tert-butoxide-promoted coupling of aryl iodides with arenes using Di-tert-butyl hyponitrite as an initiator

Article abstract of DOI:10.1246/cl.170814

The coupling reaction of aryl iodides with arenes was found to proceed under mild conditions to give biaryls through a homolytic aromatic substitution mechanism, using potassium tert-butoxide and di-tert-butyl hyponitrite as a stoichiometric promoter and a radical initiator, respectively.

Full text of DOI:10.1246/cl.170814

Advance Publication Cover Page
tert-Butoxide-Promoted Coupling of Aryl Iodides with Arenes
Using Di-tert-butyl Hyponitrite as an Initiator
Kazuya Kiriyama and Eiji Shirakwa*
Advance Publication on the web September 30, 2017
doi:10.1246/cl.170814
©
2017 The Chemical Society of Japan
Advance Publication is a service for online publication of manuscripts prior to releasing fully edited, printed versions. Entire
manuscripts and a portion of the graphical abstract can be released on the web as soon as the submission is accepted. Note that the
Chemical Society of Japan bears no responsibility for issues resulting from the use of information taken from unedited, Advance
Publication manuscripts.

1
tert-Butoxide-Promoted Coupling of Aryl Iodides with Arenes
Using Di-tert-butyl Hyponitrite as an Initiator
1
2
Kazuya Kiriyama and Eiji Shirakwa*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502
Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda,
Hyogo 669-1337
1
2
E-mail: eshirakawa@kwansei.ac.jp
1
2
3
4
5
The coupling reaction of aryl iodides with arenes was
49 the I-abstraction (step a) instead of SET to Ar–I (step a’-1) as
found to proceed under mild conditions to give biaryls
through a homolytic aromatic substitution mechanism, using
potassium tert-butoxide and di-tert-butyl hyponitrite as a
stoichiometric promoter and a radical initiator, respectively.
5
5
5
5
5
5
5
5
5
0
1
2
3
4
5
6
7
8
an entrance to the propagation cycle, where even
a
substoichiometric amount of an I-abstractor will work. We have
•
•
chosen Me as an I-abstractor for the following reasons: 1) Me
is readily generated at a relatively low temperature through two
successive
(t-BuON=NOt-Bu)
abstractor precursors such as (Me
economic and environmental points of view; 2) Me is likely to
homolysis
from
which is advantageous over common I-
Si) SiH and Bu SnH from
di-tert-butyl
hyponitrite
7
,8
,
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
The transition metal-catalyzed coupling of aryl halides
with arenes is one of the most straightforward methods to
obtain biaryl frameworks, where heteroarenes, electron-
deficient arenes, and arenes with a directing group are
3
3
3
•
have a sufficient I-abstraction ability, considering the report
•
1
59 that cyclohexyl radical, which is more stable than Me ,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
representative substrates. Iodine abstraction from an aryl
6
0 undergoes I-abstraction from iodobenzenes having a bulky
iodide (Ar–I) followed by homolytic aromatic substitution
9
•
61 substituent at an ortho-position. Here we report arylation of
(HAS) consisting of addition of the resulting aryl radical (Ar )
•
+
–
62 arenes through the KOt-Bu-promoted HAS mechanism initiated
to an arene and elimination of “ H ” (or H + e ) from the
cyclohexadienyl radical intermediate also has a high potential
•
6
3
by Me derived from t-BuON=NOt-Bu.
2
for this purpose. However, it is difficult to settle the conflict
R
R
–
between single electron (1e ) reduction in the iodine abstraction
Ar
I
+
H
Ar
–
•
3
step and 1e oxidation in the “ H ” elimination step. Curran and
coworkers solved the intrinsic conflict by use of (Me Si) SiH
and molecular oxygen as reductant and an oxidant,
Conditions
( i ) Curran's work:
Me Si) SiH (1.2 equiv), pyridine (5 equiv), O
ii ) Our previous work:
NaOt-Bu (2 equiv), Ph-phen (0.1 equiv), 155 ºC, 6–48 h
( iii ) This work:
3
3
(
3
3
2
, r.t., 3 h
a
(
3
e
•
•
3 3
respectively (Scheme 1-i). (Me Si) Si readily abstracts I
from Ar–I (step a) to give Ar (I), which adds to benzene (step
b). The cyclohexadienyl radical (II) is oxidized by molecular
oxygen, which is a mild oxidant compatible with the 1e
reduction process, giving Ar–Ph and HOO (step c). Use of a
•
4
t-BuON=NOt-Bu (0.2 equiv), KOt-Bu (2 equiv), DMSO (10 equiv), 60 ºC, 4–8 h
Mechanistic schemes
( i ) Curran's work
–
•
H
•
(SiMe ) Si
3
3
(SiMe ) Si–I
O
HO O
3
3
2
stoichiometric amount of expensive (Me
3
Si)
3
SiH is a major
Ar–I
Ar •
Ar
H
Ar
H
step a
fast
step b
step c
drawback here. On the other hand, we have recently reported a
method using NaOt-Bu and 4,7-diphenyl-1,10-phenanthroline
(Ph-phen) as stoichiometric and substoichiometric promoters,
I
II
(
ii ) Our previous work
Ph
Ph
Ar •
I–
5
D =
I
respectively. As shown in Scheme 1-ii, upon coordination by
N
N
step a'-2
step b
Ph-phen, NaOt-Bu passes an electron to Ar–I, giving anion
NaOt-Bu
•
+
•
–
D
D
radical [Ar–I] (step a’-1), which undergoes decomposition
Ar–I
[
Ar–I]• –
base-promoted HAS Ar
•
–
•
into Ar and I (step a’-2). After addition of Ar to benzene (step
step a'-1
H
fast
IV
•
–
II
b), deprotonation from II gives anion radical [Ar–Ph] (step
c’-1). Single electron transfer (SET) from [Ar–Ph] to Ar–I
gives Ar–Ph and regenerates [Ar–I] (step c’-2), where the 1e
slow
step c'-2
step c'-1
–
•
–
Ot-Bu
Ar
•
–
•
–
–
Ar
H–Ot-Bu
Ar–I
–
reduction and the 1e oxidation indispensable for the reaction to
be completed take place simultaneously. Although the intrinsic
conflict is effectively solved, a high temperature (155 °C) is
required probably due to the reluctant initiation (step a’-1). On
the other hand, Rossi and coworkers reported that KOt-Bu-
promoted reaction of aryl halides with arenes proceeds at room
temperature with the aid of photoirradiation, which is
considered to accelerate the SET process in the initiation step
III
(
iii ) This work
Ar–I
Me•
Me–I
•
Ar
step a
fast
I
step a'-2
step b
1/2 t-BuON=NOt-Bu
IV
base-promoted HAS
II
fast
Δ
1
/2 N2
step c'-2
step c'-1
•
•
t-BuO
CH3
acetone
III
6
4
6
but does not largely affect the propagation step. This
6
6
5
6
Scheme 1. Biaryl synthesis from aryl iodides through homolytic
aromatic substitution.
observation shows that the propagation step is fast enough to
proceed even at room temperature, prompting us to improve our
previous method by changing the way to get into the
propagation cycle (Scheme 1-iii). Thus, we planned to employ

2
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Treatment of 4-iodoanisole (1a: 1 equiv) with NaOt-
Bu (2 equiv) and t-BuON=NOt-Bu (0.2 equiv) in benzene
(2a: 120 equiv) in the presence of dimethyl sulfoxide (10
equiv) at 60 ºC for 8 h gave 4-methoxybiphenyl (3aa) in
34% yield (Table 1, Entry 1). By use of more basic KOt-Bu,
46 ester exchange, giving the coupling product (3ha) in 72 %
47 yield (Table 2, Entry 9). Heteroaryl iodides also participated
48 in the coupling reaction (Entries 10 and 11).
A
49 bisphenylation product was obtained from p-diiodobenzene
50 (1k) (Entry 12). Arenes other than benzene also accepted
51 arylation with 1a, giving regioisomeric mixtures in ratios
1
0
1a was fully consumed to give 3aa in 81% yield (Entry 2).
2
A drastic decrease of the yield was observed in the reaction
in the absence of t-BuON=NOt-Bu (Entry 3). t-BuOOt-Bu
also worked as a promoter at a temperature high enough to
52 characteristic of the HAS mechanism (Entries 13–16).
53
54
a
Table 2. Coupling of aryl iodides with arenes
•
1
1
1
1
1
1
1
1
1
1
2
undergo homolysis giving t-BuO albeit in a lower yield
t-BuON=NOt-Bu (0.2 equiv)
KOt-Bu (2 equiv)
(Entries 4 and 5). Although the reaction by use of
DMSO (10 equiv)
(Me
3
Si)
3
SiH
and V-70 [2,2’-azobis(4-methoxy-2,4-
1
H–Ar2
1
2
Ar –I
+
Ar –Ar
6
0 ºC, 8 h
dimethyl)valeronitrile], which produce an effective I-
1
2
3
•
abstractor, (Me
6),
3
Si)
3
Si resulted in a moderate yield (Entry
(120 equiv)
1
1,12
55
the result shows that the combination of the base-
1
2
b
promoted HAS with a conventional I-abstraction system is
valid.
Entry Ar –I (1)
Ar –H (2)
Yield/%
81
Prod.
3aa
3ba
3ca
3da
3ea
3fa
1
2
3
4
5
6
7
8
9
4-MeOC
3-MeOC
2-MeOC
6
H
H
H
4
4
4
–I (1a)
–I (1b)
–I (1c)
benzene (2a)
benzene (2a)
benzene (2a)
benzene (2a)
benzene (2a)
benzene (2a)
benzene (2a)
benzene (2a)
6
6
85
Table 1. Effect of additives in the coupling of 4-iodoanisole with
76
a
benzene
Ph–I (1d)
4-MeC
4-FC
85
additive (0.2 equiv)
KOt-Bu (2 equiv)
DMSO (10 equiv)
6
H
4
–I (1e)
75
6
H
4
–I (1f)
79
MeO
I
+
H
MeO
4-NCC
4-NCC
4-MeO
6
H
4
4
–I (1g)
–I (1g)
21
3ga
3ga
3ha
3ia
1
a
2a
120 equiv)
3aa
c,d
d,e
6
2
H
81
(
2
1
CC
6
H
4
–I (1h) benzene (2a)
72
Entry Additive
Temp.
ºC
Time
/h
Conv. of
Yield
10
11
12
2-pyridyl–I (1i)
3-thienyl–I (1j)
benzene (2a)
73
b
b
/
1a/%
/%
benzene (2a)
81
3ja
f
g
c
4-IC
6
H
4
–I (1k)
benzene (2a)
86
3ka
3ab
3ac
3ad
3ae
1
2
3
4
5
6
a
t-BuON=NOt-Bu
t-BuON=NOt-Bu
None
60
60
8
8
48
>99
19
34
81
7
h
1
1
1
1
3
4
5
6
4-MeOC
4-MeOC
4-MeOC
4-MeOC
6
6
6
6
H
H
H
H
4
4
4
4
–I (1a)
–I (1a)
–I (1a)
–I (1a)
pyridine (2b)
thiophene (2c)
fluorobenzene (2d)
90
i
70
60
8
j
79
t-BuOOt-Bu
t-BuOOt-Bu
60
24
24
8
25
9
1,4-difluorobenzene (2e) 88
120
60
>99
90
52
47
d
a
(Me
3
Si)
3
SiH, V-70
56
The reaction was carried out under a nitrogen atmosphere at 60 °C using an
5
5
5
6
6
6
6
7
8
9
0
1
2
3
aryl iodide (1: 0.20 mmol), an arene (2: 24 mmol), KOt-Bu (0.40 mmol), and
dimethyl sulfoxide (0.14 mL, 2.0 mmol) in the presence of di-tert-butyl
2
2
2
2
2
2
2
2
3
4
5
6
7
8
The reaction was carried out under a nitrogen atmosphere using 4-iodoanisole
(1a: 0.20 mmol), benzene (2.1 mL, 24 mmol), an additive (0.040 mmol), KOt-
b
c
hyponitrite (7.0 mg, 0.040 mmol). Isolated yield based on 1. NaOt-Bu was
used instead of KOt-Bu. Reaction time = 4 h. NaOMe was used instead of
b
Bu (0.40 mmol), and dimethyl sulfoxide (0.14 mL, 2.0 mmol). Determined
d
e
c
d
by GC. NaOt-Bu was used instead of KOt-Bu. (Me
3
Si)
3
SiH (0.040 mmol)
f
g
h
KOt-Bu. 1k (0.10 mmol) was used. The yield of p-terphenyl. A 41:29:30
mixture of 2-, 3-, and 4-(4-methoxypheynl)pyridines was obtained. A 79:21
and 2,2’-azobis(4-methoxy-2,4-dimethyl)valeronitrile (V-70: 0.040 mmol)
were used.
i
j
mixture of 2- and 3-(4-methoxyphenyl)thiophenes was obtained. A 47:20:33
mixture of o-, m-, and p-(4-methoxyphenyl)fluorobenzene was obtained.
64
65
66
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
The arylation of arenes by use of KOt-Bu and
t-BuON=NOt-Bu respectively as a stoichiometric promoter
and a radical initiator is applicable to various aryl iodides
and arenes (Table 2). In addition to p-iodoanisole (1a), the
meta- and ortho-isomers (1b and 1c) underwent coupling
with benzene (2a) in high yields (Entries 1–3). Use of KOt-
Bu as a base was effective also for the coupling of
iodobenzene (1d) and that having a methyl or fluoro
substituent but not for that having a cyano group, which was
•
In order to verify our hypothesis that Me derived from
67 t-BuON=NOt-Bu undergoes I-abstraction from an aryl iodide to
68 initiate the coupling, we examined what happens between these
69 two (Scheme 2). GC analysis showed that treatment of 4-
70 iodoanisole (1a) with t-BuON=NOt-Bu (1 equiv) in 1,2-
71 dichloroethane at 60 ºC for 8 h gave 4-choloroanisole (55%
72 yield) and iodomethane (44% yield). Generation of
73 iodomethane was further confirmed by trapping it with sodium
74 p-cresolate as 4-methylanisole (41% yield). 4-Chloroanisole is
75 most likely to be produced through the reaction of the aryl
76 radical intermediate with 1,2-dichloroethane, though it is
77 unclear at present what was the rest part of 1,2-dichloroethane
78 transformed to.
1
3
transformed to –C(=O)NH (Entries 4–7). Use of less basic
2
NaOt-Bu instead of KOt-Bu overcame the problem, giving
4-cycanobiphenyl in a high yield (Entry 8), where the
electron-withdrawing character of the cyano group
increased acidity of cyclohexadienyl intermediate II to relax
the requirement for basicity in step c’-1 of Scheme 1 (cf.
Table 1, Entries 1 vs. 2). For the coupling of methyl 4-
iodobenzoate (1h), NaOMe was used in order to avoid the

3
4
4
0
1
Supporting
http://dx.doi.org/10.1246/cl.******.
Information
is
available
on
MeO
Cl
t-BuON=NOt-Bu (1 equiv)
ClCH CH Cl, 60 ºC, 8 h
64% conv.
55% yield
MeO
I
+
2
2
Me–I
42 References and Notes
1
a
4
4% yield
4
3
1
For recent reviews, see: a) L. Ackermann, R. Vicente, A. R.
Kapdi, Angew. Chem., Int. Ed. 2009, 48, 9792–9826. b) G. P.
McGlacken, L. M. Bateman, Chem. Soc. Rev. 2009, 38, 2447–
2464.
For reviews, see: a) R. Bolton, G. H. Williams, Chem. Soc. Rev.
1986, 15, 261–289. b) W. R. Bowman, J. M. D. Storey, Chem.
Soc. Rev. 2007, 36, 1803–1822.
a) V. Martínez-Barrasa, A. García de Viedma, C. Burgos, J.
Alvarez-Builla, Org. Lett. 2000, 2, 3933–3935. b) P. T. F.
McLoughlin, M. A. Clyne, F. Aldabbagh, Tetrahedron 2004, 60,
8065–8071. c) A, Núñez, A. Sánchez, C. Burgos, J. Alvarez-
Builla, Tetrahedron 2004, 60, 6217–6224. d) D. Crich, M. Patel,
Tetrahedron 2006, 62, 7824–7837. e) D. P. Curran, A. I. Keller,
J. Am. Chem. Soc. 2006, 128, 13706–13707.
NaO
44
45
46
47
(
3 equiv)
MeO
THF, 85 ºC, 12 h
4
1% yield (based on 1a)
1
2
3
4
4
5
5
8
9
0
1
•
2
3
Scheme 2. Verification of I-abstraction from an aryl iodide by Me
derived from t-BuON=NOt-Bu.
1
4
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
In S 1 type reactions, high preference for double
52
RN
5
3
substitution over single in the reaction of a dihalobenzene
(X–C H –X) with a nucleophile (Nu ) is used to prove the
involvement of an anion radical intermediate corresponding
Anion radical intermediate [Nu–
C H –X] should undergo decomposition into Nu–C H
4
and X rather than pass an electron to X–C H –X. Thus,
6 4
predominant production of Nu–C H –Nu over Nu–C H –X
is a proof of anion radical intermediacy, and this was found
to hold true for the present reaction as follows. The reaction
of 4-chloroiodobenzene (1l) with benzene (2a) for a short
reaction period (5 min, 29% conv.) gave p-terphenyl (3ka)
and 4-chlorobiphenyl (3la) in 18% and 2% yields,
respectively (Scheme 3). A possibility that 3la has an
exceptional reactivity to be converted immediately to 3ka
was ruled out by the result that 4-chloro-4’-methylbiphenyl
(1m), which undoubtedly has a reactivity similar to 3la, did
not react at all under the conditions where the coupling of 1l
with 2a proceeds in 30% conversion of 1l (Scheme 3).
–
54
6
4
5
5
6
5
5
c,14,15
to III in Scheme 1.
57
58
4
5
C. Chatgilialoglu, Chem. Rev. 1995, 95, 1229–1251.
•
–
•
For our previous work, see: a) E. Shirakawa, K. Itoh, T.
Higashino, T. Hayashi, J. Am. Chem. Soc. 2010, 132, 15537–
15539. b) E. Shirakawa, T. Hayashi, Chem. Lett. 2012, 41, 130–
134. For similar examples reported coincidently as independent
studies: c) W. Liu, H. Cao. H. Zhang, H. Zhang, K. H. Chung, C.
He, H. Wang, F. Y. Kwong, A. Lei, J. Am. Chem. Soc. 2010, 132,
16737–16740. d) C.-L. Sun, H. Li, D.-G. Yu, M. Yu, X. Zhou,
X.-Y. Lu, K. Huang, S.-F. Zheng, B.-J. Li, Z.-J. Shi, Nat. Chem.
2010, 2, 1044–1049. For the coupling with pyrazine and pyridine
derivatives reported earlier, see: e) S. Yanagisawa, K. Ueda, T.
Taniguchi, K. Itami, Org. Lett. 2008, 10, 4673–4676. For a
stimulating essay leading to proper appreciation of the reaction
mechanism, see: f) A. Studer, D. P. Curran, Angew. Chem., Int.
Ed. 2011, 50, 5018–5022. For a review, see: g) C.-L. Sun, Z.-J.
Shi, Chem. Rev. 2014, 114, 9219–9280.
6
4
6
–
5
6
6
6
6
9
0
1
2
3
1
1
1
1
1
1
1
1
1
1
2
2
2
6
4
6
4
64
6
6
6
6
6
5
6
7
8
9
70
7
7
7
7
7
7
1
2
3
4
5
6
6
7
For photoinduced direct C–H arylation using KOt-Bu as a
promoter, see: a) M. E. Budén, J. F. Guastavino, R. A. Rossi,
Org. Lett. 2013, 15, 1174–1177. b) Y. Cheng, X. Gu, P. Li, Org.
Lett. 2013, 15, 2664–2667.
6 6
C H (2a: 120 equiv)
t-BuON=NOt-Bu (0.2 equiv)
KOt-Bu (2 equiv)
77
78
79
8
8
8
8
Di-tert-butyl hyponitrite is reported to undergo clean
•
DMSO (10 equiv)
decomposition into t-BuO and N with t of 29 min at 65 ºC.
2
1/2
Cl
I
Cl
Ph
+
Ph
Ph
4
–1
6
0 °C, 5 min
The rate constant is estimated to be 4.00 x 10 s in isooctane at
65 °C. H. Kiefer, T. G. Traylor, Tetrahedron Lett. 1966, 7, 6163–
6168.
1
l
3la
3ka
0
1
2
3
conv of 1l
29%
2% yield
2% yield
18% yield
16% yield
in the presence of
Cl
•
•
8
The rate constant of decomposition of t-BuO into Me and
5 –1
30%
acetone is estimated to be 1.1 × 10 s in cumene at 60 ºC. T.
Nakamura, W. K. Busfield, I. D. Jenkins, E. Rizzardo, S. H.
Thang, S. Suyama, J. Org. Chem. 2000, 65, 16–23.
conv of 1m
84
85
(
1 equiv)
<
1%
1
m
2
2
3
4
8
8
8
8
9
9
9
6
7
8
9
0
1
2
9
a) D. Dolenc, B. Plesničar, J. Am. Chem. Soc. 1997, 119, 2628–
2632. b) D. Dolenc, B. Plesničar, J. Org. Chem. 2006, 71, 8028–
8036.
Scheme 3. Proof of anion radical intermediacy.
10
The reaction under the conditions of Entry 2 of Table 1 but in the
absence of DMSO scored a lower yield (54%) with a lower
conversion (67%) of 1a. The effect of DMSO is unclear at
present but it possibly affects KOt-Bu to enhance its basicity. As
a slightly lower yield (75% with a full conversion of 1a) was
observed with an increased amount (20 equiv) of DMSO, we
used 10 equiv of DMSO as in Entry 2 of Table 1 for further
investigation.
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
In conclusion, we have introduced t-BuON=NOt-Bu as
a radical initiator into the tert-butoxide-promoted coupling
of aryl iodides with arenes to conduct the reaction at a low
temperature. t-BuON=NOt-Bu, after decomposition into
Me , is considered to act as an I-abstractor from aryl iodides
to give aryl radicals required for the base-promoted
homolytic aromatic substitution process.
93
94
•
9
9
9
9
9
5
6
7
8
9
11
The half-life of V-70 is reported to be 0.1 h at 60 ºC. A. D. Smith,
E. Lester, K. J. Thurecht, J. E. Harfi, G. Dimitrakis, S. W.
Kingman, J. P. Robinson, D. J. Irvine, Ind. Eng. Chem. Res. 2010,
Dedicated to the late Professor Yoshihiko Ito on the
occasion of the 10 anniversary of his sudden death.
th
100
49, 1703–1710.
For examples of generation of (Me
•
1
1
1
1
1
01 12
02
3
Si)
3
Si from (Me
3
Si)
3
SiH and
V-70, see: a) S. Kim, C. J. Lim, Angew. Chem., Int. Ed. 2004, 43,
5378–5380. b) J. Demarteau, A. Kermagoret, I. German, D.
Cordella, K. Robeyns, J. De Winter, P. Gerbaux, C. Jérôme, A.
Debuigne, C. Detrembleur, Chem. Commun. 2015, 51, 14334–
14337.
This work has been supported financially in part by
Grant-in-Aid for Scientific Research (B) (25288046 to E.S.)
from JSPS.
03
04
05
106

4
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
14
KOt-Bu is reported to promote hydration of nitriles into the
corresponding amides under unhydrous conditions, whereas no
hydration takes place with NaOt-Bu under the same conditions.
G. C. Midya, A. Kapat, S. Maiti, J. Dash, J. Org. Chem. 2015, 80,
4148–4151.
S
RN1 reaction is an effective reaction to achieve substitution of
aryl halides with anionic nucleophiles, proceeding through anion
radical intermediates. Its reaction mechanism shares key features
with that of the base-promoted homolytic aromatic substitution
shown in Scheme 1-ii (steps a’-1, a’-2 and c’-2) as follows.
Single electron reduction of an aryl halide (Ar–X) gives its anion
1
1
1
1
1
1
1
1
1
1
2
•
–
radical ([Ar–X] ), which undergoes decomposition to give the
•
–
corresponding aryl radical (Ar ) with elimination of X . The
•
–
reaction of Ar with an anionic nucleophile (Nu ) gives anion
radical [Ar–Nu] , which passes an electron to Ar–X to give the
•
–
•
–
substitution product (Ar–Nu) and regenerate [Ar–X] . For
reviews, see: a) J. F. Bunnett, Acc. Chem. Res. 1978, 11, 413–
420. b) R. A. Rossi, A. B. Pierini, A. B. Peñéñory, Chem. Rev.
2003, 103, 71–167.
15
J. F. Bunnett, X. Creary, J. Org. Chem. 1974, 39, 3611–3612.