Phosphazene base-catalyzed intramolecular cascade reactions of aryl-substituted enynes

Article abstract of DOI:10.1055/s-0030-1258172

A novel method for the synthesis of 9-aryl-3a,4-dihydronaphtho[2,3-c]furan- 1(3H)-ones has been developed by P₄-t-Bu-catalyzed intramolecular cascade reactions of enynes. In the presence of a catalytic amount of phosphazene P₄-t-Bu base, a variety of 3-arylallyl 3-arylpropiolates underwent the cascade cyclization reaction smoothly in moderate to excellent yields. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258172

3204
PAPER
Phosphazene Base-Catalyzed Intramolecular Cascade Reactions of
Aryl-Substituted Enynes
I
ntramolec
i
ular Cascade Rea
n
c
tions of
A
ry
-
l-Substit
S
uted
E
nynes heng Tang,a,b Ye-Xiang Xie,a Zhi-Qiang Wang,a Chen-Liang Deng,a Jin-Heng Li*a
a
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education), Hunan Normal University,
Changsha 410081, P. R. of China
Fax +86(731)88872101; E-mail: jhli@hunnu.edu.cn
Mathematics and Science Department, Hunan First Normal University, Changsha, 410205, P. R. of China
b
Received 6 April 2010; revised 28 May 2010
dronaphtho[2,3-c]furan-1(3H)-one using
a
catalytic
available)
Abstract: A novel method for the synthesis of 9-aryl-3a,4-dihy-
dronaphtho[2,3-c]furan-1(3H)-ones has been developed by P4-t-
Bu-catalyzed intramolecular cascade reactions of enynes. In the
presence of a catalytic amount of phosphazene P4-t-Bu base, a vari-
amount
of
P4-t-Bu
(commercially
(Scheme 1).4,5 It is noteworthy that these products are a
prevalent motif in many naturally occurring and biologi-
ety of 3-arylallyl 3-arylpropiolates underwent the cascade cycliza- cally active compounds, such as the known antiviral and
antitumor agents daurinol and retrochinensin.6
tion reaction smoothly in moderate to excellent yields.
Key words: P4-t-Bu base, cascade cyclization reaction, 9-aryl-
3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one, 3-arylallyl 3-arylpro-
R1
piolate
Y
R1
Ac2O, reflux
ref. 2
Y
(1)
(2)
R
O
R
O
The cascade reaction strategy is of continuing interesting
in the field of organic chemistry because it is a valuable
route for the synthesis of polysubstituted polycyclic com-
pounds.1–3 Our interest is focused on the intramolecular
Diels–Alder reactions of aryl-substituted enynes 1, which
proceeds via a cascade cyclization process (Scheme 1).
Traditionally, there are two transformations for these pur-
poses: one involves acetic anhydride mediated cyclization
via the activation of the ortho-arene C–H bond at the ter-
minal alkene (Scheme 1),2 and the other is acetic
anhydride2h or base-mediated cyclization employing the
ortho-arene C–H bond at the terminal alkyne as a reaction
partner.3 For example, Klemm and Gopinath described in-
tramolecular Diels–Alder cyclization of 3,4-(methylene-
dioxy)cinnamyl 3,4,5-trimethoxyphenylpropiolate to
afford g-apopicropodophyllin in 48% yield using acetic
anhydride as the catalyst and solvent.2a In 1972, Laird and
Ollis employed allylpropynyl ammonium cations as the
R2
R2
Z
R1
base (NaOH or KOt-Bu)
Z
Y
Y
R1
or Ac2O, reflux
ref. 3
R1
Y
R1
P4-t-Bu (10 mol%)
DCE, 100 °C
this work
Y
(3)
R2
O
R2
O
1
2
NMe2
N
P
N
P
NMe2
Me2N
P
N
N
P
NMe2
P4-t-Bu:
NMe2
Me2N
NMe2
NMe2
NMe2
Scheme 1 Intramolecular cascade reactions
substrates, shifting regioselectivity toward the ortho- Our initial investigation began with the cyclization of cin-
arene C–H bond at the terminal alkyne in the presence of namyl 3-phenylpropiolate (1a) to optimize the reaction
excess sodium methoxide.3a Subsequently, several papers conditions (Table 1). Generally, base-mediated intramo-
have been reported that extend these routes in organic lecular Diels–Alder reactions of aryl-substituted enyne 1a
synthesis, but the scope has not yet been examined and it are used with the ortho-arene C–H bond at the terminal
is often restricted to special substrates with unsatisfactory alkyne as a reaction partner.3 However, we found that only
yields. Moreover, the high acetic anhydride or base load- product 2a was obtained by activating the ortho-arene C–
ings, resulting in toxic byproducts, hardly make the two H bond at the terminal alkene using various bases (entries
transformations attractive procedures. Therefore, the de- 1–13). The results demonstrated that the amount of potas-
velopment of a novel, catalytic route for the intramolecu- sium carbonate affected the reaction (entries 1–4). While
lar cascade cyclization of enynes remains a challenging treatment of substrate 1a with two equivalents of potassi-
area. Here, we report the first intramolecular cascade cy-
um carbonate afforded the target product 2a in 20% yield
clization protocol for the synthesis of 9-aryl-3a,4-dihy- (entry 1), 5 equivalents of potassium carbonate enhanced
the yield to 80% (entry 3), and an identical result was ob-
tained in the presence of six equivalents of potassium car-
bonate (entry 4). Prompted by these results, a variety of
other bases, such as Cs2CO3, K3PO4, NaOH, NaOEt,
SYNTHESIS 2010, No. 18, pp 3204–3210
Advanced online publication: 12.07.2010
DOI: 10.1055/s-0030-1258172; Art ID: F06210SS
x
x.
x
x
.
2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

PAPER
Intramolecular Cascade Reactions of Aryl-Substituted Enynes
3205
Table 1 Screening Optimal Conditionsa
no reaction occurred (entry 15). Subsequently, a number
of other solvents, including toluene, tetrahydrofuran, and
N,N-dimethylformamide, were tested, and they were less
effective than 1,2-dichloroethane (entries 16–18). Finally,
the effect of the reaction temperature was evaluated, and
it turned out that both 80 °C and 120 °C decreased the
yield (entries 19 and 20). The structure of 2a was unam-
biguously confirmed by X-ray single-crystal diffraction
analysis (Figure 1).7
O
base
O
O
Ph
Ph
2a
O
1a
NMe2
N
P
N
P
NMe2
N
P
N
Me2N
P
N
N
P
NMe2
N
N
NMe2
Me2N
NMe2
NMe2
NMe2
P1 (BEMP)
P4-t-Bu
Entry Base (equiv)
Solvent Temp (°C) Isolated yield (%)
1
2
K2CO3 (2)
K2CO3 (4)
K2CO3 (5)
K2CO3 (6)
Cs2CO3 (5)
K3PO4 (5)
NaOH (5)
NaOEt (5)
DABCO (5)
DBU (5)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
20
52
3
80
4
75
5
44
6
61
7
trace
70
Figure 1 ORTEP diagram of the single-crystal X-ray structure of
compound 2a
8
9
20
With the optimized reaction conditions in hand, the enyne
scope was investigated (Table 2).8 Initially, a series of 3-
arylallyl 3-phenylpropiolates 1b–d, bearing electron-rich
or electron-deficient arylallyl groups, were treated with
P4-t-Bu smoothly in good yields (entries 1–3). Gratifying-
ly, a moderate yield of 2e was still isolated from het-
eroarylallyl substrate 1e (entry 4). The results showed that
several functional groups, such as methyl, methoxy, iodo,
bromo, fluoro, acetyl, and nitro groups, on the aryl ring of
the 3-arylpropiolate moiety were tolerated (entries 5–15).
The cyclization reaction of substrates 1f–h with a p-, m-,
or o-methyl group, for instance, successfully proceeded
with P4-t-Bu in moderate yields (entries 5–7). It is pleas-
ing to observe that the optimized conditions were compat-
ible with halo-substituted substrates 1k–m (entries 10–
12). Electron-deficient substrates 1n–p also underwent
the cyclization reaction with P4-t-Bu in excellent yields
(entries 13–15). It was noted that cinnamyl 3-(thiophen-2-
yl)propiolate (1q) was suitable for the reaction, affording
the corresponding product 2q in 90% yield (entry 16). In
the presence of P4-t-Bu, two N-cinnamyl-3-phenylpropi-
olamides 1r and 1s were also consistent with the reaction
conditions, and they were transformed into the desired
products 2r and 2s in 70% and 81% yields, respectively
(entries 17 and 18). However, (E)-[3-(cinnamyloxy)prop-
1-ynyl]benzene was not a suitable substrate under the op-
timized conditions.
10
11b
12b
13b
14b
15b
16
17
18
19
20
35
P4-t-Bu (0.05)
P4-t-Bu (0.1)
P4-t-Bu (0.2)
P1 (0.1)
52
82
46
80
Ph3P (0.1)
K2CO3 (5)
K2CO3 (5)
K2CO3 (5)
K2CO3 (5)
K2CO3 (5)
trace
45
toluene 100
THF
DMF
DCE
DCE
100
100
80
53
trace
34
120
65
a Conditions: 1a (0.2 mmol), base, solvent (2 mL), 24 h.
b For 60 h.
DABCO, DBU, and P4-t-Bu, were examined (entries 5–
13). We found that all but one were inferior to potassium
carbonate (entries 5–10). To our delight, 10 mol% of P4-t-
Bu, an organic superbase, gave the best results after pro-
longed the reaction time (entry 12). Identical results were
observed using P1 (BEMP) base (entry 14). Triphe-
nylphosphine was also evaluated as the catalyst, however,
Synthesis 2010, No. 18, 3204–3210 © Thieme Stuttgart · New York

3206
J.-S. Tang et al.
PAPER
Table 2 P4-t-Bu-Catalyzed Intramolecular Cyclization Reactions of
Enynes 1a
Table 2 P4-t-Bu-Catalyzed Intramolecular Cyclization Reactions of
Enynes 1a (continued)
Yieldb (%)
Entry Enyne 1
Product 2
Yieldb (%)
Entry Enyne 1
Product 2
O
Bn
N
1
92
O
18
81
Bn
N
O
O
Ph
Ph
Ph
O
Ph
Ph
Ph
O
2b
2s
1b
1s
OMe
a Reaction conditions: 1 (0.2 mmol), P4-t-Bu (10 mol%), DCE (2 mL),
O
100 °C, 60 h.
2
72
80
63
b Isolated yield.
O
OMe
O
Ph
O
2c
1c
Compared with the results for the base-mediated intramo-
lecular Diels–Alder reactions of aryl-substituted enynes
1,3 different chemoselectivity was observed in the present
reaction: the chemoselectivity was shifted towards the
ortho-arene C–H bond at the terminal alkene, which is
identical to the acetic anhydride mediated cyclization pro-
cess. Thus, we deduced that the present reaction proceeds
via a Diels–Alder mechanism,2 and the role of P4-t-Bu
base is as an acid scavenger that promotes the reaction by
a proton-transfer process (Scheme 2).
NO2
O
3
O
NO2
O
Ph
O
2d
1d
S
S
O
4
O
Ph
O
Ph
O
2e
1e
R1
R1
O
O
Diels–Alder cyclization
Y
Y
H
R2
O
O
O
R2
O
1
A
R
R
5
6
R = 4-Me 1f
R = 3-Me 1g
R = 2-Me 1h
R = 4-OMe 1i
R = 2-OMe 1j
R = 4-I 1k
R = 4-Me 2f
61
60
55
86
92
48
91
54
91
98
92
R1
[P4-t-Bu]
Y
proton transfer
R = 3-Me 2g
R = 2-Me 2h
R = 4-OMe 2i
R = 2-OMe 2j
R = 4-I 2k
O
R2
2
7
Scheme 2 A possible mechanism
8
9
In summary, we have disclosed phosphazene P4-t-Bu base
as an efficient catalyst for the intramolecular cascade cy-
clization of enynes. This work is the first to demonstrate
that the intramolecular Diels–Alder cyclization reaction
of enynes can be carried out successfully using a catalytic
amount of phosphazene P4-t-Bu base. Importantly, this
new route allows the base-catalyzed mediated intramolec-
ular cascade cyclization of enynes by activating the ortho-
arene C–H bond at the terminal alkene, not the ortho-
arene C–H bond at the terminal alkyne.3
10
11
12
13
14
15
R = 2-Br 1l
R = 2-Br 2l
R = 4-F 1m
R = 4-Ac 1n
R = 3-Ac 1o
R = 3-NO2 1p
R = 4-F 2m
R = 4-Ac 2n
R = 3-Ac 2o
R = 3-NO2 2p
O
NMR spectroscopy was performed on a Bruker-500 spectrometer
operating at 500 MHz (1H NMR) and 125 MHz (13C NMR), TMS
internal standard and CDCl3 solvent. MS analysis was performed by
GC-MS analysis (Shimadzu GCMS-QP2010 plus). Melting points
are uncorrected.
16
17
90
70
O
S
O
S
O
1q
2q
Pr
N
Phosphazene Base Catalyzed Intramolecular Cascade Reac-
tions of Aryl-Substituted Enynes; Typical Procedure
3-Arylallyl 3-arylpropiolate 1 (0.2 mmol), P4-t-Bu (10 mol%), and
DCE (2 mL) were added to a Schlenk tube and the soln was stirred
at 100 °C for the indicated time until complete consumption of start-
Pr
N
O
O
Ph
Ph
2r
1r
Synthesis 2010, No. 18, 3204–3210 © Thieme Stuttgart · New York

PAPER
Intramolecular Cascade Reactions of Aryl-Substituted Enynes
3207
ing material (TLC and GC-MS monitoring). When the reaction was
finished, the mixture was washed with brine and extracted with
Et2O. The combined extracts were dried (anhyd Na2SO4) and evap-
orated in vacuo. The residue was purified by flash column chroma-
tography (silica gel, hexane–EtOAc) to afford the desired product.
13C NMR (125 MHz, CDCl3): d = 167.3, 147.5, 145.3, 142.3, 137.4,
132.6, 130.0, 129.3, 128.9, 128.3, 124.4, 124.3, 123.4, 70.9, 35.2,
32.8.
LRMS (EI, 70 eV): m/z (%) = 307 (M+, 100), 290 (33), 260 (17),
215 (36), 101 (35).
HRMS (EI): m/z [M]+ calcd for C18H13NO4: 307.0845; found:
307.0848.
9-Phenyl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one (2a)6e
White solid; mp 182.1–183.3 °C.
IR (KBr): 1748 cm–1.
4-Phenyl-7a,8-dihydrothieno[2,3-f][2]benzofuran-5(7H)-one
1H NMR (500 MHz, CDCl3): d = 7.46–7.38 (m, 3 H), 7.34–7.29 (m,
4 H), 7.18 (t, J = 7.5 Hz, 1 H), 6.95 (d, J = 8.0 Hz, 1 H), 4.73 (t,
J = 9.0 Hz, 1 H), 4.04 (t, J = 8.5 Hz, 1 H), 3.50–3.42 (m, 1 H), 3.07,
3.05 (dd, J = 6.5, 6.5 Hz, 1 H), 2.90, 2.87 (dd, J = 15.0, 15.0 Hz, 1
H).
13C NMR (125 MHz, CDCl3): d = 168.2, 147.3, 135.9, 135.4, 134.2,
129.8, 129.1, 128.5, 128.0, 127.8, 127.2, 126.4, 122.1, 71.2, 35.5,
33.0.
(2e)6e
Yellow solid; mp 136.5–138.0 °C.
IR (KBr): 1748 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.51–7.49 (m, 1 H), 7.48–7.38 (m,
4 H), 7.07 (t, J = 6.0 Hz, 1 H), 6.72 (d, J = 5.0 Hz, 1 H), 4.71 (t,
J = 7.5 Hz, 1 H), 4.05 (t, J = 9.0 Hz, 1 H), 3.69–3.60 (m, 1 H), 3.24,
3.20 (dd, J = 8.0, 7.5 Hz, 1 H), 2.85, 2.81 (dd, J = 16.5, 16.5 Hz, 1
H).
LRMS (EI, 70 eV): m/z (%) = 262 (M+, 100), 231 (46), 217 (72),
203 (70), 101 (41).
13C NMR (125 MHz, CDCl3): d = 168.0, 144.2, 139.2, 138.1, 134.3,
129.4, 128.8, 127.8, 126.8, 122.9, 117.5, 70.5, 37.4, 27.8.
LRMS (EI, 70 eV): m/z (%) = 268 (M+, 38), 223 (33), 165 (11), 43
(100).
7-Methyl-9-phenyl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
one (2b)
White solid; mp 165.8–167.0 °C.
IR (KBr): 1748 cm–1.
9-(4-Tolyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one (2f)
White solid; mp 151.1–152.8 °C.
IR (KBr): 1748 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.45–7.44 (m, 3 H), 7.29–7.26 (m,
2 H), 7.17 (d, J = 7.5 Hz, 1 H), 7.11 (d, J = 8.0 Hz, 1 H), 6.75 (s, 1
H), 4.71 (t, J = 9.0 Hz, 1 H), 4.03 (t, J = 8.5 Hz, 1 H), 3.46–3.38 (m,
1 H), 3.03, 3.01 (dd, J = 6.5, 6.5 Hz, 1 H), 2.84, 2.81 (dd, J = 15.5,
15.5 Hz, 1 H), 2.22 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 168.3, 147.5, 136.9, 135.8, 134.3,
132.4, 130.5, 129.7, 128.5, 128.0, 127.9, 127.8, 122.1, 71.1, 35.8,
32.7, 21.1.
LRMS (EI, 70 eV): m/z (%) = 276 (M+, 53), 215 (27), 202 (29), 71
(77), 57 (100), 43 (98).
HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found:
276.1148.
1H NMR (500 MHz, CDCl3): d = 7.30–7.26 (m, 2 H), 7.26–7.20 (m,
2 H), 7.20–7.17 (m, 3 H), 6.99 (d, J = 7.5 Hz, 1 H), 4.72 (t, J = 9.0
Hz, 1 H), 4.04 (t, J = 7.5 Hz, 1 H), 3.48–3.40 (m, 1 H), 3.06, 3.01
(dd, J = 6.5, 6.5 Hz, 1 H), 2.88, 2.86 (dd, J = 15.5, 15.5 Hz, 1 H),
2.42 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 168.3, 147.6, 138.4, 136.1, 135.5,
131.2, 129.7, 129.2, 128.7, 128.0, 127.2, 121.8, 71.1, 35.6, 33.1,
21.4.
LRMS (EI, 70 eV): m/z (%) = 276 (M+, 100), 231 (98), 217 (58),
202 (60), 101 (26).
HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found:
276.1149.
7-Methoxy-9-phenyl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
one (2c)8
9-(3-Tolyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one (2g)
White solid; mp 152.2–153.0 °C.
IR (KBr): 1748 cm–1.
White solid; mp 142.0–143.8 °C.
IR (KBr): 1745 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.43–7.42 (m, 3 H), 7.31–7.29 (m,
2 H), 7.19 (d, J = 7.5 Hz, 1 H), 6.85–6.83 (m, 1 H), 6.50 (d, J = 2.5
Hz, 1 H), 4.71 (t, J = 9.0 Hz, 1 H), 4.03 (t, J = 7.5 Hz, 1 H), 3.65 (s,
3 H), 3.46–3.38 (m, 1 H), 3.02, 2.99 (dd, J = 7.0, 6.5 Hz, 1 H), 2.81,
2.77 (dd, J = 15.0, 15.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 168.2, 158.7, 147.2, 137.0, 134.1,
129.7, 128.7, 128.5, 127.8, 127.4, 122.6, 115.3, 114.6, 71.1, 55.3,
35.9, 32.1.
1H NMR (500 MHz, CDCl3): d = 7.34–7.24 (m, 3 H), 7.22–7.19 (m,
1 H), 7.18–7.09 (m, 3 H), 6.97 (d, J = 8.0 Hz, 1 H), 4.72 (t, J = 7.5
Hz, 1 H), 4.03 (t, J = 8.0 Hz, 1 H), 3.48–3.40 (m, 1 H), 3.06, 3.03,
(dd, J = 6.5, 6.5 Hz, 1 H), 2.88, 2.85 (dd, J = 15.5, 15.5 Hz, 1 H),
2.38 (s, 3 H).
13C NMR (125 MHz, CDCl3): d = 168.2, 147.5, 137.4, 136.0, 135.4,
134.2, 129.8, 129.3, 129.2, 128.0, 127.8, 127.2, 122.0, 71.7, 35.6,
33.1, 21.4.
LRMS (EI, 70 eV): m/z (%) = 292 (M+, 100), 247 (47), 231 (14),
215 (28), 203 (20).
LRMS (EI, 70 eV): m/z (%) = 276 (M+, 100), 231 (93), 215 (49),
202 (62), 101 (23).
HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found:
276.1145.
7-Nitro-9-phenyl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one
(2d)
Yellow solid; mp 188.0–189.9 °C.
IR (KBr): 1748 cm–1.
9-(2-Tolyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one (2h)
White solid; mp 126.9–128.2 °C.
IR (KBr): 1748 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.32–7.26 (m, 4 H), 7.22–7.14 (m,
2 H), 6.91 (d, J = 7.5 Hz, 1 H), 6.80 (d, J = 8.0 Hz, 1 H), 4.74 (t,
J = 6.5 Hz, 1 H), 4.07 (t, J = 9.0 Hz, 1 H), 3.51–3.46 (m, 1 H), 3.09,
1H NMR (500 MHz, CDCl3): d = 8.16–8.14 (m, 1 H), 7.80 (d,
J = 2.5 Hz, 1 H), 7.49–7.46 (m, 4 H), 7.30–7.26 (m, 2 H), 4.76 (t,
J = 7.5 Hz, 1 H), 4.08 (t, J = 9.0 Hz, 1 H), 3.55–3.47 (m, 1 H), 3.23,
3.20 (dd, J = 6.5, 6.5 Hz, 1 H), 2.97, 2.94 (dd, J = 15.5, 15.5 Hz, 1
H).
Synthesis 2010, No. 18, 3204–3210 © Thieme Stuttgart · New York

3208
J.-S. Tang et al.
PAPER
3.08 (dd, J = 3.0, 3.5 Hz, 1 H), 2.92, 2.88 (dd, J = 16.0, 15.0 Hz, 1
HRMS (EI): m/z [M]+ calcd for C18H13IO2: 387.9960; found:
H), 2.24 (s, 3 H).
387.9956.
13C NMR (125 MHz, CDCl3): d = 168.1, 168.0, 146.2, 137.0, 135.4,
135.2, 135.1, 134.7, 134.0, 131.2, 130.2, 130.1, 130.0, 129.9, 129.7,
128.6, 128.5, 128.2, 128.2, 128.0, 127.9, 127.7, 127.5, 126.5, 125.8,
125.4, 123.0, 122.7, 71.4, 35.3, 32.8, 19.5.
LRMS (EI, 70 eV): m/z (%) = 276 (M+, 74), 231 (100), 215 (84),
202 (63), 101 (21).
9-(2-Bromophenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
one (2l)
Pale–yellow solid; mp 137.5–139.0 °C.
IR (KBr): 1748 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.48–7.40 (m, 8 H), 4.31–4.27 (m,
1 H), 4.22–4.17 (m, 1 H), 4.05–4.02 (m, 1 H), 3.94, 3.92 (dd,
J = 3.5, 5.0 Hz, 1 H), 3.80, 3.79 (dd, J = 8.5, 8.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 167.9, 145.5, 135.4, 135.1, 134.4,
132.9, 132.5, 131.6, 129.9, 128.2, 127.4, 126.9, 124.2, 123.8, 122.1,
71.4, 35.3, 32.7.
HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found:
276.1148.
9-(4-Methoxyphenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
one (2i)
White solid; mp 130.0–131.5 °C.
IR (KBr): 1748 cm–1.
LRMS (EI, 70 eV): m/z (%) = 342 (M+ + 2, 1), 340 (M+, 1), 261
(100), 233 (10), 215 (15), 202 (68).
1H NMR (500 MHz, CDCl3): d = 7.32–7.26 (m, 4 H), 7.20–7.17 (m,
1 H), 7.01 (d, J = 7.5 Hz, 1 H), 6.96 (d, J = 7.5 Hz, 2 H), 4.72 (t,
J = 8.5 Hz, 1 H), 4.04 (t, J = 8.5 Hz, 1 H), 3.86 (s, 3 H), 3.45–3.40
(m, 1 H), 3.05, 3.02 (dd, J = 6.5, 6.5 Hz, 1 H), 2.88, 2.85 (dd,
J = 15.5, 15.5 Hz, 1 H).
HRMS (EI): m/z [M]+ calcd for C18H13BrO2: 340.0099; found:
340.0093.
9-(4-Fluorophenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
one (2m)
Yellow solid; mp 175.1–176.9 °C.
IR (KBr): 1748 cm–1.
13C NMR (125 MHz, CDCl3): d = 168.4, 159.9, 147.4, 136.2, 135.6,
131.5, 129.8, 129.3, 128.0, 127.2, 126.2, 121.4, 113.2, 71.1, 55.2,
35.7, 33.1.
LRMS (EI, 70 eV): m/z (%) = 292 (M+, 100), 261 (10), 247 (62),
203 (32), 189 (39).
HRMS (EI): m/z [M]+ calcd for C19H16O3: 292.1099; found:
292.1105.
1H NMR (500 MHz, CDCl3): d = 7.34–7.28 (m, 4 H), 7.26–7.24 (m,
1 H), 7.21–7.10 (m, 2 H), 6.94 (d, J = 7.5 Hz, 1 H), 4.74 (t, J = 9.0
Hz, 1 H), 4.05 (t, J = 8.5 Hz, 1 H), 3.49–3.41 (m, 1 H), 3.07, 3.04
(dd, J = 6.5, 7.0 Hz, 1 H), 2.89, 2.86 (dd, J = 15.5, 15.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 168.2, 162.9 (d, J = 246.5 Hz, 1
C), 146.3, 135.7, 135.4, 129.9, 128.9, 128.1, 127.3, 122.4, 115.0,
114.9, 71.2, 35.6, 32.9.
9-(2-Methoxyphenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
one (2j)
Colorless oil.
IR (KBr): 1748 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.42–7.39 (m, 1 H), 7.29–7.26 (m,
2 H), 7.14–7.09 (m, 1 H), 7.00–6.91 (m, 4 H), 4.70 (t, J = 8.5 Hz, 1
H), 4.05 (t, J = 9.0 Hz, 1 H), 3.55–3.38 (m, 1 H), 3.07–3.02 (m, 1
H), 3.00–2.86 (m, 1 H), 2.04 (s, 3 H).
LRMS (EI, 70 eV): m/z (%) = 280 (M+, 100), 249 (31), 221 (74).
HRMS (EI): m/z [M]+ calcd for C18H13FO2: 280.0900; found:
280.0899.
9-(4-Acetylphenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
one (2n)
White solid; mp 170.9–172.1 °C.
13C NMR (125 MHz, CDCl3): d = 171.1, 168.3, 167.9, 157.8, 156.4,
144.5, 142.9, 135.5, 135.4, 135.3, 134.8, 131.9, 130.0, 129.8, 129.6,
129.6, 129.4, 128.6, 128.0, 127.5, 127.3, 127.0, 124.0, 123.4, 123.0,
122.8, 120.4, 120.1, 111.1, 111.0, 71.2, 71.2, 55.7, 55.5, 35.4, 35.3,
32.9, 32.8.
IR (KBr): 1741, 1678 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.20 (d, J = 8.5 Hz, 2 H), 7.41–
7.39 (m, 2 H), 7.34–7.29 (m, 2 H), 7.19–7.16 (m, 1 H), 6.87 (d,
J = 7.5 Hz, 1 H), 4.75 (t, J = 7.5 Hz, 1 H), 4.06 (t, J = 9.0 Hz, 1 H),
3.51–3.43 (m, 1 H), 3.09, 3.07 (dd, J = 6.5, 6.5 Hz, 1 H), 2.89, 2.88
(dd, J = 16.0, 15.0 Hz, 1 H), 2.65 (s, 3 H).
LRMS (EI, 70 eV): m/z (%) = 292 (M+, 100), 261 (41), 247 (31),
231 (43), 215 (23), 202 (36), 101 (22).
HRMS (EI): m/z [M]+ calcd for C19H16O3: 292.1099; found:
292.1100.
13C NMR (125 MHz, CDCl3): d = 197.8, 168.1, 146.1, 136.8, 135.4,
134.7, 130.1, 128.8, 128.4, 128.2, 128.1, 127.6, 127.4, 123.0, 71.3,
35.6, 32.9, 26.6.
LRMS (EI, 70 eV): m/z (%) = 304 (M+, 100), 289 (72), 261 (12),
231 (48), 217 (35), 202 (62), 101 (30).
HRMS (EI): m/z [M]+ calcd for C20H16O3: 304.1099; found:
304.1097.
9-(4-Iodophenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one
(2k)
Yellow solid; mp 223.7–225.1 °C.
IR (KBr): 1748 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.77 (d, J = 8.5 Hz, 2 H), 7.33–
7.28 (m, 2 H), 7.18 (t, J = 8.5 Hz, 1 H), 7.06–7.03 (m, 2 H), 6.93 (d,
J = 8.0 Hz, 1 H), 4.73 (t, J = 8.5 Hz, 1 H), 4.04 (t, J = 8.0 Hz, 1 H),
3.48–3.40 (m, 1 H), 3.07, 3.04 (dd, J = 7.0, 7.0 Hz, 1 H), 2.88, 2.85
(dd, J = 16.0, 15.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 168.1, 146.1, 137.0, 135.4, 133.7,
131.7, 130.1, 128.9, 128.2, 127.4, 122.5, 94.8, 71.2, 35.6, 32.9.
9-(3-Acetylphenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
one (2o)
White solid; mp 170.0–171.6 °C.
IR (KBr): 1740, 1675 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.04–8.02 (m, 1 H), 7.90–7.83 (m,
1 H), 7.59–7.53 (m, 2 H), 7.37–7.29 (m, 2 H), 7.19–7.16 (m, 1 H),
6.69 (d, J = 9.0 Hz, 1 H), 4.74 (t, J = 8.5 Hz, 1 H), 4.06 (t, J = 6.5
Hz, 1 H), 3.52–3.44 (m, 1 H), 3.09, 3.06 (dd, J = 6.5, 6.5 Hz, 1 H),
2.91, 2.88 (dd, J = 15.5, 16.0 Hz, 1 H), 2.61 (s, 3 H).
LRMS (EI, 70 eV): m/z (%) = 388 (M+, 100), 231 (34), 217 (39),
202 (73), 101 (30).
Synthesis 2010, No. 18, 3204–3210 © Thieme Stuttgart · New York

PAPER
Intramolecular Cascade Reactions of Aryl-Substituted Enynes
IR (KBr): 1674 cm–1.
3209
13C NMR (125 MHz, CDCl3): d = 197.7, 168.0, 146.0, 139.4, 136.9,
135.3, 135.2, 130.4, 130., 128.8, 128.2, 128.0, 127.9, 127.6, 127.4,
123.0, 71.3, 35.5, 32.8, 26.6.
LRMS (EI, 70 eV): m/z (%) = 304 (M+, 100), 289 (65), 261 (13),
217 (37), 202 (56), 101 (43).
HRMS (EI): m/z [M]+ calcd for C20H16O3: 304.1099; found:
304.1098.
1H NMR (500 MHz, CDCl3): d = 7.45–7.33 (m, 3 H), 7.32–7.28 (m,
4 H), 7.28–7.20 (m, 5 H), 7.18–7.12 (m, 1 H), 6.93 (d, J = 7.5 Hz, 1
H), 4.65 (d, J = 14.5 Hz, 1 H), 4.37 (d, J = 15.0 Hz, 1 H), 3.60 (t,
J = 9.0 Hz, 1 H), 3.12–3.02 (m, 1 H), 3.01–2.96 (m, 2 H), 2.78, 2.75
(dd, J = 5.0, 16.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 166.5, 141.0, 136.5 (2 C), 135.6,
135.4, 130.2, 129.2, 128.6, 128.4, 128.3, 128.2, 127.7, 127.6, 127.5,
126.9, 56.3, 47.0, 33.9, 32.2.
9-(3-Nitrophenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one
(2p)
LRMS (EI, 70 eV): m/z (%) = 351 (M+, 14), 351 (73), 350 (33), 349
(100), 258 (62), 245 (57), 215 (42), 202 (26), 91 (50).
HRMS (EI): m/z [M]+ calcd for C25H21NO: 351.1623; found:
351.1620.
Yellow solid; mp 203.0–204.3 °C.
IR (KBr): 1772, 1732, 1719 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.32–8.28 (m, 1 H), 8.18–8.10 (m,
1 H), 7.74–7.61 (m, 2 H), 7.36–7.31 (m, 2 H), 7.22–7.19 (m, 1 H),
6.86 (d, J = 8.0 Hz, 1 H), 4.77 (t, J = 8.5 Hz, 1 H), 4.09 (t, J = 9.0
Hz, 1 H), 3.52–3.48 (m, 1 H), 3.12, 3.00 (dd, J = 6.5, 6.5 Hz, 1 H),
2.93, 2.90 (dd, J = 16.0, 15.5 Hz, 1 H).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
13C NMR (125 MHz, CDCl3): d = 167.9, 148.0, 144.4, 135.9, 135.3,
134.8, 130.4, 129.1, 128.9, 128.5, 128.4, 127.6, 127.5, 123.9, 123.5,
71.4, 35.5, 32.7.
LRMS (EI, 70 eV): m/z (%) = 307 (M+, 88), 263 (25), 215 (29), 202
(100), 101 (21).
Acknowledgment
The authors thank the Scientific Research Fund of Hunan Provincial
Education Department (No. 08A037), Hunan Normal University
(No. 080605), and National Natural Science Foundation of China
(No. 20872112) for financial support.
HRMS (EI): m/z [M]+ calcd for C18H13NO4: 307.0845; found:
307.0848.
References
9-(Thiophen-2-yl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one
(2q)
(1) (a) Norton, J. A. Chem. Rev. 1942, 31, 319. (b) Martin, J.
G.; Hill, R. K. Chem. Rev. 1961, 61, 537. (c) Carlson, R. G.
Annu. Rep. Med. Chem. 1974, 9, 270. (d) Oppolzer, W.
Angew. Chem., Int. Ed. Engl. 1977, 16, 10. (e) Brieger, G.;
Bennett, J. N. Chem. Rev. 1980, 80, 63. (f) Kagan, H. B.;
Riant, O. Chem. Rev. 1992, 92, 1007. (g) Winkler, J. D.
Chem. Rev. 1996, 96, 167. (h) Kumar, A. Chem. Rev. 2001,
101, 1. (i) Takao, K.-i.; Munakata, R.; Tadano, K.-i. Chem.
Rev. 2005, 105, 4779. (j) Wessig, P.; Müller, G. Chem. Rev.
2008, 108, 2051.
(2) (a) Klemm, L. H.; Gopinath, K. W. Tetrahedron Lett. 1963,
4, 1243. (b) Klemm, L. H.; Gopinath, K. W. J. Heterocycl.
Chem. 1965, 2, 225. (c) Klemm, L. H.; Lee, D. H.;
Gopinath, K. W.; Klopfenstein, C. E. J. Org. Chem. 1966,
31, 2376. (d) Klemm, L. H.; Olson, D. R.; White, D. V.
J. Org. Chem. 1971, 36, 3740. (e) Klemm, L. H.;
Yellow solid; mp 128.0–130.1 °C.
IR (KBr): 1748 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.49 (d, J = 5.0 Hz, 1 H), 7.33–
7.30 (m, 1 H), 7.29–7.24 (m, 3 H), 7.24–7.22 (m, 1 H), 7.14 (d,
J = 9.0 Hz, 1 H), 4.71 (t, J = 8.5 Hz, 1 H), 4.04 (t, J = 8.5 Hz, 1 H),
3.47 (m, 1 H), 3.03, 3.01 (dd, J = 7.5, 6.5 Hz, 1 H), 2.87, 2.84 (dd,
J = 15.0, 15.5 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 167.8, 140.1, 135.9, 133.9, 130.5,
129.1, 127.9, 127.4, 127.3, 126.7, 124.1 71.0, 36.0, 32.8.
LRMS (EI, 70 eV): m/z (%) = 268 (M+, 84), 223 (100), 209 (50),
165 (23).
HRMS (EI): m/z [M]+ calcd for C16H12O2S: 268.0558; found:
268.0554.
Santhanam, P. S. J. Org. Chem. 1968, 33, 1268. (f)Klemm,
L. H.; Klemm, R. A.; Santhanam, P. S.; White, D. V. J. Org.
Chem. 1971, 36, 2169. (g) Klemm, L. H.; Santhanam, P. S.
J. Heterocycl. Chem. 1972, 9, 423. (h) Klemm, L. H.;
McGuire, T. M.; Gopinath, K. W. J. Org. Chem. 1976, 41,
2571. (i) Klemm, L. H.; McGuire, T. M. J. Heterocycl.
Chem. 1972, 9, 1215.
9-Phenyl-2-propyl-2,3,3a,4-tetrahydro-1H-benzo[f]isoindol-1-
one (2r)
Yellow oil.
IR (KBr): 1675 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.42–7.37 (m, 3 H), 7.27–7.21 (m,
4 H), 7.14 (t, J = 7.5 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 3.74–3.68
(m, 1 H), 3.37–3.32 (m, 1 H), 3.23 (d, J = 8.5 Hz, 1 H), 3.15–3.11
(m, 2 H), 3.06–3.02 (m, 1 H), 3.04, 2.82–2.79 (m, 1 H), 1.60–1.55
(m, 2 H), 0.89 (t, J = 7.0 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 166.6, 140.3, 136.6, 135.6, 135.4,
130.2, 129.7, 128.3, 128.2, 127.7, 127.7, 127.6, 60.4, 50.9, 34.0,
32.4, 20.6, 11.4.
(3) (a) Laird, T.; Ollis, W. D. J. Chem. Soc., Chem. Commun.
1972, 557. (b) Bartlett, A. J.; Laird, T.; Ollis, W. D. J. Chem.
Soc., Chem. Commun. 1974, 496. (c) Oppolzer, W.; Achini,
R.; Pfenninger, E.; Weber, H. P. Helv. Chim. Acta 1976, 59,
1186. (d) Laird, T.; Ollis, W. D.; Sutherland, I. O. J. Chem.
Soc., Perkin Trans. 1 1980, 1477. (e) Chukhadzhyan, E. O.;
Chukhadzhyan, El. O.; Shakhatuni, K. G.; Babayan, A. T.
Chem. Heterocycl. Compd. (Engl. Transl.) 1991, 27, 594.
(f) Chukhadzhyan, E. O.; Gevorkyan, A. R.; Chukhadzhyan,
El. O.; Kinoyan, F. S. Russ. J. Org. Chem. (Engl. Transl.)
2005, 41, 358. (g) Chukhadzhyan, E. O.; Gevorkyan, A. R.;
Chukhadzhyan, El. O.; Kinoyan, F. S. Zh. Org. Khim. 2005,
41, 369. (h) Herz, H.-G.; Schatz, J.; Maas, G. J. Org. Chem.
2001, 66, 3176.
LRMS (EI, 70 eV): m/z (%) = 304 (72), 303 (M+, 100), 302 (27),
274 (74), 260 (47), 231 (57), 215 (30), 202 (54).
HRMS (EI): m/z [M]+ calcd for C21H21NO: 303.1623; found:
303.1622.
2-Benzyl-9-phenyl-2,3,3a,4-tetrahydro-1H-benzo[f]isoindol-1-
one (2s)
Yellow solid; mp 135.8–138.0 °C.
Synthesis 2010, No. 18, 3204–3210 © Thieme Stuttgart · New York

3210
J.-S. Tang et al.
PAPER
(4) For selected reviews on superbases: (a) Schwesinger, R.;
Schlemper, H. Angew. Chem., Int. Ed. Engl. 1987, 26, 1167.
(b) Schwesinger, R.; Schlemper, H.; Hasenfratz, C.;
Willaredt, J.; Dambacher, T.; Breuer, T.; Ottaway, C.;
Fletschinger, M.; Boele, J.; Fritz, H.; Putzas, D.; Rotter, H.
W.; Bordwell, F. G.; Satish, A. V.; Ji, G.-Z.; Peters, E.-M.;
Peters, K.; von Schnering, H. G.; Walz, L. Liebigs Ann.
Chem. 1996, 1055. (c) Schlosser, M. Pure Appl. Chem.
1988, 60, 1627. (d) Ishikawa, T. Superbases for Organic
Synthesis: Guanidines, Amidines and Phosphazenes and
Related Organocatalysts; John Wiley & Sons: Chichester,
2009.
Kondo, Y. Tetrahedron Lett. 2007, 48, 8918.
(d) Kanazawa, C.; Ito, A.; Terada, M. Synlett 2009, 638.
(e) Kanazawa, C.; Goto, K.; Terada, M. Chem. Commun.
2009, 5248. (f) Naka, H.; Koseki, D.; Kondo, Y. Adv. Synth.
Catal. 2008, 350, 1901.
(6) (a) Anastas, P. T.; Stevenson, R. J. Nat. Prod. 1991, 54,
1687. (b) Flanagan, S. R.; Harrowven, D. C.; Bradley, M.
Tetrahedron 2002, 58, 5989. (c) Cow, C.; Leung, C.;
Charlton, J. L. Can. J. Chem. 2000, 78, 553. (d) Gordaliza,
M.; Garcia, P. A.; Miguel del Corral, J. M.; Castro, M. A.;
Gomez-Zurita, M. A. Toxicon 2004, 44, 441. (e) Eghbali,
N.; Eddy, J.; Anastas, P. T. J. Org. Chem. 2008, 73, 6932.
(7) The X-ray crystallographic data for compound 2a are
summarized in Supporting Information.
(5) For selected recent papers on P4-t-Bu-catalyzed reactions,
see: (a) Imahori, T.; Kondo, Y. J. Am. Chem. Soc. 2003, 125,
8082. (b) Imahori, T.; Hori, C.; Kondo, Y. Adv. Synth. Catal.
2004, 346, 1090. (c) Ebisawa, M.; Ueno, M.; Oshima, Y.;
(8) Revesz, L.; Meigel, H. Helv. Chim. Acta 1988, 71, 1697.
Synthesis 2010, No. 18, 3204–3210 © Thieme Stuttgart · New York