Thermal (iodide) and photoinduced electron-transfer catalysis in biaryl synthesis via aromatic arylations with diazonium salts

Article abstract of DOI:10.1021/ja970599b

The dediazoniative arylation of various aromatic hydrocarbons (Ar'H) with diazonium salts (ArN₂⁺) in acetonitrile can be readily effected to biaryls (Ar-Ar') in high yields, simply by the addition of small (catalytic) amounts of sodium iodide. [In the absence of Ar'H, the competitive iodination to ArI is nearly quantitative.] Iodide catalysis of biaryl formation is efficiently mediated by aryl radicals (Ar') that participate in an efficient homolytic chain process in which ArN₂⁺ acts as a 1-electron oxidant. The complex kinetics of such an electron-transfer chain or ETC process (Scheme I) is quantitatively verified by computer simulation of the Ar'H-dependent (a) competition between arylation vs iodination and (b) catalytic efficiency of iodide. using the GEAR algorithms. ETC catalysis also pertains to the alternative photochemical procedure for arylation (in the absence of iodide), in which the deliberate irradiation of the charge-transfer band of the precursor complex (ArN₂⁺, Ar'H) initiates the same homolytic chain arylation. The latter underscores the mechanistic generality of the ETC formulation for various types of catalytic dediazoniations of aromatic diazonium salts.

Full text of DOI:10.1021/ja970599b

4846
J. Am. Chem. Soc. 1997, 119, 4846-4855
Thermal (Iodide) and Photoinduced Electron-Transfer Catalysis
in Biaryl Synthesis Via Aromatic Arylations with Diazonium
Salts
D. Kosynkin, T. M. Bockman, and J. K. Kochi*
Contribution from the Department of Chemistry, UniVersity of Houston,
Houston, Texas 77204-5641
ReceiVed February 24, 1997X
Abstract: The dediazoniative arylation of various aromatic hydrocarbons (Ar′H) with diazonium salts (ArN2+) in
acetonitrile can be readily effected to biaryls (Ar-Ar′) in high yields, simply by the addition of small (catalytic)
amounts of sodium iodide. [In the absence of Ar′H, the competitive iodination to ArI is nearly quantitative.] Iodide
catalysis of biaryl formation is efficiently mediated by aryl radicals (Ar•) that participate in an efficient homolytic
chain process in which ArN2+ acts as a 1-electron oxidant. The complex kinetics of such an electron-transfer chain
or ETC process (Scheme 1) is quantitatively verified by computer simulation of the Ar′H-dependent (a) competition
between arylation Vs iodination and (b) catalytic efficiency of iodide, using the GEAR algorithms. ETC catalysis
also pertains to the alternative photochemical procedure for arylation (in the absence of iodide), in which the deliberate
irradiation of the charge-transfer band of the precursor complex [ArN2+, Ar′H] initiates the same homolytic chain
arylation. The latter underscores the mechanistic generality of the ETC formulation for various types of catalytic
dediazoniations of aromatic diazonium salts.
Introduction
optimum procedures for the efficient dediazoniation of aromatic
diazonium cations according to eq 2.
Aromatic diazonium cations (ArN2+) represent activated aryl
group (synthons) owing to the relatively facile loss of dinitro-
gen.1 Despite their widespread use, it is often not clear as to
whether an electrophilic (Via Ar+) or a homolytic (Via Ar•)
process is involved for dinitrogen loss in even the conceptually
simple replacement by various nucleophiles (X-), i.e.
Conventionally, the synthetic transformation in eq 2 is realized
in aqueous media with aromatic diazonium cations generated
in situ with use of the Gomberg-Bachmann procedures (and
its intramolecular analogue, the Pschorr synthesis) that are
promoted by the addition of base.7,8 Since a wide variety of
+
other (undesired) reactions of ArN2 are known to be induced
by basic water,9 we focussed in this study on the alternative
use of nonaqueous solvents and highly electrophilic diazonium
cations that are separately prepared in pure (crystalline) form.
Accordingly, we report on how the pentafluorobenzenediazo-
nium salt (C6F5N2+BF4- (I)) can be employed in the high-yield
synthesis of various “push-pull” biaryls (C6F5-Ar′) of potential
use in nonlinear laser applications and liquid-crystal displays.10
For comparative purposes, some additional studies were also
carried out with the novel trichloro derivative11 II that is readily
available from I by mild treatment with hydrogen chloride.
Particularly relevant to aromatic diazonium salts in nonaque-
ous solvents is the spontaneous appearance of bright colorations
-N2
ArN2+ + X-
8 ArX
(1)
where X- ) halide, cyanide, sulfide, hydroxide, etc.2,3 The
mechanistic ambiguity is further exacerbated by the efficient
catalysis of eq 1 by (trace) metal species, such as in the
Sandmeyer, Gatterman, Meerwein, and related reactions.4,5
When weak (uncharged) aromatic nucleophiles (i.e. X- ) Ar′H)
are employed, the arylation reactions leading to biaryls, i.e.
-N2
ArN2+ + Ar′H
8 Ar-Ar′ + H+
(2)
(6) (a) Beadle, J. R.; Korzeniowski, S. H.; Rosenberg, D. E.; Garcia-
Slanga, B. J.; Gokel, G. W. J. Org. Chem. 1984, 49, 1594. (b) Ru¨chardt,
C.; Merz, E.; Freudenberg, B.; Opgenorth, H.-J.; Tan, C. C.; Werner, R.
Essays on Free-Radical Chemistry; Special Publication No. 24, Norman,
R. O. C., Ed.; Chemical Society London: London, 1970; p 51ff and
references therein.
(7) (a) Gomberg, M.; Bachmann, W. E. J. Am. Chem. Soc. 1924, 46,
2339. (b) Bachmann, W. E.; Hoffman, R. A. Org. React. 1944, 2, 224. (c)
DeTar, D. F. Org. React. 1957, 9, 409.
are commonly inefficient owing to competition from myriad
side reactions leading to reduced arene (ArH), diazenes
(ArNdNAr′), triazenes (ArNdNNHAr), and other colored
byproducts.6 As such, we view the arylation reaction as an
opportunity to utilize a mechanistic investigation to develop
X Abstract published in AdVance ACS Abstracts, May 15, 1997.
(1) (a) Wulfman, D. E. In The Chemistry of Diazonium and Diazo
Groups; Patai, S., Ed.; Wiley: New York, 1978; p 290. See also the other
chapters dealing with diazonium decompositions. (b) Zollinger, H. Diazo
Chemistry; VCH: New York, 1994; Vol. 1.
(8) (a) Pschorr, R. Chem. Ber. 1896, 29, 496. (b) Abramovitch, R. A.
AdV. Free Radical Chem. 1966, 2, 4787.
(9) Dreher, E.; Niederer, P.; Schwarz, W.; Zollinger, H. HelV. Chim Acta
1981, 64, 488.
(2) Galli, C. Chem. ReV. 1988, 88, 765.
(10) See, e.g.: (a) Marder, S. R.; Sohn, J. E.; Stucky, G. D. Materials
for Nonlinear Optics: Chemical PerspectiVes; American Chemical Soci-
ety: Washington, DC, 1991. (b) Okada, M.; Shiuchi, K.; Funada, F.;
Numada, H.; Ichinose, H.; Sasake, K.; Plach, H.; Poetsch, E. German Patent
4,426,904; 4,426,905 [Chem. Abstr. 122, 27861, 278762].
(11) (a) Treatment of I with excess HCl in nitromethane at 25 °C affords
crystalline 2,4,6-trichloro-3,5-difluorobenzenediazonium hexafluorophos-
phate in 80% yield. (b) Bockman, T. M.; Kosynkin, D.; Kochi, J. K. To be
submitted for publication.
(3) (a) Lewin, A. H.; Cohen, T. J. Org. Chem. 1967, 32, 3844. (b) Lewis,
E. S.; Johnson, M. D. J. Am. Chem. Soc. 1959, 81, 2070. (c) Waters, W. A.
J. Chem. Soc. 1942, 266.
(4) (a) Cowdrey, W. A.; Davies, D. S. Chem. Soc. Quart. ReV. 1952, 6,
358. (b) Cohen, T.; Lewarchik, R. J.; Tarino, J. Z. J. Am. Chem. Soc. 1974,
96, 7753.
(5) (a) Rondestvedt, C. S. Org. React. 1960, 11, 189. (b) Kochi, J. K. J.
Am. Chem. Soc. 1957, 79, 2942.
S0002-7863(97)00599-4 CCC: $14.00 © 1997 American Chemical Society

Electron-Transfer Catalysis in Biaryl Synthesis
J. Am. Chem. Soc., Vol. 119, No. 21, 1997 4847
Figure 1. (A) Reaction profile for iodide catalysis leading to arylation, iodination, and reduction of pentafluorobenzenediazonium with various
amounts of benzene in acetonitrile at 24 °C: (9) C6F5-Ph + 2(C6F5)2C6H4, (b) C6F5I, and (O) C6F5H. (B) Iodide requirements for the full conversion
+
of C6F5N2 (see text).
when various aromatic hydrocarbons are added.12 The progres-
sive bathochromic (red) shifts of the colors that follow the
decreasing trend in the ionization potentials are in accord with
the Mulliken formulation of intermolecular charge-transfer
complexes,13 i.e.
reaction mixture afforded the iodination product pentafluor-
oiodobenzene in 85% yield, i.e.
C6F5N2+ + I- f C6F5I + N2
(4)
However, in the presence of benzene, the reaction took an
entirely different course. For example, the addition of very
small amounts of either sodium or potassium iodide to a yellow
+
ArN2+ + Ar′H h [ArN2 , Ar′H]
(3)
Thus, the critical part of any mechanistic investigation of eq 2
must specifically address the role of these colored charge-
transfer complexes as intermediates in arylations with aromatic
diazonium salts.14
-
solution of C6F5N2+BF4 and benzene led to the complete
reaction of the diazonium salt and the evolution of a full
equivalent of N2. The major product of the reaction was
2,3,4,5,6-pentafluorobiphenyl, which was formed in high yield,
together with minor amounts of pentafluoroiodobenzene and
the bis-arylated derivative.16 The reaction was thus designated
as the thermal arylation of benzene catalyzed by iodide, i.e.
Results
The dediazoniation of the pentafluorobenzenediazonium
cation was examined in anhydrous acetonitrile solutions under
two widely different conditions. In the thermal method, a small
(catalytic) amount of an iodide salt was added to the colored
-
C6F5N2+ + PhH [I ]8 C6F5-Ph + N2 + H+
(5)
+
mixture of C6F5N2 and the aromatic hydrocarbon (Ar′H) at
The iodinated product (C6F5I) together with a small amount of
I2 accounted for all of the added iodide salt. In the absence of
room temperature. In the alternative photochemical method,
similar (diazonium) mixtures with Ar′H were initially cooled
to low temperatures (at which any thermal process was
inhibited), and the colored solutions were then deliberately
irradiated with visible light. In order to avoid contamination
by air, all reactions were carried out under an argon atmosphere
as follows.
-
sodium iodide, the colored acetonitrile solution of C6F5N2+BF4
and benzene remained unchanged for prolonged periods, and
no evolution of dinitrogen was evident (provided even adventi-
tious room light was excluded).
A. Effect of Benzene Concentration. Since the presence
of benzene was sufficient to divert the reaction from iodination
to arylation, the effect of added benzene was systematically
surveyed with sodium iodide as the catalyst owing to its ready
solubility in anhydrous acetonitrile. Figure 1 shows that the
progressive increase in the initial concentration of benzene
resulted in a corresponding increase in the yields of the arylation
product (C6F5-Ph) at the expense of the iodination product
(C6F5I). Concomitant with these trends, the amount of NaI
needed to effect complete reaction decreased (see Figure 1B).
In the presence of a large excess of benzene, less than 1 mol %
of NaI was sufficient to promote the complete arylation (Table
1), and the yield of pentafluorobiphenyl was close to quantita-
tive. The overall trend is presented in column 4 of Table 1, in
which the turnover number (i.e. T.N. ) extent of reaction
induced by each equivalent of NaI) is tabulated.
-
I. Pentafluorophenylation of Benzene with C6F5N2+BF4
and Catalytic Amounts of Sodium Iodide. The diazonium
group in the pentafluorobenzenediazonium cation could be
readily replaced with an iodo substituent.15 Thus, the addition
of 1 equiv of sodium iodide to a colorless solution of
C6F5N2+BF4- in acetonitrile at 24 °C (in the dark) immediately
led to the evolution of 1 equiv of dinitrogen. Workup of the
(12) Kampar, V. E.; Kokars, V. R.; Neiland, O. Ya. Zh. Obs. Khim. (Engl.
Transl.) 1977, 47, 858. See also: Koller, S.; Zollinger, H. HelV. Chim.
Acta 1970, 53, 78.
(13) (a) Mulliken, R. S. J. Am. Chem. Soc. 1952, 74, 811. See also:
Foster, R. F. Organic Charge-Transfer Complexes; Academic: New York,
1965. Briegleb, G. Elektronen Donator-Acceptor Komplexe; Springer:
Berlin, 1961. (b) This charge-transfer formulation is now confirmed by the
isolation and X-ray crystallography of various types of intermolecular
complexes in eq 3 (to be submitted for publication).
(14) Compare: Kochi, J. K. Pure. Appl. Chem. 1991, 63, 255.
(15) (a) Abeywickrema, A. N.; Beckwith, A. L. J. J. Org. Chem. 1987,
52, 2768. (b) Carey, J. G.; Jones, G.; Millar, I. T. Chem. Ind. 1959, 1018.
(c) Carey, J. G.; Millar, I. T. Chem. Ind. 1960, 97.
(16) The mixture consisted of ortho, meta, and para isomers of bis-
(pentafluorophenyl)benzene.11b

4848 J. Am. Chem. Soc., Vol. 119, No. 21, 1997
Kosynkin et al.
Table 1. Pentafluorophenylation of Benzene Induced by Sodium Iodidea
products (%)d
C6F5H
f
PhH (M)
NaIb (mmol)
additive (mmol)
T. N.c
C6F5Ph
C6F5I
Bise
I2
0
0.98
0.41
0.26
0.12
0.07
0.02
0.01
0.24
0.47
0.22
0.44
0.83
0.24
0
0
0
0
0
0
0
1.0
2.8
6.9
16
31
74
0
36
56
73
83
93
94
74
67
76
55
19
67
85
31
14
6
4
4
3
2
0.9
0.3
0
0
13
14
10
6
3
2
0.031
0.075
0.039
0.028
0.019
0.003
<0.001
0.062
0.15
0.17
0.34
0.67
1.38
5.52
11.0
1.38
1.38
1.38
1.38
1.38
1.38
3
0.6
0.5
5
10
11
38
70
6g
85
O2 (0.2)
O2 (0.8)
I2 (0.1)
I2 (1.0)
CH2I2 (8.0)
CBrCl3 (8.0)
4.2
2.1
4.5
2.3
1.2
4.2
0.050
0.048
-
a In acetonitrile (6 mL) containing 1.0 mmol C6F5N2+BF4 and benzene at 24 °C. b Added in 0.01-0.05-mmol aliquots. c Turnover number
defined as mmol of N2 evolved per mmol of NaI for the initial phase of reaction. d Based on ArN2+, unless noted otherwise. e Isomeric mixture of
bis-substituted benzenes (C6F5)2C6H4, see Bockman et al.11b f In mmol, based on iodometry. g In addition, 5 mmol C6F5Br formed.
Table 2. Iodide Catalysis in the Thermal Arylations of Various
Table 3. Other (Nonionic) Reducing Agents as Catalysts for
- a
Arenes with C6F5N2+BF4
Pentafluorophenylationa
Products (%)b
(mmol) T.N.b C6F5-Ar′ C6F5I isomer distribution
catalyst (mmol)
T.N.b
yield of C6F5Ph (%)c
arene
NaIb
iodide (Na+) (0.07)
31
d
9.0
6.7
1.3
2.5e
83
84
83
85
43
56
Ar′H
iodide (K+) (0.20)
toluene
0.08
0.17
0.17
0.19
0.14
0.22
12.5
5.9
5.9
5.3
7.1
4.5
1.8
1.6
17
78
64
73
76
79
64
43
24
76
2.1 o:m:p 49:27:24
3.6
5.0
3.2 3:4
3.1
10
31
37
ferrocene (0.11)
p-dimethoxybenzene (0.05)
zinc (granule) (0.40)
isopropylbenzene
tert-butylbenzene
o-xylene
p-xylene
chlorobenzene
p-dichlorobenzene 0.55
nitrobenzene
naphthalene
33:37:30
32:40:28
53:47
o:m:p 43:28:29
a In acetonitrile solution containing C6F5N2+BF4 (1 mmol) and
benzene (8 mmol) at 24 °C, unless noted otherwise. b Turnover number;
defined as mmol of N2 evolved per mmol of catalyst added. c Isolated
yield of 2,3,4,5,6-pentafluorobiphenyl. d Indeterminate (owing to in-
solubility). e With 64 mmol of benzene.
-
0.62
0.16
o:m:p 23:61:16
2.1 R:â
64:36
a In acetonitrile (3 mL) containing 1.0 mmol of C6F5N2+BF4 and
-
8.0 mmol of arene at 24 °C. b Turnover number; see Table 1.
Catalysis by iodide was most effective for the arenes
substituted with electron-donating alkyl groups. For chloroben-
zene, dichlorobenzene, and nitrobenzene, on the other hand, the
turnover number was diminished, and the yield of the pen-
tafluorophenylated arene was significantly decreased. The lower
yields were accompanied by increased yields of pentafluor-
oiodobenzene, to indicate competition from the iodination
reaction (eq 4).
B. Retardation of Iodide Catalysis. The effect of additives
on the arylation reaction was explored by the addition of either
dioxygen, diiodine, or polyhalomethane. The results in Table
1 show that O2 drastically reduced the efficiency of the reaction
(as reflected in the turnover number in column 4), but had only
a minor effect on the distribution of products between C6F5-Ph
and C6F5I. Added I2 had a similar deleterious effect on the
catalytic efficiency, but was more effective in diverting the
course of the reaction from arylation to iodination (compare
columns 5 and 6 in Table 1). The polyhalomethanes, CH2I2
and BrCCl3, also retarded the reaction (note the lower turnover
number in entries 12 and 13). However, diiodomethane was
more effective in altering the reaction pathway, as shown by a
comparison of the relatively low yield of C6F5Br in entry 13
with the high yield of C6F5I in entry 12.
III. Catalysis of Pentafluorophenylation by (Nonionic)
Reducing Agents. The catalytic role of iodide (by the use of
NaI in Tables 1 and 2) was underscored by the equivalent
promotion of the pentafluorophenylation by potassium iodide
which was quite insoluble in acetonitrile. Effective catalysis
of the pentafluorophenylation was also achieved with other
nonionic reducing agents, such as ferrocene (Eox0 ) 0.40 V vs
SCE)17 and a heterogeneous suspension of a zinc granule, as
indicated by the turnover numbers listed in Table 3 (column
3). More striking was the catalytic role of the aromatic donor
II. Iodide-Promoted Pentafluorophenylation of Aromatic
Donors. The arylations of various aromatic substrates (Ar′H)
-
with C6F5N2+BF4 were also carried out under the conditions
0
p-dimethoxybenzene (Eox ) 1.3 V vs SCE).18 Thus, a pale
that pertained to benzene. High yields of pentafluorophenylation
products (C6F5-Ar′) could be obtained by the addition of small
amounts (10-20 mol %) of sodium iodide to an acetonitrile
solution of C6F5N2+BF4- and the aromatic compound under an
argon atmosphere. The isomer distributions of the pentafluo-
rophenylated arenes in Table 2 indicated that substitution was
quite unselective. For example, toluene was arylated at all three
positions (ortho, meta, and para) with only a slight preference
being shown for reaction at the ortho and para positions.
Moreover, the arylation was also rather insensitive to steric
hindrance, as shown by the slightly lower yields of the ortho-
arylated products of the reactions of cumene and tert-butylben-
zene (entries 2 and 3). Nitrobenzene yielded a preponderance
of the m-pentafluorophenylated nitrobenzene, but again, the
selectivity was poor. Naphthalene reacted preferentially at the
R-position.
+
yellow solution of C6F5N2 and benzene in acetonitrile was
quiescent for rather prolonged periods in the dark. When a
catalytic amount (0.05 mmol) of p-dimethoxybenzene was
added, the solution immediately turned distinctively pink and
began to slowly evolve dinitrogen and finally produced pen-
tafluorobiphenyl (85% yield). The fate of p-dimethoxybenzene
was traced to the arylated product pentafluorophenyl-1,4-
dimethoxybenzene and the dimeric 2,2′,5,5′-tetramethoxybi-
phenyl.19
IV. Spontaneous Formation of Charge-Transfer Com-
plexes of Pentafluorobenzenediazonium and Aromatic Com-
pounds. When pentafluorobenzenediazonium fluoroborate
(17) Gritzner, G.; Kuta, J. Pure Appl. Chem. 1984, 56, 461.
(18) Rathore, R.; Bosch, E.; Kochi, J. K. Tetrahedron 1994, 23, 6727.
(19) Margaretha, P.; Tissot, P. Org. Synth. 1977, 57, 92.

Electron-Transfer Catalysis in Biaryl Synthesis
J. Am. Chem. Soc., Vol. 119, No. 21, 1997 4849
+
+
Figure 2. Charge-transfer spectra of the intermolecular complexes of various arenes (as indicated) with (A) C6F5N2 and (B) C6F2Cl3N2 in
acetonitrile. The dashed curves are the absorption tails of the uncomplexed diazonium cations.
Table 4. Charge-Transfer Absorption of Aromatic Diazonium
robenzenediazonium I as the wavelength (λCT) at which it
arbitrarily reached the critical absorbance of An (see Table 4),
Complexes with Various Arenesa
as previously proposed by Tsubomura and Mulliken.21
A
C6F5N2+ (nm)c C6F2Cl3N2+ (nm)c
similar treatment was also applied to the charge-transfer spectra
from the trichloro derivative II, and the results are included in
Table 4.
arene (Ar′H)
benzene
toluene
p-xylene
mesitylene
IPb (eV)
λ0.1
λ0.5
λ0.5
λ1.0
9.08
8.81
8.84
8.40
8.12
7.90
391
400 381
447 388
d
448
496
501
568
668
434
473
479
533
620
V. Direct Arylations with [ArN2+, Ar′H] Complexes Wia
the Photoirradiation of Their Charge-Transfer Bands.
Inspection of Figure 2 and Table 4 revealed that visible
naphthalene
p-dimethoxybenzene
510 450
579 490
(excitation) light with λexc > 410 nm22 was sufficient to
+
a In acetonitrile containing 0.02 M C6F5N2+BF4 or 0.05 M
C6F2Cl3N2+BF4- and 0.4 M Ar′H at -30 °C. b Ionization potential from
ref 20. c λn is the CT wavelength at which the absorbance reached An.
d An too low.
-
selectively photoactivate only the intermolecular [C6F5N2
,
Ar′H] complexes comprised of aromatic donors with ionization
potentials (IP) lower than that of p-xylene in Table 4. [This
excitation light ensured that there could be no ambiguity as to
the adventitious photoexcitation of the local bands of either the
dissolved in acetonitrile was treated with benzene, the solution
immediately took on a distinctive yellow coloration (but no gas
was evolved and the constituents could be recovered intact).
The pale yellow color progressively deepened when either
toluene or p-xylene was added. An orange color developed with
naphthalene, and the solution turned red when p-dimethoxy-
benzene was added. The quantitative effect of these color
changes is represented by the series of UV-vis absorption
spectra (Figure 2A) that were measured at -30 °C to minimize
any complications arising from competing thermal reactions.
The progressive bathochromic shifts of the low-energy spectral
tails in the order Ar′H ) benzene < toluene < p-xylene <
naphthalene < p-dimethoxybenzene followed the decreasing
trend of the ionization potential of the aromatic compounds
(Table 4).20 Indeed, such a spectral behavior was predicted for
the charge-transfer bands of intermolecular (π,π) complexes,
i.e. [ArN2+, Ar′H], which are of the type originally described
by Mulliken (compare eq 3).13b The analogous charge-transfer
absorptions (Figure 2B) obtained with the trichloro derivative
II were slightly red-shifted relative to those of I, in accord with
expectations based on the Mulliken theory.13 The spectral
maxima of these new absorption bands were unfortunately
obscured by the low-energy cutoffs of the uncomplexed aromatic
diazonium cations (see Figure 2, dashed curves). Thus for
purposes of quantitative comparison, we chose to evaluate the
charge-transfer band of the aromatic complexes with pentafluo-
+
uncomplexed C6F5N2 or Ar′H.]
A. Charge-Transfer Arylation. The deliberate irradiation
+
of the clear yellow solution of C6F5N2 and p-xylene in
acetonitrile (under an argon atmosphere) with λexc > 410 nm
led to the steady evolution of roughly 1 equiv of dinitrogen
and to the complete conversion of C6F5N2+ to afford pentafluo-
rophenyl-p-xylene in 62% (isolated) yield, i.e.
hνCT
C6F5N2+ + Ar′H
8 C6F5-Ar′ + N2 + H+
(6)
-48 °C
where Ar′H ) p-xylene. The photolysate was always main-
tained at low temperature (-48 °C) to obviate any complication
from thermal processes, and the photochemical transformation
is thus designated hereafter as charge-transfer or CT arylation.
Most importantly, Table 5 also shows that similar results were
obtained with naphthalene to yield a mixture of R/â pentafluo-
rophenylated isomers that was experimentally indistinguishable
from that derived by iodide catalysis (compare Table 2, entry
9). Analogous arylations of benzene and toluene could not be
unambiguously carried out owing to the very low CT absor-
bances (see Figure 2 and Table 4) derived from these rather
weak aromatic donors. Nonetheless, the charge-transfer ary-
lations of mesitylene and naphthalene with the trichloro acceptor
II were successfully carried out to the same high conversions.
(21) Tsubomura, H.; Mulliken, R. S. J. Am. Chem. Soc. 1960, 82, 5966.
(22) For λexc > 410 nm, the output of a 500-W high-pressure mercury
light was successively passed through a Pyrex sharp cutoff filter (Corning
CS 3-74) and a IR water filter.
(20) (a) Birks, J. B. Photophysics of Aromatic Molecules; Wiley: New
York, 1970, p 457ff. (b) Bock, H.; Wagner, G. Tetrahedron Lett. 1971,
3713.

4850 J. Am. Chem. Soc., Vol. 119, No. 21, 1997
Kosynkin et al.
Table 5. Charge-Transfer Arylations of Aromatic Hydrocarbons
Table 7. Quantum Yields for Charge-Transfer Arylation. The
with Various Aromatic Diazonium Saltsa
Deleterious Effect of Dioxygena
products (%)c
benzenediazonium
arene
(Ar′H)
diazonium
conv
+
(ArN2
)
add.b (%)c
ArAr′ ArH
ArX
+
substituent
mmol Ar′Hb (mmol) Ar′H/ArN2
Φ
+
p-xylene
C6F5N2
0
0
0
0
100 62
d
34
d
3,5-difluoro-
2,4,6-trichloro 0.096
0.055
3.0 N
1.9 N
2.0 N
1.2 N
1.4 N
1.2 N
0.93 N
0.66 N
8.1 X
8.1 X
54
20
23
8.2
14
13
8.0
4.0
90
320
11.0
7.5
+
mesitylene C6F2Cl3N2
100 60
naphthalene C6F5N2
100 66 (3.6)e
+
0.087
0.15
0.10
0.095
0.12
0.16
0.088
0.025
6.7 (6.0)c
100 43 (2.9)e 35
+
naphthalene C6F2Cl3N2
4.5
95 90 (5.0)e
1
d
d
d
+
+
+
+
4.6 (0.11)d (5.5)e
naphthalene (O2N)2C6H3N2
naphthalene (O2N)2C6H3N2
naphthalene (O2N)2C6H3N2
naphthalene (O2N)2C6H3N2
0
2 (-)d
8 (ArI)
5 (ArBr)
d
5.0 (0.20)d (6.6)e
CH2I2
CBr4
CCl4
10
51f 31 (4.2)e
82 75 (5.8)e
3,5-dinitro
2.9
1.5
4.5
3.1
+
a In acetonitrile (6 mL) containing ArN2 (1 mmol) and aromatic
hydrocarbon (Ar′H ) 3 mmol) and irradiated with λexc > 410 mm at
+
-48 °C. b Additive (8.0 mmol). c Conversion based on ArN2
determined. e Ratio of R/â isomers. f At 0 °C.
.
d Not
a Irradiation at λexc ) 420 ( 10 nm of acetonitrile (3 mL) solutions
containing ArN2+ and Ar′H, as specified, at 24 °C. b N ) naphthalene,
X ) p-xylene. c In the presence of 0.5 mmol of BrCCl3. d After the
introduction of 0.04 mmol of dioxygen. e Following 3 successive
freeze-pump-thaw cycles.
Table 6. Inhibitory Effects of Diiodomethane on Charge-Transfer
Arylationsa
products(%)e
c
λexc
conve
+ b
Figure 2B).25 Quantum yields significantly greater than unity
were consistently measured (Table 7), and they generally
increased with the molar ratio of [Ar′H]/[ArN2+] (see column
4). Highly reproducible measurements of Φ were difficult to
obtain, since they were subject to a rather strong negative effect
by air contamination. For example, the deliberate addition of
as little as 0.04 mmol of dioxygen to the argon atmosphere over
the orange solution prior to irradiation was sufficient to
drastically decrease the quantum yield from 5 to only Φ ) 0.1
(entry 5). [The quantum yield was completely restored after
the (partially transformed) photolysate was deaerated by 3
successive freeze-pump-thaw cycles.] The presence of small
amounts of bromotrichloromethane also led to reduced values
of Φ (entry 3).
ArN2
3,5-dinitro
(nm) add.d
(%) ArAr′ ArH ArI
410
410 CH2I2
410
410 CH2I2
0
99
92
44
55
40
40
30
37
60
42
100
83
13
23
4
20
36
16
7
10
g
8
3
11
g
0f
79
0
42
0
4-nitro
3-nitro
0
400
0
0
0
3,5-bis(trifluoromethyl) 380
0
4-bromo
380
11
g
45
g
0
22
0
37
0
380 CH2I2
410
410 CH2I2
410
4-carboethoxy
3,5-bis(carboethoxy)
0
9
g
29
0
62
+
a In acetonitrile (6 mL) containing ArN2 (1 mmol) and p-
dimethoxybenzene (Ar′H ) 3 mmol) at -48 °C. b As tetrafluoroborate
or hexafluorophosphate salt. c High-energy cutoff. d Diiodomethane (8.0
+
mmol) added. e Conversion based on ArN2
.
f 2,5-Dimethoxypheny-
The quantum yields for charge-transfer arylations with the
3,5-dinitrobenzenediazonium complexes of naphthalene and
p-xylene were slightly lower than that from II, but otherwise
they more or less followed the same (concentration) trend as
listed in Table 7 (last 4 entries).
lacetonitrile (5%) also observed. g Not determined.
Moreover, the charge-transfer arylation of naphthalene was
readily effected with the nonfluorinated 3,5-dinitrobenzenedia-
zonium cation, and the high yields of the 3,5-dinitrophenyl
derivatives (Table 5, entry 5) enabled us to examine the strong
inhibitory effects of diiodomethane (entry 6), carbon tetrachlo-
ride (entry 8), and tetrabromide (entry 7) on this charge-transfer
arylation.
Discussion
The facile iodo-dediazoniation of aromatic diazonium cations
+
(ArN2 in eq 1 with X- ) iodide) bears a direct mechanistic
relationship to the dediazoniative arylation in eq 2, in that the
iodination product (ArI) is easily diverted to the arylation
product (Ar-Ar′) when the reaction in eq 4 is simply carried
out in the presence of an aromatic donor (Ar′H). As described
in Table 1, the diversionary pathway is so efficient that the biaryl
synthesis in eq 5 can be made quantitative with only catalytic
amounts (<1 mol %) of added iodide. Indeed, the monotonic
changeover from ArI to Ar-Ar′ in the presence of increasing
amounts of Ar′H, as illustrated in Figure 1, indicates that these
products are derived from a common intermediate.26
I. ETC Mechanism for Iodide (Thermal) Catalysis of
Arylation. The quantitative comparisons of the isomeric
pentafluorophenylated biaryls (C6F5-Ar′) obtained in Table 2
coincide (within experimental uncertainty) with the isomeric
product distributions in Table 8 that were previously observed
in homolytic arylations effected with the pentafluorophenyl
radical from various sources,27,28 i.e.
B. Inhibition of Charge-Transfer Arylation. In order to
examine the inhibitory effects of additives such as di-
iodomethane, the charge-transfer arylation of p-dimethoxyben-
+
zene was examined with a series of aromatic diazonium (ArN2
)
salts containing different (nuclear) substituents. The results in
Table 6 show that the reduced yields of arylated products were
directly traceable to the diversion of the aromatic moiety to the
corresponding aromatic iodide (ArI). The material balance was
largely made up by small (but significant) amounts of the
reduced arene (ArH).
V. Photoefficiency of Charge-Transfer Arylation. The
charge-transfer complex of the trichlorodiazonium derivative
II with naphthalene was particularly useful in quantitative
photochemical reactions since the irradiation of its charge-
transfer absorption band cleanly led to the steady bleaching of
the orange color to finally yield a completely colorless pho-
tolysate.23 Accordingly, the quantum yield (Φ) was determined
with the aid of ferrioxalate actinometry24 by continuously
monitoring the progressive diminution of the charge-transfer
(tail) absorbance upon irradiation of the acetonitrile solution
with monochromatic light at λexc ) 420 ( 10 mm (compare
•
C6F5 + Ar′H f C6F5-Ar′, etc.
(7)
As applied to pentafluorobenzenediazonium, the most economi-
(23) The extreme sensitivity of I to even traces of moisture caused
(yellow) coloring and thus precluded the use of C6F5N2 for quantitative
photochemical studies.
(25) The output of a 450-W Xenon lamp was passed through an
+
interference filter (Oriel 53810) with bandwidth (fwhm) (10 nm.
+
(26) The cation ArN2 cannot be the common precursor since it does
(24) Hatchard, C. G.; Parker, C. A. Proc. R. Soc. 1956, 253, 518.
not directly react (thermally) with the arenes in Tables 1 and 2.

Electron-Transfer Catalysis in Biaryl Synthesis
J. Am. Chem. Soc., Vol. 119, No. 21, 1997 4851
Table 8. Pentafluorophenylation of Toluene, Nitrobenzene, and Anisole
isomer distributiona of C6F5-Ar
arene (ArH)
toluene
reagent
o
m
p
ref
27e
28c
28a
27f
this work
27f
28a
this work
27e
this work
C6F5CO2-O2CC6F5
C6F5I/hν
44
38
44
49
39
17
18
20
35
29
19
20
19
25
22
42
53
52
7
37
42
37
26
39
41
29
28
57
61
C6F5Xe+
C6F5NH2/RONO
C6F5N2+/cat. NaI
C6F5NH2/RONO
C6F5Xe+
nitrobenzene
anisole
C6F5N2+/cat. NaI
C6F5CO2-O2CC6F5
C6F5N2+/cat. KI
10
a Corrected statistically for two ortho and meta positions.
•
cal pathway for the source of C6F5 involves an initial 1-electron
reduction, as in eq 8.2,29
the cyclohexadienylic (radical) adduct, i.e.35
Scheme 1
kI
C6F5
kA
•
C6F5N2+ + I- 98 C6F5 + N2 + I•
(8)
C6F5• + Ar′H
Ar′
(11)
(12)
•
H
C6F5
H
Such a redox process is consistent with the catalytic efficiency
of other (nonionic) reducing agents in Table 3, such as ferrocene,
the well-known 1-electron reagent,32 i.e.
–H+
–N2
+
•
Ar′
+ C6F5N2
C6F5–Ar′ + C6F5 , etc.
•
The overall 1-electron oxidation in eq 12 most likely proceeds
via a rate-limiting electron transfer (kET) that is followed by
the rapid deprotonation of the cationic Wheland adduct (C6F5-
Ar′H+)36 to afford the biaryl (C6F5-Ar′) and the rapid dediazo-
niation of the transient pentafluorophenyldiazenyl radical
•
C6F5N2+ + Cp2Fe f C6F5 + N2 + Cp2Fe+
(9)
If so, the subsequent arylation of Ar′H must involve a homolytic
chain process in order to account for (a) the catalytic turnover
numbers (in excess of unity) found in Tables 1 and 2, and (b)
the drastically reduced catalytic efficiency observed in the
presence of aryl radical traps (Table 1). Thus, the diminished
turnover numbers induced by dioxygen (entries 8 and 9), without
materially affecting the product ratio [C6F5-Ph]/[C6F5I], point
to the interception of the aryl radicals prior to both arylation
and iodination.33 Moreover, the reduced efficiency inflicted by
diiodine and diiodomethane (entries 10-12), which is ac-
companied by the progressively diminished ratio of [C6F5-Ar′]/
[C6F5I], derives from the facile iodine-atom transfer,34 i.e.
• 31
•
(C6F5N2 ) to regenerate the aryl radical (C6F5 ). According
to this formulation, iodide catalysis proceeds via an initial
+
reduction of ArN2 in eq 8 to generate the critical aryl radical
(Ar•), which is then involved in the homolytic chain process
shown in Scheme 1.37 Since the overall catalytic cycle includes
a critical electron-transfer step (eq 12), the iodide-induced
arylation is appropriately described as an electron-transfer chain
or ETC catalysis,38 of which a number of examples have been
previously identified in various organic and organometallic
reactions.39,40
II. Competition between Arylation and Iodination. Any
mechanistic formulation of iodide catalysis must quantitatively
account for the two important facets of the iodide-promoted
arylation that are illustrated in Figure 1, namely, (a) the
countercurrent trends in the yields of the arylation (C6F5-Ph)
and iodination (C6F5I) products with changes in benzene
concentration (Figure 1A) and (b) the steep monotonic fall in
•
C6F5 + CH2I2 f C6F5I + CH2I•, etc.
(10)
In order to accommodate the arylation step (eq 7) in the catalytic
cycle, we propose that the well-known homolytic addition of
C6F5 onto Ar′H (eq 11) is followed by the rapid oxidation of
•
(27) (a) Bolton, R.; Williams, G. H. AdV. Free Radical Chem. 1975, 5,
1. (b) Burdon, J.; Campbell, J. G.; Tatlow, J. C. J. J. Chem. Soc. (C) 1969,
822. (c) Oldham, P. H.; Williams, G. H. J. Chem. Soc. (C) 1970, 1260. (d)
Bolton, R.; Coleman, M. W.; Williams, G. H. Fluorine Chem. 1974, 4,
363. (e) Bolton, R.; Williams, G. H. Chem. Soc. ReV. 1986, 15, 261. (f)
Oldham, P. H.; Williams, G. H.; Wilson, B. A. J. Chem. Soc. (C) 1971,
1094.
(28) (a) Frohn, H. J.; Klose, A.; Bardin, V. V. J. Fluorine Chem. 1993,
64, 201. (b) Birchall, J. M.; Haszeldine, R. N.; Wilkinson, M. J. Chem.
Soc., Perkin Trans. 1 1974, 1740. (c) Birchall, J. M.; Hazard, R.; Haszeldine,
R. N.; Wakalski, W. W. J. Chem. Soc. (C) 1967, 47.
(35) See: Bolton, R.; Williams, G. H. in ref 27e.
(36) Taylor, R. Electrophilic Aromatic Substitution; Wiley: New York,
1990; p 278ff.
+
(37) Although there are previous examples of ArN2 undergoing
homolytic chain reactions,1,2 this is the first unequivocal example in which
the intermolecular (Gomberg-Bachmann) arylation is shown to proceed
via a chain process.
(38) We suggest that the iodide-promoted intramolecular Pschorr cy-
clization also proceeds via an analogous ETC mechanism. Compare: (a)
Wassmundt, F. W.; Kiesman, W. F. J. Org. Chem. 1995, 60, 196. (b)
Beckwith, A. L. J.; Meijs, G. F. J. Org. Chem. 1987, 52, 1922. (c) Karady,
S.; Abramson, N. L.; Dolling, U.-H.; Douglas, A. W.; McManemin, G. J.;
Marcune, B. J. Am. Chem. Soc. 1995, 117, 5425.
(29) Equation 8 proceeds via a 2-step process involving the rate-limiting
30
electron transfer (kET
)
followed by the rapid dediazoniation of the
aryldiazenyl radical as described in eq 18.31 Such a two-step sequence was
originally proposed as the initial stage of the iododediazoniation reaction.30a
(30) See: (a) Singh, P. R.; Kumar, R. Aust. J. Chem. 1972, 25, 2133.
(b) Pladziewicz, J. R.; Doyle, M. P. J. Imaging Sci. 1989, 33, 57. (c) Brown,
K. C.; Doyle, M. P. J. Org. Chem. 1988, 53, 3255. (d) Andersen, M. L.;
Handoo, K. L.; Parker, V. D. Acta Chem. Scand. 1991, 45, 983. (e) Gilbert,
B. C.; Hanson, P.; Jones, J. R.; Whitwood, J. C.; Timms, A. W. J. Chem.
Soc., Perkin Trans. 2 1992, 629.
(39) (a) Chanon, M.; Tobe, M. L. Angew. Chem., Int. Ed. Engl. 1982,
21, 1. (b) Darchen, A.; Mahe, C.; Patin, H. New J. Chem. 1983, 7, 453. (c)
Kochi, J. K. J. Organomet. Chem. 1986, 300, 139. (d) Colbran, S. B.;
Robinson, B. H.; Simpson, J. Organometallics 1983, 2, 943.
(40) In a more general context, the ETC catalysis, as presented in eq 18
and Schemes 1-3, relates directly to other catalytic reactions of diazonium
cations by various metal species,2 as well as other radical-chain reactions
such as the SRN1 and hole-catalyzed processes.41
(41) See: (a) Bunnett, J. F. Acc. Chem. Res. 1978, 11, 413. (b) Rossi,
R. A.; De Rossi, R. H. Aromatic Substitution by the SRN1 Mechanism;
American Chemical Society: Washington, DC, 1983. (c) Mirafzal, G. A.;
Liu, J. P.; Bauld, N. L. J. Am. Chem. Soc. 1993, 115, 6072. (d) Bosch, E.;
Kochi, J. K. J. Am. Chem. Soc. 1996, 118, 1319.
(31) Suehiro, T. ReV. Chem. Intermed. 1988, 10, 101.
(32) Connelly, N. G.; Geiger, W. E. Chem. ReV. 1996, 96, 877.
(33) DeTar, D. F.; Turetzky, M. N. J. Am. Chem. Soc. 1955, 77, 1745.
(34) Ingold, K. U. In Free Radicals; Kochi J. K., Ed; Wiley: New York,
1973; Vol. I, p 37.

4852 J. Am. Chem. Soc., Vol. 119, No. 21, 1997
Kosynkin et al.
Figure 3. Computer simulation of the kinetics based on eq 8 and Scheme 1-3 for the effect of benzene concentration on (A) the formation of
arylation and iodination products and (B) catalytic efficiency of iodide (right scale). The simulated points in parts A and B correspond to the
experimental data described in Figure 1, parts A and B, respectively.
the iodide requirement for efficient catalysis (Figure 1B). If
the propagation steps for arylation are described by Scheme 1,
the homolytic (chain-transfer) process for iodination stemming
from the initiation (eq 8) is
observed in the thermal catalysis. Thus, the isomeric product
distribution obtained in the charge-transfer arylations of naph-
thalene with ArN2 accord with the low selectivities charac-
+
teristic of other homolytic arylations with aryl radicals generated
from unambiguous (Ar•) sources.44 Such aryl radicals are
rapidly trapped by diiodomethane (Table 6) and other halogen-
atom transfer agents such as CBr4 (Table 5). Most importantly,
the enhanced magnitude of the quantum yields (consistently in
excess of unity in Table 7) for photochemical promotion
indicates that a chain process is operative. The latter can be
readily formulated as the electron-transfer chain or ETC
mechanism presented in Scheme 1, which does not depend on
any species (such as I•) derived from the initiator. Further
diagnostic of the homolytic chain mechanism based on Scheme
1 for charge-transfer arylation is the marked attenuation of the
quantum yields in the presence of the radical-trap (dioxygen)
and the halogen-atom transfer agents found to be effective in
the retardation of thermal catalysis (compare the results in Tables
1 and 7).
IV. Importance of Charge-Transfer Complexes in ETC
Initiation. Relevant to the photochemical procedure for ary-
lations with aromatic diazonium salts is the specific irradiation
of the charge-transfer absorption bands (hνCT) described in Table
4. Figure 4 illustrates the direct relationship of these charge-
transfer bands from diazonium salts I and II with the electron-
donor strength of the aromatic hydrocarbon (Ar′H), as measured
by the ionization potential (IP). According to Mulliken,45 such
a direct correlation derives from the photoinduced electron
transfer that occurs within the precursor complex (see eq 3) to
generate the radical-ion pair, i.e.46,47
Scheme 2
kP
C6F5• + I2
C6F5I + I•
(13)
and the termination process is then described by the pair of
radical-annihilation steps
Scheme 3
kC
C6F5• + I•
I• + I•
C6F5I
(14)
(15)
kD
I2
In order to validate the participation of the initiation step (eq
8), the propagation steps (Schemes 1 and 2), and the termination
steps (Scheme 3), we carried out the computer simulation of
the kinetics based on the GEAR Iterator developed by Weigert.42
As presented in Figure 3A, the successful simulation of the
opposed trends for arylation (C6F5-Ph) and iodination (C6F5I)
in the experimental Figure 1A derives from the competition
between homolytic addition (eq 11) and iodine-atom transfer
(eq 13),43 and the quantitative curve fittings largely reflect the
relative magnitudes of the second-order rate constants, kA/kP ∼
10-2, as described in the Experimental Section. Furthermore,
the simulation in Figure 3B correctly predicts the sharp rise in
the catalytic efficiency of iodide at rather low benzene concen-
trations (compare Figure 1B) to derive from the chain character
of the ETC arylation, as described in Scheme 1.
III. ETC Mechanism for Charge-Transfer Arylation.
The charge-transfer arylations exemplified by eq 6 represent
the photochemical equivalent to the thermal (iodide) process
in eq 5, without the obvious complications arising from
competing iodinations. Otherwise, the charge-transfer arylations
in Table 5 show the same mechanistic earmarks as those
hνCT
+
•
[ArN2 , Ar′H]
8 [ArN2 , Ar′H•+]
(16)
•
Loss of dinitrogen from the transient diazenyl radical (ArN2 )
yields the aryl radical required for the propagation sequence in
Scheme 1.48
The photochemical activation of the aromatic diazonium
cation as presented in eq 16 has its thermal (dark) counterpart
(42) (a) Weigert, F. J. Comput. Chem. 1987, 11, 273. (b) The program
is available from Project Seraphim, 1101 University Ave., Madison, WI
53706.
(43) The reaction of Ar• with I- to give the iodoarene radical anion ArI•-
+
followed by its reduction of ArN2 has been proposed as a propagation
(44) See: Williams, G. H. et al. in ref 27.
sequence for iododediazoniation.30a However, the intermediacy of ArI•-
has been challenged2 on account of its very rapid reversion to Ar• and iodide,
with a rate constant of 1010 s-1. (See: Andrieux, C. P.; Blocman, C.; Dumas-
Bouchiat, J. M.; Save´ant, J.-M. J. Am. Chem. Soc. 1979, 101, 3431.) We
find that the inclusion of ArI•- (its formation, decomposition, and reaction
with ArN2+) as an intermediate in the GEAR simulations of Schemes 1-3
does not alter the predicted yields of either Ar-Ar′ or ArI (see the
Experimental Section).
(45) Mulliken, R. S.; Person, W. B. Molecular Complexes: A Lecture
and Reprint Volume; Wiley: New York, 1969.
(46) The charge-transfer activity of various ArN2 ions has been
demonstrated: Becker, H. G. O.; Israel, G.; Oertel, U.; Vetter, H.-U. J.
Prakt. Chem. 1985, 327, 399 and related papers.
(47) For a review of time-resolved (spectral) studies of photogenerated
radical-ion pairs as in eq 16, see: Kochi, J. K. Acta Chem. Scand. 1990,
44, 409.
+

Electron-Transfer Catalysis in Biaryl Synthesis
J. Am. Chem. Soc., Vol. 119, No. 21, 1997 4853
Figure 4. Mulliken correlation of the charge-transfer energy (hνCT) of intermolecular complexes of (A) C6F5N2+ and (B) C6F2Cl3N2+ with various
arenes (as indicated).
kT, which is especially applicable to electron-rich Ar′H such as
p-dimethoxybenzene (DMB), i.e.
ediazoniation. Indeed, the time scale for diffusive separation
of the radical pair (τ ∼ 10-10 s), which is at least an order of
magnitude shorter than that required for dediazoniation (kN
∼
2
kT
9
+
•
108 s-1),31 accounts for the high efficiencies that can be attained
in iodide catalysis of arylation.53
[ArN2 , DMB]
8 [ArN2 , DMB•+], etc.
(17)
owing to the enhanced stability of the cation radical (DMB+•).18
Such an adiabatic charge-transfer process49 is responsible for
the thermal initiation of arylation by DMB (in the absence of
iodide), as described in Table 3 (entry 4). Viewed from a
slightly different perspective, the adiabatic charge transfer in
eq 17 represents a simple oxidation-reduction reaction associated
with the redox interaction of a relatively strong oxidant (e.g.,
Summary and Conclusions
The arylation of various aromatic hydrocarbons (Ar′H) can
be effected by pentafluorobenzenediazonium and related cations
(ArN2+) to afford the biaryls (Ar-Ar′) by two independent
procedures. Thus, the thermal arylation is promoted by small
(catalytic) amounts of sodium iodide at 24 °C, and the biaryls
(Ar-Ar′) are produced in high yields together with the iodination
products (ArI). The product ratio [Ar-Ar′]/[ArI] increases
markedly with Ar′H concentration, and the catalytic efficiency
of iodide for biaryl formation can be made to exceed turnover
numbers in excess of 85. Comparisons of the isomer distribu-
tion obtained from toluene, nitrobenzene, and naphthalene with
those reported previously for free-radical aromatic substitutions
with aryl radicals (generated from unambiguous sources) identify
Ar• as the reactive intermediate. According to the catalytic chain
mechanism presented in Scheme 1, the homolytic addition of
Ar• onto the aromatic hydrocarbon (eq 11) is followed by a
rapid electron transfer from the adduct (Ar-Ar′H•) to the
diazonium cation acting as a 1-electron oxidant in eq 12. Such
an oxidation-reduction is thus characteristic of an electron-
transfer chain or ETC mechanism, which is verified by the
computer simulation of the complex kinetics with the GIT
program based on the GEAR algorithm.42
+
0
C6F5N2 with Ered ∼ 0.8 V)50 coupled with a reasonable
0
reducing agent (DMB with Eox ) 1.3 V).18
In a more general context, the same charge (electron) transfer
formulation applies to the iodide-induced reductive dediazo-
+
niation of ArN2 in eq 8 via the contact (charge-transfer) ion
pair,51 i.e.
kET
fast
+
•
[ArN2 , I-] 8 [ArN2 , I•] 8 Ar• + N2 + I• (18)
Most importantly, the radical pair in eq 18 does not undergo
cage collapse as in a conventional mechanism for iododedia-
zoniation of ArN2 ,
+ 52 since the efficient diversion of iodination
to arylation by added benzene, as well as the GEAR simulations
shown in Figure 3, indicates that virtually all the aryl radicals
(Ar•) can be scavenged by benzene. Clearly, diffusive separa-
tion of the radical pair, followed by chain transfer (eq 13) and
termination (eqs 14 and 15), is needed to account for iodod-
(48) Alternatively, the aryl radical Ar• can react with the aromatic cation
radical to directly afford the Wheland intermediate (Ar-Ar′H+), which
yields the biaryl following deprotonation. For related examples, see: Parker,
V. D.; Tilset, M. J. Am. Chem. Soc. 1987, 109, 2521. Bockman, T. M.;
Kochi, J. K. J. Phys. Org. Chem. 1994, 7, 325.
(49) For some examples in which charge-transfer complexes (that contain
very good electron donors) readily undergo thermal electron transfer as in
eq 17, see: Kochi, J. K. AdV. Phys. Org. Chem. 1994, 29, 185 and related
papers.
The photochemical arylation (in the absence of iodide) is
alternatively induced by the deliberate irradiation of the charge-
transfer absorption bands of the intermolecular complexes of
ArN2+ and various arenes (Ar′H) that are characterized in Table
4. The charge-transfer activation of these precursor complexes
according to eq 16 affords aryl radicals to initiate the homolytic
chain mechanism in Scheme 1. Otherwise the catalytic process
(50) Estimated from: Elofson, R. M.; Gadallah, F. F. J. Org. Chem.
1969, 34, 854. Compare: Kochi, J. K. J. Am. Chem. Soc. 1955, 77, 3208.
(53) (a) Iodide efficiencies approaching 100% in Figure 3 are to be
contrasted with the more limited escape efficiencies measured in other azo
decompositions. See: Koenig, T.; Fischer, H. In Free Radicals; Kochi, J.
K., Ed.; Wiley: New York, 1973; Vol. I, p 157. (b) Note that the rate of
initiation in eq 18 represents a lower limit for kET, since back electron
transfer to regenerate [ArN2+, I-] cannot be evaluated. Compare the CIDNP
observations of Becker et al. in ref 46.
0
(51) Based on the 1-electron oxidation potential of iodide (Eox ≈ 1.0
V),2 the driving force for oxidation by ArN2+ is roughly isergonic, and the
rate of electron transfer is thus expected to be very fast (see GEAR
simulation in the Experimental Section).
(52) See, e.g.: Nonhebel, D. C.; Walton, J. C. Free-Radical Chemistry;
Cambridge: London, 1974; p 356.

4854 J. Am. Chem. Soc., Vol. 119, No. 21, 1997
Kosynkin et al.
catalyzed by sodium iodide. The formation of the blue color of the
ferrocenium cation was observed immediately after the addition of
ferrocene (60 µL, 0.167 M in acetonitrile) to the yellow acetonitrile
solution of pentafluorobenzenediazonium tetrafluoroborate (1.00 mmol)
and the arene (8 mmol). The dark blue reaction mixture was treated
with zinc granules (0.1 g), quenched with water (50 mL), and extracted
with dichloromethane (3 × 25 mL). The combined yellow dichlo-
romethane extracts were washed with water (3 × 50 mL), dried over
magnesium sulfate, and subjected to GC analysis after the addition of
p-xylene (100 µL, 86.4 mg) as an internal standard. Evaporation of
the solvent, recrystallization from methanol, and repeated sublimation
(45 °C, 0.3 Torr) of the yellowish crystalline residue afforded slightly
yellowish 2,3,4,5,6-pentafluorobiphenyl (203 mg, 83%, purity 99.6%
by GC). (b) Dimethoxybenzene: The addition of the dimethoxyben-
zene solution (20 µL, 0.500 M in acetonitrile) to the solution of benzene
(8.0 mmol) and the diazonium salt (1.00 mmol) resulted in a relatively
slow evolution of nitrogen that did not cease even after 30 min. An
additional 0.05 mmol of dimethoxybenzene was added, and the dark
green reaction mixture was finally treated with zinc granules (100 mg)
to result in a complete bleaching of the coloration. After workup,
evaporation of the solvent and repeated sublimation (45 °C, 0.3 Torr)
of the yellowish crystalline residue afforded pure colorless 2,3,4,5,6-
pentafluorobiphenyl (207 mg, 84.5%, purity 99.6% by GC). (c) Zn
Metal (with 64 mmol of Benzene): The reaction was run with
pentafluorobenzenediazonium tetrafluoroborate (282 mg, 1.00 mmol)
and benzene (5.00 g, 5.71 mL, 64 mmol) in acetonitrile (5.8 mL). The
reaction was started by dropping a zinc granule (17.6 mg, 0.54 mg‚-
atom) into the degassed reaction mixture. After 23 ( 0.8 mL (0.94
mmol, 94% a 24 °C) of nitrogen was evolved, the pressure stabilized
and the resulting orange reaction mixture was quenched with water
(30 mL) and extracted with dichloromethane (3 × 25 mL). The
consumption of zinc was determined to be 13.1 mg (0.40 mequiv).
The combined dichloromethane extracts were washed with water (3 ×
50 mL), dried over magnesium sulfate, and subjected to GC analysis
after the addition of p-xylene (100 µl, 86.4 mg) as an internal standard.
The yield of the biphenyl was 0.60 mmol, 60%. Evaporation of the
solvent and repeated sublimation (45 °C, 0.3 Torr) of the yellow
crystalline residue afforded pure colorless 2,3,4,5,6-pentafluorobiphenyl
(136 mg, 56%). The reaction was repeated in the same conditions with
8 mmol of benzene (624 mg, 714 µL). The gas evolution was more
sluggish, and the entire granule of zinc was consumed after 18 ( 0.8
mL (0.74 mmol at 24 °C) of nitrogen had evolved. The analysis of
the product mixture showed the presence of 2,3,4,5,6-pentafluorobi-
phenyl (0.43 mmol, 43%) and small amounts of byproducts.
for the photochemical arylation is equivalent to the mechanism
of the thermal (iodide) process.
Experimental Section
Preparation of Pentafluorobenzenediazonium Tetrafluoroborate.
A 250-mL Schlenk flask equipped with a magnetic stirring bar and a
rubber septum was charged with finely dispersed nitrosonium tetrafluo-
roborate (11.8 g, 0.10 mol) under argon. Dry acetonitrile (20 mL) was
then injected with the aid of a hypodermic needle, and the flask was
immersed in an acetonitrile/dry ice bath. After the solution cooled to
-30 °C, 2,3,4,5,6-pentafluoroaniline (18.3 g, 0.10 mol) in acetonitrile
(20 mL) was added over 30 min (syringe). The yellow reaction mixture
containing an abundant heavy precipitate was stirred for an hour at
-30 °C, treated with dry dichloromethane (150 mL), and filtered. The
white crystalline precipitate was washed with dry dichloromethane (3
× 50 mL), dissolved in a minimum volume of dry acetonitrile (ca. 60
mL), and reprecipitated by the slow addition of dichloromethane (200
mL) to yield shiny clear octahedra of the diazonium salt (22.9 g,
81%): mp 124-126 °C dec; IR (Nujol) 2314, 1655, 1648, 1578, 1571,
1561, 1538, 1524, 1504, 1438, 1326, 1158, 1112, 1070, 1052, 1037,
1020, 1005, 980, 956, 943 cm-1
;
13C NMR (CD3CN) δ 139.87 (dm, J
) 260 Hz), 149.08 (dm, J ) 280 Hz), 154.43 (dm, J ) 278 Hz); 19F
NMR (CD3CN) δ -40.09 (m, 1F), -43.70 (m, 2F), -71.82 (s, 4F),
-73.02 (m, 2F). Anal. Calcd for C6BF9N2: C, 25.57; H, 0.00; N,
9.95. Found: C, 25.37; H, 0.11; N, 9.90. The diazonium salt was
stable overnight at room temperature under an argon atmosphere, but
further storage at 24 °C led to appreciable decomposition. Exposure
of the diazonium salt to the atmospheric moisture caused yellow
discoloration after 2-3 h and total degradation after 2 days. The
synthesis of 3,5-difluoro-2,4,6-trichlorobenzenediazonium hexafluoro-
phosphate (II) as well as that of the other diazonium salts utilized in
Tables 5 and 6 is described separately.11b
Iodide-Promoted Arylations with Diazonium Salts. In a typical
procedure, a 75-mL flask having two Teflon O-ring sidearm stopcocks
was charged in a drybox equipped with a magnetic stirring bar and a
rubber septum with the diazonium salt (1.00 mmol). The pressure
transducer was attached to one of the sidearms, and the flask was
evacuated and refilled with argon. Acetonitrile (5.8 mL) and arene
(0.71 mL, 8 mmol) were injected with the aid of hypodermic syringes,
and the flask was evacuated and refilled with argon three times. The
evacuated flask was then closed off, and argon (25 mL at 24 °C) was
then injected via a gas-tight syringe to calibrate the output of the
transducer. The calibration was repeated with further additions of
argon. Following the calibration procedure, the flask was degassed as
described above and allowed to equilibrate until no observable change
in the transducer output occurred over 5 min. The reaction was
subsequently started by the injection of an oxygen-free solution of
sodium iodide (20 µL, 0.500 M) in acetonitrile via a gas-tight
microsyringe. The immediate appearance of a brown coloration (I2)
and gas evolution were observed. After the pressure remained
unchanged for 2 min, a new aliquot of the iodide solution (20 µL, 0.500
M) was injected. If the addition of first three aliquots of sodium iodide
(20 µL, 0.500 M) led to the evolution of less than 0.20 mmol of
nitrogen, further addition was performed with larger aliquots (100 µL,
0.500 M). The initiation process was continued until no further pressure
change was caused by addition of sodium iodide. The brown reaction
mixture was quenched with water (30 mL) containing a few drops of
a starch solution and titrated with 0.020 N sodium thiosulfate.
Following the titration, the reaction mixture was extracted with
dichloromethane (3 × 25 mL). The combined dichloromethane extracts
were washed with water (3 × 50 mL), dried over magnesium sulfate,
and subjected to GC analysis after the addition of p-xylene (100 µL,
86.4 mg) as an internal standard.
Charge-Transfer Photoarylations of Aromatic Donors. A Schlenk
flask was typically charged with the diazonium salt (1.00 mmol) and
the arene donor (3.00 mmol) under an argon atmosphere in a drybox
and sealed with a rubber septum. Acetonitrile (20 mL) was added with
the aid of a hypodermic syringe. The immediate appearance of the
yellow to red coloration of the EDA complex was noted upon the
dissolution of the reagents. The reaction mixture was irradiated at -48
°C with a 410-nm cut-off filter. The irradiation was continued until
no gas evolution could be observed. The final colorless reaction mixture
was poured in a separatory funnel containing water (100 mL),
concentrated hydrochloric acid (20 mL), and chloroform (20 mL)
several times. The combined chloroform extracts were washed with
water (3 × 20 mL), dried over molecular sieves, and analyzed by GC
and GC-MS after addition of p-xylene (100 µL, 86.4 mg) as an internal
standard.
Determination of the Quantum Yields. The actinic output of a
150-W short arc xenon lamp equipped with a 420-nm interference filter
was measured by using the original ferrioxalate technique by Hatchard
and Parker.24
A solution of the diazonium salt and arene in acetonitrile
(3 mL) was prepared in a Schlenk cell for UV-vis spectroscopy (1.000-
cm path) with the total volume of 21 mL at 24 °C in the dark. The
cell was placed in a water bath at 24 °C and irradiated with the focused
beam of the xenon lamp. The irradiation was periodically interrupted
and the UV-vis spectra of the solution recorded. A steady bleaching
of the charge-transfer absorption band was observed. The amount of
the diazonium salt in the solution for each spectrum was determined
by measuring the charge-transfer absorbance of the [diazonium, arene]
EDA complex [C] and calculating the amount of the unreacted
diazonium cation with use of the Benesi-Hildebrand approximation.
Inhibition of the Iodide-Promoted Pentafluorophenylation of
Benzene. After the degassing and calibration procedures (described
above for the uninhibited reaction) were carried out, dry oxygen (5
mL, 0.2 mmol at 25 °C) was injected into the reaction flask containing
pentafluorobenzenediazonium hexafluorophosphate (282 mg, 1.00
mmol), acetonitrile (5.8 mL), and benzene (0.71 mL, 8 mmol) via a
gas-tight syringe. The amount of iodide required for the complete
evolution of nitrogen (1 mmol) was determined by iodometric titration.
Pentafluorophenylation of Benzene with Other Catalysts. (a)
Ferrocene: The experiment was run as described above for the reaction

Electron-Transfer Catalysis in Biaryl Synthesis
J. Am. Chem. Soc., Vol. 119, No. 21, 1997 4855
Thus, if A ) ꢀC[C]l (where ꢀC is the extinction coefficient of the
complex and l is the optical path) and K ) [C]/(([D] - [C])([ArH] -
[C])) ≈ [C]/(([D] - [C])[ArH]) (where ArH and D are the arene and
diazonium cation, respectively), then A ) ꢀCl[D][ArH]/([ArH] - 1/K])
≈ [D0] constant. The amount of the residual diazonium was calculated
for each time point by using a wavelength value outside of the perturbed
range (400-430 nm). The initial slope of the [D] versus time curve
was considered the initial rate of the reaction, and the quantum yield
was calculated by dividing this rate by the light flux. (a) Inhibition
with Oxygen. A solution of the diazonium salt (40.3 mg, 0.102 mmol)
and naphthalene (182 mg, 1.42 mmol) in acetonitrile (3 mL) was
prepared and irradiated in a Schlenk UV cell as described above. After
exposing the solution to light (15 min), dry oxygen (1 mL, 0.04 mmol)
was injected via a gas-tight syringe. The quantum yield of the CT
band bleaching dropped to 0.11. The solution was then degassed by 3
freeze-thaw cycles and subjected to further irradiation. The Φ value
of 5.49 was determined. The experiment was repeated under the same
conditions and yielded initial quantum yields of 5.02 and 4.98. Addition
of oxygen (2 mL, 0.08 mmol) reduced these to 0.20 and 0.22. Oxygen
removal restored the quantum yields to 6.02 and 5.26. Addition of a
smaller amount of oxygen (0.100 mL, 0.004 mmol) reduced the
quantum yield to 1.69 (0.008 mmol, 20 min of exposure). Further
addition of oxygen (0.100 mL, 0.004 mmol) reduced the quantum yield
again to 1.02 (0.008 mmol, 20 min exposure). (b) Inhibition with
Bromotrichloromethane. A solution of the diazonium salt (38.0 mg,
0.0962 mmol) and naphthalene (198 mg, 1.89 mmol) in acetonitrile (3
mL) was irradiated in a Schlenk UV cell as described above. The initial
Φ value of 6.73 fell to 6.00 upon addition of bromotrichloromethane
(198 mg, 0.507 mmol).
of the reaction of 0.17 M pentafluorobenzenediazonium and an
equimolar amount of benzene in the presence of 8 × 10-3 M sodium
iodide was simulated, and allowed to run until the concentration of
iodide fell to less than 10-7 M (0.5-5 s). The concentrations of
C6F5N2+ and benzene calculated at this point were used as input for a
second cycle of calculations, starting with a concentration of iodide of
8 × 10-3 M. The process was repeated until the concentration of
diazonium cation fell to less than 10-3 M. The amounts of aryl iodide
and biaryl coupling products generated in each cycle of simulation were
added to calculate the final (simulated) concentrations for comparison
with the experimental yields in Table 1. The simulation was repeated
for benzene concentrations of 0.34, 0.67, and 1.38 M to correspond
with the experimental conditions in Table 1 and Figure 1A. The fit
shown in Figure 3A corresponds to a rate constant for the addition
step of kA ) 6 × 104 M-1 s-1. Simulations using values of kA ) 4 ×
104 and 8 × 104 M-1 s-1 led to substantially worse fits, with all the
calculated values of the yield of arylation products either less than (for
kA ) 4 × 104 M-1 s-1) or greater than (for kA ) 8 × 104 M-1 s-1) the
experimental yields. The overall rate constant for addition of C6F5• to
benzene is thus estimated as kA ) 6 ( 2 × 104 M-1 s-1
. For
comparison of the experimental data with the simulation, the total yield
for arylation was taken as the sum of yield of C6F5Ph and of twice the
yield of the doubly-arylated products11 in Table 1. No attempt was
made to simulate the yield of the minor products (I2 and C6F5H) or the
participation of other iodine-containing species such as triiodide, etc.
To test for the intermediacy of C6F5I•-, we repeated the calculation
•
with the following reaction steps included: (a) the reaction of C6F5
with I- to form C6F5I•-, which was assumed to proceed with a rate
•
constant of 107 M-1 s-1, (b) the reversion of C6F5I•- to C6F5 and I-
for which a rate constant of 1010 s-1 was used,2 and (c) the reaction of
Simulation of the Kinetics of the ETC Mechanism in Schemes
1-3. The system of six kinetic equations (eq 8 and Schemes 1-3)
was simulated with use of the MS-FORTRAN program GEAR.42,43 The
rate constants for the simulation were chosen as follows. The rate
constant for the initiation step (eq 8) was taken as kI ) 1.2 × 102 M-1
s-1 from the simulation of the rate of nitrogen evolution. The rate
+
•
C6F5I•- with C6F5N2 to generate C6F5I, C6F5 , and N2, which was
assumed to proceed at a diffusion-controlled rate. The (simulated)
yields of C6F5I and C6F5-Ph, as well as the amount of iodide required
for complete conversion, were identical with those obtained without
inclusion of reactions a-c. We conclude, therefore, that the reaction
•
between C6F5 and I- does not control the partitioning between
•
constants kC and kD for the coupling of C6F5 with I• (eq 14) and I•
iododediazoniation and biaryl formation in eqs 4 and 5, respectively.
dimerization (eq 15), respectively, were assumed to be diffusion
controlled, and the rate constant of 1010 M-1 s-1 was used for both.54
•
Acknowledgment. We thank the National Science Founda-
tion and the R. A. Welch Foundation for financial assistance.
The chain transfer of C6F5 with I2 (eq 13) was assumed to proceed
with a rate constant of kP ) 107 M-1 s-1 34
Preliminary simulation
.
experiments indicated that varying the rate constant for the electron-
transfer step (eq 12) between 106 and 1010 M-1 s-1 had no effect on
the yields of either the arylation products or C6F5I. Accordingly, the
value was fixed at kET ) 109 M-1 s-1. The rate constant for the addition
step (eq 11) was treated as a variable parameter. Initially, the kinetics
Supporting Information Available: Materials, instrumenta-
tion, charaterizations, and product yields for the thermal (iodide-
catalyzed) and photochemical arylations in Tables 1-3, 5, and
6 (10 pages). See any current masthead page for ordering and
Internet access instructions.
(54) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photochem-
istry; Dekker: New York, 1993; p 207.
JA970599B