Copper-catalyzed regioselective cross-dehydrogenative coupling of coumarins with benzylic Csp3-H bonds

Article abstract of DOI:10.1002/ejoc.201403068

A new copper-catalyzed regioselective cross-dehydrogenative coupling of coumarins with benzylic C_sp3-H bonds has been developed. This reaction provides direct access to a wide range of 3-benzylcoumarins in moderate to good yields. The protocol was also extended successfully to other heterocyclic compounds, such as quinolinones.

Full text of DOI:10.1002/ejoc.201403068

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FULL PAPER
DOI: 10.1002/ejoc.201403068
Copper-Catalyzed Regioselective Cross-Dehydrogenative Coupling of
Coumarins with Benzylic Csp3–H Bonds
Shi-Liu Zhou,[a] Li-Na Guo,[a] and Xin-Hua Duan*[a]
Keywords: Copper / C–C coupling / Benzylation / Coumarins / Quinolinones / Radical reactions
A
new copper-catalyzed regioselective cross-dehydro-
a wide range of 3-benzylcoumarins in moderate to good
yields. The protocol was also extended successfully to other
heterocyclic compounds, such as quinolinones.
genative coupling of coumarins with benzylic Csp3–H bonds
has been developed. This reaction provides direct access to
scarcely described in the literature.[1,2] Recently, we and
Introduction
others
have
developed
metal-catalyzed
cross-de-
Cross-dehydrogenative coupling (CDC) between two dif-
ferent partners with C–H bonds has received much atten-
tion and has become an attractive strategy in modern or-
ganic synthesis.[1] In the past decade, a number of metal-
free or metal-promoted protocols for carbon–carbon bond
formation with different C–H bonds have been reported in
the literature.[1] In this context, the more challenging pro-
cesses involving direct coupling of Csp3–H bonds with other
C–H bonds have also been explored.[2] For example, a vari-
hydrogenative coupling/cyclization of activated alkenes with
benzylic C–H bonds for the synthesis of heterocycles.[6] At-
tracted by the results of the highly regioselective benz-
ylation of alkenes with benzyl radicals,[6a,6d] we envisioned
that this radical process might be an ideal alternative strat-
egy for the regioselective benzylation at C-3 or C-4 of cou-
marins. Herein we report a novel copper-catalyzed regiose-
lective 3-benzylation of coumarins via the direct intermo-
lecular cross-dehydrogenative coupling of a benzylic Csp3
H bond and the alkenyl Csp2–H bond of coumarin.
–
ety of reactions with respect to the catalytic conversion of
[3c]
benzylic C–H bonds to Csp3–Csp,[3a,3b] Csp3–Csp2
and
[3d–3i]
C
sp3–Csp3
bonds have been developed. Although there
have been significant advances in direct dehydrogenative
coupling of Csp3–H bonds, the development of regioselec-
tive cross-dehydrogenative Csp3–C bond forming reactions
involving benzylic C–H bonds are still rare.[1]
Results and Discussion
We initially investigated the reaction of coumarin 1a with
toluene 2a using different metal catalysts and oxidants at
120 °C for 24 h (for details, see Supporting Information).
Notably, the reaction shows excellent regioselectivity, and
the 3-benzylcoumarin 3a was observed as the sole product
in all cases (Table 1). As shown in Table 1, the best yield
was obtained using 5 mol-% of Cu2O as a catalyst and
2 equiv. of tert-butylperoxy benzoate (TBPB) as the oxi-
dant. Other peroxides were less efficient (Entries 1–3).
Among several copper salts so far screened, Cu(OAc)2 ap-
peared to be the most effective one (Entries 4–6). Iron cata-
lysts, such as Fe(OAc)2 were also efficient for this reaction,
albeit in low yields (Entry 7). When the reaction was carried
out at 100 °C, the yield of 3a was improved to 76% (En-
try 8), but only a trace amount of the desired product 3a
was detected at 80 °C. It should be noted that decreasing
the catalyst loading to 2.5 mol-% or increasing to 10 mol-
% did not significantly affect the yield of 3a (Entries 9 and
10). However, only 15% yield of 3a was obtained without
catalyst (Entry 11). We also found that no reaction took
place in the absence of TBPB, which suggested that perox-
ide was crucial for this transformation (Entry 12).
Coumarins are an important class of natural products
that display a diverse range of biological activities,[4a–4e] and
they are also widely used in organic materials due to their
good optical properties.[4f–4h] In addition, simple coumarins
have recently been used successfully in transition-metal-cat-
alyzed direct C–H bond activation reactions with different
nucleophiles.[5] For example, the palladium-catalyzed direct
C-4 regioselective arylation of coumarins has been reported
by Jafarpour, Li and Hong using arylboronic acids[5a,5b]
and simple arenes,[5c] respectively. Lately, elegant examples
of catalytic direct C-3 functionalization of coumarins have
also been developed.[5d–5f] However, to the best of our
knowledge, the direct oxidative coupling of coumarins with
reactants containing unactivated Csp3–H bonds has been
[a] Department of Chemistry, School of Science and MOE Key
Laboratory for Nonequilibrium Synthesis and Modulation of
Condensed Matter, Xi’an Jiaotong University,
Xi’an 710049, China
E-mail: duanxh@mail.xjtu.edu.cn
http://gr.xjtu.edu.cn/web/duanxh
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403068.
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S.-L. Zhou, L.-N. Guo, X.-H. Duan
FULL PAPER
Table 1. Optimization of the reaction conditions.[a]
To explore the generality and scope of this de-
hydrogenative coupling reaction, a variety of benzylic hy-
drocarbons and coumarins were tested under the optimized
reaction conditions (Table 2). As shown in Table 2, toluene
derivatives bearing electron-donating or -withdrawing
groups on the para-substituted position afforded the desired
3-benzylcoumarins 3b–g in moderate to good yields with
high regioselectivities. Remarkably, several functional
groups such as halogen, acetyl and cyano group were toler-
ated well under the reaction conditions (giving 3c–g). Grati-
fyingly, in addition to para-substituted toluenes, ortho-sub-
stituted substrates 2h and 2i were also successfully applied
to this transformation (giving 3h and 3i). Furthermore, tol-
uene derivatives containing multiple methyl groups such as
xylenes and mesitylene, gave only the monobenzylation
products (3b, 3h, 3j and 3k). We subsequently investigated
reactions to produce other substituted coumarins (3l–r).
The coumarins containing electron-donating substituents
on the aromatic ring usually gave good yields of the desired
Entry
Catalyst [mol-%] Oxidant [equiv.]
Yield[b] [%]
1
Cu2O (5)
TBPB (2)
TBHP (2)
DTBP (2)
TBPB (2)
TBPB (2)
TBPB (2)
TBPB (2)
TBPB (2)
TBPB (2)
TBPB (2)
TBPB (2)
–
52
17
2
Cu2O (5)
3
Cu2O (5)
CuCl (5)
Cu(OAc)2 (5)
CuBr2 (5)
21
4
63
5
70
6
52
7
Fe(OAc)2 (5)
Cu(OAc)2 (5)
Cu(OAc)2 (2.5)
Cu(OAc)2 (10)
–
44
8
76[c] (80)[d]
69[c]
72[c]
15[c]
n.r.[c,e]
9
10
11
12
Cu(OAc)2 (5)
[a] Reaction conditions: 5 mol-% catalyst, 1a (0.2 mmol, 1 equiv.),
oxidant (2 equiv.), toluene (1 mL), 120 °C, 24 h. [b] Yield of iso-
lated product. [c] At 100 °C. [d] Yield on a 1 mmol scale is given
in parentheses. [e] n.r. = no reaction.
Table 2. Scope of coumarins and benzylic hydrocarbons.[a]
[a] Reaction conditions: 5 mol-% Cu(OAc)2, 1 (0.2 mmol, 1 equiv.), TBPB (2 equiv.), 2 (1 mL), 100 °C, 24 h. [b] 0.5 mL of 2e and 2f were used.
2
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Copper-Catalyzed Coupling of Coumarins with Benzylic Csp3–H Bonds
products (3l, 3n, 3p and 3q). In contrast, electron-with- Table 4. Dehydrogenative coupling of heterocyclic compounds with
toluene 2a.[a]
drawing groups led to lower yields (3m, 3o, 3r). Moreover,
some ortho-methyl-substituted coumarins also showed good
reactivities, affording the corresponding products 3l, 3p and
3q in good yields. These results suggest that the electronic
effects of substituents on the phenyl ring exerts a significant
effect on the reactivity of the coumarins. Unfortunately,
when ethylbenzene was employed as a substrate, only a
trace amount of the product 3s was detected.
It is noteworthy that this reaction could also be extended
to other types of unactivated Csp3–H bonds (Table 3). For
example, alcohols or ethers also led to the corresponding
C-3 substituted coumarins 4 under the standard conditions,
albeit with low yields due to the low conversion of 1a
(Table 3, compounds 4a–d).[7] Importantly, the oxidative
coupling reaction could also be applied to simple alkanes.
Treatment of cyclohexane with 1a furnished the 3-cyclohex-
ylcoumarin 4e in 48% isolated yield. However, no desired
product 4f was observed when cyclohexene was used. In
[a] Reaction conditions: 5 mol-% Cu(OAc)2, heterocycles
(0.2 mmol, 1 equiv.), TBPB (2 equiv.), 2a (1 mL), 100 °C, 24 h.
this case, the corresponding 2-cyclohexenyl benzoate (4fЈ)
was isolated as the major product, which was formed by
the direct coupling of TBPB with cyclohexene.[8]
Finally, some control experiments have been performed
to gain insights into the mechanism of the reaction. When
radical-trapping reagents, such as TEMPO or BHT were
added, the reaction of 1a with 2a was completely sup-
pressed (Scheme 1). Furthermore, an additional competitive
experiment involving a 1:1 mixture of 2a/D8-2a was also
carried out under the standard conditions, and an intermo-
lecular kinetic isotope effect (KIE, kH/kD = 2.2) was ob-
tained (Scheme 2). However, the kinetic isotope effect (KIE
= 0.71) determined by the comparison of rates of two inde-
pendent reactions with toluene or [D8]toluene as the sub-
strate indicated that the cleavage of the benzyl C–H bond
is not a rate-determining step.[9] Based on the above results
and the previous reports, we proposed that the reaction
probably proceeds by a radical pathway (Scheme 3).[3,6] Ini-
tially, a tert-butoxyl radical could be generated by homoly-
sis of TBPB or single-electron transfer of the CuI complex
to TBPB. The tert-butoxyl radical then abstracts a hydrogen
atom from toluene to afford the benzyl radical 2aЈ, which
selectively adds to the double bond of the coumarin 1a to
give the more stable radical intermediate II.[10] Finally, the
single-electron oxidation of radical II by CuII leads to the
corresponding benzylic carbocation III, which furnishes the
product 3a by the loss of H+.
Table 3. Dehydrogenative coupling of coumarin 1a with alcohols,
ethers and alkanes.[a]
[a] Reaction conditions: 5 mol-% Cu(OAc)2, 1a (0.2 mmol,
1 equiv.), TBPB (2 equiv.), alcohols/ethers/alkanes (1 mL), 100 °C,
24 h.
Next, we turned our attention to apply this method to
other heterocyclic compounds (Table 4). To our delight, the
reaction of 1-methyl-2-quinolinones with toluene proceeded
smoothly to afford products 5a–c in 66%, 77% and 70%
yields, respectively. Direct benzylation of 2-quinolinones at
the C-3 position were also observed in all cases. In addition,
2-phenyl-4-chromone and 2-methyl-1,4-naphthoquinone
were also suitable substrates for this transformation (5d and
5e). However, no reaction occurred for 1-methyl-4-quinol-
inone (5f).
Scheme 1. Control experiments.
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S.-L. Zhou, L.-N. Guo, X.-H. Duan
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Scheme 2. Kinetic isotope effect experiments.
of the reaction, the mixture was diluted with EtOAc. The solvent
was then removed under vacuum. The residue was purified by
chromatography on silica gel (gradient eluent of EtOAc/petroleum
ether, 1:15 to 1:5) to give the corresponding products 3 in yields
listed in Table 2.
3-Benzylchromen-2-one (3a): White solid (35.9 mg, 76%),[11a] Rf =
1
0.5 (EtOAc/petroleum ether, 1:5). H NMR (400 MHz, CDCl3): δ
= 7.48–7.44 (t, J = 7.6 Hz, 1 H), 7.38–7.28 (m, 8 H), 7.24–7.20 (t,
J = 7.6 Hz, 1 H), 3.90 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 161.5, 152.9, 139.2, 137.5, 130.7, 129.3, 129.2, 128.6, 127.3,
126.7, 124.2, 119.3, 116.2, 36.4 ppm.
Scheme 3. Proposed mechanism.
3-(4-Methylbenzyl)chromen-2-one (3b): White solid (37.5 mg,
75%),[11b] Rf = 0.4 (EtOAc/petroleum ether, 1:5). 1H NMR
(400 MHz, CDCl3): δ = 7.47–7.43 (td, J = 7.6, 1.6 Hz, 1 H), 7.36–
7.28 (m, 3 H), 7.24–7.15 (m, 5 H), 3.86 (s, 2 H), 2.36 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 161.7, 153.0, 139.0, 136.3, 134.4,
130.6, 129.6, 129.4, 129.2, 127.3, 124.2, 119.4, 116.3, 36.1,
21.0 ppm.
Conclusions
We have developed a copper-catalyzed direct regioselec-
tive coupling of a benzylic Csp3–H bond and a vinylic Csp2
–
H center of coumarins, providing a convenient method for
the preparation of diverse coumarins benzylated at the 3-
position. The reaction exhibits a broad substrate scope,
wide functional group compatibility and excellent regiose-
lectivity. A reasonable radical mechanism was proposed for
this transformation.
3-(4-Fluorobenzyl)chromen-2-one (3c): White solid (39.1 mg, 77%),
Rf = 0.35 (EtOAc/petroleum ether, 1:5), m.p. 107–109 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.49–7.45 (m, 1 H), 7.39–7.37 (dd, J = 8.0,
1.6 Hz, 1 H), 7.32–7.21 (m, 5 H), 7.05–7.01 (m, 2 H), 3.86 (s, 2 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 161.8 (d, J = 243.6 Hz),
161.5, 153.1, 139.2, 133.3 (d, J = 3.2 Hz), 130.9, 130.8 (d, J =
7.9 Hz), 129.1, 127.4, 124.3, 119.3, 116.4, 115.5 (d, J = 21.2 Hz),
35.8 ppm. IR (KBr): ν
= 1712, 1507, 1221 cm–1. HRMS (ESI):
˜
max
calcd. for C16H11FNaO2 [M + Na]+ 277.0635; found 277.0643.
Experimental Section
3-(4-Chlorobenzyl)chromen-2-one (3d): White solid (43.7 mg,
81%),[11b] Rf = 0.35 (EtOAc/petroleum ether, 1:5). 1H NMR
(400 MHz, CDCl3): δ = 7.49–7.45 (td, J = 8.4, 1.2 Hz, 1 H), 7.39–
7.37 (dd, J = 7.6, 1.2 Hz, 1 H), 7.32–7.30 (m, 4 H), 7.26–7.22 (m,
3 H), 3.86 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.5,
153.1, 139.4, 136.1, 132.7, 130.9, 130.6, 128.9, 128.8, 127.4, 124.3,
119.2, 116.4, 36.0 ppm.
General Information: All reactions were carried out under nitrogen
with strict exclusion of air. Column chromatography was carried
out on silica gel. 1H NMR and 13C NMR spectra were recorded
at 400 MHz and 100 MHz in solvents as indicated. Chemical shifts
are reported in ppm from CDCl3 using TMS as internal standard.
IR spectra were recorded with an FT-IR spectrometer and only
major peaks are reported (in cm–1). HRMS data were obtained
with a Q-TOF micro spectrometer. Melting points were determined
using a microscopic apparatus and were uncorrected. The struc-
tures of known compounds were further corroborated by compar-
ing their NMR spectroscopic data with those found in the litera-
ture.
3-(4-Bromobenzyl)chromen-2-one (3e): White solid (43.3 mg, 69%),
1
Rf = 0.5 (EtOAc/petroleum ether, 1:5), m.p. 130–131 °C. H NMR
(400 MHz, CDCl3): δ = 7.50–7.46 (m, 3 H), 7.39–7.37 (dd, J = 8.0,
1.6 Hz, 1 H), 7.33–7.30 (m, 2 H), 7.24–7.22 (m, 1 H), 7.19–7.17 (d,
J = 8.4 Hz, 2 H), 3.85 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 161.5, 153.1, 139.4, 136.7, 131.8, 131.1, 131.0, 128.8, 127.4,
General Procedure for Cross-Dehydrogenative Coupling of Couma-
rins with Benzylic Csp3–H Bonds: A 10 mL oven-dried Schlenk tube
was charged with Cu(OAc)2 (1.8 mg, 5 mol-%) and coumarin 1
(0.2 mmol, 1.0 equiv.). The tube was evacuated and backfilled with
nitrogen three times. TBPB (0.4 mmol, 2.0 equiv.) in benzylic hy-
drocarbons (1 mL) was added by syringe. The tube was then sealed,
and the mixture was stirred at 100 °C for 24 h. Upon completion
124.4, 120.8, 119.3, 116.5, 36.1 ppm. IR (KBr): ν
= 1701, 1607,
˜
max
1066 cm–1. HRMS (ESI): calcd. for C16H11BrNaO2 [M + Na]+
336.9835; found 336.9836.
3-(4-Acetylbenzyl)chromen-2-one (3f): White solid (37.3 mg, 67%),
Rf = 0.15 (EtOAc/petroleum ether, 1:5), m.p. 120–121 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.95–7.93 (d, J = 8.4 Hz, 2 H), 7.50–7.46
4
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Copper-Catalyzed Coupling of Coumarins with Benzylic Csp3–H Bonds
(td, J = 8.4, 1.2 Hz, 1 H), 7.41–7.37 (m, 3 H), 7.34–7.31 (m, 2 H), (400 MHz, CDCl3): δ = 7.37–7.34 (m, 2 H), 7.31–7.26 (m, 5 H),
7.26–7.22 (t, J = 8.0 Hz, 1 H), 3.95 (s, 2 H), 2.60 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 197.7, 161.4, 153.1, 143.3, 139.7,
135.8, 131.1, 129.5, 128.8, 128.3, 127.4, 124.4, 119.2, 116.5, 36.6,
7.22–7.18 (m, 2 H), 3.87 (s, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 160.9, 153.2, 138.4, 137.2, 136.5, 129.5, 129.4, 128.8,
128.1, 126.9, 124.8, 117.9, 116.7, 36.5 ppm. IR (KBr): νmax = 1727,
˜
26.6 ppm. IR (KBr): ν
= 1702, 1608, 1268, 1055 cm–1. HRMS 1604, 1046, 701 cm–1. HRMS (ESI): calcd. for C16H11ClNaO2 [M
˜
max
(ESI): calcd. for C18H14NaO3 [M + Na]+ 301.0835; found 301.0839.
+ Na]+ 293.0340; 293.0346.
3-Benzyl-6-methylchromen-2-one (3n): White solid (38.0 mg,
76%),[11b] Rf = 0.45 (EtOAc/petroleum ether, 1:5). 1H NMR
(400 MHz, CDCl3): δ = 7.37–7.33 (m, 2 H), 7.29–7.24 (m, 4 H),
7.20–7.18 (m, 2 H), 7.13 (s, 1 H), 3.88 (s, 2 H), 2.35 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 161.8, 151.1, 139.2, 137.7, 133.8,
131.7, 129.3, 129.2, 128.7, 127.2, 126.7, 119.1, 116.0, 36.5,
20.7 ppm.
4-(2-Oxo-2H-chromen-3-ylmethyl)benzonitrile (3g): White solid
(31.3 mg, 60%), Rf = 0.35 (EtOAc/petroleum ether, 1:5), m.p. 175–
177 °C. 1H NMR (400 MHz, CDCl3): δ = 7.62–7.60 (d, J = 8.4 Hz,
2 H), 7.51–7.47 (td, J = 8.4, 1.2 Hz, 1 H), 7.43–7.41 (m, 4 H), 7.32–
7.24 (m, 2 H), 3.94 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 161.2, 153.2, 143.4, 140.0, 132.4, 131.3, 129.9, 127.6, 127.5, 124.5,
119.0, 118.7, 116.5, 110.7, 36.9 ppm. IR (KBr): ν
= 2230, 1708,
˜
max
1607, 1050 cm–1. HRMS (ESI): calcd. for C17H11NNaO2 [M +
Na]+ 284.0682; found 284.0683.
3-Benzyl-6-nitrochromen-2-one (3o): Yellow solid (25.9 mg, 46%),
1
Rf = 0.5 (EtOAc/petroleum ether, 1:5), m.p. 158–160 °C. H NMR
(400 MHz, CDCl3): δ = 8.34–8.29 (m, 2 H), 7.45–7.37 (m, 3 H),
7.33–7.28 (m, 4 H), 3.92 (s, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 160.1, 156.4, 144.0, 137.8, 136.5, 132.1, 129.4, 129.0,
3-(2-Methylbenzyl)chromen-2-one (3h): White solid (31.0 mg, 62%),
Rf = 0.45 (EtOAc/petroleum ether, 1:5), m.p. 93–95 °C. H NMR
(400 MHz, CDCl3): δ = 7.47–7.43 (td, J = 7.6, 1.6 Hz, 1 H), 7.34–
7.28 (m, 2 H), 7.25–7.18 (m, 5 H), 6.99 (s, 1 H), 3.89 (d, J = 0.8 Hz,
2 H), 2.26 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.7,
152.9, 138.5, 136.9, 135.4, 130.7, 130.6, 130.4, 128.5, 127.3, 127.2,
1
127.3, 125.6, 123.2, 119.4, 117.5, 36.6 ppm. IR (KBr): νmax = 1735,
˜
1528, 1342 cm–1. HRMS (ESI): calcd. for C16H11NNaO4 [M +
Na]+ 304.0580; found 304.0582.
3-Benzyl-5,8-dimethylchromen-2-one (3p): White solid (45.4 mg,
86%), Rf = 0.3 (EtOAc/petroleum ether, 1:10), m.p. 93–94 °C. H
126.4, 124.2, 119.3, 116.3, 33.9, 19.3 ppm. IR (KBr): ν
= 1718,
˜
max
1
1609, 1168, 1039 cm–1. HRMS (ESI): calcd. for C17H14NaO2 [M +
Na]+ 273.0886; found 273.0894.
NMR (400 MHz, CDCl3): δ = 7.52 (s, 1 H), 7.33–7.25 (m, 5 H),
7.18–7.16 (d, J = 7.2 Hz, 1 H), 6.95–6.93 (d, J = 7.6 Hz, 1 H), 3.91
(s, 2 H), 2.39 (s, 3 H), 2.36 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 161.7, 151.9, 138.0, 136.7, 132.8, 131.8, 129.1, 128.6,
128.0, 126.7, 125.0, 123.5, 117.8, 36.8, 18.0, 15.3 ppm. IR (KBr):
3-(2-Chlorobenzyl)chromen-2-one (3i): White solid (36.2 mg, 67%),
Rf = 0.4 (EtOAc/petroleum ether, 1:5), m.p. 108–110 °C. H NMR
(400 MHz, CDCl3): δ = 7.48–7.20 (m, 9 H), 4.02 (d, J = 0.8 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.5, 153.0, 139.3,
135.2, 134.5, 131.8, 130.8, 129.8, 128.5, 127.4, 127.2, 127.1, 124.2,
1
ν
= 1719, 1603, 1261, 1170, 1069 cm–1. HRMS (ESI): calcd. for
˜
max
C18H16NaO2 [M + Na]+ 287.1043; found 287.1046.
119.3, 116.4, 34.2 ppm. IR (KBr): ν
= 1720, 1608, 1170, 1045,
˜
max
752 cm–1. HRMS (ESI): calcd. for C16H11ClNaO2 [M + Na]+
3-Benzyl-6,8-dimethylchromen-2-one (3q): White solid (40.7 mg,
77%), Rf = 0.5 (EtOAc/petroleum ether, 1:5), m.p. 77–79 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.36–7.32 (t, J = 7.2 Hz, 2 H), 7.29–
7.25 (m, 3 H), 7.19 (s, 1 H), 7.11 (s, 1 H), 6.95 (s, 1 H), 3.87 (s, 2
H), 2.40 (s, 3 H), 2.30 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 162.0, 149.5, 139.6, 137.8, 133.3, 133.2, 129.3, 128.7, 128.6,
293.0340; found 293.0346.
3-(3-Methylbenzyl)chromen-2-one (3j): White solid (38.0 mg, 76%),
Rf = 0.45 (EtOAc/petroleum ether, 1:5), m.p. 81–83 °C. H NMR
1
(400 MHz, CDCl3): δ = 7.47–7.42 (td, J = 8.4, 1.2 Hz, 1 H), 7.36–
7.34 (dd, J = 8.0, 1.2 Hz, 1 H), 7.31–7.21 (m, 4 H), 7.19–7.08 (m,
3 H), 3.85 (s, 2 H), 2.35 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 161.6, 153.0, 139.2, 138.3, 137.5, 130.7, 130.0, 129.4,
128.6, 127.5, 127.3, 126.3, 124.2, 119.4, 116.3, 36.4, 21.4 ppm. IR
126.7, 125.4, 124.9, 118.8, 36.4, 20.6, 15.3 ppm. IR (KBr): ν
=
˜
max
1717, 1594, 1166, 1052 cm–1. HRMS (ESI): calcd. for C18H16NaO2
[M + Na]+ 287.1042; found 287.1049.
3-Benzyl-6,8-dichlorochromen-2-one (3r): Colorless oil (16.4 mg,
(KBr): ν
= 1721, 1608, 1169, 1050 cm–1. HRMS (ESI): calcd.
˜
max
27%), Rf
=
0.5 (EtOAc/petroleum ether, 1:10). 1H NMR
for C17H14NaO2 [M + Na]+ 273.0886; found 273.0896.
(400 MHz, CDCl3): δ = 7.50–7.49 (d, J = 2.4 Hz, 1 H), 7.38–7.35
(t, J = 7.2 Hz, 2 H), 7.31–7.24 (m, 4 H), 7.14 (s, 1 H), 3.90 (s, 2 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 159.9, 147.3, 137.5, 136.7,
131.8, 130.7, 129.4, 129.3, 128.9, 127.1, 125.2, 122.2, 121.2,
3-(3,5-Dimethylbenzyl)chromen-2-one (3k): White solid (42.3 mg,
80%), Rf = 0.45 (EtOAc/petroleum ether, 1:5), m.p. 97–99 °C. H
1
NMR (400 MHz, CDCl3): δ = 7.48–7.44 (td, J = 8.4, 1.6 Hz, 1 H),
7.39–7.37 (dd, J = 8.0, 1.2 Hz, 1 H), 7.33–7.30 (m, 2 H), 7.25–7.21
(t, J = 7.6 Hz, 1 H), 6.92 (s, 3 H), 3.83 (s, 2 H), 2.32 (s, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 161.7, 153.0, 139.2, 138.2, 137.5,
130.6, 129.5, 128.4, 127.3, 124.2, 119.4, 116.3, 36.3, 21.2 ppm. IR
36.5 ppm. IR (KBr): ν
= 1736, 1632, 1250, 1040, 731 cm–1.
˜
max
HRMS (ESI): calcd. for C16H10Cl2NaO2 [M + Na]+ 326.9950;
found 326.9961.
General Procedure for Cross-Dehydrogenative Coupling of Coumarin
1a with Alcohols, Ethers and Alkanes: A 10 mL oven-dried Schlenk
tube was charged with Cu(OAc)2 (1.8 mg, 5 mol-%) and coumarin
1a (0.2 mmol, 1.0 equiv.). The tube was evacuated and backfilled
with nitrogen three times. TBPB (0.4 mmol, 2.0 equiv.) in alcohols,
ethers or alkanes (1 mL) was added by syringe. The tube was then
sealed, and the mixture was stirred at 100 °C for 24 h. Upon com-
pletion of the reaction, the mixture was diluted with EtOAc. The
solvent was then removed under vacuo. The residue was purified
by column chromatography on silica gel (gradient eluent of EtOAc/
petroleum ether, 1:15 to 1:3) to give the corresponding products 4
in yields listed in Table 3.
(KBr): ν
= 1720, 1607, 1169, 1052 cm–1. HRMS (ESI): calcd.
˜
max
for C18H16NaO2 [M + Na]+ 287.1043; found 287.1050.
3-Benzyl-8-methylchromen-2-one (3l): White solid (36.0 mg, 72%),
Rf = 0.4 (EtOAc/petroleum ether, 1:5), m.p. 59–61 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.37–7.26 (m, 7 H), 7.19–7.18 (d, J =
6.4 Hz, 1 H), 7.13–7.10 (t, J = 7.6 Hz, 1 H), 3.90 (s, 2 H), 2.45 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.8, 151.4, 139.6,
137.8, 132.1, 129.4, 129.0, 128.7, 126.8, 125.9, 125.1, 123.8, 119.1,
36.5, 15.4 ppm. IR (KBr): ν
= 1720, 1607, 1174, 1069 cm–1.
˜
max
HRMS (ESI): calcd. for C17H14NaO2 [M + Na]+ 273.0886; found
273.0889.
3-Benzyl-7-chlorochromen-2-one (3m): White solid (21.1 mg, 39%),
Rf = 0.5 (EtOAc/petroleum ether, 1:5), m.p. 98–100 °C. H NMR
3-(1-Hydroxyethyl)chromen-2-one (4a): Colorless oil (14.8 mg,
39%), Rf = 0.2 (EtOAc/petroleum ether, 1:3). 1H NMR (400 MHz,
1
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O43068
/KAP1
Date: 30-10-14 17:27:32
Pages: 8
S.-L. Zhou, L.-N. Guo, X.-H. Duan
chromatography on silica gel (gradient eluent of EtOAc/petroleum
FULL PAPER
CDCl3): δ = 7.76 (s, 1 H), 7.52–7.48 (m, 2 H), 7.33–7.28 (m, 2 H),
4.95–4.89 (m, 1 H), 3.15–3.13 (d, J = 5.2 Hz, 1 H), 1.55–1.53 (d, J ether, 1:15 to 1:5) to give the corresponding products 5 in yields
= 6.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.2,
listed in Table 4.
153.0, 137.3, 132.0, 131.3, 127.9, 124.6, 119.1, 116.4, 66.0,
3-Benzyl-1-methyl-1H-quinolin-2-one (5a): White solid (32.9 mg,
66%), Rf = 0.5 (EtOAc/petroleum ether, 1:5), m.p. 69–71 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.51–7.47 (t, J = 7.2 Hz, 1 H), 7.44–
7.42 (d, J = 7.6 Hz, 1 H), 7.32–7.30 (m, 6 H), 7.26–7.23 (m, 1 H),
7.19–7.16 (t, J = 7.6 Hz, 1 H), 3.97 (s, 2 H), 3.74 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 162.3, 139.0, 135.7, 133.3, 129.6,
129.4, 128.5, 128.2, 126.3, 121.9, 120.5, 113.8, 37.0, 29.7 ppm. IR
21.8 ppm. IR (KBr): ν
= 3431, 1716, 1610, 1176, 1047 cm–1.
˜
max
HRMS (ESI): calcd. for C11H10NaO3 [M + Na]+ 213.0522; found
213.0525.
3-(1-Hydroxy-1-methylethyl)chromen-2-one (4b): Colorless oil
1
(10.6 mg, 26%), Rf = 0.3 (EtOAc/petroleum ether, 1:3). H NMR
(400 MHz, CDCl3): δ = 7.74 (s, 1 H), 7.55–7.51 (m, 2 H), 7.36–
7.29 (m, 2 H), 4.00 (s, 1 H), 1.65 (s, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 161.4, 153.1, 136.8, 134.2, 131.4, 128.1,
(KBr): ν
= 1645, 1596, 1402 cm–1. HRMS (ESI): calcd. for
˜
max
C17H15NNaO [M + Na]+ 272.1046; found 272.1049.
124.6, 119.1, 116.3, 71.3, 28.5 ppm. IR (KBr): ν
= 3456, 1697,
˜
max
3-Benzyl-1,6-dimethyl-1H-quinolin-2-one (5b): White solid (40.5 mg,
77%), Rf = 0.5 (EtOAc/petroleum ether, 1:5), m.p. 74–76 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.33–7.29 (m, 5 H), 7.25–7.20 (m, 4
H), 3.97 (s, 2 H), 3.73 (s, 3 H), 2.37 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 162.2, 139.2, 137.0, 135.5, 133.3, 131.4,
130.8, 129.4, 128.5, 128.1, 126.3, 120.5, 113.7, 37.0, 29.7, 20.5 ppm.
1611, 1121 cm–1. HRMS (ESI): calcd. for C12H12NaO3 [M + Na]+
227.0679; found 227.0682.
3-[1,4]Dioxan-2-ylchromen-2-one (4c): Colorless oil (13.0 mg, 28%),
Rf = 0.35 (EtOAc/petroleum ether, 1:5). 1H NMR (400 MHz,
CDCl3): δ = 7.88 (s, 1 H), 7.52–7.50 (d, J = 7.6 Hz, 2 H), 7.34–
7.27 (m, 2 H), 4.79–4.77 (d, J = 9.6 Hz, 1 H), 4.28–4.25 (dd, J =
11.2, 2.8 Hz, 1 H), 3.99–3.91 (m, 2 H), 3.84–3.81 (m, 1 H), 3.72–
3.65 (td, J = 10.8, 4.0 Hz, 1 H), 3.27–3.21 (dd, J = 11.2, 10.0 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.9, 153.2, 139.2,
131.5, 128.0, 126.1, 124.5, 119.0, 116.5, 72.7, 71.0, 67.3, 66.4 ppm.
IR (KBr): ν
= 1646, 1235, 1094 cm–1. HRMS (ESI): calcd. for
˜
max
C18H17NNaO [M + Na]+ 286.1202; found 286.1202.
3-Benzyl-1,8-dimethyl-1H-quinolin-2-one (5c): White solid (36.8 mg,
70%), Rf = 0.5 (EtOAc/petroleum ether, 1:5), m.p. 84–86 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.33–7.29 (m, 5 H), 7.26–7.24 (m, 2
H), 7.13 (s, 1 H), 7.02–7.00 (d, J = 8.0 Hz, 1 H), 3.96 (s, 2 H), 3.73
(s, 3 H), 2.48 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
162.4, 140.1, 139.3, 139.1, 135.7, 132.1, 129.4, 128.4, 128.1, 126.3,
IR (KBr): νmax = 1721, 1610, 1117, 1030 cm–1. HRMS (ESI): calcd.
˜
for C13H12NaO4 [M + Na]+ 255.0628; found 255.0636.
3-(Tetrahydrofuran-2-yl)chromen-2-one (4d): Colorless oil (11.2 mg,
123.3, 118.3, 114.1, 37.0, 29.7, 22.2 ppm. IR (KBr): ν
= 1645,
˜
1
max
26%), Rf 0.35 (EtOAc/petroleum ether, 1:5). H NMR (400 MHz,
1606, 1454, 1233 cm–1. HRMS (ESI): calcd. for C18H17NNaO [M
+ Na]+ 286.1202; found 286.1202.
CDCl3): δ = 7.80 (s, 1 H), 7.50–7.46 (m, 2 H), 7.34–7.32 (dd, J =
8.4, 4.0 Hz, 1 H), 7.29–7.25 (m, 1 H), 4.98–4.94 (td, J = 7.2, 1.6 Hz,
1 H), 4.14–4.08 (m, 1 H), 3.98–3.92 (dd, J = 15.2, 7.2 Hz, 1 H),
2.56–2.48 (m, 1 H), 2.07–1.88 (m, 2 H), 1.81–1.72 (m, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 160.5, 153.1, 136.4, 131.0, 130.9,
127.8, 124.4, 119.2, 116.4, 75.9, 68.9, 32.2, 25.6 ppm. IR (KBr):
3-Benzyl-2-phenylchromen-4-one (5d): White solid (21.2 mg, 34%),
1
Rf = 0.35 (EtOAc/petroleum ether, 1:15), m.p. 81–83 °C. H NMR
(400 MHz, CDCl3): δ = 8.28–8.26 (dd, J = 8.0, 1.6 Hz, 1 H), 7.70–
7.66 (td, J = 8.4, 1.6 Hz, 1 H), 7.57–7.45 (m, 6 H), 7.43–7.39 (t, J
= 8.0 Hz, 1 H), 7.24–7.21 (m, 2 H), 7.17–7.12 (m, 3 H), 3.98 (s, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 178.2, 162.9, 156.2,
140.1, 133.5, 133.2, 130.4, 128.6, 128.5, 128.4, 128.1, 126.1, 126.0,
ν
=
1718, 1609, 1047 cm–1. HRMS (ESI): calcd. for
˜
max
C13H12NaO3 [M + Na]+ 239.0679; found 239.0689.
3-Cyclohexylchromen-2-one (4e): White solid (21.9 mg, 48%), Rf =
0.25 (EtOAc/petroleum ether, 1:40), m.p. 72–74 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.47–7.44 (m, 3 H), 7.31–7.23 (m, 2 H),
2.81–2.74 (m, 1 H), 2.00–1.97 (dd, J = 12.8, 1.2 Hz, 2 H), 1.88–
1.83 (dt, J = 16.4, 3.2 Hz, 2 H), 1.80–1.75 (m, 1 H), 1.47–1.39 (m,
2 H), 1.35–1.22 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
161.5, 152.7, 136.3, 134.9, 130.4, 127.3, 124.1, 119.6, 116.3, 38.1,
124.9, 123.0, 120.6, 117.9, 31.2 ppm. IR (KBr): ν
= 1637,
˜
max
1387 cm–1. HRMS (ESI): calcd. for C22H16NaO2 [M + Na]+
335.1043; found 335.1041.
2-Benzyl-3-methyl-[1,4]naphthoquinone (5e): Yellow solid (29.3 mg,
1
56%), Rf = 0.3 (EtOAc/petroleum ether, 1:20), m.p. 76–78 °C. H
NMR (400 MHz, CDCl3): δ = 8.10–8.08 (dd, J = 5.6, 3.2 Hz, 2 H),
7.71–7.69 (dd, J = 5.6, 3.2 Hz, 2 H), 7.27–7.19 (m, 5 H), 4.04 (s, 2
H), 2.25 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 185.4,
184.6, 145.3, 144.4, 138.0, 133.5, 133.4, 132.1, 132.0, 128.6, 128.5,
32.1, 26.5, 26.1 ppm. IR (KBr): ν
= 1715, 1631, 1279 cm–1.
˜
max
HRMS (ESI): calcd. for C15H16NaO2 [M + Na]+ 251.1043; found
251.1043.
126.5, 126.4, 126.3, 32.4, 13.3 ppm. IR (KBr): ν
= 1660,
˜
max
Cyclohex-2-enyl Benzoate (4fЈ): Colorless oil (35.6 mg, 88%),[3] Rf
= 0.3 (EtOAc/petroleum ether, 1:50). 1H NMR (400 MHz, CDCl3):
δ = 8.07–8.05 (d, J = 7.2 Hz, 2 H), 7.56–7.52 (t, J = 7.2 Hz, 1 H),
7.45–7.41 (t, J = 7.2 Hz, 2 H), 6.03–5.98 (m, 1 H), 5.86–5.82 (m, 1
H), 5.52–5.51 (m, 1 H), 2.16–1.94 (m, 3 H), 1.92–1.82 (m, 2 H),
1.73–1.1.67 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.1,
132.8, 132.7, 130.7, 129.5, 128.2, 125.7, 68.5, 28.3, 24.9, 18.9 ppm.
1294 cm–1. HRMS (ESI): calcd. for C18H14NaO2 [M + Na]+
285.0886; found 285.0892.
Supporting Information (see footnote on the first page of this arti-
cle): Investigation of the reaction mechanism and copies of 1H and
13C NMR spectra for all products 3, 4, and 5.
Acknowledgments
General Procedure for Cross-Dehydrogenative Coupling of Heterocy-
clic Compounds with 2a: A 10 mL oven-dried Schlenk tube was
charged with Cu(OAc)2 (1.8 mg, 5 mol-%) and heterocyclic com-
pounds 7 (0.2 mmol, 1.0 equiv.). The tube was evacuated and back-
filled with nitrogen three times. TBPB (0.4 mmol, 2.0 equiv.) in tol-
uene (1 mL) was added by syringe. The tube was then sealed, and
the mixture was stirred at 100 °C for 24 h. Upon completion of the
reaction, the mixture was diluted with EtOAc. The solvent was then
removed under vacuo. The residue was purified by column
Financial support from National Natural Science Foundation of
China (Nos. 21102110, 21102111) and the Fundamental Research
Funds of the Central Universities (Nos. 2012jdhz28, xjj2012100)
are greatly appreciated.
[1] For recent reviews, see: a) C.-J. Li, Z. Li, Pure Appl. Chem.
2006, 78, 935; b) C.-J. Li, Acc. Chem. Res. 2009, 42, 335; c)
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O43068
/KAP1
Date: 30-10-14 17:27:32
Pages: 8
Copper-Catalyzed Coupling of Coumarins with Benzylic Csp3–H Bonds
C. J. Scheuermann, Chem. Asian J. 2010, 5, 436; d) C. S. Yeung,
V. M. Dong, Chem. Rev. 2011, 111, 1215; e) C.-L. Sun, B.-J.
Li, Z.-J. Shi, Chem. Rev. 2011, 111, 1293; f) K. Hirano, M.
Miura, Chem. Commun. 2012, 48, 10704; g) S. I. Kozhushkov,
L. Ackermann, Chem. Sci. 2013, 4, 886.
Dixit, A. Kumar, R. Konwar, A. S. Negi, A. Gupta, Bioorg.
Med. Chem. Lett. 2013, 23, 1322; d) Q. Zou, Y. Fang, Y. Zhao,
H. Zhao, Y. Wang, Y. Gu, F. Wu, J. Med. Chem. 2013, 56,
5288; e) Y. Chen, S. Wang, X. Xu, X. Liu, M. Yu, S. Zhao, S.
Liu, Y. Qiu, T. Zhang, B.-F. Liu, G. Zhang, J. Med. Chem.
2013, 56, 4671; f) A. R. Jagtap, V. S. Satam, R. N. Rajule, V. R.
Kanetkar, Dyes Pigm. 2009, 82, 84; g) C.-H. Chang, H.-C.
Cheng, Y.-J. Lu, K.-C. Tien, H.-W. Lin, C.-L. Lin, C.-J. Yang,
C.-C. Wu, Org. Electron. 2010, 11, 247; h) K. V. Sashidhara,
M. Kumar, V. Khedgikar, P. Kushwaha, R. K. Modukuri, A.
Kumar, J. Gautam, D. Singh, B. Sridhar, R. Trivedi, J. Med.
Chem. 2013, 56, 109.
[2] For recent reviews, see: a) S. A. Girard, T. Knauber, C.-J. Li,
Angew. Chem. Int. Ed. 2014, 53, 74; Angew. Chem. 2014, 126,
76; for recent CDC reactions involving Csp3–H bond adjacent
to a heteroatom, see: b) Z. Li, H. Li, X. Guo, L. Cao, R. Yu,
H. Li, S. Pan, Org. Lett. 2008, 10, 803; c) Y. Shen, M. Li, S.
Wang, T. Zhan, Z. Tan, C.-C. Guo, Chem. Commun. 2009, 953;
d) T. Sugiishi, H. Nakamura, J. Am. Chem. Soc. 2012, 134,
2504; for recent CDC reactions involving Csp3–H bond of al-
kanes, see: e) G. Deng, L. Zhao, C.-J. Li, Angew. Chem. Int.
Ed. 2008, 47, 6278; Angew. Chem. 2008, 120, 6374; f) R. Xia,
H.-Y. Niu, G.-R. Qu, H.-M. Guo, Org. Lett. 2012, 14, 5546; g)
G. Deng, K. Ueda, S. Yanagisawa, K. Itami, C.-J. Li, Chem.
Eur. J. 2009, 15, 333; h) A. P. Antonchick, L. Burgmann, An-
gew. Chem. Int. Ed. 2013, 52, 3267; Angew. Chem. 2013, 125,
3349; for recent CDC reactions involving Csp3–H bond of carb-
onyl compounds, see: i) C. Galli, P. Gentili, O. Lanzalunga,
Angew. Chem. Int. Ed. 2008, 47, 4790; Angew. Chem. 2008, 120,
4868; j) Z. Li, R. Yu, H. Li, Angew. Chem. Int. Ed. 2008, 47,
7497; Angew. Chem. 2008, 120, 7607; k) Á. Pintér, A. Sud, D.
Sureshkumar, M. Klussmann, Angew. Chem. Int. Ed. 2010, 49,
5004; Angew. Chem. 2010, 122, 5124; l) C. He, S. Guo, J. Ke,
J. Hao, H. Xu, H. Chen, A. Lei, J. Am. Chem. Soc. 2012, 134,
5766; m) J. Zhang, B. Tiwari, C. Xing, X. Chen, Y. R. Chi,
Angew. Chem. Int. Ed. 2012, 51, 3649; Angew. Chem. 2012, 124,
3709; n) K. Alagiri, P. Devadig, K. R. Prabhu, Chem. Eur. J.
2012, 18, 5160.
[5]
[6]
a) M. Khoobi, M. Alipour, S. Zarei, F. Jafarpour, A. Shafiee,
Chem. Commun. 2012, 48, 2985; b) Y. Li, Z. Qi, H. Wang, X.
Fu, C. Duan, J. Org. Chem. 2012, 77, 2053; c) M. Min, S.
Hong, Chem. Commun. 2012, 48, 9613; d) M. Min, Y. Kim, S.
Hong, Chem. Commun. 2013, 49, 196; e) X. Mi, M. Huang, J.
Zhang, C. Wang, Y. Wu, Org. Lett. 2013, 15, 6266; f) F. Jafarp-
our, H. Hazrati, N. Mohasselyazdi, M. Khoobi, A. Shafiee,
Chem. Commun. 2013, 49, 10935.
a) S.-L. Zhou, L.-N. Guo, H. Wang, X.-H. Duan, Chem. Eur.
J. 2013, 19, 12970; b) M.-B. Zhou, C.-Y. Wang, R.-J. Song, Y.
Liu, W.-T. Wei, J.-H. Li, Chem. Commun. 2013, 49, 10817; c)
Z. Li, Y. Zhang, L. Zhang, Z.-Q. Liu, Org. Lett. 2014, 16, 382;
d) S.-L. Zhou, L.-N. Guo, S. Wang, X.-H. Duan, Chem. Com-
mun. 2014, 50, 3589.
In fact, a number of catalysts, oxidants and additives have been
screened for the direct coupling of coumarins and alcohols or
ethers. Unfortunately, the yields of desired products 4a–c have
been unsatisfactory so far.
Treatment of coumarin 1a with Cu(OAc)2 (5 mol-%) and TBPB
(2 equiv.) in cyclohexene (1 mL) at 100 °C for 12 h led to the
2-cyclohexenyl benzoate 4fЈ in 88% yield. For the methods for
preparation of allylic esters via acyloxy radicals, see: a) K. No-
zaki, P. D. Bartlett, J. Am. Chem. Soc. 1946, 68, 1686; b) E.
Shi, Y. Shao, S. Chen, H. Hu, Z. Liu, J. Zhang, X. Wang, Org.
Lett. 2012, 14, 3384.
[7]
[8]
[3] a) C. A. Correia, C.-J. Li, Adv. Synth. Catal. 2010, 352, 1446;
b) S.-K. Xiang, B. Zhang, L.-H. Zhang, Y. Cui, N. Jiao, Sci.
China Chem. 2012, 55, 50; c) Y.-Z. Li, B.-J. Li, X.-Y. Lu, S.
Lin, Z.-J. Shi, Angew. Chem. Int. Ed. 2009, 48, 3817; Angew.
Chem. 2009, 121, 3875; d) Z. Li, L. Cao, C.-J. Li, Angew. Chem.
Int. Ed. 2007, 46, 6505; Angew. Chem. 2007, 119, 6625; e) N.
Borduas, D. A. Powell, J. Org. Chem. 2008, 73, 7822; f) S. Lin,
C.-X. Song, G.-X. Cai, W.-H. Wang, Z.-J. Shi, J. Am. Chem.
Soc. 2008, 130, 12901; g) A. J. Young, M. C. White, J. Am.
Chem. Soc. 2008, 130, 14090; h) S. Pan, J. Liu, Y. Li, Z. Li,
Chin. Sci. Bull. 2012, 57, 2382; i) F.-F. Wang, C.-P. Luo, G.
Deng, L. Yang, Green Chem. 2014, 16, 2428; j) S. Guin, S. K.
Rout, A. Banerjee, S. Nandi, B. K. Patel, Org. Lett. 2012, 14,
5294.
[9] E. M. Simmons, J. F. Hartwig, Angew. Chem. Int. Ed. 2012,
51, 3066; Angew. Chem. 2012, 124, 3120. For details, see the
Supporting Information. We gratefully acknowledge valuable
suggestions by the reviewers for the reaction mechanism.
[10] a) P. Zhou, Y.-J. Jiang, J.-P. Zou, W. Zhang, Synthesis 2012, 44,
1043; b) X.-H. Cao, X. Pan, P.-J. Zhou, J.-P. Zou, O. T. Asekun,
Chem. Commun. 2014, 50, 3359.
[11] a) V. Rempel, N. Volz, F. Gläser, M. Nieger, S. Bräse, C. E.
Müller, J. Med. Chem. 2013, 56, 4798; b) Y. Jiang, W. Chen,
W. Lu, RSC Adv. 2012, 2, 1540.
[4] For recent examples, see: a) B. Li, R. Pai, M. Di, D. Aiello,
M. H. Barnes, M. M. Butler, T. F. Tashjian, N. P. Peet, T. L.
Bowlin, D. T. Moir, J. Med. Chem. 2012, 55, 10896; b) P. An-
and, B. Singh, N. Singh, Bioorg. Med. Chem. 2012, 20, 1175;
c) I. Ahmad, J. P. Thakur, D. Chanda, D. Saikia, F. Khan, S.
Received: August 12, 2014
Published Online: ᭿
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Job/Unit: O43068
/KAP1
Date: 30-10-14 17:27:32
Pages: 8
S.-L. Zhou, L.-N. Guo, X.-H. Duan
FULL PAPER
Copper-Catalyzed C–H Coupling
S.-L. Zhou, L.-N. Guo,
X.-H. Duan* ..................................... 1–8
Copper-Catalyzed Regioselective Cross-
Dehydrogenative Coupling of Coumarins
with Benzylic Csp3–H Bonds
An efficient copper-catalyzed regioselective
dehydrogenative benzylation of coumarins
has been developed. Both the quinolinones
and naphthoquinones are also suitable sub-
strates for this transformation. More im-
portantly, the excellent selectivity of the re-
action could be controlled by using a series
of unactivated Csp3–H bonds.
Keywords: Copper / C–C coupling / Benzyl-
ation / Coumarins / Quinolinones / Radical
reactions
8
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