Copper-Catalyzed Alkenylation of Alcohols with β-Nitrostyrenes via a Radical Addition-Elimination Process

Article abstract of DOI:10.1055/s-0034-1380445

A new method for the preparation of allylic alcohol derivatives has been developed via a radical mechanism using DTBP as the radical initiator promoted by copper salt. The C(sp³)-H bond in various alcohols, toluene derivatives, and alkanes were successfully converted into C-C bonds to yield the desired products in moderate to good yields.

Full text of DOI:10.1055/s-0034-1380445

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1961–1968
letter
1961
S.-r. Guo, Y.-q. Yuan
Letter
Synlett
Copper-Catalyzed Alkenylation of Alcohols with β-Nitrostyrenes
via a Radical Addition–Elimination Process
OH
Sheng-rong Guo
OH
NO2
Cu(OAc)2 (2 mol%)
R2
R3
Yan-qin Yuan*
R1
R1
R2
R3
(E)
+
(E)
H
DTBP (2 equiv)
100 °C, 2–12 h
Department of Chemistry, Lishui University, Lishui,
323000, P. R. of China
yuanyq5474@lsu.edu.cn
R1 = EWG or EDG
45 examples
32–85% yield
R
R
2 = H or Alk
3 = H or Alk
Received: 16.03.2015
Accepted after revision: 17.05.2015
Published online: 09.07.2015
as reactants still remains a challenge to chemists, and the
α-C(sp3)–H bond functionalization of alcohols for the for-
mation of allylic alcohol derivatives has not been thorough-
ly investigated although much progress has been achieved
in the field of direct oxidative C(sp3)–H bond functionaliza-
tion.8,9
On the other hand, substituted (E)-β-nitrostyrenes are
flexible intermediates in organic synthesis, which are used
in many classes of reactions.10 Yao et al.11a–d reported a se-
ries of reactions of (E)-β-nitrostyrenes with ethers and cy-
cloalkanes in the presence of benzoyl peroxide (Scheme 1,
a). Alcohols could be used as ideal alkylation reagents via α-
hydroxy carbon centered radical mechanism under oxida-
tive conditions.1–7 We envisioned that such a radical proce-
dure might be applicable to (E)-β-nitrostyrenes, so we
herein present a facile copper-catalyzed radical addition–
elimination alkenylation of alcohol α-C(sp3)–H bond for the
first time (Scheme 1, b).
DOI: 10.1055/s-0034-1380445; Art ID: st-2015-w0187-l
Abstract A new method for the preparation of allylic alcohol deriva-
tives has been developed via a radical mechanism using DTBP as the
radical initiator promoted by copper salt. The C(sp3)–H bond in various
alcohols, toluene derivatives, and alkanes were successfully converted
into C–C bonds to yield the desired products in moderate to good
yields.
Key words (E)-β-nitrostyrenes, alkenylation, alcohols, free-radical,
C(sp3)–H bonds
In the 1980s, Minisci reported the direct coupling of
electron-deficient N-heteroaromatics with alcohols – pro-
moted by a peroxide – to generate a new C–C bond while
retaining the hydroxyl group.1 Over the past decades, im-
pressive progress has been made in developing this trans-
formation including transition-metal-catalyzed cross-cou-
pling of alcohols with N-heterocycles,2 alkenes,3 alkynes,4
cinnamic acids,5 and H-phosphonates.6 In addition, a few
metal-free catalytic systems have also been reported.7
However, this kind of transformation using simple alcohols
The initial investigation was focused on the optimiza-
tion of reaction conditions. A direct alkenylation using (E)-
β-nitrostyrene (1a) and isopropanol (2a) was chosen as a
model reaction to optimize suitable conditions (Table 1). It
was found that the radical initiator and catalyst were criti-
(a) Yao's work
NO2
H
X
Bz2O2
R
R
+
X
reflux, 12 h
X = C, O
(b) this work
R1
OH
NO2
OH
R2
R3
Cu(OAc)2, DTBP
100 °C, 12 h
R1
+
R2
H
R3
Scheme 1 Scope of Application of β-nitrostyrenes
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1961–1968

1962
S.-r. Guo, Y.-q. Yuan
Letter
Synlett
cal to the reaction efficiency. Treatment of 1a with di-tert-
butyl peroxide (DTBP, 2.0 equiv) in 3 mL of isopropanol at
100 °C for six hours led to the desired product 3aa in 12%
yield in the absence of metal catalyst (Table 1, entry 1).
When we scanned the metal catalysts, it was found that
copper salts exhibited good catalytic activity. The best cata-
lyst was Cu(OAc)2, and the desired product was isolated in
83% yield by using 2 mol% Cu(OAc)2 (Table 1, entry 3). CuO,
Cu2O, and copper powder were catalytically less reactive in
the model reaction (Table 1, entries 3–5). Addition of 0.5
mol% Cu(OAc)2 and 5 mol% Cu(OAc)2 led to the generation
of the product in 66% and 82% yields, respectively (Table 1,
entries 6 and 7). It should be noted that palladium and iron
catalysts such as Pd(OAc)2 and Fe(acac)3 are not suitable to
this transformation and gave poor yields (Table 1, entries 8
and 9). With respect to the amount of radical initiator used
in the reaction, two equivalents of DTBP was found to be
optimal. The model reaction was not completed with less
than two equivalents of DTBP. However, no significant in-
crease of yield of 3aa was observed with more than two
equivalents of DTBP (Table 1, entries 10 and 11). A 61% yield
was obtained at 120 °C, and only a trace amount of 3aa was
detected when the reaction temperature was 90 °C, even
prolonging the reaction time to 24 hours (Table 1, entries
12 and 13). In the case of solvent effects, DCE and MeCN are
also suitable for this transformation (Table 1, entries 14 and
15), in view of its nontoxicity and environment friendly. We
used alcohol as solvent. It was found that other radical initi-
ator, such as dicumyl peroxide (DCP), benzoyl peroxide
(BPO), and azobisisobutyronitrile (AIBN), were inferior and
generated 3aa in 71%, 54%, and 61% yields, respectively (Ta-
ble 1, entries 16–18). In addition, when the TBHP and
PhI(OAc)2 were used as radical initiator but no desired 3aa
was isolated (Table 1, entries 19 and 20). It is noteworthy
that the reaction shows excellent stereospecificity and the Z
Table 1 Optimization of the Reaction Conditionsa
OH
OH
NO2
+
radical initiator
catalyst
(E)
H
(E)
3aa
1a
2a
Entry
Catalyst
–
Oxidant (equiv)
Yield (%)b
1
2
DTBP (2)
DTBP (2)
DTBP (2)
DTBP (2)
DTBP (2)
DTBP (2)
DTBP (2)
DTBP (2)
DTBP (2)
DTBP (1)
DTBP (4)
DTBP (2)
DTBP (2)
DTBP (2)
DTBP (2)
DCP (2)
12
Cu(OAc)2
CuO
83
3
72
4
Cu2O
76
5
Cu
79
6
Cu(OAc)2
Cu(OAc)2
Pd(OAc)2
Fe(acac)3
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
66
7
82
8
38
9
46
10
11
12
13
14
15
16
17
18
19
20
72
77
61c
<5d
81e
80f
71
BPO (2)
54
AIBN (2)
TBHP
61
n.r.g
n.r.g
PhI(OAc)2
a Reaction conditions: β-nitrostyrene (0.5 mmol), i-PrOH (3.0 mL), catalyst
(2.0 mol%), oxidant (2.0 equiv) at 100 °C under an argon atmosphere for 6
h.
b Isolated yield.
c At 120 °C.
1
isomer was not observed according to the GC–MS and H
NMR spectra.
d At 90 °C.
e Using 10 equiv i-PrOH in 3 mL DCE.
f Using 10 equiv i-PrOH in 3 mL MeCN.
g Not detected by GC–MS.
With the optimized conditions in hand, the substrate
scope of (E)-β-nitrostyrenes 1 was investigated, and the
corresponding results are listed in Table 2. The (E)-β-nitro-
styrenes with an electron-rich group on the aromatic ring
reacted smoothly in moderate to good yields (Table 2, en-
tries 1–4), though the di-methyl substituted β-nitrosty-
renes showed relatively lower efficiency (Table 2, entry 5).
Electron-withdrawing substituent on the aromatic ring of
β-nitrostyrenes showed higher efficiency with shorter re-
action time using the same conditions, and good yields
were observed (Table 2, entries 6–9). The bulky (E)-1-(2-ni-
trovinyl) naphthalene was also a good substrate for this
coupling reaction with 78% yield obtained (Table 2, entry
10). It is noteworthy that the heteroaryl β-nitrostyrenes
could also be used as the coupling partners with isopropa-
nol to produce the desired allylic alcohols in moderate
yields under the reaction conditions (Table 2, entries 11 and
12). Furthermore, the (E)-β-nitrostyrenes bearing ortho or
meta substituents on the aromatic ring also afforded the
corresponding products in moderate to good yields (Table 2,
entries 13–17), so the steric-bulk effect on the aromatic
moiety plays little role in yield or efficiency. In contrast, the
electronic and steric effect on the vinyl moiety did affect
the reaction. β-Methyl-β-nitrostyrene only gave the desired
products in poor 32% yield (Table 2, entry 18), and only
trace product was detected by GC–MS when α-trifluoro-
methyl-β-nitrostyrene was used (Table 2, entry19). Unfor-
tunately, no desired products were obtained when reacting
isopropanol with alkyl-substituted β-nitroalkenes such as
1-nitrocyclohex-1-ene and (E)-1-nitrobut-1-ene (Table 2,
entries 20 and 21).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1961–1968

1963
S.-r. Guo, Y.-q. Yuan
Letter
Synlett
Table 2 Scope of the (E)-β-Nitrostyrenes with Isopropanola,b
Table 2 (continued)
Entry
Product 314
Yield (%)
78
NO2
R
(E)
1a–p
OH
OH
10
3aj
Cu(OAc)2 (2 mol%)
+
R
(E)
DTBP (2 equiv)
100 °C, 2–6 h
OH
3aa–ap
OH
OH
H
O
S
11
12
3ak
3al
64
73
2a
Entry
1
Product 314
Yield (%)
83
OH
3aa
OH
13
14
15
16
17
18
3am
3an
3ao
3ap
3aq
3ar
77
81
74
67
78
32
OH
2
3
3ab
3ac
81
72
OH
Br
OH
OH
OH
MeO
MeS
4
5
6
7
3ad
3ae
3af
71
SMe
OH
OH
OH
61
Cl
OH
84c
80c
OH
F
OH
Cl
3ag
CF3
OH
19
20
21
3as
3at
3au
trace
Cl
OH
OH
8
9
3ah
3ai
85c
82c
0
0
F3C
OH
OH
MeO2S
a Reaction conditions: 1a–u (0.5 mmol), 2a (3 mL), heated at 100 °C for
2–6 h with 2 mol% Cu(OAc)2.
b Isolated yield.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1961–1968

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S.-r. Guo, Y.-q. Yuan
Letter
Synlett
We then evaluated the scope of alcohols with (E)-β-ni-
trostyrenes, and the results are summarized in Table 3. Oth-
er secondary alcohols such as 2-butanol and cyclohexanol
were also subjected to the optimized protocol to give the
desired α-alkenylation products in moderate to excellent
yields (Table 3, entries 1–6). Owing to the high boiling point
and steric effect, the cyclohexanol gave only moderate iso-
lated yields (Table 3, entries 5 and 6). Aliphatic primary al-
cohols such as methanol, ethanol, 1-propanol, 1-butanol, 1-
pentanol, and 3-methyl-1-butanol were all effective sub-
strates in this system, and the desired products were also
isolated in moderate to good yields. The electronic effect of
the substituted group on the aromatic ring of β-nitrosty-
renes was similar to isopropanol. Increasing aliphatic alco-
hol chain length had no effect on the isolated yield. Only
methanol gave the desired product in moderate yield (Table
3, entries 7 and 8). The products can be also obtained in
moderate yield when using ethanol with some low-reactiv-
ity β-nitrostyrenes (Table 3, entries 9–12). 1-Pentanol gave
relatively lower yields of the products 3cj (Table 3, entry 16)
and other primary alcohols gave the corresponding prod-
ucts in moderate to good yields (Table 3, entries 13–15, 17,
18). However, allyl alcohol, phenylmethanol, and tert-buta-
nol did not give the desired product.
Under the typical reaction conditions, a number of oth-
er compounds containing C(sp3)–H bonds were also investi-
gated (Table 4). It was found that toluene and its derivatives
such as ethylbenzene, p-xylene, m-xylene, o-xylene, and
mesitylene all worked well and were effectively converted
into the corresponding (E)-β-alkylstyrenes in good to excel-
lent yields (Table 4, entries 1–6). The reaction of xylenes
and mesitylene with (E)-β-nitrostyrenes only yielded its
monocoupling products without affecting the other methyl
groups. Furthermore, this radical addition–nitro-elimina-
tion reaction could be applied to inert cycloalkanes such as
cyclooctane, norbornane, and adamantine and gave the cor-
responding products in good yield (Table 4, entries 7–9). In
the case of norbornane and adamantine, it is not the meth-
ylene group but the methine group that was selectively
alkenylated by β-nitrostyrenes.
Table 3 Cu(OAc)2-Catalyzed Alkenylation of Alcohols with Various (E)-
β-Nitrostyrenesa–c
NO2
R1
OH
1
R2
R3
Cu(OAc)2 (2 mol%)
R1
+
DTBP (2 equiv)
100 °C, 6–12 h
OH
3
R2
R3
H
2
Entry
1
Product 3
Yield (%)
85
OH
3ba
OH
2
3
4
3bb
3bc
3bd
87
84
86
F
OH
OH
SMe
5
6
3be
3bf
78
75
OH
Cl
OH
OH
7
8
3ca
3cb
65
75
Cl
OH
OH
9
3cc
82
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1961–1968

1965
S.-r. Guo, Y.-q. Yuan
Letter
Synlett
Table 3 (continued)
Table 4 Alkenylation of Toluene Derivatives and Alkanes with (E)-β-Ni-
trostyrenes Catalyzed by Cu(OAc)2
a,b
Entry
10
Product 3
Yield (%)
78
Entry
1
Product 3
Yield (%)
84
OH
MeO
MeO
Ph
Ph
3cd
3da
OMe
OH
2
3db
82
11
12
3ce
3cf
64
73
3
4
3dc
3dd
85
83
OH
S
OH
13
14
15
3cg
3ch
3ci
77
81
74
5
6
3de
3df
80
81
F3C
OH
OH
7
3fa
86
F
OH
OH
OH
16
3cj
67
8
9
3fb
3fc
78
81
F
17
18
3ck
3cl
78
75
Cl
a Reaction conditions: 1a (0.5 mmol), toluene derivatives and alkanes (5
equiv), DCE (3 mL) heated at 100 °C for 2–6 h with 2 mol% Cu(OAc)2.
b Isolated yield.
a Reaction conditions: 1 (0.5 mmol), 2 (3 mL) heated at 100 °C for 2–8 h
with 2 mol% Cu(OAc)2.
tions the product of 3ac could finish an elimination reac-
tion giving the desired 1,3-diene compound of 4a in excel-
lent yield at room temperature (Scheme 2).
b Reaction conditions: 1 (0.5 mmol), 2 (for cyclohexanol, 1-pentanol, and
3-methyl-1-butanol, 10 equiv), DCE (3 mL) heated at 100 °C for 6–12 h
with 2 mol% Cu(OAc)2.
c Isolated yield.
OH
Interestingly, the products of tertiary alcohol could be
further functionalized. It was found the 1,3-diene deriva-
tives, which are important materials in organic synthesis,
could be obtained easily.12 For example, under acidic condi-
AcOH (5 mol%)
DCE, r.t., 2 h
MeX
MeX
3ac X = O
3ad X = S
4a X = O 98%
4b X = S 98%
X = O, S
Scheme 2 Further synthetic functionalization of 3ac and 3ad
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1961–1968

1966
S.-r. Guo, Y.-q. Yuan
Letter
Synlett
OH
(a)
OH
3cm
major, 90%
OH
H
NO2
+
Cu(OAc)2 (2 mol%)
DTBP (2 equiv)
100 °C, 12 h
OH
3ab
H
minor, 10%
OH
HO
(b)
3cn
H
H
NO2
major, 95%
OH
Cu(OAc)2 (2 mol%)
+
DTBP (2 equiv)
100 °C, 12 h
HO
3cm
minor, 5%
Scheme 3 Intermolecular competition reaction
Interestingly, comparing with primary alcohols, the
yields of isomeric second alcohols were higher (Table 2 and
Table 3, e.g., 3ah vs. 3cg and 3bb vs. 3ci). Despite the higher
yields seen with secondary alcohols, while in competitive
reactions, the reactivity of the C(sp3)–H bonds of primary
alcohols was found to be higher than that for secondary al-
cohols. The higher reactivity may be due to steric or elec-
tronic factors of the corresponding carbon-centered radical
(Scheme 3, a and b).
To investigate the mechanism of this copper(II)-cata-
lyzed alkenylation, some control experiments were carried
out. It is believed to proceed via a similar radical addition–
elimination process to that proposed by Liu,5 Yao,11 and
(a)
OH
Cu(OAc)2 (2 mol%)
DTBP (2 equiv)
OH
NO2
+
H
3aa
TEMPO (2 equiv)
100 °C, 12 h
(0.25 mmol)
trace
(b)
(c)
DTBP (2 equiv)
NO2
Cu(OAc)2 (2 mol%)
DCE (3 mL), 100 °C, 6 h,
without alcohol
(0.5 mmol)
25% yield (GC–MS)
OH
OH
Cu(OAc)2 (2 mol%)
DTBP (2 equiv)
NO2
H
D
3ab
(1mL)
OD
OD
+
100 °C, 12 h
CD3
CD3
(0.25 mmol)
CD3
CD3
KH/KD = 4.8
3ab'
(1 mL)
(d)
OH
OH
Cu(OAc)2 (2 mol%)
(Z)
+
NO2
(0.25 mmol)
(E)
H
3aa
DTBP (2 equiv)
100 °C, 12 h
80% yield
Scheme 4 Investigation into the reaction mechanism
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1961–1968

1967
S.-r. Guo, Y.-q. Yuan
Letter
Synlett
Fuchs.13 When the radical scavenger TEMPO was added into
the reaction system, no product was obtained, which indi-
cates that the transformation may proceed via a radical pro-
cess (Scheme 4, a). In the absence of alcohol, only denitro
methylation product was obtained and the self-coupling of
β-nitrostyrenes was not observed, which suggested that the
styrene radical is not formed in the reaction system
(Scheme 4, b). Moreover, an intermolecular kinetic isotope
effect (KIE) experiment was carried out for isopropanol,
and a significant KIE value of kH/kD = 4.8 was observed
(Scheme 4, c). It indicates that the rate-determining step of
the sp3 C–H bond cleavage should be involved in this proce-
dure. Interestingly, (Z)-1a was used to react with 2a under
the optimized conditions, the same product (E)-3aa was
also obtained in 80% yield (Scheme 4, d).
via activation of the C(sp3)–H bond in this work might be
novel and attractive in radical chemistry. The alkyl-substi-
tuted β-nitroalkenes are not suitable to this protocol, and
the β-alkyl-substituted β-nitrostyrenes gave the desired
products in low yield, which limits the scope of application.
Further investigation of this procedure, including extension
of the substrate scope and catalytic cycle, is under way in
our laboratory.
Acknowledgment
This work was supported by Normal Foundation of Zhejiang Educa-
tion Department (No.Y201329988), Research on Public Welfare Tech-
nology Application Projects of Lishui, China (2014GYX049), and NSFC
of China (No. 21276068).
Based on the above results and similar reported litera-
ture,7–9,11 a plausible radical addition–elimination mecha-
nism is illustrated in Scheme 5. First, homolytic cleavage of
DTBP gives the tert-butoxy radical catalyzed by Cu(OAc)2,
which abstracts the α-hydrogen of isopropanol to form an
α-carbon-centered radical. Then, addition of the α-carbon-
centered radical to the β-position of the double bond would
give a benzylic intermediate. Finally, under the help of hy-
pervalent copper complex which may be formed in the re-
action process, the more stable E-allylic alcohols were
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380445.
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References and Notes
(1) (a) Minisci, F.; Citterio, A.; Vismara, E. Tetrahedron 1985, 41,
4157. (b) Minisci, F.; Vismara, A.; Fontana, F.; Morini, G.;
Serravalle, M. J. Org. Chem. 1986, 51, 476. (c) Coppa, F.; Fontana,
F.; Lazzarini, E.; Minisci, F.; Pianese, G.; Zhao, L. Chem. Lett.
1992, 1295. (d) Fontana, F.; Minisci, F.; Yan, Y. M.; Zhao, L. Tetra-
hedron Lett. 1993, 34, 2517.
(2) Correia, C. A.; Yang, L.; Li, C.-J. Org. Lett. 2011, 13, 4581.
(3) (a) Shi, L.; Tu, Y.-Q.; Wang, M.; Zhang, F.-M.; Fan, C.-A.; Zhao, Y.-
M.; Xia, W.-J. J. Am. Chem. Soc. 2005, 127, 10836. (b) Jiang, Y.-J.;
Tu, Y.-Q.; Zhang, E.; Zhang, S.-Y.; Cao, K.; Shi, L. Adv. Synth. Catal.
2008, 350, 552. (c) Zhang, S.-Y.; Tu, Y.-Q.; Fan, C.-A.; Jiang, Y.-J.;
Shi, L.; Cao, K.; Zhang, E. Chem. Eur. J. 2008, 14, 10201. (d) Zhang,
S.-Y.; Tu, Y.-Q.; Fan, C.-A.; Zhang, F.-M.; Shi, L. Angew. Chem. Int.
Ed. 2009, 48, 8761.
(4) (a) Oka, R.; Nakayama, M.; Sakaguchi, S.; Ishii, Y. Chem. Lett.
2006, 35, 1104. (b) Liu, Z.-Q.; Sun, L.; Wang, J.-G.; Han, J.; Zhao,
Y.-K.; Zhou, B. Org. Lett. 2009, 11, 1437.
(5) Cui, Z.; Shang, X.; Shao, X.-F.; Liu, Z.-Q. Chem. Sci. 2012, 3, 2853.
(6) Zhao, Z.; Xue, W.; Gao, Y.; Tang, G.; Zhao, Y. Chem. Asian J. 2013,
8, 713.
•
achieved via a rapid elimination of the NO2 radical. Unfor-
tunately, the exact role of copper salts and how it catalyzes
this transformation is still unclear, but it should be noted
that the reaction did not work well in the absence of the
copper catalyst.
Cu(OAc)2
O
O
+
•
O
+
OH
OH
•
t-BuOH
•
O
rate-determining
fast
OH
OH
•
NO2
OH
+
Ar
•
Ar
NO2
(7) (a) Meng, Y.; Guo, L.-N.; Wang, H.; Duan, X.-H. Chem. Commun.
2013, 49, 7540. (b) Liu, Z.-Q.; Sun, L.; Wang, J.-G.; Han, J.; Zhao,
Y.-K.; Zhou, B. Org. Lett. 2009, 11, 1437. (c) He, T.; Yu, L.; Zhang,
L.; Wang, L.; Wang, M. Org. Lett. 2011, 13, 5016.
OH
•
•
– NO2
Ar
Ar
fast
NO2
(8) (a) Liu, C.; Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780.
(b) Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M.
C. Chem. Rev. 2013, 113, 6234. (c) Bellina, F.; Rossi, R. Chem. Rev.
2010, 110, 3850. (d) Sun, C. L.; Li, B. J.; Shi, Z. J. Chem. Rev. 2011,
111, 1293. (e) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.;
Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890. (f) Cho, S.
H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068.
(g) Ramirez, T. A.; Zhao, B.; Shi, Y. Chem. Soc. Rev. 2012, 41, 931.
(h) Shen, C.; Zhang, P.; Sun, Q.; Bai, S.; Andy, T. S.; Liu, X. Chem.
Soc. Rev. 2015, 44, 291. (i) Che, C.-M.; Lo, V. K.; Zhou, C.-Y.;
Huang, J.-S. Chem. Soc. Rev. 2011, 40, 1950. (j) Zhang, S.-Y.;
Scheme 5 A possible mechanism
In summary, this work demonstrates a novel copper(II)-
promoted approach for the stereospecific synthesis of allyl-
ic alcohols through the denitro coupling reaction of β-nitro-
styrenes with alcohols. Various substituted β-nitrostyrenes
were shown to proceed readily via the radical addition and
nitro-elimination mechanism. In addition, compared with
the traditional method to synthesize the (E)-β-alkylsty-
renes and its derivatives, the direct C–C bond construction
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1961–1968

1968
S.-r. Guo, Y.-q. Yuan
Letter
Synlett
Zhang, F.-M.; Tu, Y.-Q. Chem. Soc. Rev. 2011, 40, 1937.
(k) Campos, K. R. Chem. Soc. Rev. 2007, 36, 1069. (l) Tang, S.; Liu,
K.; Liu, C.; Lei, A. Chem. Soc. Rev. 2015, 44, 1070.
dron Lett. 2001, 42, 3613. (g) Liu, J. T.; Yao, C. F. Tetrahedron Lett.
2001, 42, 6147. (h) Jang, Y.-J.; Wu, J. Y.; Lin, Y.-F.; Yao, C.-F. Tetra-
hedron 2004, 60, 6565. (i) Ouvry, G.; Quiclet, B.; Zard, S. Z. Org.
Lett. 2003, 5, 2907.
(9) (a) Stowers, K. J.; Fortner, K. C.; Sanford, M. S. J. Am. Chem. Soc.
2011, 133, 6541. (b) Wei, W.-T.; Zhou, M.-B.; Fan, J.-H.; Liu, W.;
Song, R.-J.; Liu, Y.; Hu, M.; Xie, P.; Li, J.-H. Angew. Chem. Int. Ed.
2013, 52, 3638. (c) Li, Z.; Fan, F.; Yang, J.; Liu, Z.-Q. Org. Lett.
2014, 16, 3396. (d) Cai, S.; Chen, C.; Shao, P.; Xi, C. Org. Lett.
2014, 16, 3142. (e) Li, Z.; Zhang, Y.; Zhang, L.; Liu, Z.-Q. Org. Lett.
2014, 16, 382. (f) Tsuchikama, K.; Kasagawa, M.; Endo, K.;
Shibata, T. Org. Lett. 2009, 11, 1821.
(10) (a) Graaff, C.; Ruijter, E.; Romano, V. A. Chem. Soc. Rev. 2012, 41,
3969. (b) Yan, G.; Borah, A. J.; Wang, L. Org. Biomol. Chem. 2014,
12, 6049. (c) Lancianesi, S.; Palmieri, A.; Petrini, M. Chem. Rev.
2014, 114, 7108. (d) Volla, C. M. R.; Atodiresei, I.; Rueping, M.
Chem. Rev. 2014, 114, 2390. (e) Li, G. X.; Wu, L.; Lv, G.; Liu, H. X.;
Fu, Q. Q.; Zhang, X. M.; Tang, Z. Chem. Commun. 2014, 50, 6246.
(f) Ge, X.; Hoang, K. L. M.; Leow, M. L.; Liu, X. W. RSC Adv. 2014,
4, 45191. (g) Garcia-Torres, A.; Cruz-Almanza, R.; Miranda, L. D.
Tetrahedron Lett. 2004, 45, 2085.
(12) Soriano, E.; Fernandez, I. Chem. Soc. Rev. 2014, 43, 3041.
(13) (a) Gong, J.; Fuchs, P. L. J. Am. Chem. Soc. 1996, 118, 4486.
(b) Xiang, J.; Fuchs, P. L. J. Am. Chem. Soc. 1996, 118, 11986.
(c) Xiang, J.; Jiang, W.; Gong, J.; Fuchs, P. L. J. Am. Chem. Soc.
1997, 119, 4123.
(14) Typical Procedure
To a Schlenk tube equipped with a magnetic stir bar were
added, under argon, β-nitrostyrene (0.5 mmol) and Cu(OAc)2
(0.01 mmol). Under argon, isopropanol (3.0 mL) and di-tert-
butyl peroxide (DTBP, 1 mmol) were added. The resulting reac-
tion mixture was kept stirring at the required temperature for
2–6 h. After the required reaction time, the mixture was cooled
down to r.t. Evaporation of the solvent followed by purification
by flash chromatography (PE–EtOAc = 5:1) afforded the corre-
sponding product 3aa in 83% yield.
(E)-2-Methyl-4-phenylbut-3-en-2-ol (3aa)
(11) (a) Jang, Y.-J.; Shih, Y.-K.; Liu, J.-Y.; Kuo, W.-Y.; Yao, C.-F. Chem.
Eur. J. 2003, 9, 2123. (b) Liu, J.-T.; Jang, Y.-J.; Shih, Y.-K.; Hu, S.-R.;
Chu, C.-M.; Yao, C.-F. J. Org. Chem. 2001, 66, 6021. (c) Jang, Y.-J.;
Yan, M.-C.; Lin, Y.-F.; Yao, C.-F. J. Org. Chem. 2004, 69, 3961.
(d) Yao, C.-F.; Chu, C.-M.; Liu, J.-T. J. Org. Chem. 1998, 63, 719.
(e) Chu, C.-M.; Liu, J.-T.; Lin, W.-W.; Yao, C.-F. J. Chem. Soc.,
Perkin Trans. 1 1999, 47. (f) Liu, J. Y.; Liu, J. T.; Yao, C. F. Tetrahe-
Colorless oil. 1H NMR (300 MHz, CDCl3): δ = 7.39 (dd, J = 8.2, 1.3
Hz, 2 H), 7.35–7.28 (m, 2 H), 7.25 (dd, J = 5.9, 4.2 Hz, 1 H), 6.60
(d, J = 16.1 Hz, 1 H), 6.36 (d, J = 16.1 Hz, 1 H), 1.64 (s, 1 H), 1.43
(s, 6 H). 13C NMR (75 MHz, CDCl3): δ = 137.59, 131.75, 128.60,
127.47, 126.46, 117.31, 71.10, 29.95. HRMS (TOF, EI+): m/z calcd
for C11H14O: 162.1045; found: 162.1044.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1961–1968