3204 PAPER

Phosphazene Base-Catalyzed Intramolecular Cascade Reactions of

Aryl-Substituted Enynes
IntramolecularCascadeReactionsofAryl-SubstiutedEnynes
Jian-Sheng 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: [email protected]
b
Mathematics and Science Department, Hunan First Normal University, Changsha, 410205, P. R. of China
Received 6 April 2010; revised 28 May 2010

dronaphtho[2,3-c]furan-1(3H)-one using a catalytic

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- amount of P4-t-Bu (commercially available)
Bu-catalyzed intramolecular cascade reactions of enynes. In the (Scheme 1).4,5 It is noteworthy that these products are a
presence of a catalytic amount of phosphazene P4-t-Bu base, a vari- 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
tion reaction smoothly in moderate to excellent yields. antitumor agents daurinol and retrochinensin.6
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
Ac2O, reflux Y R1

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Y (1)
R ref. 2
O R
O
The cascade reaction strategy is of continuing interesting
R2 R2
in the field of organic chemistry because it is a valuable Z
R1 base (NaOH or KOt-Bu)
route for the synthesis of polysubstituted polycyclic com- Y Z
(2)
or Ac2O, reflux Y R1
pounds.1–3 Our interest is focused on the intramolecular
ref. 3
Diels–Alder reactions of aryl-substituted enynes 1, which
R1
proceeds via a cascade cyclization process (Scheme 1).
Traditionally, there are two transformations for these pur- P4-t-Bu (10 mol%)
Y R1
Y
poses: one involves acetic anhydride mediated cyclization R2 DCE, 100 °C
(3)
O R2
via the activation of the ortho-arene C–H bond at the ter- O this work
1
minal alkene (Scheme 1),2 and the other is acetic 2

anhydride2h or base-mediated cyclization employing the

ortho-arene C–H bond at the terminal alkyne as a reaction NMe2 N NMe2

partner.3 For example, Klemm and Gopinath described in- P4-t-Bu: Me2N P N P N P NMe2
NMe2 N NMe2
tramolecular Diels–Alder cyclization of 3,4-(methylene- Me2N P NMe2
dioxy)cinnamyl 3,4,5-trimethoxyphenylpropiolate to NMe2
afford g-apopicropodophyllin in 48% yield using acetic
anhydride as the catalyst and solvent.2a In 1972, Laird and Scheme 1 Intramolecular cascade reactions
Ollis employed allylpropynyl ammonium cations as the
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-
SYNTHESIS 2010, No. 18, pp 3204–3210xx. 201
Advanced online publication: 12.07.2010 bonate (entry 4). Prompted by these results, a variety of
DOI: 10.1055/s-0030-1258172; Art ID: F06210SS other bases, such as Cs2CO3, K3PO4, NaOH, NaOEt,
© 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
O
N,N-dimethylformamide, were tested, and they were less
O
base effective than 1,2-dichloroethane (entries 16–18). Finally,
Ph O Ph the effect of the reaction temperature was evaluated, and
O
1a 2a it turned out that both 80 °C and 120 °C decreased the
yield (entries 19 and 20). The structure of 2a was unam-
NMe2 N NMe2 N
biguously confirmed by X-ray single-crystal diffraction
Me2N P N P N P NMe2 N P N analysis (Figure 1).7
NMe2 N NMe2 N
Me2N P NMe2
NMe2
P1 (BEMP)
P4-t-Bu

Entry Base (equiv) Solvent Temp (°C) Isolated yield (%)

1 K2CO3 (2) DCE 100 20

2 K2CO3 (4) DCE 100 52

3 K2CO3 (5) DCE 100 80

4 K2CO3 (6) DCE 100 75

5 Cs2CO3 (5) DCE 100 44

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6 K3PO4 (5) DCE 100 61

7 NaOH (5) DCE 100 trace

Figure 1 ORTEP diagram of the single-crystal X-ray structure of
8 NaOEt (5) DCE 100 70 compound 2a
9 DABCO (5) DCE 100 20
With the optimized reaction conditions in hand, the enyne
10 DBU (5) DCE 100 35
scope was investigated (Table 2).8 Initially, a series of 3-
11b P4-t-Bu (0.05) DCE 100 52 arylallyl 3-phenylpropiolates 1b–d, bearing electron-rich
or electron-deficient arylallyl groups, were treated with
12b P4-t-Bu (0.1) DCE 100 82 P4-t-Bu smoothly in good yields (entries 1–3). Gratifying-
13 b
P4-t-Bu (0.2) DCE 100 46 ly, a moderate yield of 2e was still isolated from het-
eroarylallyl substrate 1e (entry 4). The results showed that
14b P1 (0.1) DCE 100 80 several functional groups, such as methyl, methoxy, iodo,
15 b
Ph3P (0.1) DCE 100 trace bromo, fluoro, acetyl, and nitro groups, on the aryl ring of
the 3-arylpropiolate moiety were tolerated (entries 5–15).
16 K2CO3 (5) toluene 100 45 The cyclization reaction of substrates 1f–h with a p-, m-,
17 K2CO3 (5) THF 100 53
or o-methyl group, for instance, successfully proceeded
with P4-t-Bu in moderate yields (entries 5–7). It is pleas-
18 K2CO3 (5) DMF 100 trace ing to observe that the optimized conditions were compat-
ible with halo-substituted substrates 1k–m (entries 10–
19 K2CO3 (5) DCE 80 34
12). Electron-deficient substrates 1n–p also underwent
20 K2CO3 (5) DCE 120 65 the cyclization reaction with P4-t-Bu in excellent yields
a (entries 13–15). It was noted that cinnamyl 3-(thiophen-2-
Conditions: 1a (0.2 mmol), base, solvent (2 mL), 24 h.
b
For 60 h. 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-
DABCO, DBU, and P4-t-Bu, were examined (entries 5– olamides 1r and 1s were also consistent with the reaction
13). We found that all but one were inferior to potassium conditions, and they were transformed into the desired
carbonate (entries 5–10). To our delight, 10 mol% of P4-t- products 2r and 2s in 70% and 81% yields, respectively
Bu, an organic superbase, gave the best results after pro- (entries 17 and 18). However, (E)-[3-(cinnamyloxy)prop-
longed the reaction time (entry 12). Identical results were 1-ynyl]benzene was not a suitable substrate under the op-
observed using P1 (BEMP) base (entry 14). Triphe- timized conditions.
nylphosphine was also evaluated as the catalyst, however,

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3206 J.-S. Tang et al. PAPER

Table 2 P4-t-Bu-Catalyzed Intramolecular Cyclization Reactions of Table 2 P4-t-Bu-Catalyzed Intramolecular Cyclization Reactions of
Enynes 1a Enynes 1a (continued)

Entry Enyne 1 Product 2 Yieldb (%) Entry Enyne 1 Product 2 Yieldb (%)

O Bn N
1 O 92 18 Bn N 81
Ph O Ph Ph O Ph
O O
2b 2s
1b 1s
a
OMe Reaction conditions: 1 (0.2 mmol), P4-t-Bu (10 mol%), DCE (2 mL),
O 100 °C, 60 h.
2 O OMe 72 b
Isolated yield.
Ph O Ph
O
2c
1c Compared with the results for the base-mediated intramo-
NO2
lecular Diels–Alder reactions of aryl-substituted enynes
O 1,3 different chemoselectivity was observed in the present
3 O NO2 80 reaction: the chemoselectivity was shifted towards the
Ph O Ph
O
ortho-arene C–H bond at the terminal alkene, which is
2d identical to the acetic anhydride mediated cyclization pro-
1d
cess. Thus, we deduced that the present reaction proceeds
S via a Diels–Alder mechanism,2 and the role of P4-t-Bu

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S O
4 O 63 base is as an acid scavenger that promotes the reaction by
Ph O Ph a proton-transfer process (Scheme 2).
O
2e
1e
R1

O Diels–Alder cyclization Y R1
Y
O H
O R2 O R2
R O 1 A
O R

5 R = 4-Me 1f R = 4-Me 2f 61 [P4-t-Bu] Y R1

proton transfer
6 R = 3-Me 1g R = 3-Me 2g 60
O R2
7 R = 2-Me 1h R = 2-Me 2h 55 2

Scheme 2 A possible mechanism

8 R = 4-OMe 1i R = 4-OMe 2i 86

9 R = 2-OMe 1j R = 2-OMe 2j 92
In summary, we have disclosed phosphazene P4-t-Bu base
10 R = 4-I 1k R = 4-I 2k 48
as an efficient catalyst for the intramolecular cascade cy-
11 R = 2-Br 1l R = 2-Br 2l 91 clization of enynes. This work is the first to demonstrate
that the intramolecular Diels–Alder cyclization reaction
12 R = 4-F 1m R = 4-F 2m 54
of enynes can be carried out successfully using a catalytic
13 R = 4-Ac 1n R = 4-Ac 2n 91 amount of phosphazene P4-t-Bu base. Importantly, this
new route allows the base-catalyzed mediated intramolec-
14 R = 3-Ac 1o R = 3-Ac 2o 98
ular cascade cyclization of enynes by activating the ortho-
15 R = 3-NO2 1p R = 3-NO2 2p 92 arene C–H bond at the terminal alkene, not the ortho-
arene C–H bond at the terminal alkyne.3
O

16 90 NMR spectroscopy was performed on a Bruker-500 spectrometer

O S O
operating at 500 MHz (1H NMR) and 125 MHz (13C NMR), TMS
S
O internal standard and CDCl3 solvent. MS analysis was performed by
1q 2q GC-MS analysis (Shimadzu GCMS-QP2010 plus). Melting points
are uncorrected.
Pr N Phosphazene Base Catalyzed Intramolecular Cascade Reac-
17 Pr N 70
tions of Aryl-Substituted Enynes; Typical Procedure
Ph O Ph
O
3-Arylallyl 3-arylpropiolate 1 (0.2 mmol), P4-t-Bu (10 mol%), and
2r DCE (2 mL) were added to a Schlenk tube and the soln was stirred
1r
at 100 °C for the indicated time until complete consumption of start-

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PAPER Intramolecular Cascade Reactions of Aryl-Substituted Enynes 3207

13
ing material (TLC and GC-MS monitoring). When the reaction was C NMR (125 MHz, CDCl3): d = 167.3, 147.5, 145.3, 142.3, 137.4,
finished, the mixture was washed with brine and extracted with 132.6, 130.0, 129.3, 128.9, 128.3, 124.4, 124.3, 123.4, 70.9, 35.2,
Et2O. The combined extracts were dried (anhyd Na2SO4) and evap- 32.8.
orated in vacuo. The residue was purified by flash column chroma- LRMS (EI, 70 eV): m/z (%) = 307 (M+, 100), 290 (33), 260 (17),
tography (silica gel, hexane–EtOAc) to afford the desired product. 215 (36), 101 (35).
9-Phenyl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one (2a)6e HRMS (EI): m/z [M]+ calcd for C18H13NO4: 307.0845; found:
White solid; mp 182.1–183.3 °C. 307.0848.
IR (KBr): 1748 cm–1. 4-Phenyl-7a,8-dihydrothieno[2,3-f][2]benzofuran-5(7H)-one
1
H NMR (500 MHz, CDCl3): d = 7.46–7.38 (m, 3 H), 7.34–7.29 (m, (2e)6e
4 H), 7.18 (t, J = 7.5 Hz, 1 H), 6.95 (d, J = 8.0 Hz, 1 H), 4.73 (t, Yellow solid; mp 136.5–138.0 °C.
J = 9.0 Hz, 1 H), 4.04 (t, J = 8.5 Hz, 1 H), 3.50–3.42 (m, 1 H), 3.07, IR (KBr): 1748 cm–1.
3.05 (dd, J = 6.5, 6.5 Hz, 1 H), 2.90, 2.87 (dd, J = 15.0, 15.0 Hz, 1
1
H). H NMR (500 MHz, CDCl3): d = 7.51–7.49 (m, 1 H), 7.48–7.38 (m,
13
4 H), 7.07 (t, J = 6.0 Hz, 1 H), 6.72 (d, J = 5.0 Hz, 1 H), 4.71 (t,
C NMR (125 MHz, CDCl3): d = 168.2, 147.3, 135.9, 135.4, 134.2, J = 7.5 Hz, 1 H), 4.05 (t, J = 9.0 Hz, 1 H), 3.69–3.60 (m, 1 H), 3.24,
129.8, 129.1, 128.5, 128.0, 127.8, 127.2, 126.4, 122.1, 71.2, 35.5, 3.20 (dd, J = 8.0, 7.5 Hz, 1 H), 2.85, 2.81 (dd, J = 16.5, 16.5 Hz, 1
33.0. H).
LRMS (EI, 70 eV): m/z (%) = 262 (M+, 100), 231 (46), 217 (72), 13
C NMR (125 MHz, CDCl3): d = 168.0, 144.2, 139.2, 138.1, 134.3,
203 (70), 101 (41). 129.4, 128.8, 127.8, 126.8, 122.9, 117.5, 70.5, 37.4, 27.8.
7-Methyl-9-phenyl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)- LRMS (EI, 70 eV): m/z (%) = 268 (M+, 38), 223 (33), 165 (11), 43
one (2b) (100).
White solid; mp 165.8–167.0 °C.
9-(4-Tolyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one (2f)

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IR (KBr): 1748 cm–1. White solid; mp 151.1–152.8 °C.
1
H NMR (500 MHz, CDCl3): d = 7.45–7.44 (m, 3 H), 7.29–7.26 (m, IR (KBr): 1748 cm–1.
2 H), 7.17 (d, J = 7.5 Hz, 1 H), 7.11 (d, J = 8.0 Hz, 1 H), 6.75 (s, 1
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, H NMR (500 MHz, CDCl3): d = 7.30–7.26 (m, 2 H), 7.26–7.20 (m,
1 H), 3.03, 3.01 (dd, J = 6.5, 6.5 Hz, 1 H), 2.84, 2.81 (dd, J = 15.5, 2 H), 7.20–7.17 (m, 3 H), 6.99 (d, J = 7.5 Hz, 1 H), 4.72 (t, J = 9.0
15.5 Hz, 1 H), 2.22 (s, 3 H). Hz, 1 H), 4.04 (t, J = 7.5 Hz, 1 H), 3.48–3.40 (m, 1 H), 3.06, 3.01
13
(dd, J = 6.5, 6.5 Hz, 1 H), 2.88, 2.86 (dd, J = 15.5, 15.5 Hz, 1 H),
C NMR (125 MHz, CDCl3): d = 168.3, 147.5, 136.9, 135.8, 134.3, 2.42 (s, 3 H).
132.4, 130.5, 129.7, 128.5, 128.0, 127.9, 127.8, 122.1, 71.1, 35.8,
13
32.7, 21.1. C 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,
LRMS (EI, 70 eV): m/z (%) = 276 (M , 53), 215 (27), 202 (29), 71 21.4.
(77), 57 (100), 43 (98).
LRMS (EI, 70 eV): m/z (%) = 276 (M+, 100), 231 (98), 217 (58),
HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found: 202 (60), 101 (26).
276.1148.
HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found:
7-Methoxy-9-phenyl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)- 276.1149.
one (2c)8
White solid; mp 142.0–143.8 °C. 9-(3-Tolyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one (2g)
White solid; mp 152.2–153.0 °C.
IR (KBr): 1745 cm–1.
1
IR (KBr): 1748 cm–1.
H NMR (500 MHz, CDCl3): d = 7.43–7.42 (m, 3 H), 7.31–7.29 (m,
1
2 H), 7.19 (d, J = 7.5 Hz, 1 H), 6.85–6.83 (m, 1 H), 6.50 (d, J = 2.5 H NMR (500 MHz, CDCl3): d = 7.34–7.24 (m, 3 H), 7.22–7.19 (m,
Hz, 1 H), 4.71 (t, J = 9.0 Hz, 1 H), 4.03 (t, J = 7.5 Hz, 1 H), 3.65 (s, 1 H), 7.18–7.09 (m, 3 H), 6.97 (d, J = 8.0 Hz, 1 H), 4.72 (t, J = 7.5
3 H), 3.46–3.38 (m, 1 H), 3.02, 2.99 (dd, J = 7.0, 6.5 Hz, 1 H), 2.81, Hz, 1 H), 4.03 (t, J = 8.0 Hz, 1 H), 3.48–3.40 (m, 1 H), 3.06, 3.03,
2.77 (dd, J = 15.0, 15.0 Hz, 1 H). (dd, J = 6.5, 6.5 Hz, 1 H), 2.88, 2.85 (dd, J = 15.5, 15.5 Hz, 1 H),
13
2.38 (s, 3 H).
C NMR (125 MHz, CDCl3): d = 168.2, 158.7, 147.2, 137.0, 134.1,
13
129.7, 128.7, 128.5, 127.8, 127.4, 122.6, 115.3, 114.6, 71.1, 55.3, C NMR (125 MHz, CDCl3): d = 168.2, 147.5, 137.4, 136.0, 135.4,
35.9, 32.1. 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).
7-Nitro-9-phenyl-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one HRMS (EI): m/z [M]+ calcd for C19H16O2: 276.1150; found:
(2d) 276.1145.
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)
1
White solid; mp 126.9–128.2 °C.
H 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, IR (KBr): 1748 cm–1.
J = 7.5 Hz, 1 H), 4.08 (t, J = 9.0 Hz, 1 H), 3.55–3.47 (m, 1 H), 3.23, 1
H NMR (500 MHz, CDCl3): d = 7.32–7.26 (m, 4 H), 7.22–7.14 (m,
3.20 (dd, J = 6.5, 6.5 Hz, 1 H), 2.97, 2.94 (dd, J = 15.5, 15.5 Hz, 1 2 H), 6.91 (d, J = 7.5 Hz, 1 H), 6.80 (d, J = 8.0 Hz, 1 H), 4.74 (t,
H). J = 6.5 Hz, 1 H), 4.07 (t, J = 9.0 Hz, 1 H), 3.51–3.46 (m, 1 H), 3.09,

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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.
13
C 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, 9-(2-Bromophenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
128.6, 128.5, 128.2, 128.2, 128.0, 127.9, 127.7, 127.5, 126.5, 125.8, one (2l)
125.4, 123.0, 122.7, 71.4, 35.3, 32.8, 19.5. Pale–yellow solid; mp 137.5–139.0 °C.

LRMS (EI, 70 eV): m/z (%) = 276 (M+, 74), 231 (100), 215 (84), IR (KBr): 1748 cm–1.
1
202 (63), 101 (21). H NMR (500 MHz, CDCl3): d = 7.48–7.40 (m, 8 H), 4.31–4.27 (m,
+
HRMS (EI): m/z [M] calcd for C19H16O2: 276.1150; found: 1 H), 4.22–4.17 (m, 1 H), 4.05–4.02 (m, 1 H), 3.94, 3.92 (dd,
276.1148. J = 3.5, 5.0 Hz, 1 H), 3.80, 3.79 (dd, J = 8.5, 8.5 Hz, 1 H).
13
C NMR (125 MHz, CDCl3): d = 167.9, 145.5, 135.4, 135.1, 134.4,
9-(4-Methoxyphenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)- 132.9, 132.5, 131.6, 129.9, 128.2, 127.4, 126.9, 124.2, 123.8, 122.1,
one (2i) 71.4, 35.3, 32.7.
White solid; mp 130.0–131.5 °C. LRMS (EI, 70 eV): m/z (%) = 342 (M+ + 2, 1), 340 (M+, 1), 261
IR (KBr): 1748 cm–1. (100), 233 (10), 215 (15), 202 (68).
1
H NMR (500 MHz, CDCl3): d = 7.32–7.26 (m, 4 H), 7.20–7.17 (m, HRMS (EI): m/z [M]+ calcd for C18H13BrO2: 340.0099; found:
1 H), 7.01 (d, J = 7.5 Hz, 1 H), 6.96 (d, J = 7.5 Hz, 2 H), 4.72 (t, 340.0093.
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, 9-(4-Fluorophenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
J = 15.5, 15.5 Hz, 1 H). one (2m)
13
C NMR (125 MHz, CDCl3): d = 168.4, 159.9, 147.4, 136.2, 135.6, Yellow solid; mp 175.1–176.9 °C.
131.5, 129.8, 129.3, 128.0, 127.2, 126.2, 121.4, 113.2, 71.1, 55.2, IR (KBr): 1748 cm–1.
35.7, 33.1.

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1
H NMR (500 MHz, CDCl3): d = 7.34–7.28 (m, 4 H), 7.26–7.24 (m,
LRMS (EI, 70 eV): m/z (%) = 292 (M+, 100), 261 (10), 247 (62), 1 H), 7.21–7.10 (m, 2 H), 6.94 (d, J = 7.5 Hz, 1 H), 4.74 (t, J = 9.0
203 (32), 189 (39). Hz, 1 H), 4.05 (t, J = 8.5 Hz, 1 H), 3.49–3.41 (m, 1 H), 3.07, 3.04
HRMS (EI): m/z [M]+ calcd for C19H16O3: 292.1099; found: (dd, J = 6.5, 7.0 Hz, 1 H), 2.89, 2.86 (dd, J = 15.5, 15.5 Hz, 1 H).
13
292.1105. C 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,
9-(2-Methoxyphenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)- 114.9, 71.2, 35.6, 32.9.
one (2j) LRMS (EI, 70 eV): m/z (%) = 280 (M+, 100), 249 (31), 221 (74).
Colorless oil.
HRMS (EI): m/z [M]+ calcd for C18H13FO2: 280.0900; found:
IR (KBr): 1748 cm–1. 280.0899.
1
H 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 9-(4-Acetylphenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
H), 4.05 (t, J = 9.0 Hz, 1 H), 3.55–3.38 (m, 1 H), 3.07–3.02 (m, 1 one (2n)
H), 3.00–2.86 (m, 1 H), 2.04 (s, 3 H). White solid; mp 170.9–172.1 °C.
13
C NMR (125 MHz, CDCl3): d = 171.1, 168.3, 167.9, 157.8, 156.4, IR (KBr): 1741, 1678 cm–1.
144.5, 142.9, 135.5, 135.4, 135.3, 134.8, 131.9, 130.0, 129.8, 129.6, 1
H NMR (500 MHz, CDCl3): d = 8.20 (d, J = 8.5 Hz, 2 H), 7.41–
129.6, 129.4, 128.6, 128.0, 127.5, 127.3, 127.0, 124.0, 123.4, 123.0, 7.39 (m, 2 H), 7.34–7.29 (m, 2 H), 7.19–7.16 (m, 1 H), 6.87 (d,
122.8, 120.4, 120.1, 111.1, 111.0, 71.2, 71.2, 55.7, 55.5, 35.4, 35.3, J = 7.5 Hz, 1 H), 4.75 (t, J = 7.5 Hz, 1 H), 4.06 (t, J = 9.0 Hz, 1 H),
32.9, 32.8. 3.51–3.43 (m, 1 H), 3.09, 3.07 (dd, J = 6.5, 6.5 Hz, 1 H), 2.89, 2.88
LRMS (EI, 70 eV): m/z (%) = 292 (M+, 100), 261 (41), 247 (31), (dd, J = 16.0, 15.0 Hz, 1 H), 2.65 (s, 3 H).
231 (43), 215 (23), 202 (36), 101 (22). 13
C NMR (125 MHz, CDCl3): d = 197.8, 168.1, 146.1, 136.8, 135.4,
HRMS (EI): m/z [M]+ calcd for C19H16O3: 292.1099; found: 134.7, 130.1, 128.8, 128.4, 128.2, 128.1, 127.6, 127.4, 123.0, 71.3,
292.1100. 35.6, 32.9, 26.6.
LRMS (EI, 70 eV): m/z (%) = 304 (M+, 100), 289 (72), 261 (12),
9-(4-Iodophenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one 231 (48), 217 (35), 202 (62), 101 (30).
(2k)
Yellow solid; mp 223.7–225.1 °C. HRMS (EI): m/z [M]+ calcd for C20H16O3: 304.1099; found:
304.1097.
IR (KBr): 1748 cm–1.
1
H NMR (500 MHz, CDCl3): d = 7.77 (d, J = 8.5 Hz, 2 H), 7.33– 9-(3-Acetylphenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-
7.28 (m, 2 H), 7.18 (t, J = 8.5 Hz, 1 H), 7.06–7.03 (m, 2 H), 6.93 (d, one (2o)
J = 8.0 Hz, 1 H), 4.73 (t, J = 8.5 Hz, 1 H), 4.04 (t, J = 8.0 Hz, 1 H), White solid; mp 170.0–171.6 °C.
3.48–3.40 (m, 1 H), 3.07, 3.04 (dd, J = 7.0, 7.0 Hz, 1 H), 2.88, 2.85 IR (KBr): 1740, 1675 cm–1.
(dd, J = 16.0, 15.0 Hz, 1 H).
1
13
H NMR (500 MHz, CDCl3): d = 8.04–8.02 (m, 1 H), 7.90–7.83 (m,
C NMR (125 MHz, CDCl3): d = 168.1, 146.1, 137.0, 135.4, 133.7, 1 H), 7.59–7.53 (m, 2 H), 7.37–7.29 (m, 2 H), 7.19–7.16 (m, 1 H),
131.7, 130.1, 128.9, 128.2, 127.4, 122.5, 94.8, 71.2, 35.6, 32.9. 6.69 (d, J = 9.0 Hz, 1 H), 4.74 (t, J = 8.5 Hz, 1 H), 4.06 (t, J = 6.5
LRMS (EI, 70 eV): m/z (%) = 388 (M+, 100), 231 (34), 217 (39), Hz, 1 H), 3.52–3.44 (m, 1 H), 3.09, 3.06 (dd, J = 6.5, 6.5 Hz, 1 H),
202 (73), 101 (30). 2.91, 2.88 (dd, J = 15.5, 16.0 Hz, 1 H), 2.61 (s, 3 H).

Synthesis 2010, No. 18, 3204–3210 © Thieme Stuttgart · New York

PAPER Intramolecular Cascade Reactions of Aryl-Substituted Enynes 3209

13
C NMR (125 MHz, CDCl3): d = 197.7, 168.0, 146.0, 139.4, 136.9, IR (KBr): 1674 cm–1.
135.3, 135.2, 130.4, 130., 128.8, 128.2, 128.0, 127.9, 127.6, 127.4, 1
H NMR (500 MHz, CDCl3): d = 7.45–7.33 (m, 3 H), 7.32–7.28 (m,
123.0, 71.3, 35.5, 32.8, 26.6. 4 H), 7.28–7.20 (m, 5 H), 7.18–7.12 (m, 1 H), 6.93 (d, J = 7.5 Hz, 1
LRMS (EI, 70 eV): m/z (%) = 304 (M+, 100), 289 (65), 261 (13), H), 4.65 (d, J = 14.5 Hz, 1 H), 4.37 (d, J = 15.0 Hz, 1 H), 3.60 (t,
217 (37), 202 (56), 101 (43). J = 9.0 Hz, 1 H), 3.12–3.02 (m, 1 H), 3.01–2.96 (m, 2 H), 2.78, 2.75
HRMS (EI): m/z [M]+ calcd for C20H16O3: 304.1099; found: (dd, J = 5.0, 16.0 Hz, 1 H).
13
304.1098. C 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,
9-(3-Nitrophenyl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one 126.9, 56.3, 47.0, 33.9, 32.2.
(2p) LRMS (EI, 70 eV): m/z (%) = 351 (M+, 14), 351 (73), 350 (33), 349
Yellow solid; mp 203.0–204.3 °C. (100), 258 (62), 245 (57), 215 (42), 202 (26), 91 (50).
IR (KBr): 1772, 1732, 1719 cm–1. HRMS (EI): m/z [M]+ calcd for C25H21NO: 351.1623; found:
1
H NMR (500 MHz, CDCl3): d = 8.32–8.28 (m, 1 H), 8.18–8.10 (m, 351.1620.
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), Supporting Information for this article is available online at
2.93, 2.90 (dd, J = 16.0, 15.5 Hz, 1 H). http://www.thieme-connect.com/ejournals/toc/synthesis.
13
C 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, Acknowledgment
71.4, 35.5, 32.7.
The authors thank the Scientific Research Fund of Hunan Provincial
LRMS (EI, 70 eV): m/z (%) = 307 (M+, 88), 263 (25), 215 (29), 202 Education Department (No. 08A037), Hunan Normal University
(100), 101 (21).
(No. 080605), and National Natural Science Foundation of China

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HRMS (EI): m/z [M]+ calcd for C18H13NO4: 307.0845; found: (No. 20872112) for financial support.
307.0848.

9-(Thiophen-2-yl)-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one References
(2q)
(1) (a) Norton, J. A. Chem. Rev. 1942, 31, 319. (b) Martin, J.
Yellow solid; mp 128.0–130.1 °C.
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IR (KBr): 1748 cm–1. Annu. Rep. Med. Chem. 1974, 9, 270. (d) Oppolzer, W.
1
H NMR (500 MHz, CDCl3): d = 7.49 (d, J = 5.0 Hz, 1 H), 7.33– Angew. Chem., Int. Ed. Engl. 1977, 16, 10. (e) Brieger, G.;
7.30 (m, 1 H), 7.29–7.24 (m, 3 H), 7.24–7.22 (m, 1 H), 7.14 (d, Bennett, J. N. Chem. Rev. 1980, 80, 63. (f) Kagan, H. B.;
J = 9.0 Hz, 1 H), 4.71 (t, J = 8.5 Hz, 1 H), 4.04 (t, J = 8.5 Hz, 1 H), Riant, O. Chem. Rev. 1992, 92, 1007. (g) Winkler, J. D.
3.47 (m, 1 H), 3.03, 3.01 (dd, J = 7.5, 6.5 Hz, 1 H), 2.87, 2.84 (dd, Chem. Rev. 1996, 96, 167. (h) Kumar, A. Chem. Rev. 2001,
J = 15.0, 15.5 Hz, 1 H). 101, 1. (i) Takao, K.-i.; Munakata, R.; Tadano, K.-i. Chem.
13
Rev. 2005, 105, 4779. (j) Wessig, P.; Müller, G. Chem. Rev.
C NMR (125 MHz, CDCl3): d = 167.8, 140.1, 135.9, 133.9, 130.5, 2008, 108, 2051.
129.1, 127.9, 127.4, 127.3, 126.7, 124.1 71.0, 36.0, 32.8. (2) (a) Klemm, L. H.; Gopinath, K. W. Tetrahedron Lett. 1963,
LRMS (EI, 70 eV): m/z (%) = 268 (M+, 84), 223 (100), 209 (50), 4, 1243. (b) Klemm, L. H.; Gopinath, K. W. J. Heterocycl.
165 (23). Chem. 1965, 2, 225. (c) Klemm, L. H.; Lee, D. H.;
Gopinath, K. W.; Klopfenstein, C. E. J. Org. Chem. 1966,
HRMS (EI): m/z [M]+ calcd for C16H12O2S: 268.0558; found:
31, 2376. (d) Klemm, L. H.; Olson, D. R.; White, D. V.
268.0554.
J. Org. Chem. 1971, 36, 3740. (e) Klemm, L. H.;
Santhanam, P. S. J. Org. Chem. 1968, 33, 1268. (f) Klemm,
9-Phenyl-2-propyl-2,3,3a,4-tetrahydro-1H-benzo[f]isoindol-1-
L. H.; Klemm, R. A.; Santhanam, P. S.; White, D. V. J. Org.
one (2r)
Chem. 1971, 36, 2169. (g) Klemm, L. H.; Santhanam, P. S.
Yellow oil.
J. Heterocycl. Chem. 1972, 9, 423. (h) Klemm, L. H.;
IR (KBr): 1675 cm–1. McGuire, T. M.; Gopinath, K. W. J. Org. Chem. 1976, 41,
1
H NMR (500 MHz, CDCl3): d = 7.42–7.37 (m, 3 H), 7.27–7.21 (m, 2571. (i) Klemm, L. H.; McGuire, T. M. J. Heterocycl.
4 H), 7.14 (t, J = 7.5 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 3.74–3.68 Chem. 1972, 9, 1215.
(m, 1 H), 3.37–3.32 (m, 1 H), 3.23 (d, J = 8.5 Hz, 1 H), 3.15–3.11 (3) (a) Laird, T.; Ollis, W. D. J. Chem. Soc., Chem. Commun.
(m, 2 H), 3.06–3.02 (m, 1 H), 3.04, 2.82–2.79 (m, 1 H), 1.60–1.55 1972, 557. (b) Bartlett, A. J.; Laird, T.; Ollis, W. D. J. Chem.
(m, 2 H), 0.89 (t, J = 7.0 Hz, 3 H). Soc., Chem. Commun. 1974, 496. (c) Oppolzer, W.; Achini,
13
R.; Pfenninger, E.; Weber, H. P. Helv. Chim. Acta 1976, 59,
C NMR (125 MHz, CDCl3): d = 166.6, 140.3, 136.6, 135.6, 135.4, 1186. (d) Laird, T.; Ollis, W. D.; Sutherland, I. O. J. Chem.
130.2, 129.7, 128.3, 128.2, 127.7, 127.7, 127.6, 60.4, 50.9, 34.0, Soc., Perkin Trans. 1 1980, 1477. (e) Chukhadzhyan, E. O.;
32.4, 20.6, 11.4. Chukhadzhyan, El. O.; Shakhatuni, K. G.; Babayan, A. T.
LRMS (EI, 70 eV): m/z (%) = 304 (72), 303 (M+, 100), 302 (27), Chem. Heterocycl. Compd. (Engl. Transl.) 1991, 27, 594.
274 (74), 260 (47), 231 (57), 215 (30), 202 (54). (f) Chukhadzhyan, E. O.; Gevorkyan, A. R.; Chukhadzhyan,
HRMS (EI): m/z [M]+ calcd for C21H21NO: 303.1623; found: El. O.; Kinoyan, F. S. Russ. J. Org. Chem. (Engl. Transl.)
303.1622. 2005, 41, 358. (g) Chukhadzhyan, E. O.; Gevorkyan, A. R.;
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one (2s) 2001, 66, 3176.
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

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