.;
Kochi, T.; Mutsutani, H.; Kobayashi, N.; Urano, S.; Sato, M.; Nishi-
yama, S.; Tanabe, T. J. Am. Chem. Soc. 2009, 131, 11310–11311. (q)
Zhao, X.; Dimitrijeviꢀ, E.; Dong, V. M. J. Am. Chem. Soc. 2009, 131,
3466–3467. (r) Song, B.; Zheng, X.; Mo, J.; Xu, B. Adv. Synth. Catal.
2010, 352, 329–335. (s) Bedford, R. B.; Engelhart, J. U.; Haddow, M.
F.; Mitchell, C. J.; Webster, R. L. Dalton Trans. 2010, 39, 10464–
10472. (t) Mei, T.-S.; Wang, D.-H.; Yu, J.-Q. Org. Lett. 2010, 12,
3140–3143. (u) Dudnik, A. S.; Chernyak, N.; Huang, C.; Gevorgyan,
V. Angew. Chem. Int. Ed. 2010, 49, 8729–8732. (v) Powers, D. C.;
Xiao, D. Y.; Geibel, M. A. L.; Ritter, T. J. Am. Chem. Soc. 2010, 132,
14530–14536. (w) Wang, W.; Pan, C.; Chen, F.; Cheng, J. Chem.
Commun. 2011, 47, 3978–3980. (x) Dubost, E.; Fossey, C.; Cailly, T.;
Rault, S.; Fabis, F. J. Org. Chem. 2011, 76, 6414–6420. (y) Bedford,
R. B.; Haddow, M. F.; Mitchell, C. J.; Webster, R. L. Angew. Chem.
Int. Ed. 2011, 50, 5524–5527. (z) Schröder, N.; Wencel-Delord, J.;
Glorius, F. J. Am. Chem. Soc. 2012, 134, 8298–8301. (a’) John, A.;
Nicholas, K. M. J. Org. Chem. 2012, 77, 5600–5605. (b’) Wang, X.-
C.; Hu, Y.; Bonacorsi, S.; Hong, Y.; Burrell, R.; Yu, J.-Q. J. Am.
Chem. Soc. 2013, 135, 10326–10329. (c’) Chu, L.; Xiao, K.-J.; Yu, J.-
Q. Science 2014, 346, 451–455. (d’) Haines, B. E.; Xu, H.; Verma, P.;
Wang, X.-C.; Yu, J.-Q.; Musaev, D. G. J. Am. Chem. Soc. 2015, 137,
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
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9022–9031. (e’) Li, B.; Liu, B.; Shi, B.-F. Chem. Commun. 2015, 51,
P.; Sanchez, C.; Cornella, J.; Larrosa, I. Org. Lett. 2009, 11, 5710–
5713; c) Seo, S.; Taylor, J. B.; Greaney, M. F. Chem. Commun. 2012,
48, 8270–8272; d) Grainger, R.; Nikmal, A.; Cornella, J.; Larrosa, I.
Org. Biomol. Chem. 2012, 10, 3172–3174.
5093–5096. (f’) Teskey, C. J.; Lui, A. Y. W.; Greaney, M. F. Angew.
Chem. Int. Ed. 2015, 54, 11677–11680; from aryl diazonium salts see
(g’) Sandmeyer, T. Ber. Dtsch. Chem. Ges. 1884, 17, 1633–1635. (h’)
Hodgson, H. H. Chem. Rev. 1947, 40, 251–277. (i’) Roglans, A.; Pla-
Quintana, A.; Moreno-Mañas, M. Chem. Rev. 2006, 106, 4622–4643;
via halogen exchange (HalEx) see (j’) Lindley, J. Tetrahedron 1984,
40, 1433–1456. (k’) Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc.
2002, 124, 14844–14845. (l’) Sheppard, T. D. Org. Biomol. Chem.
2009, 7, 1043-1052. (m’) Casitas, A.; Canta, M.; Solà, M.; Costas,
M.; Ribas, X. J. Am. Chem. Soc. 2011, 133, 19386–19392. (n’) Cant,
A. A.; Bhalla, R.; Pimlott, S. L.; Sutherland, A. Chem. Commun.
2012, 48, 3993-3995. (o’) Font, M.; Acuña-Parés, F.; Parella, T.;
Serra, J.; Luis, J. M.; Lloret-Fillol, J.; Costas, M.; Ribas, X. Nat.
Commun. 2014, 5, 4373. (p’) Serra, J.; Whiteoak, C. J.; Acuña-Parés,
F.; Font, M.; Luis, J. M.; Lloret-Fillol, J.; Ribas, X. J. Am. Chem. Soc.
2015, 137, 13389–13397. (q’) Chen, M.; Ichikawa, S.; Buchwald, S.
L. Angew. Chem. Int. Ed. 2015, 54, 263–266. (r’) Li, L.; Liu, W.;
Zeng, H.; Mu, X.; Cosa, G.; Mi, Z.; Li, C.-J. J. Am. Chem. Soc. 2015,
137, 8328–8331.
(10) (a) Borodine, A. Justus Liebigs Ann. Chem. 1861, 119, 121–
123; (b) Hunsdiecker, H.; Hunsdiecker, C. Ber. Dtsch. Chem. Ges.
1942, 75B, 291–297; (c) Wilson, C. in Org. React., John Wiley &
Sons, Inc., Hoboken, NJ, USA, 2011, pp. 332–387; (d) Crich, D. In
Comprehensive Organic Synthesis; Trost B. M., Fleming I., Eds.;
Pergamon Press, 1991; Vol. 7, pp 717–734; (e) Crich, D.; Sasaki, K.
in Comprehensive Organic Synthesis II; Knochel, P., Molander, G.
A. , Eds.; Elsevier, 2014, pp. 818–836.
(11) (a) Dauben, W. G.; Tilles, H. J. Am. Chem. Soc. 1950, 72,
3185–3187. (b) Barnes, R. A.; Prochaska, R. J. J. Am. Chem. Soc.
1950, 72, 3188–3191. (c) Oldham, J. W. H. J. Chem. Soc. 1950, 100–
108.
(12) For reports that require stoichiometric transition metals see ref
11 and: (a) Kiely, J. S.; Nelson, L. L.; Boudjouk, P. J. Org. Chem.
1977, 42, 1480. (b) Uemura, S.; Tanaka, S.; Okano, M.; Hamana, M.
J. Org. Chem. 1983, 48, 3297–3301. (c) Luo, Y.; Pan, X.; Wu, J.
Tetrahedron Lett. 2010, 51, 6646–6648; d) Cornella, J.; Rosillo-
Lopez, M.; Larrosa, I. Adv. Synth. Catal. 2011, 353, 1359–1366. (e)
Peng, X.; Shao, X.-F.; Liu, Z.-Q. Tetrahedron Lett. 2013, 54, 3079–
3081. (f) Fu, Z.; Li, Z.; Song, Y.; Yang, R.; Liu, Y.; Cai, H. J. Org.
Chem. 2016, 81, 2794–2803.
(13) For reports that show limited scope and/or poor selectivity see:
(a) Barton, D. H. R.; Lacher, B.; Zard, S. Z. Tetrahedron Lett. 1985,
26, 5939–5942. (b) Barton, D. H. R.; Lacher, B.; Zard, S. Z. Tetrahe-
dron 1987, 43, 4321–4328. (c) Singh, R.; Just, G. Synth. Commun.
1988, 18, 1327–1330; (d) Camps, P.; Lukach, A. E.; Pujol, X.;
Vázquez, S. Tetrahedron 2000, 56, 2703–2707. (e) Koo, B.-S.; Kim,
E.-H.; Lee, K.-J. Synth. Commun. 2002, 32, 2275–2286. (f) Putey, A.;
Popowycz, F.; Joseph, B. Synlett 2007, 419–422. (g) Hamamoto, H.;
Hattori, S.; Takemaru, K.; Miki, Y. Synlett 2011, 1563–1566 (h)
Kulbitski, K.; Nisnevich, G.; Gandelman, M. Adv. Synth. Catal. 2011,
353, 1438–1442. (i) Li, Z.; Wang, K.; Liu, Z.-Q. Synlett 2014, 25,
2508–2512.
(14) A common route in the literature is 1) conversion of the car-
boxyl group to an acyl chloride, 2) conversion of the acyl chloride to
the acyl azide and subsequent conversion to the aromatic amine (Cur-
tius rearrangement), 3) conversion of the aromatic amine to the diazo-
nium salt and subsequent iodination (Sandmeyer reaction). For exam-
ples see: (a) Moriconi, A.; Cesta, M. C.; Cervellera, M. N.; Aramini,
A.; Coniglio, S.; Colagioia, S.; Beccari, A. R.; Bizzarri, C.; Cavicchia,
M. R.; Locati, M.; Galliera, E.; Di Benedetto, P.; Vigilante, P.; Ber-
tini, R.; Allegretti, M. J. Med. Chem. 2007, 50, 3984–4002. (b)
Zhang, Y. J.; Wei, H.; Zhang, W. Tetrahedron 2009, 65, 1281–1286.
(c) Yang, X.; Sun, G.; Yang, C.; Wang, B. ChemMedChem 2011, 6,
2294–2301. (d) Zhang, A. S.; Ho, J. Z.; Braun, M. P. J. Label.
Compd. Radiopharm. 2011, 54, 163–167. (e) Gluyas, J. B. G.; Bur-
schka, C.; Dörrich, S.; Vallet, J.; Gronemeyer, H.; Tacke, R. Org.
Biomol. Chem. 2012, 10, 6914–6929.
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2
3
4
5
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7
8
(16) For example, Yu and co-workers have previously observed
that mixing 2-methoxybenzoic acid 1a with I2 and AgOAc causes
iodination para to the methoxy group to give 1a’, but on switching to
CsOAc no para iodination is observed, see ref. 9m and 9b’.
(17) The reason for the sensitivity to water has not been thoroughly
investigated. Currently we speculate that the benzoyl hypoiodite
(ArCO2I) intermediate may react with water in an unproductive path-
way. The addition of molecular sieves did not aid this reaction. Over-
all, the reaction system must be anhydrous, however, the reaction can
be carried out on the bench if desired (see SI).
(18) The methoxy group on meta-anisic acid (2d) will donate elec-
tron density to the positions ortho/para to itself, but will withdraw
electron density at the meta position to itself. As the carboxyl group is
meta to the methoxy group it is deactivated in this substrate. Like-
wise, 3,5-dimethoxybenzoic acid was not successful in this reaction.
(19) For a room temperature transition-metal catalysed decarboxy-
lative Heck reaction of highly activated, di-ortho-substituted benzoic
acids see A. Hossian, S. K. Bhunia, R. Jana, J. Org. Chem. 2016, 81,
2521–2533.
(20) a) Dickstein, J. S.; Mulrooney, C. A.; O’Brien, E. M.; Morgan,
B. J.; Kozlowski, M. C. Org. Lett. 2007, 9, 2441; b) Dickstein, J. S.;
Curto, J. M.; Gutierrez, O.; Mulrooney, C. A.; Kozlowski, M. C. J.
Org. Chem. 2013, 78, 4744.
(21) Unfortunately, acyclic amine (e.g. NMe2) substituents were
not tolerated under the reaction conditions and led to decomposition.
The reason for decomposition has not been investigated.
(22) a) Hammett, L. P. J. Am. Chem. Soc. 1937, 59, 96–103; b)
Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165–195.
(23) The reaction with 2-fluorobenzoic acid gave a poor yield (4%
NMR yield). Further studies are necessary to describe the reactivity of
polyfluorinated benzoic acids, however, previous transition-metal
promoted decarboxylative functionalisations have also shown unique
reactivity for polyfluorinated benzoic acids. See reference 19 and: (a)
R. Shang, Q. Xu, Y.-Y. Jiang, Y. Wang, L. Liu, Org. Lett. 2010, 12,
1000–1003. (b) L. W. Sardzinski, W. C. Wertjes, A. M. Schnaith, D.
Kalyani, Org. Lett. 2015, 17, 1256–1259.
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50
51
52
53
54
55
56
57
58
59
60
(24) Luo, J.; Preciado, S.; Xie, P.; Larrosa, I. Chem. Eur. J. 2016,
22, 6798–6802.
(25) Although 4-substituted benzoic acids (NO2, CF3 and CN) are
unreactive these groups are tolerated in the reaction as demonstrated
in the robustness screen (see SI, Tables S2a and S2b).
(26) See the Supporting Information for more detailed information
on the conditions for these procedures.
(27) a) Collins, K. D.; Glorius, F. Nat. Chem. 2013, 5, 597–601. b)
Collins, K. D.; Glorius, F. Tetrahedron 2013, 69, 7817–7825. c) Col-
lins, K. D.; Rühling, A.; Lied, F.; Glorius, F. Chem. Eur. J. 2014, 20,
3800–3805. d) Collins, K. D.; Rühling, A.; Glorius, F. Nat. Protoc.
2014, 9, 1348–1353.
(28) For previous decarboxylative iodinations of cinnamic acids us-
ing other iodinating agents see: a) Naskar, D.; Chowdhury, S.; Roy, S.
Tetrahedron Lett. 1998, 39, 699–702; b) Homsi, F.; Rousseau, G.
Tetrahedron Lett. 1999, 40, 1495–1498; c) Das, J. P.; Roy, S. J. Org.
Chem. 2002, 67, 7861–7864.
(29) The cost of the reagents (1f, I2, K3PO4 and MeCN) is approx-
imately 10 times cheaper than the aryl iodide 2f (£300/mol vs.
£3080/mol respectively). Prices are taken from Sigma Aldrich and are
correct from April 2016.
(30) Attempts to establish benzoyl hypoiodite I as a definite inter-
mediate were unsuccessful. However, the formation of acyl hypo-
halites is reported in the literature and we believe it is reasonable to
suggest its presence in this system. See (a) Kleinberg, J. J. Chem.
Educ. 1946, 23, 559–562. (b) Zingaro, R. A.; Goodrich, J. E.; Klein-
berg, J.; Vanderwerf, A. J. Am. Chem. Soc. 1949, 71, 575–576. (c)
Tanner, D. D.; Bunce, N. J. In Acyl Halides; Patai, S., Eds; John
Wiley & Sons, Ltd.: Chichester, UK, 1972; pp 455–500. (d) Barton,
D. H. R.; Faro, H. P.; Serebryakov, E. P.; Woolsey, N. F. J. Chem.
(15) a) Cornella, J.; Sanchez, C.; Banawa, D. Larrosa, I. Chem.
Commun. 2009, 7176–7178; b) Gooßen, L. J.; Linder, C.; Rodríguez,
N.; Lange, P. P.; Fromm, A. Chem. Commun. 2009, 7173–7175; Lu,
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Soc. 1965, 2438–2444. (e) Srivastava, P. C.; Singh, P.; Tangiri, M.;
(35) Although our studies provide insight into the mechanism for
Sinha, A.; Bajpai, S. J. Indian Chem. Soc. 1997, 74, 443–445.
(31) See ref 20a and (a) Tanaka, D.; Romeril, S. P.; Myers, A. G. J.
Am. Chem. Soc. 2005, 127, 10323–10333; (b) Gooßen, L. J.; Thiel,
W. R.; Rodríguez, N.; Linder, C.; Melzer, B. Adv. Synth. Catal. 2007,
349, 2241–2246. (c) Gooßen, L. J.; Rodríguez, N.; Linder, C.; Lange,
P. P.; Fromm, A. ChemCatChem 2010, 2, 430–442. (d) Xue, L.; Su,
W.; Lin, Z. Dalton Trans. 2011, 40, 11926–11936. (e) Xue, L.; Su,
W.; Lin, Z. Dalton Trans. 2010, 39, 9815–9822. (f) Zhang, S.-L.; Fu,
Y.; Shang, R.; Guo, Q.-X.; Liu, L. J. Am. Chem. Soc. 2010, 132, 638–
646. (g) Xie, H.; Lin, F.; Lei, Q.; Fang, W. Organometallics 2013, 32,
6957–6968. (h) Grainger, R.; Cornella, J.; Blakemore, D. C.; Larrosa,
I.; Campanera, J. M. Chem. Eur. J. 2014, 20, 16680–16687. (i)
Fromm, A.; van Wüllen, C.; Hackenberger, D.; Gooßen, L. J. J. Am.
Chem. Soc. 2014, 136, 10007–10023.
(32) (a) Johnston, L. J.; Lusztyk, J.; Wayner, D. D. M.; Abeywick-
reyma, A. N.; Beckwith, A. L. J.; Scaiano, J. C.; Ingold, K. U. J. Am.
Chem. Soc. 1985, 107, 4594–4596; (b) Newcomb, M. in Encycl. Rad-
icals Chem. Biol. Mater., John Wiley & Sons, Ltd, Chichester, UK,
2012, pp. 1–19.
(33) Ground-state and transition state for the decarboxylation step
were calculated by DFT using Gaussian 09. B97D3 and 6-31G(d)
were used for C,H,O atoms, and LanL2DZ was used for I. See the
Supporting Information for details.
the decarboxylative iodination of electron-rich benzoic acids, we do
not believe this mechanism holds true for polyfluorobenzoic acids.
Further studies are necessary to explain the unexpected reactivity of
polyfluorobenzoic acids. These studies are ongoing in our laboratory.
(36) (a) Do, H.-Q.; Daugulis, O. Chem. Commun. 2009, 6433–
6435. (b) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2011, 133,
13577–13586. For related studies see (c) Do, H.-Q; Daugulis, O.
2008, 129, 12404–12405. (d) Do, H.-Q.; Daugulis, O. J. Am. Chem.
Soc. 2008, 130, 1128–1129. (e) Do, H.-Q.; Kashif Khan, R. M.; Dau-
gulis, O. J. Am. Chem. Soc. 2008, 130, 15185–15192. (f) Daugulis,
O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42, 1074–1086.
(g) Do, H.-Q.; Daugulis, O. Org. Lett. 2009, 11, 421–423.
(37) The exact process by which the amine quenches iodine has not
been determined, though the reaction between amines and iodine has
been previously investigated. See (a) Bist, H. D.; Person, W. B. J.
Phys. Chem. 1969, 73, 482–489. (b) Schug, J. C.; Kogan, M. J. J.
Magn. Reson. 1973, 11, 406–415. (c) Koepler, O.; Laschat, S.; Mieh-
lich, B.; Baro, A.; Fischer, P. Helv. Chim. Acta 2004, 87, 1927–1934.
(38) In this report we demonstrate the use of this one-pot, three-
step method for the cross coupling of benzoic acids with arenes or a
second benzoic acid, however, we believe this method may also be
applicable to a range of cross-couplings with, for example, amines
(Buchwald-Hartwig coupling), aryl boronic acids (Suzuki coupling)
and many others.
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24
25
26
27
28
29
30
31
32
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35
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37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(34) Okamoto, Y.; Brown, H. C. J. Org. Chem. 1957, 22, 485–494.
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1 (a) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359–1470. (b) Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Angew. Chem. Int. Ed. 2012, 51, 5062–5085. (c) Bolm, C.; Hildebrand, J. P.; Muniz, K.; Hermanns, N. Angew. Chem. Int. Ed.
2001, 40, 3284–3308.
2
(a) Bringmann, G.; Günther, C.; Ochse, M.; Schupp, O.; Tasler, S. Biaryls in Nature: A Multi-Facetted Class of Stereochemically, Biosynthetically, and Pharmacologically Intriguing Secondary Metabolites; In Progress in the Chemistry of Organic Natural Products; Herz, W., Falk, H., Kirby, G. W.,
Moore, R. E., Eds.; Springer Vienna: 2001; Vol. 82, pp 1-249. (b) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893–930. (c) Grimsdale, A. C.; Chan, K. L.; Martin, R. E.; Jokisz, P. G.; Holmes, A. B. Chem. Rev. 2009, 109, 897–1091.
3 For selected reviews on C–H activation see: (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174–238. (b) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem. Int. Ed. 2009, 48, 9792–9826. (c) Boorman, T. C.; Larrosa, I. Chem. Soc. Rev. 2011, 40, 1910–1925. (d) Wencel-Delord, J.;
Dröge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740–4761. (e) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.; Glorius, F. Angew. Chem. Int. Ed. 2012, 51, 10236–10254. (f) Kakiuchi, F.; Kochi, T.; Murai, S. Synlett 2014, 25, 2390–2414. (g) Ahlsten, N.; Cambeiro, X. C.; Perry, G. J. P.; Larrosa, I. In
Topics in Heterocyclic Chemistry; Bandini M., Eds.; Springer International Publishing, 2016; Vol. 46, pp 175–226. (h) Font, M.; Quibell, J. M.; Perry, G. J. P.; Larrosa, I. Chem. Commun. 2017, 53, 5584–5597. (i) Simonetti, M.; Cannas, D. M.; Larrosa I.; In Advances in Organometallic Chemistry; Pérez, P. J.,
Eds.; Elsevier, 2017; Vol. 67, pp 299–399. (j) Murakami, K.; Perry, G. J. P.; Itami, K. Org. Biomol. Chem. 2017 doi: 10.1039/C7OB00985B (k) Yi, H.; Zhang, G.; Wang, H.; Huang, Z.; Wang, J.; Sing, A. K.; Lei, A. Chem. Rev. 2017, 117, 9016–9085.
4 For selected reviews on decarboxylative activation see: (a) Gooßen, L. J.; Gooßen, K.; Rodríguez, N.; Blanchot, M.; Linder, C.; Zimmermann, B. Pure Appl. Chem. 2008, 80, 1725–1733. (b) Gooßen, L. J.; Rodríguez, N.; Gooßen, K. Angew. Chem. Int. Ed. 2008, 47, 3100–3120. (c) Gooßen, L. J.; Collet,
F.; Gooßen, K. Isr. J. Chem. 2010, 50, 617–629. (d) Shang, R.; Liu, L. Sci. China Chem. 2011, 54, 1670–1687. (e) Rodríguez, N.; Gooßen, L. J. Chem. Soc. Rev. 2011, 40, 5030–5048. (f) Dzik, W. I.; Lange, P. P.; Gooßen, L. J. Chem. Sci. 2012, 3, 2671–2678. (g) Cornella, J.; Larrosa, I. Synthesis 2012, 44, 653–
676; (h) Gooßen, L. J.; Gooßen, K. Decarboxylative Coupling Reactions; In Topics in Organometallic Chemistry; Gooßen, L. J., Eds.; Springer-Verlag Berlin Heidelberg: 2013; Vol. 44 pp. 121–142. (i) Perry, G. J. P.; Larrosa, I. Eur. J. Org. Chem. 2017, 3517–3527. For a review on deamidative cross-coupling
see: Liu, C.; Szostak, M. Chem. Eur. J, 2017, 23, 7157–7173.
5 For the coupling of benzoic acids with arenes see (a) Voutchkova, A.; Coplin, A.; Leadbeater, N. E.; Crabtree, R. H. Chem. Commun. 2008, 6312–6314. (b) Wang, C.; Piel, I.; Glorius, F. J. Am. Chem. Soc. 2009, 131, 4194–4195. (c) Cornella, J.; Lu, P.; Larrosa, I. Org. Lett. 2009, 11, 5506–5509. (d) Zhou,
J.; Hu, P.; Zhang, M.; Huang, S.; Wang, M.; Su, W. Chem. Eur. J. 2010, 16 , 5876–5881. (e) Xie, K.; Yang, Z.; Zhou, X.; Li, X.; Wang, S.; Tan, Z.; An, X.; Guo, C.-C. Org. Lett. 2010, 12, 1564–1567. (f) Zhang, F.; Greaney, M. F. Angew. Chem. Int. Ed. 2010, 49, 2768–2771. (g) Zhao, H.; Wei, Y.; Xu, J.; Kan,
J.; Su, W.; Hong, M. J. Org. Chem. 2011, 76, 882–893. (h) Hu, P.; Zhang, M.; Jie, X.; Su, W. Angew. Chem. Int. Ed. 2012, 51, 227–231. (i) Luo, H.-Q.; Dong, W.; Loh, T.-P. Tetrahedron Lett. 2013, 54, 2833–2836. (j) Pei, K.; Jie, X.; Zhao, H.; Su, W. Eur. J. Org. Chem. 2014, 4230–4233. (k) Suresh, R.;
Muthusubramanian, S.; Kumaran, R. S.; Manickam, G. Asian J. Org. Chem. 2014, 3, 604–608. (l) Yang, K.; Wang, P.; Zhang, C.; Kadi, A. A.; Fun, H.-K.; Zhang, Y.; Lu, H. Eur. J. Org. Chem. 2014, 7586–7589. (m) Chen, L.; Ju, L.; Bustin, K. A.; Hoover, J. M. Chem. Commun. 2015, 51, 15059–15062. (n)
Zhao, S.; Liu, Y.-J.; Yan, S.-Y.; Chen, F.-J.; Zhang, Z.-Z.; Shi, B.-F. Org. Lett. 2015, 17, 3338–3341. (o) Kan, J.; Huang, S.; Lin, J.; Zhang, M.; Su, W. Angew. Chem. Int. Ed. 2015, 54, 2199–2203. (p) Patra, T.; Nandi, S.; Sahoo, S. K.; Maiti, D. Chem. Commun. 2016, 52, 1432–1435. (q) Candish, L.; Freitag, M.;
Gensch T.; Glorius F. Chem. Sci, 2017, 8, 3618–3622.
6
For the coupling of two benzoic acids see (a) Cornella, J.; Lahlali, H.; Larrosa, I. Chem. Commun. 2010, 46, 8276–8278. (b) Xie, K.; Wang, S.; Yang, Z.; Liu, J.; Wang, A.; Li, X.; Tan, Z.; Guo, C.-C.; Deng, W. Eur. J. Org. Chem. 2011, 5787–5790. (c) Hu, P.; Shang, Y.; Su, W. Angew. Chem. Int. Ed.
2012, 51, 5945–5949. (d) Fu, Z.; Li, Z.; Xiong, Q.; Cai, H. RSC Adv. 2015, 5, 52101–52104.
7 For a comprehensive review on this subject see Iodine chemistry and Applications (Ed.: T. Kaiho), Wiley-VCH, Weinheim, 2015.
8 For the use of aryl iodides: in cross-couplings see ref 1; nucleophilic substitution see (a) Burnett, J. F.; Zahler, R. E. Chem. Rev. 1951, 49, 273–412; (b) Hartwig, J. F. Synlett 2006, 1283–1294; in metalation see (c) Knochel, P.; Dohle, W.; Gommermann, N.; Kneisel, F. F.; Kopp, F.; Korn, T.; Sapountzis,
I.; Vu, V. A. Angew. Chem. Int. Ed. 2003, 42, 4302–4320. (d) Tilly, D.; Chevallier, F.; Mongin, F.; Gros, P. C. Chem. Rev. 2014, 114, 1207–1257. (e) Handbook of Grignard Reagents; Silverman, G. S., Rakita, P. E., Eds.; Dekker: New York, NY, 1996. (f) Sotomayor, N.; Lete, E. Curr. Org. Chem. 2003, 7, 275–
300; in aryl radical formation see (g) Neumann, W. P. Synthesis 1987, 665–683. (h) Kim, H.; Lee, C.; Angew. Chem. Int. Ed. 2012, 51, 12303–12306. (i) Nguyen, J. D.; D’Amato, E. M.; Narayanam, J. M. R.; Stephenson, C. R. J. Nat. Chem. 2012, 4, 854–859. (j) Ghosh, I.; Ghosh, T.; Bardagi, J. I.; Konig, B.
Science 2014, 346, 725–728. (k) Liu, Y. X.; Xue, D.; Wang, J.-D.; Zhao, C.-J.; Zou, Q.-Z.; Wang, C.; Xiao, J. Synlett 2013, 24, 507–513; in aryne generation see (l) Pellissier, H.; Santelli, M. Tetrahedron 2003, 59, 701–730. (m) Moss, R.A.; Platz, M. S.; Jones, Jr, M. In Reactive Intermediate Chemistry; Winkler,
M.; Wenk, H. H.; Sander, W., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2005; pp 741–794; as hypervalent iodine species see (n) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299–5358. (o) Merritt, E. A.; Olofsson, B. Angew. Chem. Int. Ed. 2009, 48, 9052–9070. (p) Deprez, N. R.; Sanford, M.
S.; Inorg. Chem. 2007, 46, 1924–1935. (q) Cambeiro, X. C.; Boorman, T. C.; Lu, P.; Larrosa, I. Angew. Chem. Int. Ed. 2013, 52, 1781–1784. (r) Cambeiro, X. C.; Ahlsten, N.; Larrosa, I. J. Am. Chem. Soc. 2015, 137, 15636–15639; in natural products see (s) Wang, L.; Zhou, X.; Fredimoses, M.; Liao, S.; Liu, Y.
RSC Adv. 2014, 4, 57350–57376. (t) Markou, K.; Georgopoulos, N.; Kyriazopoulou, V.; Vagenakis, A. G. Thyroid 2001, 11, 501–510. (u) Hair, P. I.; McCormack, P. L.; Curran, M. P. Drugs 2008, 68, 1415–1434. (v) Quinn, M. J.; Fitzgerald, D. J. Circulation 1999, 100, 1667–1672. (w) Boger, D. L. Med. Res.
Rev. 2001, 21, 356–381. (x) DeLeon, A; Patel, N. C.; Crismon, M. L. Clin. Ther. 2004, 26, 649–666; in medical imaging agents see (y) Seevers, R. H.; Counsell, R. E. Chem. Rev. 1982, 82, 575–590. (z) Schlyer, D. J. Ann. Acad. Med. Singapore 2004, 33, 146–154; in organic materials see (a’) Tang, M. L.;
Bao, Z. Chem. Mater. 2011, 23, 446–455.
9 For the preparation of aryl iodides: via electrophilic aromatic substitution (SEAr) see (a) Taylor, R. In Electrophilic Aromatic Substitution; John Wiley: New York, 1990. (b) Barluenga, J.; Gonzalez, J. M.; Garcia-Martin, M. A.; Campos, P. J.; Asensio, G. J. Org. Chem. 1993, 58, 2058–2060. (c) Rodriguez,
R. A.; Pan, C.-M.; Yabe, Y.; Kawamata, Y.; Eastgate, M. D.; Baran, P. S. J. Am. Chem. Soc. 2014, 136, 6908–6911; via directed ortho-metalation (DoM) see (d) Snieckus, V. Chem. Rev. 1990, 90, 879–933; using directing groups (e) Fahey, D. R. J. Organomet. Chem. 1971, 27, 283–292. (f) Dick, A. R.; Hull, K.
L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 126, 2300–2301. (g) Giri, R.; Chen, X.; Yu, J.-Q. Angew. Chem. Int. Ed. 2005, 44, 2112–2115. (h) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 6790–6791. (i) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S. Tetrahedron 2006,
62, 11483–11498. (j) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S. Org. Lett. 2006, 8, 2523–2526. (k) Wan, X.; Ma, Z.; Li, B.; Zhang, K.; Cao, S.; Zhang, S.; Shi, Z. J. Am. Chem. Soc. 2006, 128, 7416–7417. (l) Whitfield, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2007, 129, 15142–15143. (m) Mei, T.-
S.; Giri, R.; Maugel, N.; Yu, J.-Q. Angew. Chem. Int. Ed. 2008, 47, 5215–5219. (n) Li, J.-J.; Mei, T.-S.; Yu, J.-Q. Angew. Chem. Int. Ed. 2008, 47, 6452–6455. (o) Whitfield, S. R.; Sanford, M. S. Organometallics 2008, 27, 1683–1689. (p) Kakiuchi, F.; Kochi, T.; Mutsutani, H.; Kobayashi, N.; Urano, S.; Sato,
M.; Nishiyama, S.; Tanabe, T. J. Am. Chem. Soc. 2009, 131, 11310–11311. (q) Zhao, X.; Dimitrijević, E.; Dong, V. M. J. Am. Chem. Soc. 2009, 131, 3466–3467. (r) Song, B.; Zheng, X.; Mo, J.; Xu, B. Adv. Synth. Catal. 2010, 352, 329–335. (s) Bedford, R. B.; Engelhart, J. U.; Haddow, M. F.; Mitchell, C. J.;
Webster, R. L. Dalton Trans. 2010, 39, 10464–10472. (t) Mei, T.-S.; Wang, D.-H.; Yu, J.-Q. Org. Lett. 2010, 12, 3140–3143. (u) Dudnik, A. S.; Chernyak, N.; Huang, C.; Gevorgyan, V. Angew. Chem. Int. Ed. 2010, 49, 8729–8732. (v) Powers, D. C.; Xiao, D. Y.; Geibel, M. A. L.; Ritter, T. J. Am. Chem. Soc.
2010, 132, 14530–14536. (w) Wang, W.; Pan, C.; Chen, F.; Cheng, J. Chem. Commun. 2011, 47, 3978–3980. (x) Dubost, E.; Fossey, C.; Cailly, T.; Rault, S.; Fabis, F. J. Org. Chem. 2011, 76, 6414–6420. (y) Bedford, R. B.; Haddow, M. F.; Mitchell, C. J.; Webster, R. L. Angew. Chem. Int. Ed. 2011, 50, 5524–
5527. (z) Schröder, N.; Wencel-Delord, J.; Glorius, F. J. Am. Chem. Soc. 2012, 134, 8298–8301. (a’) John, A.; Nicholas, K. M. J. Org. Chem. 2012, 77, 5600–5605. (b’) Wang, X.-C.; Hu, Y.; Bonacorsi, S.; Hong, Y.; Burrell, R.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135, 10326–10329. (c’) Chu, L.; Xiao, K.-J.;
Yu, J.-Q. Science 2014, 346, 451–455. (d’) Haines, B. E.; Xu, H.; Verma, P.; Wang, X.-C.; Yu, J.-Q.; Musaev, D. G. J. Am. Chem. Soc. 2015, 137, 9022–9031. (e’) Li, B.; Liu, B.; Shi, B.-F. Chem. Commun. 2015, 51, 5093–5096. (f’) Teskey, C. J.; Lui, A. Y. W.; Greaney, M. F. Angew. Chem. Int. Ed. 2015,
54, 11677–11680; from aryl diazonium salts see (g’) Sandmeyer, T. Ber. Dtsch. Chem. Ges. 1884, 17, 1633–1635. (h’) Hodgson, H. H. Chem. Rev. 1947, 40, 251–277. (i’) Roglans, A.; Pla-Quintana, A.; Moreno-Mañas, M. Chem. Rev. 2006, 106, 4622–4643; via halogen exchange (HalEx) see (j’) Lindley,
J. Tetrahedron 1984, 40, 1433–1456. (k’) Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 14844–14845. (l’) Sheppard, T. D. Org. Biomol. Chem. 2009, 7, 1043-1052. (m’) Casitas, A.; Canta, M.; Solà, M.; Costas, M.; Ribas, X. J. Am. Chem. Soc. 2011, 133, 19386–19392. (n’) Cant, A. A.;
Bhalla, R.; Pimlott, S. L.; Sutherland, A. Chem. Commun. 2012, 48, 3993-3995. (o’) Font, M.; Acuña-Parés, F.; Parella, T.; Serra, J.; Luis, J. M.; Lloret-Fillol, J.; Costas, M.; Ribas, X. Nat. Commun. 2014, 5, 4373. (p’) Serra, J.; Whiteoak, C. J.; Acuña-Parés, F.; Font, M.; Luis, J. M.; Lloret-Fillol, J.; Ribas, X.
J. Am. Chem. Soc. 2015, 137, 13389–13397. (q’) Chen, M.; Ichikawa, S.; Buchwald, S. L. Angew. Chem. Int. Ed. 2015, 54, 263–266. (r’) Li, L.; Liu, W.; Zeng, H.; Mu, X.; Cosa, G.; Mi, Z.; Li, C.-J. J. Am. Chem. Soc. 2015, 137, 8328–8331.
10 (a) Borodine, A. Justus Liebigs Ann. Chem. 1861, 119, 121–123; (b) Hunsdiecker, H.; Hunsdiecker, C. Ber. Dtsch. Chem. Ges. 1942, 75B, 291–297; (c) Wilson, C. in Org. React., John Wiley & Sons, Inc., Hoboken, NJ, USA, 2011, pp. 332–387; (d) Crich, D. In Comprehensive Organic Synthesis; Trost
B. M., Fleming I., Eds.; Pergamon Press, 1991; Vol. 7, pp 717–734; (e) Crich, D.; Sasaki, K. in Comprehensive Organic Synthesis II; Knochel, P., Molander, G. A. , Eds.; Elsevier, 2014, pp. 818–836.
11 (a) Dauben, W. G.; Tilles, H. J. Am. Chem. Soc. 1950, 72, 3185–3187. (b) Barnes, R. A.; Prochaska, R. J. J. Am. Chem. Soc. 1950, 72, 3188–3191. (c) Oldham, J. W. H. J. Chem. Soc. 1950, 100–108.
12 For reports that require stoichiometric transition metals see ref 11 and: (a) Kiely, J. S.; Nelson, L. L.; Boudjouk, P. J. Org. Chem. 1977, 42, 1480. (b) Uemura, S.; Tanaka, S.; Okano, M.; Hamana, M. J. Org. Chem. 1983, 48, 3297–3301. (c) Luo, Y.; Pan, X.; Wu, J. Tetrahedron Lett. 2010, 51, 6646–6648;
d) Cornella, J.; Rosillo-Lopez, M.; Larrosa, I. Adv. Synth. Catal. 2011, 353, 1359–1366. (e) Peng, X.; Shao, X.-F.; Liu, Z.-Q. Tetrahedron Lett. 2013, 54, 3079–3081. (f) Fu, Z.; Li, Z.; Song, Y.; Yang, R.; Liu, Y.; Cai, H. J. Org. Chem. 2016, 81, 2794–2803.
13 For reports that show limited scope and/or poor selectivity see: (a) Barton, D. H. R.; Lacher, B.; Zard, S. Z. Tetrahedron Lett. 1985, 26, 5939–5942. (b) Barton, D. H. R.; Lacher, B.; Zard, S. Z. Tetrahedron 1987, 43, 4321–4328. (c) Singh, R.; Just, G. Synth. Commun. 1988, 18, 1327–1330; (d) Camps, P.;
Lukach, A. E.; Pujol, X.; Vázquez, S. Tetrahedron 2000, 56, 2703–2707. (e) Koo, B.-S.; Kim, E.-H.; Lee, K.-J. Synth. Commun. 2002, 32, 2275–2286. (f) Putey, A.; Popowycz, F.; Joseph, B. Synlett 2007, 419–422. (g) Hamamoto, H.; Hattori, S.; Takemaru, K.; Miki, Y. Synlett 2011, 1563–1566 (h) Kulbitski, K.;
Nisnevich, G.; Gandelman, M. Adv. Synth. Catal. 2011, 353, 1438–1442. (i) Li, Z.; Wang, K.; Liu, Z.-Q. Synlett 2014, 25, 2508–2512.
14 A common route in the literature is 1) conversion of the carboxyl group to an acyl chloride, 2) conversion of the acyl chloride to the acyl azide and subsequent conversion to the aromatic amine (Curtius rearrangement), 3) conversion of the aromatic amine to the diazonium salt and subsequent iodination
(Sandmeyer reaction). For examples see: (a) Moriconi, A.; Cesta, M. C.; Cervellera, M. N.; Aramini, A.; Coniglio, S.; Colagioia, S.; Beccari, A. R.; Bizzarri, C.; Cavicchia, M. R.; Locati, M.; Galliera, E.; Di Benedetto, P.; Vigilante, P.; Bertini, R.; Allegretti, M. J. Med. Chem. 2007, 50, 3984–4002. (b) Zhang, Y.
J.; Wei, H.; Zhang, W. Tetrahedron 2009, 65, 1281–1286. (c) Yang, X.; Sun, G.; Yang, C.; Wang, B. ChemMedChem 2011, 6, 2294–2301. (d) Zhang, A. S.; Ho, J. Z.; Braun, M. P. J. Label. Compd. Radiopharm. 2011, 54, 163–167. (e) Gluyas, J. B. G.; Burschka, C.; Dörrich, S.; Vallet, J.; Gronemeyer, H.;
Tacke, R. Org. Biomol. Chem. 2012, 10, 6914–6929.
15 a) Cornella, J.; Sanchez, C.; Banawa, D. Larrosa, I. Chem. Commun. 2009, 7176–7178; b) Gooßen, L. J.; Linder, C.; Rodríguez, N.; Lange, P. P.; Fromm, A. Chem. Commun. 2009, 7173–7175; Lu, P.; Sanchez, C.; Cornella, J.; Larrosa, I. Org. Lett. 2009, 11, 5710–5713; c) Seo, S.; Taylor, J. B.; Greaney,
M. F. Chem. Commun. 2012, 48, 8270–8272; d) Grainger, R.; Nikmal, A.; Cornella, J.; Larrosa, I. Org. Biomol. Chem. 2012, 10, 3172–3174.
16 For example, Yu and co-workers have previously observed that mixing 2-methoxybenzoic acid 1a with I2 and AgOAc causes iodination para to the methoxy group to give 1a’, but on switching to CsOAc no para iodination is observed, see ref. 9m and 9b’.
17 The reason for the sensitivity to water has not been thoroughly investigated. Currently we speculate that the benzoyl hypoiodite (ArCO2I) intermediate may react with water in an unproductive pathway. The addition of molecular sieves did not aid this reaction. Overall, the reaction system must be anhy-
drous, however, the reaction can be carried out on the bench if desired (see SI).
18 The methoxy group on meta-anisic acid (2d) will donate electron density to the positions ortho/para to itself, but will withdraw electron density at the meta position to itself. As the carboxyl group is meta to the methoxy group it is deactivated in this substrate. Likewise, 3,5-dimethoxybenzoic acid was not
successful in this reaction.
19 For a room temperature transition-metal catalysed decarboxylative Heck reaction of highly activated, di-ortho-substituted benzoic acids see A. Hossian, S. K. Bhunia, R. Jana, J. Org. Chem. 2016, 81, 2521–2533.
20 a) Dickstein, J. S.; Mulrooney, C. A.; O’Brien, E. M.; Morgan, B. J.; Kozlowski, M. C. Org. Lett. 2007, 9, 2441; b) Dickstein, J. S.; Curto, J. M.; Gutierrez, O.; Mulrooney, C. A.; Kozlowski, M. C. J. Org. Chem. 2013, 78, 4744.
21 Unfortunately, acyclic amine (e.g. NMe2) substituents were not tolerated under the reaction conditions and led to decomposition. The reason for decomposition has not been investigated.
22 a) Hammett, L. P. J. Am. Chem. Soc. 1937, 59, 96–103; b) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165–195.
23 The reaction with 2-fluorobenzoic acid gave a poor yield (4% NMR yield). Further studies are necessary to describe the reactivity of polyfluorinated benzoic acids, however, previous transition-metal promoted decarboxylative functionalisations have also shown unique reactivity for polyfluorinated benzo-
ic acids. See reference 19 and: (a) R. Shang, Q. Xu, Y.-Y. Jiang, Y. Wang, L. Liu, Org. Lett. 2010, 12, 1000–1003. (b) L. W. Sardzinski, W. C. Wertjes, A. M. Schnaith, D. Kalyani, Org. Lett. 2015, 17, 1256–1259.
24 Luo, J.; Preciado, S.; Xie, P.; Larrosa, I. Chem. Eur. J. 2016, 22, 6798–6802.
25 Although 4-substiuted benzoic acids (NO2, CF3 and CN) are unreactive these groups are tolerated in the reaction as demonstrated in the robustness screen (see SI, Tables S2a and S2b).
26 See the Supporting Information for more detailed information on the conditions for these procedures.
27 a) Collins, K. D.; Glorius, F. Nat. Chem. 2013, 5, 597–601. b) Collins, K. D.; Glorius, F. Tetrahedron 2013, 69, 7817–7825. c) Collins, K. D.; Rühling, A.; Lied, F.; Glorius, F. Chem. Eur. J. 2014, 20, 3800–3805. d) Collins, K. D.; Rühling, A.; Glorius, F. Nat. Protoc. 2014, 9, 1348–1353.
28 For previous decarboxylative iodinations of cinnamic acids using other iodinating agents see: a) Naskar, D.; Chowdhury, S.; Roy, S. Tetrahedron Lett. 1998, 39, 699–702; b) Homsi, F.; Rousseau, G. Tetrahedron Lett. 1999, 40, 1495–1498; c) Das, J. P.; Roy, S. J. Org. Chem. 2002, 67, 7861–7864.
29 The cost of the reagents (1f, I2, K3PO4 and MeCN) is approximately 10 times cheaper than the aryl iodide 2f (£300/mol vs. £3080/mol respectively). Prices are taken from Sigma Aldrich and are correct from April 2016.
30 Attempts to establish benzoyl hypoiodite I as a definite intermediate were unsuccessful. However, , the formation of acyl hypohalites is reported in the literature and we believe it is reasonable to suggest its presence in this system. See (a) Kleinberg, J. J. Chem. Educ. 1946, 23, 559–562. (b) Zingaro, R.
A.; Goodrich, J. E.; Kleinberg, J.; Vanderwerf, A. J. Am. Chem. Soc. 1949, 71, 575–576. (c) Tanner, D. D.; Bunce, N. J. In Acyl Halides; Patai, S., Eds; John Wiley & Sons, Ltd.: Chichester, UK, 1972; pp 455–500. (d) Barton, D. H. R.; Faro, H. P.; Serebryakov, E. P.; Woolsey, N. F. J. Chem. Soc. 1965, 2438–
2444. (e) Srivastava, P. C.; Singh, P.; Tangiri, M.; Sinha, A.; Bajpai, S. J. Indian Chem. Soc. 1997, 74, 443–445.
31 See ref 20 and (a) Tanaka, D.; Romeril, S. P.; Myers, A. G. J. Am. Chem. Soc. 2005, 127, 10323–10333; (b) Gooßen, L. J.; Thiel, W. R.; Rodríguez, N.; Linder, C.; Melzer, B. Adv. Synth. Catal. 2007, 349, 2241–2246. (c) Gooßen, L. J.; Rodríguez, N.; Linder, C.; Lange, P. P.; Fromm, A. ChemCatChem
2010, 2, 430–442. (d) Xue, L.; Su, W.; Lin, Z. Dalton Trans. 2011, 40, 11926–11936. (e) Xue, L.; Su, W.; Lin, Z. Dalton Trans. 2010, 39, 9815–9822. (f) Zhang, S.-L.; Fu, Y.; Shang, R.; Guo, Q.-X.; Liu, L. J. Am. Chem. Soc. 2010, 132, 638–646. (g) Xie, H.; Lin, F.; Lei, Q.; Fang, W. Organometallics 2013, 32,
6957–6968. (h) Grainger, R.; Cornella, J.; Blakemore, D. C.; Larrosa, I.; Campanera, J. M. Chem. Eur. J. 2014, 20, 16680–16687. (i) Fromm, A.; van Wüllen, C.; Hackenberger, D.; Gooßen, L. J. J. Am. Chem. Soc. 2014, 136, 10007–10023.
32 (a) Johnston, L. J.; Lusztyk, J.; Wayner, D. D. M.; Abeywickreyma, A. N.; Beckwith, A. L. J.; Scaiano, J. C.; Ingold, K. U. J. Am. Chem. Soc. 1985, 107, 4594–4596; (b) Newcomb, M. in Encycl. Radicals Chem. Biol. Mater., John Wiley & Sons, Ltd, Chichester, UK, 2012, pp. 1–19.
33 Ground-state and transition state for the decarboxylation step were calculated by DFT using Gaussian 09. B97D3 and 6-31G(d) were used for C,H,O atoms, and LanL2DZ was used for I. See the Supporting Information for details.
34 Okamoto, Y.; Brown, H. C. J. Org. Chem. 1957, 22, 485–494.
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