Tunable Phosphine-Triggered Cascade Reactions of MBH Derivatives and 3-Acyl-2H-chromen-2-ones: Highly Selective Synthesis of Diverse Chromenones

Article abstract of DOI:10.1002/ejoc.201301358

Diverse chromenones were synthesized through tunable phosphine-mediated cascade reactions between 3-acyl-2H-chromen-2-ones and Morita-Baylis-Hillman (MBH) derivatives. With different phosphine loadings and reaction temperatures, MBH derivatives act either

Full text of DOI:10.1002/ejoc.201301358

FULL PAPER
DOI: 10.1002/ejoc.201301358
Tunable Phosphine-Triggered Cascade Reactions of MBH Derivatives and 3-
Acyl-2H-chromen-2-ones: Highly Selective Synthesis of Diverse Chromenones
Wei Yuan,[a] Hu-Fei Zheng,[a] Zhi-Hua Yu,[a] Zi-Long Tang,[b] and De-Qing Shi*[a]
Keywords: Cascade reactions / Oxygen heterocycles / Fused-ring systems / Phosphanes / Molecular diversity
Diverse chromenones were synthesized through tunable
phosphine-mediated cascade reactions between 3-acyl-2H-
chromen-2-ones and Morita–Baylis–Hillman (MBH) deriva-
tives. With different phosphine loadings and reaction tem-
peratures, MBH derivatives act either as C1 or C3 synthons
for the construction of potential biologically active 3-di-
hydrofuran-fused chromen-2-ones, 4-allyl-3-acyl-chromen-
2-ones, or 6H-benzo[c]chromen-6-ones. This method has the
advantages of mild conditions, simple workup, and wide sub-
strate scope, which make it powerful for the synthesis of di-
verse chromenone derivatives.
phosphines were used, MBH derivatives acted C3 synthons
and biaryls were obtained (Scheme 1A).
Introduction
In 2012 we reported a catalyst-based controllable pro-
cedure that permitted selection between [4+2] or [3+2]
cycloadditions between 3-acyl-2H-chromen-2-ones and
ethyl buta-2,3-dienoate (Scheme 1, B) catalyzed either by
DABCO or by Bu3P, in which ethyl buta-2,3-dienoate
served as a C2 or a C3 synthon, respectively.[6c] Because of
their convenient availability and versatile reactivity patterns,
MBH derivatives have been used as 1,3-zwitterionic C3 or
C1 synthons in phosphine-mediated [3+n] and [1+n] annu-
lations[7] or applied in the synthesis of natural products.[8]
As part of our ongoing interest in developing concise, con-
venient, and environmentally benign methods for the syn-
thesis of important biologically active heterocycles, we now
wish to report highly selective phosphine-triggered cascade
annulations between MBH derivatives and 3-acyl-2H-
chromen-2-ones (Scheme 1, C) to afford structurally diverse
chromenone derivatives.
Chromenone derivatives receive continuing attention due
to their versatile pharmaceutical activities[1] as, for example,
anticancer,[1a,1b] antimicrobial,[1c,1d] and antiinflammato-
ry[1e] agents, selective human dopamine D4 antagonists,[1f]
lipid peroxidation agents,[1g] and aromatase,[1i] monoamine
oxidase,[1j] and acetylcholinesterase inhibitors.[1k,1l] Re-
cently, nucleophilic phosphine-catalyzed organic reactions
in the construction of complicated cyclic compounds or
natural product skeletons have attracted the interest of or-
ganic chemists.[2] Phosphine-catalyzed cascade annulation
processes involving allenoates or Morita–Baylis–Hillman
(MBH) derivatives have been well documented.[3] Tunable
organic reactions for selective synthesis of different prod-
ucts from the same starting materials represent a great and
challenging goal for organic chemists.[4] Most such reac-
tions involve transition-metal catalysts,[5] however, and only
a few tunable phosphine-catalyzed domino reactions have
been reported,[6] although during the preparation of this
manuscript Huang and co-workers reported tunable phos-
phine-mediated domino reactions between MBH carbon-
ates and β,γ-unsaturated α-keto esters.[6b] In that context,
when catalytic amounts of phosphines were used, MBH
carbonates acted as C1 synthons and 2,3-dihydrofurans
were obtained, whereas when stoichiometric amounts of
Results and Discussion
We began our study by treating MBH carbonate 2a
(Table 1) and 3-benzoylchromen-2-one (1a) with 10 mol-%
PPh3 at room temperature. To our delight, the reaction pro-
ceeded smoothly and gave [4+1] annulation product 3a
(73%) and allylation product 4a (5%) after 16 h (Table 1,
Entry 1). The more strongly nucleophilic PPh2Me and
PPhEt2 and the bifunctional phosphine LBBA-1 [3Ј-(di-
phenylphosphanyl)biphenyl-2-ol], however, were less effec-
tive than Ph3P, whereas tributyl phosphine was ineffective
(Table 1, Entries 2–5). The effects of solvents on the [4+1]
annulation were then investigated (Table 1, Entries 6–12):
THF proved best. Neither raising nor lowering of the reac-
tion temperature resulted in higher yields of 3a (Table 1,
[a] Key Laboratory of Pesticide & Chemical Biology, Ministry of
Education, College of Chemistry, Central China Normal
University,
152 Luoyu Road, Wuhan, Hubei 430079, China
E-mail: chshidq@mail.ccnu.edu.cn
http://klpcb.ccnu.edu.cn/subject/shideqing/
[b] College of Chemistry and Chemical Engineering,
Hunan University of Science and Technology,
Xiangtan, Hunan 411201, China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301358.
Eur. J. Org. Chem. 2014, 583–591
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
583

W. Yuan, H.-F. Zheng, Z.-H. Yu, Z.-L. Tang, D.-Q. Shi
FULL PAPER
Scheme 1. Tunable phosphine-catalyzed cascade reactions.
Entries 14 and 15). Interestingly, though, increasing the tries 4, 11–14). Finally, the amount of PPh3 also affected
PPh3 loading resulted in an improvement in the yield of the yield of 5a (Table 2, Entries 4, 15–16), with 1.1 equiv. of
allylation product 4a and a reduction in the yield of 3a PPh3 giving the best result.
(Table 1, Entries 13 and 16): when 1.0 equiv. of PPh3 was
In addition, as shown in Figure 1, the relationship be-
used, 4a was obtained in 78% yield (Table 1, Entry 16).
tween the yield of 5a and different phosphine loadings (10–
From the above results, the yields of 3a and 4a showed 120 mol-%) was also examined.
a high dependence on PPh3 loading, so we examined the
With the optimized conditions to hand, a variety of sub-
relationships between PPh3 loading (10–100 mol-%) and the strates 1 and 2 were examined in the [4+1] annulation reac-
yields of 3a or 4a. The results show that the yield of 4a tion. As shown in Table 3, the desired products 3 were ob-
varies in proportion to the phosphine loading whereas the tained in moderate to excellent yields and only trace
yield of 3a demonstrates an opposite trend (Figure 1). The amounts of allylation products 4 (yields Ͻ5%) we observed,
optimal reaction conditions for the selective synthesis of 3a irrespective of the electronic and steric properties of the aryl
are therefore: 1a (0.5 mmol), 2a (0.75 mmol), PPh3 (10 mol- substituents R1 and R2 and the position(s) of R1. The re-
%) in THF (5 mL) under N2 at room temperature. The opti- sults showed that substrates 1 with electron-rich R1 substit-
mal conditions for 4a are similar to those for 3a except for uents were more suitable for [4+1] annulations. Moreover,
the different PPh3 loading (1.0 equiv.).
this reaction had a good tolerance for 3-(furylcarbonyl)-2H-
During our optimization of the conditions for the syn- chromen-2-one, albeit with a slight lower yield and the need
thesis of 4a, when the reaction mixture was stirred in the for a prolonged reaction time (Table 3, Entry 14). When R1
presence of PPh3 (1.0 equiv.) under air at 40 °C, 4a (72%) was a strongly electron-withdrawing nitro group, however,
and the unexpected 6H-benzo[c]chromen-6-one 5a (Table 2, only a trace amount of 3 was observed (Table 3, Entry 13),
8%) were obtained. We wondered whether the product dis- and when 3-acetyl-2H-chromen-2-one was used the product
tribution between 4a and 5a could be controlled by choos- mixture became complex (Table 3, Entry 15). With regard
ing different conditions. In order to optimize the reaction to different MBH derivatives 2, both tert-butyl (2-methoxy-
conditions for selective synthesis of 5a, the effects of the carbonylallyl) carbonate and methyl 2-(bromomethyl)-
nucleophilicities of phosphines on the formation of 5a were acrylate were suitable candidates for the [4+1] annulations
explored (Table 2, Entries 1–4); the results indicated that (Table 3, Entries 18–19), but, when tert-butyl (2-cyanoallyl)
PPh3 was the most effective catalyst. Secondly, the effects of carbonate was used, only a trace of product was detected
solvents on the benzannulation reaction were also explored (Table 3, Entry 17).
(Table 2, Entries 4–10): when CH3CN, DMSO, or DMF
Next, the substrate scope of the cascade allylation reac-
were used 5a could be obtained in good yields, with DMF tion catalyzed by PPh3 (1.0 equiv.) was also examined
giving the best results. Furthermore, the benzannulation re- (Table 4). The results indicated that the scope of substrates
action benefitted from higher temperatures (Table 2, En- for the allylation was similar to that of the [4+1] annulation.
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Eur. J. Org. Chem. 2014, 583–591

Tunable Cascade Reactions: Selective Synthesis of Chromenones
Table 1. Optimization of conditions for the selective synthesis of 3a
or 4a.[a]
Table 2. Optimization of the benzannulation for the synthesis of
5a.[a]
Entry Phosphine Solvent
Temp. [°C] t [h] Yield [%][b]
1
2
3
4
5
6
7
8
PBu3
PPh2Me
PPhEt2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
DMF
DMF
DMF
DMF
80
80
80
80
80
80
80
80
4
4
4
4
4
6
6
4
4
4
8
4
4
4
4
0
41
62
83
46
34
78
36
59
80
45
68
78
73
80
THF
Entry Phosphine Solvent
t [h]
Yield [%][b]
1,4-dioxane
CH3CN
ethanol
toluene
DMSO
DMF
DMF
DMF
DMF
DMF
3a
4a
1
2
3
PPh3
THF
THF
THF
THF
16
16
16
16
24
18
16
16
24
18
18
17
12
24
12
5
73
0
5
0
6
9
80
80
PBu3
PPh2Me
PPhEt2
LBBA-1
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
10
11
13
14
15[c]
16[d]
54
29
46
41
52
50
20
51
56
38
68
45
64
trace
room temp.
4
trace
5[c]
6
THF
trace
Ͻ5
trace
Ͻ5
7
Ͻ5
Ͻ5
trace
12
60
120
80
toluene
CH3CN
CH2Cl2
ethanol
CHCl3
1,4-dioxane
DMF
THF
7
8
9
10
11
12
13[d]
14[e]
15[f]
16[g]
80
[a] Unless otherwise noted, the reaction conditions are: a mixture
of 1a (0.5 mmol), 2a (0.75 mmol), and phosphine (0.55 mmol) in a
solvent (5.0 mL) was stirred under air at 80 °C. [b] Isolated yields
based on 1a. [c] 0.4 mmol Ph3P was used. [d] 0.6 mmol Ph3P was
used.
PPh3
PPh3
PPh3
PPh3
THF
THF
THF
trace
8
78
was also a suitable candidate substrate (Table 4, Entry 10).
With the substrate bearing a nitro substituent or with 3-
acetyl-2H-chromen-2-one, however, only traces of 4 were
observed (Table 4, Entries 8 and 9).
As shown in Table 5, a series of 3-acyl-2H-chromen-2-
ones were effective candidates for the benzannulation reac-
tions (Table 5, Entries 1–10), irrespective of the electronic
and steric properties and position(s) of the aryl substituents
R1. It is worth noting that in this case when R1 was a
strongly electron-withdrawing nitro group, 5g could be ob-
tained in 83% yield (Table 5, Entry 7). However, when 3-
acetyl-2H-chromen-2-one was used, the product mixture
became complex (Table 5, Entry 11).
[a] Unless otherwise noted, the reaction conditions were: 1a
(0.5 mmol), 2a (0.75 mmol), phosphine (0.05 mmol) in solvent
(5.0 mL) under N2 at room temperature. [b] Isolated yields based
on 1a. [c] LBBA-1 is 3Ј-(diphenylphosphinyl)biphenyl-2-ol.
[d] Ph3P (20 mol-%) was used. [e] Stirred at 0 °C. [f] Stirred at
40 °C. [g] Ph3P (1.0 equiv.) was used.
In addition, control experiments were performed to in-
vestigate the mechanism and to explain how the different
phosphine loadings influenced the selection of the final
products 3, 4, and 5. Both compound 3a and compound 4a
could indeed be transformed into 5a under air in the pres-
ence of PPh3 (1.1 equiv.) at 80 °C (Scheme 2). Compound
3a could be converted into 4a in the presence of a stoichio-
metric amount of PPh3, in 23% yield (Scheme 2). The
transformation of 4a into 3a in the presence of a catalytic
amount of phosphine was difficult, however. These results
revealed that the product distribution of the cascade reac-
Figure 1. The effects of phosphine loading on the yields of 3a, 4a,
and 5a.
Firstly, the desired products 4 were formed in moderate to tion could be controlled by choosing a different phosphine
excellent yields (Table 4, Entries 1–7), irrespective of the loading and suitable reaction conditions.
electronic and steric properties and position(s) of the aryl
A plausible reaction mechanism based on our experi-
substituents R1. Acetyl (2-methoxycarbonylallyl) carbonate mental results and the related literature[6b] has been pro-
Eur. J. Org. Chem. 2014, 583–591
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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585

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FULL PAPER
Table 3. Substrate scope of phosphine-mediated [4+1] annulation
domino reactions.[a]
Table 5. Substrate scope of phosphine-mediated benzannulation
domino reactions for the construction of 6H-benzo[c]chromen-6-
ones.[a]
Entry R1
R2
R3
R4
t [h] Yield [%][b]
Entry R1
R2
t [h]
Yield [%][b]
1
H
Ph
Ph
Ph
4-ClC6H4
4-BrC6H4
CO2Me BocO 16
CO2Me BocO 16
CO2Me BocO 18
CO2Me BocO 18
CO2Me BocO 24
73 (3a)
61 (3b)
60 (3c)
64 (3d)
62 (3e)
66 (3f)
74 (3g)
82 (3h)
77 (3i)
80 (3j)
72 (3k)
61 (3l)
trace
1
2
H
6-F
Ph
Ph
Ph
Ph
4-BrC6H4
Ph
Ph
2-furyl
1-naphthyl
4
3
4
8
5
4
3.5
6
4
6
83 (5a)
90 (5b)
82 (5c)
75 (5d)
87 (5e)
86 (5f)
83 (5g)
78 (5h)
71 (5i)
74 (5j)
complex
2
3
4
6-Cl
6-F
H
3
4
5
6-tert-butyl
7,8-(CH3)2
H
5
H
6
H
4-MeOC6H4 CO2Me BocO 24
Ph
6
7
8
6-EtO2C
6-NO2
H
7
6-MeO
CO2Me BocO 24
CO2Me BocO 18
CO2Et BocO 24
CO2Me BocO 18
CO2Me BocO 18
CO2Me BocO 18
CO2Me BocO 16
CO2Me BocO 24
CO2Me BocO 16
CO2Me BocO 18
8
6-tert-butyl Ph
9
6-MeO
7-CH3
7,8-CH3
6-EtO2C
6-NO2
H
H
H
H
H
Ph
Ph
Ph
Ph
9
10
11
H
10
11
12
13
14
15
16
17
18[c]
19[c]
naphthylethyl Ph
CH3
H
4
Ph
[a] Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol), and PPh3
(0.55 mmol) in DMF (5.0 mL) were stirred under air at 80 °C.
[b] Isolated yields based on 1.
2-furyl
CH3
1-naphthyl
Ph
Ph
Ph
45 (3m)
complex
84 (3n)
trace
CN
CO2Me Br
CO2Me AcO
BocO 16
20
20
70 (3a)
72 (3a)
H
[a] Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol), and PPh3
(0.05 mmol) in THF (5.0 mL) were stirred under N2 at room tem-
perature. [b] Isolated yields based on 1. [c] K2CO3 (0.75 mmol,
103 mg) was added.
Table 4. Substrate scope of phosphine-mediated allylation of 3-
acyl-2H-chromen-2-ones and MBH carbonates.[a]
Entry R1
R2
R3
R4
t [h] Yield [%][b]
1
2
3
4
5
6
7
8
9
10
H
6,8-Cl2
6-tert-butyl Ph
7,8-CH3
6-EtO2C
6-EtO2C
H
6-NO2
H
Ph
Ph
CO2Me BocO
CO2Me BocO
CO2Me BocO
CO2Me BocO
CO2Me BocO
6
6
6
12
5
5
8
8
8
6
78 (4a)
61 (4b)
81 (4c)
65 (4d)
83 (4e)
85 (4f)
80 (4 g)
trace
Scheme 2. The mutual transformation relationships of 3a, 4a, and
5a.
Ph
Ph
Ph
CO2Et
BocO
subsequent deprotonation. Michael addition of the result-
ant ylides A to 3-acyl-2H-chromen-2-ones 1 would generate
B by a favored γ-carbon attack pattern, which could trans-
form variously into C, D, or F through proton transfer pro-
cesses. Intermediates C could then undergo reversible intra-
molecular oxygen anion Michael addition to yield the ki-
netically favored products 3 with the release of PPh3. Com-
pounds 5 could be formed through intramolecular Wittig
1-naphthyl CO2Me BocO
Ph
CH3
Ph
CO2Me BocO
CO2Me BocO
CO2Me AcO
trace
70 (4a)
H
[a] Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol), and PPh3
(0.5 mmol) in THF (5.0 mL) were stirred under N2 at room tem-
perature. [b] Isolated yields based on 1.
posed (Scheme 3). Firstly, allylic phosphorus ylides A could reaction of D, followed by an oxidative aromatization pro-
be formed through a process of addition/elimination and cess. Meanwhile, the allylation products 4 could be gener-
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Eur. J. Org. Chem. 2014, 583–591

Tunable Cascade Reactions: Selective Synthesis of Chromenones
Scheme 3. Plausible mechanism for the tunable phosphine-catalyzed cascade reactions.
(600 MHz, CDCl3): δ = 8.19 (d, J = 7.2 Hz, 2 H), 7.46 (ddd, J =
ated from F through elimination in the presence of a stoi-
chiometric amount of phosphine.
20.4, 14.9, 7.8 Hz, 4 H), 7.27 (dd, J = 15.6, 7.8 Hz, 1 H), 7.18 (t, J
= 7.5 Hz, 1 H), 7.11 (d, J = 7.8 Hz, 1 H), 6.57 (s, 1 H), 6.12 (s, 1
H), 5.86 (d, J = 8.6 Hz, 1 H), 4.62 (d, J = 8.6 Hz, 1 H), 3.86 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.22, 164.91, 160.82,
151.19, 138.39, 131.75, 129.27, 128.40, 128.04, 127.98, 127.73,
125.03, 124.50, 124.45, 116.89, 97.13, 84.28, 52.23, 47.42 ppm. MS
(EI, 70 eV): m/z (%) = 348 (6.4) [M]+, 346 (42), 330 (12), 287 (47),
262 (60), 105 (100), 77 (48). C21H16O5 (348.35): calcd. C 72.41, H
4.63; found C 72.29, H 4.50.
The different phosphine loadings and reaction conditions
governed the transformation of 3 as well as the formation
of 5 and 4. Higher temperatures, O2, and a suitable solvent
(DMF) are beneficial to the formation of 5, whereas room
temperature, absence of O2, and a suitable solvent (THF)
are better for the formation of 4. In brief, the reaction con-
ditions (temperature and solvent) and different phosphine
loadings determined the pathway of the tunable phosphine-
mediated cascade reactions.
Methyl
2-(6-Chloro-4-oxo-3-phenyl-1,9b-dihydro-4H-furo[3,4-c]-
chromen-1-yl)acrylate (3b): Yield 61%. White solid, m.p. 126–
127 °C. 1H NMR (600 MHz, CDCl3): δ = 8.19 (d, J = 7.8 Hz, 2
H), 7.50 (dd, J = 15.0, 7.2 Hz, 2 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.27–
7.21 (m, 1 H), 7.04 (d, J = 8.6 Hz, 1 H), 6.57 (s, 1 H), 6.12 (s, 1
H), 5.82 (d, J = 8.3 Hz, 1 H), 4.58 (d, J = 8.3 Hz, 1 H), 3.87 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.44, 165.10, 160.27,
149.81, 138.12, 131.98, 129.53, 129.32, 128.39, 128.06, 128.02,
127.53, 126.80, 124.76, 118.27, 96.28, 83.97, 52.31, 47.55 ppm. MS
(EI, 70 eV): m/z (%) = 382 (6.4) [M]+, 323 (7.3), 297 (34), 296 (56),
205 (5.6), 105 (100), 77 (32). C21H15ClO5 (382.80): calcd. C 65.89,
H 3.95; found C 65.97, H 3.72.
Conclusions
In summary, we have developed a tunable phosphine-me-
diated cascade reaction process based on 3-acyl-chromen-
2-ones 1 and MBH derivatives 2. Under different phosphine
loading conditions and reaction temperatures, MBH deriva-
tives act as C1 or C3 synthons for selective construction of
potential biologically active 2,3-dihydrofuran-fused
chromen-2-ones, 4-allyl-3-acyl-chromen-2-ones, and 6H-
benzo[c]chromen-6-ones. This method has the advantages
of mild conditions, simple workup, and wide substrate
scope, which make it powerful for the synthesis of diverse
chromenones.
Methyl
2-(6-Fluoro-4-oxo-3-phenyl-1,9b-dihydro-4H-furo[3,4-c]-
chromen-1-yl)acrylate (3c): Yield 60%. White solid, m.p. 84–85 °C.
1H NMR (600 MHz, CDCl3): δ = 8.19 (d, J = 7.6 Hz, 2 H), 7.49
(t, J = 7.3 Hz, 1 H), 7.43 (t, J = 7.6 Hz, 2 H), 7.24 (dd, J = 9.0,
2.4 Hz, 1 H), 7.05 (dd, J = 8.9, 5.4 Hz, 1 H), 6.96 (td, J = 9.0,
3.0 Hz, 1 H), 6.56 (s, 1 H), 6.11 (s, 1 H), 5.80 (d, J = 8.3 Hz, 1 H),
4.57 (d, J = 8.3 Hz, 1 H), 3.86 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 165.18, 160.54, 159.13 (d, J = 242.3 Hz), 147.29 (d, J
= 2.2 Hz), 138.22, 131.92, 129.29, 128.06, 127.83, 127.59, 126.83
(d, J = 7.6 Hz), 118.22, 115.09, 114.86, 111.65 (d, J = 22.4 Hz),
96.41, 83.93, 52.29, 47.84 ppm. MS (EI, 70 eV): m/z (%) = 366 (5.5)
[M]+, 348 (10), 305 (9.3), 281 (37), 280 (50), 105 (100), 77 (41).
C21H15FO5 (366.34): calcd. C 68.85, H 4.13; found C 69.03, H 4.26.
Experimental Section
General Procedure for the Synthesis of 2,3-Dihydrofuran-Fused
Chromene-2-ones 3: A mixture of a 3-acyl-2H-chromen-2-one 1
(0.5 mmol),
a MBH derivative 2 (0.75 mmol), and PPh3
(0.05 mmol) in anhydrous THF (5.0 mL) was stirred at room tem-
perature under N2. After the reaction was complete (monitoring by
TLC), the workup involved the addition of water (5 mL), extraction
with ethyl acetate (3ϫ10 mL), and drying over anhydrous Na2SO4.
After the solvent had been removed under reduced pressure, the
crude product was purified by flash column chromatography on
silica gel (petroleum ether/EtOAc 10–20:1) to afford the appropri-
ate compound 3.
Methyl
2-[3-(4-Chlorophenyl)-4-oxo-1,9b-dihydro-4H-furo[3,4-c]-
chromen-1-yl]acrylate (3d): Yield 64%. White solid, m.p. 107–
108 °C. 1H NMR (600 MHz, CDCl3): δ = 8.18 (d, J = 9.0 Hz, 2
H), 7.42 (dd, J = 14.4, 7.8 Hz, 3 H), 7.29 (t, J = 7.7 Hz, 1 H), 7.19
(t, J = 7.8 Hz, 1 H), 7.12 (d, J = 8.1 Hz, 1 H), 6.58 (s, 1 H), 6.12
(s, 1 H), 5.84 (d, J = 8.8 Hz, 1 H), 4.64 (d, J = 8.8 Hz, 1 H), 3.86
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.20, 163.70,
160.77, 151.19, 138.31, 137.90, 130.76, 128.56, 128.36, 128.27,
126.23, 124.84, 124.61, 124.54, 117.01, 97.74, 84.60, 52.32,
Methyl 2-(4-Oxo-3-phenyl-1,9b-dihydro-4H-furo[3,4-c]chromen-1-
1
yl)acrylate (3a): Yield 73%. White solid, m.p. 80–81 °C. H NMR
Eur. J. Org. Chem. 2014, 583–591
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
587

W. Yuan, H.-F. Zheng, Z.-H. Yu, Z.-L. Tang, D.-Q. Shi
FULL PAPER
47.40 ppm. MS (EI, 70 eV): m/z (%) = 382 (10) [M]+, 323 (11), 297
14.13 ppm. MS (EI, 70 eV): m/z (%) = 392 (11.0) [M]+, 374 (5.6),
(51), 271 (11), 205 (13),139 (100), 111 (28). C21H15ClO5 (382.80): 317 (13), 292 (48), 287 (8.9), 105 (100), 77 (34). C23H20O6 (392.41):
calcd. C 65.89, H 3.95; found C 65.61, H 4.00. calcd. C 70.40, H 5.14; found C 70.53, H 5.24.
Methyl 2-[3-(4-Bromophenyl)-4-oxo-1,9b-dihydro-4H-furo[3,4-c]- Methyl 2-(7-Methyl-4-oxo-3-phenyl-1,9b-dihydro-4H-furo[3,4-c]-
chromen-1-yl]acrylate (3e): Yield 62%. White solid, m.p. 126–
128 °C. 1H NMR (600 MHz, CDCl3): δ = 8.10 (d, J = 8.5 Hz, 2
H), 7.57 (d, J = 8.5 Hz, 2 H), 7.43 (d, J = 7.2 Hz, 1 H), 7.29 (t, J
= 7.7 Hz, 1 H), 7.18 (t, J = 7.8 Hz, 1 H), 7.12 (d, J = 8.1 Hz, 1 H),
chromen-1-yl)acrylate (3j): Yield 80%. White solid, m.p. 61–62 °C.
1H NMR (600 MHz, CDCl3): δ = 8.18 (d, J = 7.5 Hz, 2 H), 7.48
(t, J = 7.3 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 2 H), 7.31 (d, J = 7.8 Hz,
1 H), 6.98 (d, J = 7.8 Hz, 1 H), 6.92 (s, 1 H), 6.55 (s, 1 H), 6.11 (s,
6.58 (s, 1 H), 6.11 (s, 1 H), 5.84 (d, J = 8.8 Hz, 1 H), 4.63 (d, J = 1 H), 5.81 (d, J = 8.6 Hz, 1 H), 4.57 (d, J = 8.6 Hz, 1 H), 3.85 (s,
8.8 Hz, 1 H), 3.86 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ 3 H), 2.33 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.22,
= 165.19, 163.75, 160.76, 151.18, 138.31, 131.34, 130.89, 128.57,
128.28, 126.67, 126.53, 124.82, 124.62, 124.54, 117.03, 97.87, 84.62,
52.33, 47.44 ppm. MS (EI, 70 eV): m/z (%) = 426 (6.0) [M]+, 367
(10.0), 342 (43), 271 (11), 182 (100), 154 (27), 115 (10). C21H15BrO5
(427.25): calcd. C 59.04, H 3.54; found C 58.89, H 3.39.
164.72, 160.96, 151.06, 138.63, 138.45, 131.66, 129.26, 129.20,
127.94, 127.81, 125.13, 124.20, 121.94, 117.28, 97.43, 84.46, 52.17,
47.16, 20.99 ppm. MS (EI, 70 eV): m/z (%) = 362 (8.1) [M]+, 360
(21), 344 (11), 301 (20), 276 (71), 105 (100), 77 (42). C22H18O5
(362.38): calcd. C 72.92, H 5.01; found C 79.80, H 4.87.
Methyl 2-[3-(4-Methoxyphenyl)-4-oxo-1,9b-dihydro-4H-furo[3,4-c]-
chromen-1-yl]acrylate (3f): Yield 66%. White solid, m.p. 122–
123 °C. 1H NMR (600 MHz, CDCl3): δ = 8.24 (d, J = 9.0 Hz, 2
H), 7.42 (d, J = 7.8 Hz, 1 H), 7.26 (t, J = 7.8 Hz, 1 H), 7.16 (t, J
Methyl 2-(7,8-Dimethyl-4-oxo-3-phenyl-1,9b-dihydro-4H-furo[3,4-c]-
chromen-1-yl)acrylate (3k): Yield 72%. White solid, m.p. 111–
113 °C. 1H NMR (600 MHz, CDCl3): δ = 8.20 (d, J = 7.7 Hz, 2
H), 7.48 (t, J = 7.8 Hz, 1 H), 7.43 (t, J = 7.8 Hz, 2 H), 7.17 (d, J
= 7.2 Hz, 1 H), 7.10 (d, J = 8.4 Hz, 1 H), 6.93 (d, J = 8.4 Hz, 2 = 7.8 Hz, 1 H), 6.98 (d, J = 7.8 Hz, 1 H), 6.54 (s, 1 H), 6.10 (s, 1
H), 6.57 (s, 1 H), 6.11 (s, 1 H), 5.80 (d, J = 8.8 Hz, 1 H), 4.61 (d,
J = 8.8 Hz, 1 H), 3.85 (s, 3 H), 3.84 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 165.29, 165.15, 162.30, 161.12, 151.35,
138.56, 131.42, 128.34, 128.13, 125.10, 124.47, 124.36, 120.29,
116.88, 113.35, 95.22, 84.04, 55.28, 52.23, 47.27 ppm. MS (EI,
H), 5.83 (d, J = 8.3 Hz, 1 H), 4.55 (d, J = 8.3 Hz, 1 H), 3.85 (s, 3
H), 2.28 (s, 3 H), 2.25 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 165.28, 164.22, 161.23, 149.34, 138.68, 137.38, 131.61, 129.17,
128.00, 127.92, 127.68, 125.34, 124.92, 122.55, 120.94, 97.67, 84.30,
52.20, 47.78, 19.89, 12.06 ppm. MS (EI, 70 eV): m/z (%) = 376 (8.6)
70 eV): m/z (%) = 378 (3.0) [M]+, 360 (3.6), 317 (6.0), 292 (25), 221 [M]+, 347 (7.4), 318 (32), 287 (17), 243 (5.6), 105 (100), 77 (34).
(6.0), 135 (100), 77 (9). C22H18O6 (378.38): calcd. C 69.83, H 4.79; C23H20O5 (376.41): calcd. C 73.39, H 5.36; found C 73.31, H 5.33.
found C 69.96, H 4.51.
Ethyl
1-(3-Methoxy-3-oxoprop-1-en-2-yl)-4-oxo-3-phenyl-1,9b-di-
Methyl 2-(6-Methoxy-4-oxo-3-phenyl-1,9b-dihydro-4H-furo[3,4-c]- hydro-4H-furo[3,4-c]chromene-8-carboxylate (3l): Yield 61%. White
chromen-1-yl)acrylate (3g): Yield 74%. White solid, m.p. 106–
solid, m.p. 131–133 °C. 1H NMR (600 MHz, CDCl3): δ = 8.20–
8.17 (m, 3 H), 7.98 (d, J = 7.8 Hz, 1 H), 7.51 (t, J = 7.8 Hz, 1 H),
108 °C. 1H NMR (600 MHz, CDCl3): δ = 8.19 (d, J = 7.8 Hz, 2
H), 7.49 (t, J = 7.2 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 2 H), 7.07–7.01 7.45 (t, J = 7.8 Hz, 2 H), 7.15 (d, J = 8.4 Hz, 1 H), 6.61 (s, 1 H),
(m, 2 H), 6.80 (d, J = 8.9 Hz, 1 H), 6.56 (s, 1 H), 6.12 (s, 1 H), 6.15 (s, 1 H), 5.90 (d, J = 8.6 Hz, 1 H), 4.66 (d, J = 8.6 Hz, 1 H),
5.84 (d, J = 8.4 Hz, 1 H), 4.58 (d, J = 8.4 Hz, 1 H), 3.86 (s, 3 H),
3.82 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.22,
164.71, 161.11, 156.21, 145.12, 138.53, 131.71, 129.27, 127.99,
4.39 (q, J = 7.1 Hz, 2 H), 3.88 (s, 3 H), 1.41 (t, J = 7.1 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.88, 165.63, 164.99,
159.96, 154.63, 138.25, 132.05, 130.17, 129.42, 128.40, 128.09,
127.84, 127.79, 126.01, 117.56, 112.94, 110.23, 97.19, 84.08, 55.58, 127.56, 126.64, 126.47, 125.20, 117.01, 96.25, 84.54, 61.10, 52.30,
52.26, 47.95 ppm. MS (EI, 70 eV): m/z (%) = 378 (14) [M]+, 360 47.28, 14.26 ppm. MS (EI, 70 eV): m/z (%) = 420 (3.0) [M]+, 418
(4.7), 319 (11), 292 (37), 232 (7.2), 105 (100), 77 (31). C22H18O6 (6.0), 373 (11), 346 (35), 187 (15), 105 (100), 77 (42). C21H15FO5
(378.38): calcd. C 69.83, H 4.79; found C 69.67, H 4.88.
(366.34): calcd. C 68.57, H 4.80; found C 68.60, H 4.71.
Methyl 2-[6-(tert-Butyl)-4-oxo-3-phenyl-1,9b-dihydro-4H-furo[3,4-c]-
Methyl 2-[3-(Furan-2-yl)-4-oxo-1,9b-dihydro-4H-furo[3,4-c]chrom-
chromen-1-yl]acrylate (3h): Yield 82%. White solid, m.p. 128– en-1-yl]acrylate (3m): Yield 45%, Pale yellow solid, m.p. 65–66 °C.
130 °C. 1H NMR (600 MHz, CDCl3): δ = 8.19 (d, J = 7.9 Hz, 2
H), 7.48 (d, J = 11.0 Hz, 2 H), 7.43 (t, J = 7.5 Hz,2 H), 7.29 (d, J
1H NMR (600 MHz, CDCl3): δ = 8.03 (d, J = 3.6 Hz, 1 H), 7.58
(s, 1 H), 7.33 (d, J = 7.8 Hz, 1 H), 7.27 (t, J = 7.8 Hz, 1 H), 7.15
= 8.5 Hz, 1 H), 7.04 (d, J = 8.5 Hz, 1 H), 6.58 (s, 1 H), 6.13 (s, 1 (t, J = 7.8 Hz, 1 H), 7.12 (d, J = 7.8 Hz, 1 H), 6.63 (s, 1 H), 6.60–
H), 5.90 (d, J = 8.4 Hz, 1 H), 4.60 (d, J = 8.4 Hz, 1 H), 3.87 (s, 3
H), 1.34 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.19,
164.78, 161.04, 148.99, 147.46, 138.91, 131.68, 129.30, 127.98,
6.56 (m, 1 H), 6.21 (s, 1 H), 5.80 (d, J = 9.6 Hz, 1 H), 4.70 (d, J =
9.6 Hz, 1 H), 3.86 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 164.99, 159.91, 155.21, 151.32, 145.39, 142.39, 137.86, 129.50,
127.85, 125.33, 124.21, 121.43, 116.35, 97.45, 84.31, 52.26, 48.07, 128.46, 124.44, 124.34, 119.73, 117.01, 112.41, 95.43, 86.48, 52.18,
34.53, 31.41, 31.31 ppm. MS (EI, 70 eV): m/z (%) = 404 (10) [M]+, 46.04, 29.52 ppm. MS (EI, 70 eV): m/z (%) = 338 (16) [M]+, 336
347 (11), 318 (34), 303 (20), 287 (19), 105 (100), 77 (30). C25H24O5 (24), 320 (81), 277 (27), 148 (20), 139 (30), 95 (100). C19H14O6
(404.46): calcd. C 74.24, H 5.98; found C 74.32, H 6.11. (338.32): calcd. C 67.45, H 4.17; found C 67.63, H 4.25.
Ethyl
2-(6-Methoxy-4-oxo-3-phenyl-1,9b-dihydro-4H-furo[3,4-c]- Methyl 2-[3-(Naphthalen-1-yl)-4-oxo-1,9b-dihydro-1H-furo[3,4-c]-
chromen-1-yl)acrylate (3i): Yield 77%. White solid, m.p. 142–
chromen-1-yl]acrylate (3n): Yield 84%. White solid, m.p. 188–
143 °C. 1H NMR (600 MHz, CDCl3): δ = 8.19 (d, J = 7.8 Hz, 2
189 °C. 1H NMR (600 MHz, CDCl3): δ = 8.04 (d, J = 7.8 Hz, 1
H), 7.48 (t, J = 7.2 Hz, 1 H), 7.43 (t, J = 7.8 Hz, 2 H), 7.03 (dd, J H), 7.95–7.93 (m, 2 H), 7.84 (d, J = 7.2 Hz, 1 H), 7.53 (t, J =
= 4.8, 1.2 Hz, 2 H), 6.78 (dd, J = 9.0, 2.2 Hz, 1 H), 6.55 (s, 1 H),
6.09 (s, 1 H), 5.83 (d, J = 8.5 Hz, 1 H), 4.59 (d, J = 8.5 Hz, 1 H),
4.31 (q, J = 7.2 Hz, 2 H), 3.81 (s, 3 H), 1.34 (t, J = 7.2 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 164.82, 161.17, 156.24,
145.18, 138.88, 131.74, 129.30, 128.03, 127.98, 127.87, 127.69,
7.8 Hz, 1 H), 7.50–7.45 (m, 2 H), 7.41 (d, J = 7.2 Hz, 1 H), 7.28
(t, J = 7.8 Hz, 1 H), 7.18 (t, J = 7.8 Hz, 1 H), 7.11 (d, J = 7.8 Hz,
1 H), 6.59 (s, 1 H), 6.17 (s, 1 H), 5.96 (d, J = 9.0 Hz, 1 H), 4.80 (d,
J = 9.0 Hz, 1 H), 3.85 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 167.08, 165.09, 159.69, 151.49, 138.14, 133.24, 131.66, 130.78,
126.12, 117.60, 112.87, 110.40, 97.23, 84.26, 61.36, 55.63, 47.97, 130.11, 129.12, 128.59, 128.36, 126.78, 126.07, 125.16, 125.08,
588
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 583–591

Tunable Cascade Reactions: Selective Synthesis of Chromenones
124.84, 124.66, 124.55, 124.48, 117.24, 100.45, 86.98, 52.22,
128.08, 127.97, 127.25, 118.15, 117.51, 61.52, 52.33, 30.60,
46.00 ppm. MS (EI, 70 eV): m/z (%) = 398 (4.2) [M]+, 380 (8.7),
14.20 ppm. MS (EI, 70 eV): m/z (%) = 420 (4.6) [M]+, 346 (46), 334
337 (8.3), 312 (99), 255 (21), 155 (100), 127 (83). C25H18O5 (398.41): (49), 306 (10), 287 (21), 105 (100), 77 (78). C24H20O7 (420.42):
calcd. C 75.37, H 4.55; found C 75.32, H 4.64.
calcd. C 68.57, H 4.80; found C 68.42, H 4.66.
General Procedure for the Synthesis of 4-Allyl-3-acyl-2H-chromen-
2-ones 4: The procedure was similar to that used for compounds 3,
except for the different PPh3 loading (1.0 equiv., 0.5 mmol).
Ethyl 3-Benzoyl-4-[2-(ethoxycarbonyl)allyl]-2-oxo-2H-chromene-6-
carboxylate (4f): Yield 85%. White solid, m.p. 139–140 °C. 1H
NMR (600 MHz, CDCl3): δ = 8.33 (d, J = 1.8 Hz, 1 H), 8.26 (dd,
J = 8.7, 1.8 Hz, 1 H), 7.91 (d, J = 7.2 Hz, 2 H), 7.63 (t, J = 7.4 Hz,
1 H), 7.50–7.45 (m, 3 H), 6.29 (s, 1 H), 5.55 (s, 1 H), 4.41 (q, J =
7.2 Hz, 2 H), 4.22 (q, J = 7.2 Hz, 2 H), 3.80 (s, 2 H), 1.41 (t, J =
7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 192.00, 165.63, 164.84, 157.93, 156.06, 150.56, 135.63,
135.35, 134.41, 133.30, 129.26, 128.85, 128.26, 127.97, 127.20,
118.15, 117.45, 61.45, 61.34, 30.50, 14.15, 14.00 ppm. MS (EI,
70 eV): m/z (%) = 434 (3.0) [M]+, 388 (10), 360 (28), 334 (36), 287
(25), 105 (100), 77 (52). C25H22O7 (434.44): calcd. C 69.12, H 5.10;
found C 69.01, H 5.08.
Methyl 2-[(3-Benzoyl-2-oxo-2H-chromen-4-yl)methyl]acrylate (4a):
Yield 78%. White solid, m.p. 152–153 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.92 (d, J = 7.2 Hz, 2 H), 7.63–7.57 (m, 3 H), 7.47 (t,
J = 7.6 Hz, 2 H), 7.42 (d, J = 8.4 Hz, 1 H), 7.32 (t, J = 7.6 Hz, 1
H), 6.29 (s, 1 H), 5.55 (s, 1 H), 3.77 (s, 3 H), 3.74 (s, 2 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 192.44, 166.39, 158.57, 153.47,
150.41, 135.79, 135.22, 134.34, 132.61, 129.32, 128.85, 128.23,
127.64, 125.89, 124.82, 118.18, 117.33, 52.33, 30.64 ppm. MS (EI,
70 eV): m/z (%) = 348 (4.0) [M]+, 330 (32), 289 (13), 262 (100), 239
(12), 105 (79), 77 (60). C21H16O5 (348.35): calcd. C 72.41, H 4.63;
found C 72.33, H 4.51.
Methyl 2-{[3-(1-Naphthoyl)-2-oxo-2H-chromen-4-yl]methyl}acrylate
(4g): Yield 80%. White solid, m.p. 126–127 °C. 1H NMR
(400 MHz, CDCl3): δ = 9.16 (d, J = 8.4 Hz, 1 H), 8.05 (d, J =
8.0 Hz, 1 H), 7.91 (t, J = 6.8 Hz, 2 H), 7.68 (t, J = 7.6 Hz, 1 H),
7.61–7.55 (m, 3 H), 7.42 (dd, J = 13.6, 8.0 Hz, 2 H), 7.30 (dd, J =
16.0, 7.6 Hz, 1 H), 6.31 (s, 1 H), 5.60 (s, 1 H), 3.83 (s, 2 H), 3.71
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.18, 166.26,
158.62, 153.35, 149.90, 135.33, 135.04, 133.98, 132.48, 132.32,
132.20, 130.60, 128.86, 128.46, 128.06, 126.70, 125.90, 125.87,
125.86, 124.73, 124.16, 118.22, 117.17, 52.19, 30.67 ppm. MS (EI,
70 eV): m/z (%) = 398 (10) [M]+, 380 (6.8), 339 (80), 312 (56), 169
(20), 155 (44), 127 (100). C25H18O5 (398.41): calcd. C 75.37, H 4.55;
found C 75.40, H 4.39.
Methyl 2-[(3-Benzoyl-6,8-dichloro-2-oxo-2H-chromen-4-yl)methyl]-
1
acrylate (4b): Yield 61%. White solid, m.p. 151–152 °C. H NMR
(600 MHz, CDCl3): δ = 7.89 (d, J = 7.2 Hz, 2 H), 7.64 (dd, J =
12.0, 1.8 Hz, 2 H), 7.48 (dd, J = 12.6, 7.8 Hz, 3 H), 6.31 (s, 1 H),
5.56 (s, 1 H), 3.78 (s, 3 H), 3.69 (s, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 191.47, 166.12, 156.85, 149.09, 147.81, 135.19, 134.69,
134.61, 132.49, 129.98, 129.30, 129.08, 128.93, 128.65, 123.91,
123.20, 120.36, 52.46, 30.72 ppm. MS (EI, 70 eV): m/z (%) = 416
(2.6) [M]+, 398 (10), 357 (7.4), 331 (36), 330 (27), 105 (100), 77 (58).
C21H14Cl2O5 (417.24): calcd. C 60.45, H 3.38; found C 60.58, H
3.34.
Methyl 2-{[3-Benzoyl-6-(tert-butyl)-2-oxo-2H-chromen-4-yl]meth-
yl}acrylate (4c): Yield 81%. White solid, m.p. 139–141 °C. 1H
NMR (600 MHz, CDCl3): δ = 7.93 (d, J = 7.8 Hz, 2 H), 7.62 (dd,
J = 18.0, 9.0 Hz, 2 H), 7.56 (s, 1 H), 7.48 (t, J = 7.8 Hz, 2 H), 7.35
(d, J = 9.0 Hz, 1 H), 6.33 (s, 1 H), 5.69 (s, 1 H), 3.79 (s, 3 H), 3.76
(s, 2 H), 1.32 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
192.75, 166.54, 158.90, 151.48, 151.15, 147.90, 135.94, 135.37,
134.26, 130.22, 129.31, 128.82, 128.63, 127.16, 122.16, 117.41,
116.80, 52.36, 34.66, 31.17, 30.26 ppm. MS (EI, 70 eV): m/z (%) =
404 (8) [M]+, 386 (17), 371 (10), 318 (41), 303 (21), 105 (100), 77
(38). C25H24O5 (404.46): calcd. C 74.24, H 5.98; found C 74.31, H
5.87.
General Procedure for the Synthesis of 6H-Benzo[c]chromen-6-ones
5: A mixture of a 3-acyl-2H-chromen-2-one 1 (0.5 mmol), an allylic
carbonate 2 (0.75 mmol), and PPh3 (0.55 mmol) in DMF (5.0 mL)
was stirred at 80 °C under air. After the reaction was complete,
the workup involved the addition of water (5 mL), extraction with
CH2Cl2 (3ϫ10 mL), and drying over anhydrous Na2SO4. After the
solvent had been removed under reduced pressure, the crude prod-
uct was purified by flash column chromatography on silica gel (pe-
troleum ether/CH2Cl2 1:3–4) to afford 5.
9-(Methoxycarbonyl)-7-phenyl-6H-benzo[c]chromen-6-one
(5a):
Yield 83%. White solid, m.p. 211–212 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.75 (s, 1 H), 8.13 (d, J = 8.0 Hz, 1 H), 8.00 (s, 1 H),
7.51–7.39 (m, 4 H), 7.32 (dd, J = 14.8, 7.8 Hz, 4 H), 3.98 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.47, 158.38, 151.34,
147.16, 140.97, 136.29, 134.06, 132.15, 130.92, 128.07, 127.80,
127.50, 124.41, 123.25, 122.29, 121.38, 117.43, 117.31, 52.72 ppm.
MS (EI, 70 eV): m/z (%) = 330 (60) [M]+, 329 (100), 299 (3.7), 271
(9.0), 215 (14), 135 (16), 94 (10). C21H14O4 (330.34): calcd. C 76.35,
H 4.27; found C 76.39, H 4.43.
Methyl 2-[(3-Benzoyl-7,8-dimethyl-2-oxo-2H-chromen-4-yl)methyl]-
1
acrylate (4d): Yield 65%. White solid, m.p. 165–166 °C. H NMR
(600 MHz, CDCl3): δ = 7.92 (d, J = 7.2 Hz, 2 H), 7.61 (t, J =
7.2 Hz, 1 H), 7.47 (t, J = 7.8 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 1 H),
7.12 (d, J = 8.0 Hz, 1 H), 6.28 (s, 1 H), 5.52 (s, 1 H), 3.76 (s, 3 H),
3.71 (s, 2 H), 2.42 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 192.87, 166.45, 158.98, 151.70, 150.95, 142.62, 136.00, 135.52,
134.16, 129.32, 128.76, 127.98, 126.18, 126.07, 125.05, 122.63,
115.89, 52.26, 30.67, 20.36, 11.58 ppm. MS (EI, 70 eV): m/z (%) =
376 (10) [M]+, 358 (36), 317 (19), 290 (100), 267 (18), 105 (83), 77
(41). C23H20O5 (376.41): calcd. C 73.39, H 5.36; found C 79.22, H
5.25.
2-Fluoro-9-(methoxycarbonyl)-7-phenyl-6H-benzo[c]chromen-6-one
(5b): Yield 90 %. White solid, m.p. 208–210 °C. 1H NMR
(600 MHz, CDCl3): δ = 8.69 (s, 1 H), 8.07 (s, 1 H), 7.84 (d, J =
9.0 Hz, 1 H), 7.45 (d, J = 7.2 Hz, 3 H), 7.32 (dd, J = 12.6, 7.2 Hz,
3 H), 7.22 (t, J = 7.8 Hz, 1 H), 4.01 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 165.34, 159.15 (d, J = 242.0 Hz), 158.09,
147.50 (d, J = 3.4 Hz), 140.75, 135.49, 134.32, 132.91, 128.08,
127.89, 127.66, 122.50, 121.41, 118.97 (d, J = 8.2 Hz), 118.69 (d, J
= 8.2 Hz), 118.32 (d, J = 23.8 Hz), 109.44, 109.19, 52.84 ppm. MS
(EI, 70 eV): m/z (%) = 348 (64) [M]+, 347 (100), 289 (8.0), 260 (11),
233 (13), 157 (6), 115 (7.0). C21H13FO4 (348.33): calcd. C 72.41, H
3.76; found C 72.60, H 3.56.
Ethyl 3-Benzoyl-4-[2-(methoxycarbonyl)allyl]-2-oxo-2H-chromene-6-
carboxylate (4e): Yield 83%. White solid, m.p. 111–112 °C. 1H
NMR (600 MHz, CDCl3): δ = 8.32 (s, 1 H), 8.26 (d, J = 8.5 Hz, 1
H), 7.91 (d, J = 7.8 Hz, 2 H), 7.63 (t, J = 6.6 Hz, 1 H), 7.50–7.45
(m, 3 H), 6.30 (s, 1 H), 5.57 (s, 1 H), 4.41 (q, J = 7.2 Hz, 2 H),
3.80 (s, 2 H), 3.77 (s, 3 H), 1.42 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 191.99, 166.15, 164.88, 157.96, 156.10,
150.41, 135.64, 135.11, 134.48, 133.35, 129.30, 128.90, 128.57,
Eur. J. Org. Chem. 2014, 583–591
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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589

W. Yuan, H.-F. Zheng, Z.-H. Yu, Z.-L. Tang, D.-Q. Shi
FULL PAPER
2-(tert-Butyl)-9-(methoxycarbonyl)-7-phenyl-6H-benzo[c]chromen-6-
one (5c): Yield 82 %. White solid, m.p. 227–228 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.81 (s, 1 H), 8.14 (s, 1 H), 8.01 (s, 1 H),
7.56 (d, J = 7.2 Hz, 1 H), 7.33 (dd, J = 44.8, 20.5 Hz, 6 H), 4.01
(s, 3 H), 1.44 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
165.72, 158.67, 149.39, 147.45, 147.23, 141.17, 136.74, 134.02,
131.95, 128.59, 128.06, 127.81, 127.45, 122.13, 121.52, 119.41,
116.94, 116.64, 52.76, 34.73, 31.42 ppm. MS (EI, 70 eV): m/z (%)
= 386 (40) [M]+, 371 (100), 343 (4.6), 283 (5.1), 185 (8.8), 171 (39).
C25H22O4 (386.45): calcd. C 77.70, H 5.74; found C 77.62, H 5.83.
MS (EI, 70 eV): m/z (%) = 320 (100) [M]+, 319 (7.8), 292 (17), 260
(12), 233 (28), 205 (35), 176 (30), 88 (26). C19H12O5 (320.30): calcd.
C 71.25, H 3.78; found C 71.00, H 3.81.
9-(Methoxycarbonyl)-7-(naphthalen-1-yl)-6H-benzo[c]chromen-6-
one (5i): Yield 71 %. White solid, m.p. 236–237 °C. 1H NMR
(600 MHz, CDCl3): δ = 8.90 (s, 1 H), 8.20 (d, J = 7.8 Hz, 1 H),
8.09 (s, 1 H), 7.91 (d, J = 6.7 Hz, 2 H), 7.54 (t, J = 7.2 Hz, 1 H),
7.50–7.41 (m, 2 H), 7.33 (dd, J = 12.0, 7.8 Hz, 4 H), 7.28 (d, J =
8.4 Hz, 1 H), 3.94 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 165.55, 157.86, 151.46, 145.36, 139.07, 136.25, 134.47, 133.17,
132.63, 131.63, 131.02, 128.32, 127.90, 126.06, 125.64, 125.14,
125.03, 124.96, 124.49, 123.33, 123.06, 122.85, 117.49, 117.44,
52.73 ppm. MS (EI, 70 eV): m/z (%) = 380 (100) [M]+, 363 (56),
321 (18), 263 (19), 160 (21), 131 (43), 118 (14). C25H16O4 (380.40):
9-(Methoxycarbonyl)-3,4-dimethyl-7-phenyl-6H-benzo[c]chromen-6-
one (5d): Yield 75 %. White solid, m.p. 237–238 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.67 (s, 1 H), 7.95 (s, 1 H), 7.81 (d, J =
8.0 Hz, 1 H), 7.43 (q, J = 5.2 Hz, 3 H), 7.37–7.31 (m, 2 H), 7.09
(d, J = 8.0 Hz, 1 H), 3.97 (s, 3 H), 2.35 (s, 3 H), 2.31 (s, 3 H) ppm. calcd. C 78.94, H 4.24; found C 79.03, H 4.15.
13C NMR (100 MHz, CDCl3): δ = 165.64, 158.74, 149.48, 146.91,
7-(Methoxycarbonyl)-5-phenyl-4H-benzo[d]naphtha[1,2-b]pyran-4-
141.14, 140.34, 136.94, 133.90, 131.39, 128.13, 127.75, 127.40,
125.69, 124.78, 122.23, 120.68, 119.92, 114.95, 52.66, 20.11,
11.50 ppm. MS (EI, 70 eV): m/z (%) = 358 (72) [M]+, 357 (100),
299 (5.8), 255 (7.9), 228 (6.0), 163 (7.5), 148 (11). C23H18O4
(358.39): calcd. C 77.08, H 5.06; found C 77.25, H 4.95.
one (5j): Yield 74%. White solid, m.p. 219–221 °C. 1H NMR
(600 MHz, CDCl3): δ = 9.25 (s, 1 H), 8.73 (d, J = 8.4 Hz, 1 H),
8.07 (s, 1 H), 7.94 (dd, J = 11.4, 8.4 Hz, 2 H), 7.72 (t, J = 8.4 Hz,
1 H), 7.57 (t, J = 7.2 Hz, 1 H), 7.50–7.42 (m, 4 H), 7.39 (d, J =
7.8 Hz, 2 H), 4.01 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 165.76, 158.58, 150.10, 146.82, 140.90, 136.84, 133.56, 132.09,
131.43, 131.30, 129.30, 129.24, 128.38, 128.14, 127.86, 127.64,
127.04, 125.38, 124.57, 122.63, 116.92, 112.25, 52.80 ppm. MS (EI,
70 eV): m/z (%) = 380 (100) [M]+, 379 (41), 321 (14), 292 (15), 263
(22), 182 (15), 131 (19). C25H16O4 (380.40): calcd. C 78.94, H 4.24;
found C 78.87, H 4.30.
7-(4-Bromophenyl)-9-(methoxycarbonyl)-6H-benzo[c]chromen-6-one
(5e): Yield 87 %. White solid, m.p. 249–250 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.81 (s, 1 H), 8.18 (d, J = 6.8 Hz, 1 H),
7.98 (s, 1 H), 7.54 (dd, J = 21.2, 6.8 Hz, 3 H), 7.36 (dd, J = 15.6,
6.8 Hz, 2 H), 7.21 (d, J = 6.4 Hz, 2 H), 4.00 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 165.46, 158.54, 151.42, 145.96,
139.96, 136.60, 134.35, 132.04, 131.19, 131.06, 129.87, 124.63,
123.39, 122.80, 121.92, 121.40, 117.48, 117.44, 52.88 ppm. MS (EI,
70 eV): m/z (%) = 408 (84) [M]+, 409 (100) [M + 1]+, 407 (99), 270
(28), 213 (46), 164 (21), 135 (53), 93 (19). C21H13BrO4 (409.24):
calcd. C 61.63, H 3.20; found C 61.49, H 3.05.
General Procedure for the Effect of Phosphine Loading on the 3a/4a
Ratio: The general procedure for the investigation of the effect of
phosphine loading (PPh3 ranging from 0.1 to 1.0 equiv.) on the 3a/
4a ratio was similar to the procedure used for the synthesis of prod-
ucts 3 and the results are summarized in Figure 1.
2-(Ethoxycarbonyl)-9-(methoxycarbonyl)-7-phenyl-6H-benzo[c]-
chromen-6-one (5f): Yield 86%. White solid, m.p. 206–207 °C. 1H
NMR (400 MHz, CDCl3): δ = 8.86 (s, 1 H), 8.16 (d, J = 8.4 Hz, 1
H), 8.06 (s, 1 H), 7.44 (d, J = 1.4 Hz, 3 H), 7.34 (dd, J = 15.2,
8.4 Hz, 3 H), 4.47 (q, J = 7.2 Hz, 2 H), 4.03 (s, 3 H), 1.47 (t, J =
7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.37,
157.76, 154.21, 147.38, 140.66, 135.65, 134.49, 132.78, 131.86,
128.07, 127.89, 127.67, 126.82, 125.45, 122.54, 121.29, 117.50,
61.47, 52.85, 14.34 ppm. MS (EI, 70 eV): m/z (%) = 402 (100)
[M]+, 401 (98), 373 (27), 357 (28), 213 (20), 178 (22), 106 (16).
C24H18O6 (402.40): calcd. C 71.64, H 4.51; found C 76.80, H 4.33.
General Procedure for the Effect of Phosphine Loading on the Yield
of 5a: The general procedure for the investigation of the effect of
phosphine loading (PPh3 ranging from 0.1 to 1.2 equiv.) on the
yield of 5a was similar to the procedure used for synthesis of prod-
ucts 5. The results are summarized in Figure 1.
Supporting Information (see footnote on the first page of this arti-
cle): General Remarks, General Procedure of control experiments
1
and copies of H and 13C NMR spectra of all new products 3, 4,
and 5.
9-(Methoxycarbonyl)-2-nitro-7-phenyl-6H-benzo[c]chromen-6-one
(5g): Yield 83%. White solid, m.p. Ͼ 250 °C. 1H NMR (400 MHz,
CDCl3/CF3CO2D): δ = 9.31 (s, 1 H), 9.10 (s, 1 H), 8.50 (d, J =
8.8 Hz, 1 H), 8.29 (s, 1 H), 7.61 (d, J = 9.2 Hz, 1 H), 7.52–7.45 (m,
Acknowledgments
The authors are grateful to the National Natural Science Founda-
tion of China (NSFC) (grant number 21342004) and the Open Pro-
3 H), 7.43–7.36 (m, 2 H), 4.21 (s, 3 H) ppm. 13C NMR (100 MHz, ject of Key Laboratory of Theoretical Chemistry & Molecular Sim-
CDCl3/CF3CO2D): δ = 168.33, 161.17, 155.00, 149.32, 145.13,
ulation of Ministry of Education, Hunan University of Science and
140.07, 135.85, 135.41, 134.50, 128.69, 128.61, 128.27, 126.66, Technology (grant number LKF1206) for financial support of this
123.48, 121.34, 120.56, 119.35, 119.05, 54.18 ppm. MS (EI, 70 eV):
m/z (%) = 375 (84) [M]+, 374 (100), 328 (23), 270 (9.0), 213 (22),
134 (9.3), 106 (21). C21H13NO6 (375.34): calcd. C 67.20, H 3.49, N
3.73; found C 67.07, H 3.32, N 3.91.
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7.59 (s, 1 H), 7.46 (t, J = 7.5 Hz, 1 H), 7.29 (t, J = 9.2 Hz, 2 H),
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590
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Received: September 8, 2013
Published Online: November 19, 2013
Eur. J. Org. Chem. 2014, 583–591
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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