Radical addition of arylboronic acids to various olefins under oxidative conditions

Article abstract of DOI:10.1021/ol101818k

Arylboronic acids are shown to be valuable precursors for aryl radicals upon treatment with manganese triacetate. Under these oxidative conditions the intermediately generated aryl radicals undergo addition to olefins to give the arylhydroxylation products A in the presence of dioxygen. In the absence of dioxygen, for some olefins double olefin addition and subsequent homolytic aromatic substitution provide tetrahydronaphthaline derivatives B in moderate to good yields.

Full text of DOI:10.1021/ol101818k

ORGANIC
LETTERS
2010
Vol. 12, No. 18
3972-3974
Radical Addition of Arylboronic Acids to
Various Olefins under Oxidative
Conditions
Arne Dickschat and Armido Studer*
Organisch-Chemisches Institut, Westfa¨lische Wilhelms-UniVersita¨t, Corrensstrasse 40,
48149 Mu¨nster, Germany
studer@uni-muenster.de
Received June 11, 2010
ABSTRACT
Arylboronic acids are shown to be valuable precursors for aryl radicals upon treatment with manganese triacetate. Under these oxidative
conditions the intermediately generated aryl radicals undergo addition to olefins to give the arylhydroxylation products A in the presence of
dioxygen. In the absence of dioxygen, for some olefins double olefin addition and subsequent homolytic aromatic substitution provide
tetrahydronaphthaline derivatives B in moderate to good yields.
It is well-known that trialkylboron compounds react with
O-centered radicals to liberate the corresponding alkyl
radicals.1 More recently, Renaud showed that alkylcatechol-
boron derivatives are valuable precursors for alkyl radicals
upon reaction with heteroatom centered radicals.2 Unfortu-
nately, these methods do not allow generation of more
reactive aryl radicals. However, Demir published a radical
biaryl synthesis by reacting arylboronic acids with Mn(OAc)3
in the presence of an arene as a solvent (Scheme 1).3 Upon
applying microwaves, this reaction could be conducted in
EtOH by using only a slight excess of the arene acceptor.4
Herein we present the first results on the application of
arylboronic acids as aryl radical precursors in intermolecular
addition reactions to various activated olefins. To our
knowledge, oxidative radical addition of arylboronic acids
to olefins is unknown.5
Scheme 1. Aryl Boronic Acids as Aryl Radical Precursors
We found that reaction of commercially available phenyl-
boronic acid with vinyl dimethylphosphonate (6 equiv) in
dichloroethane (DCE, 0.2 M) in the presence of Mn(OAc)3 (3
equiv) under argon at 80 °C for 6 h provided tetrahydronaph-
thaline 1a in 65% isolated yield as a 6.3:1 (cis/trans) mixture
of diastereoisomers (Scheme 2, Table 1, entry 1). Product 1a
(1) (a) Brown, H. C.; Midland, M. M. Angew. Chem., Int. Ed. Engl.
1972, 11, 692. (b) Davies, A. G.; Roberts, B. P. Acc. Chem. Res. 1972, 5,
387.
(2) (a) Ollivier, C.; Renaud, P. Chem. ReV. 2001, 101, 3415. (b)
Darmeceny, V.; Renaud, P. Top. Curr. Chem. 2006, 263, 71.
¨
(3) Demir, A. S.; Omer, R.; Emrullahoglu, M. J. Org. Chem. 2003, 68,
578.
(5) Intermolecular aryl radical additions to olefins by using aryldiazonium
salts as precursors; see: Heinrich, M. R. Chem.sEur. J. 2009, 15, 820.
(4) Guchhait, S. K.; Kashyap, M.; Saraf, S. Synthesis 2010, 1166.
10.1021/ol101818k  2010 American Chemical Society
Published on Web 08/18/2010

such as diacetoxyiodobenzene, 2-iodoxybenzoic acid, and
FeCl3 in dichloroethane, either the cascade reaction failed
or lower yields were achieved (entries 2-6).
Scheme 2. Synthesis of Tetrahydronaphthaline Derivatives
Various arylboronic acids were then reacted with vinyl
dimethylphosphonate in DCE with Mn(OAc)3 as an oxidant
under optimized conditions (Table 1).10,11 Para-substituted
phenylboronic acids provided the corresponding naphthaline
derivatives 1b-h with moderate to good yields (entries
7-13). A lower yield was achieved with the ortho-F-
substituted phenyl boronic acid (f 1i, entry 14) and by using
ortho-tolylboronic or ortho-ethoxyboronic acid the reaction
failed (not shown in the table) clearly documenting that steric
effects, as expected, play an important role in the initial
intermolecular aryl radical addition reaction. We found that
phenylvinylsulfone is a suitable radical acceptor for our
double addition/homolytic substitution process. Products 1j-l
were isolated in acceptable yields (entries 15-17). However,
with methyl acrylate and with acrylonitrile as acceptors, only
low yields of the corresponding tetrahydronaphthalene
derivatives 1m and 1n were obtained in the reaction with
phenylboronic acid under the applied conditions (entries 18
and 19).
was derived from a double olefin addition with subsequent
homolytic aromatic substitution (see discussion on the mech-
anism below).6 This remarkable cascade reaction comprises
three C-C bond forming steps!7 Transition-metal-mediated
addition of arylboronic acids to 2 equiv of an alkyne and
subsequent cyclization to give naphthalene derivatives have been
reported.8 However, analogous metal-mediated reactions by
using alkenes as acceptors leading to tetrahydronaphthalenes,
as reported herein, are unknown. The assignment of the relative
configuration was based on NMR spectroscopy by careful
analysis of the vicinal 3J(CCCP) coupling constants.9
Interestingly, we found that reaction of phenylboronic acid
and methyl acrylate with Mn(OAc)3 in the presence of dioxygen
(balloon, 1 atm) did not provide the targeted tetrahydronaph-
thalene derivative but delivered product 2a as a result of a
radical hydroxyarylation (Scheme 3, Table 1, entry 1).11 Radical
Table 1. Reaction of Various Arylboronic Acids with Various
Olefins
entry R1 R2
R3
solvent dr(cis/trans) no. yield[%]
a
1
2
3
H
H
H
H
H
H
CH3
Ph
F
H
H
H
H
H
H
H
H
H
H
H
H
H
F
PO(OMe)2 DCE
6.:1
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
65
45
20
0
10
0
64
67
57
60
45
44
34
33
48
44
49
27
19
a
PO(OMe)2 DCM
5.3:1
7.0:1
-
6.2:1
-
a
PO(OMe)2 TFT
a
4b
5c
6d
7
PO(OMe)2 DCE
Scheme 3. Oxidative Radical Hydroxyarylation
a
PO(OMe)2 DCE
a
PO(OMe)2 DCE
a
PO(OMe)2 DCE
7.0:1
4.5:1
4.8:1
4.1:1
3.9:1
3.5:1
7.0:1
3.4:1
1.8:1
1:1.3
1.3:1
1.7:1
1:4.0
a
8
9
PO(OMe)2 DCE
a
PO(OMe)2 DCE
a
10 Cl
11 Br
12
13 OCH3
14
15
16 Cl
17 Ph
18
PO(OMe)2 DCE
a
PO(OMe)2 DCE
a
I
PO(OMe)2 DCE
a
PO(OMe)2 DCE
a
H
H
PO(OMe)2 DCE
hydroxyalkylations are well established;12 however, the corre-
sponding arylhydroxylation process is not well investigated to
date.13 This is not unexpected since, due to the high reactivity
of aryl radicals, intermolecular aryl radical additions are
generally very difficult to achieve.14 A slightly better yield was
obtained for the reaction with acrylonitrile under the same
H
H
H
H
H
SO2Pha
SO2Pha
SO2Pha
CO2Mee
CNe
DCE
DCE
DCE
DCE
DCE
H
H
1m
1n
19
a 6 equiv of olefin were used. b Diacetoxyiodobenzene was used as
oxidant. c 2-Iodoxybenzoic acid was used as oxidant. d FeCl3 was used as
an oxidant. e 10 equiv of olefin were used.
(8) Fukutani, T.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2009, 11,
5198.
(9) Thiem, J.; Meyer, B. Org. Magn. Reson. 1978, 11, 50.
(10) Mn(OAc)3 (1.5 mmol) and vinyldimethylphosphonate (3.0 mmol)
were added to a solution of the corresponding arylboronic acid (0.50 mmol)
in ClCH2CH2Cl (2.5 mL). The reaction mixture was stirred at 80 °C under
an argon atmosphere for 6 h. The suspension was filtered through a pad of
celite, and the volatiles were removed under reduced pressure. The residue
was purified by FC (CH2Cl2/MeOH ) 40:1).
In other solvents (dichloromethane (DCM), R,R,R-trifluo-
rotoluene (TFT)) with Mn(OAc)3 or by using other oxidants
(6) Reviews on homolytic aromatic substitutions: (a) Studer, A.; Bossart,
M. In Radicals in Organic Synthesis, Vol. 2; Renaud, P., Sibi, M., Eds;
Wiley-VCH: Weinheim, 2001; p 62. (b) Studer, A.; Bossart, M. Tetrahedron
2001, 57, 9649. (c) Bowmann, W. R.; Storey, J. M. D. Chem. Soc. ReV.
2007, 36, 1803. (e) Vaillard, S. E.; Schulte, B.; Studer, A. In Modern
Arylation Methods; Ackermann, L., Ed; Wiley-VCH: Weinheim, 2009; p
475.
(11) Oxidative formal hydroxyarylation of olefins; see: Kirchberg, S.;
Fro¨hlich, R.; Studer, A. Angew. Chem., Int. Ed. 2009, 48, 4235
.
(12) Radical hydroxyalkylation; see: Ueda, M.; Miyabe, H.; Kimura,
T.; Kondoh, E.; Naito, T.; Miyata, O. Org. Lett. 2009, 11, 4632, and
references cited therein.
(13) Formal radical hydroxyarylation; see: Heinrich, M. R.; Wetzel, A.;
Kirschstein, M. Org. Lett. 2007, 9, 3833.
(7) Such a cascade, although in low yield, has been reported for the
decomposition of dibenzoylperoxide in the presence of an olefin; see:
Araneo, S.; Fontana, F.; Minisci, F.; Recupero, F.; Serri, A. Tetrahedron
Lett. 1995, 36, 4307.
(14) For a highly efficient intermolecular aryl radical addition, see:
Vaillard, S. E.; Mu¨ck-Lichtenfeld, C.; Grimme, S.; Studer, A. Angew. Chem.,
Int. Ed. 2007, 46, 6533.
Org. Lett., Vol. 12, No. 18, 2010
3973

Table 2. Radical Hydroxyarylation
Scheme 4. Suggested Mechanism
entry R1 inArB(OH)
R2
R3
dr
no. yield[%]
1a
H
H
H
H
4-CH3
3-CH3
2-CH3
4-F
4-Cl
4-Br
4-I
H
H
CO2Me
CN
-
-
2a
2b
33
39
43
48
38
27
23
46
53
46
34
37
40
2a
3a
CO2Me CO2Me 2.6:1 2c
CO2Me CO2Me 2.6:1 2c
CO2Me CO2Me 1.5:1 2d
CO2Me CO2Me 3.0:1 2e
CO2Me CO2Me 2.2:1 2f
CO2Me CO2Me 2.4:1 2g
CO2Me CO2Me 1.9:1 2h
CO2Me CO2Me 1.7:1 2i
CO2Me CO2Me 2.0:1 2j
CO2Me CO2Me 1.1:1 2k
CO2Me CO2Me 2.1:1 2l
4b
5b
6b
7b
8b
9b
10b
11b
12b
13b
To further establish the radical nature of our reactions we
reacted arylboronic acid 3 with Mn(OAc)3 in the presence
of dioxygen (Scheme 5). Hydroxylated dihydrobenzofurane
4-MeO
3-Cl
a 10 equiv of olefin were used. b Neat in olefin.
conditions (f 2b, entry 2). We tried to increase the yield by
increasing the concentration of the aryl radical acceptor.
However, upon running these two reactions in neat olefin,
polymerization occurred. Dimethylmaleate reacted with phe-
nylboronic acid under oxidative conditions producing hydroxy
ester 2c which was isolated in 43% yield as a 2.6:1 mixture of
diastereoisomers (entry 3).15 The yield was further improved
to 48% upon increasing the concentration of the olefin (entry
4). Para- and meta-substituted phenylboronic acid derivatives
reacted with acceptable yields with dimethyl maleate (entries
5, 6, and 8-13). As expected, the lowest yield was achieved
for the ortho-substituted tolylboronic acid (entry 7). With vinyl
dimethylphosphonate as an acceptor, we obtained the double
olefin addition/homolytic aromatic substitution product 1a even
in the presence of dioxygen. It is important to note that aryl
halides, which are substrates under radical tin hydride condi-
tions, are not transformed under the reaction conditions.
We suggest the following mechanism for our reactions.
Reaction of Mn(OAc)3 with an arylboronic acid provides
an aryl radical A which undergoes intermolecular addition
to the olefin acceptor to give B (Scheme 4). If the reaction
of B with the alkene is slow and if oxygen is present, radical
B is trapped by O2 to give the corresponding peroxyl radical
which is eventually further transformed to the hydroxy
derivative 2.16 In the absence of dioxygen, adduct radical B
undergoes renewed addition to the olefin to generate radical
C which then further cylizes onto the arene to give the
cyclohexadienyl radical D. This radical is readily oxidized
to give the tetrahydronaphthalene derivative 1.
Scheme 5. Oxidative Cyclization
4 was obtained in 28% yield. That cyclization reaction
strongly supports the radical character of our Mn-mediated
oxidative processes.
In summary, we presented the first intermolecular aryl
radical additions to various olefins starting with readily
available arylboronic acids. Arylboronic acids upon reaction
with Mn(OAc)3 are valuable aryl radical precursors. In the
presence of electron-poor olefins, aryl radical addition to the
olefin is followed by renewed addition and subsequent
homolytic aromatic substitution to eventually give tetrahy-
dronaphthaline derivatives. These cascade reactions that
comprise three C-C bond forming steps are experimentally
very easy to conduct (simply mixing commercially available
compounds and heating). In the presence of dioxygen, the
initially generated adduct radical may react with O2 to give
the corresponding arylhydroxylation products.
Acknowledgment. We thank the DFG for funding our
work.
Supporting Information Available: Experimental details
and characterization data for the products. This material is
available free of charge via the Internet at http://pubs.acs.org.
(15) We were not able to unambiguously assign the relative configuration
of the major isomer.
(16) The mechanism for conversion of the alkyl peroxyl radical to the
corresponding hydroxy compound under oxidative conditions is unknown.
OL101818K
3974
Org. Lett., Vol. 12, No. 18, 2010