One-pot synthesis of spirofuran and benzocycloalka[1,2-b]furan derivatives using manganese(III)-mediated oxidative radical cyclization

Article abstract of DOI:10.1055/s-2005-861807

New spiro[furan-2(3H),1′-(benzocycloalkane)] derivatives were obtained by the oxidation of methylenebenzocycloalkanes with manganese(III) acetate in the presence of 1,3-dicarbonyl compounds. A similar oxidation of the benzocycloalkene derivatives produced the functionalized benzocycloalka[1,2-b] furans in good yields. However, 1-benzyl-3,4-dihydronaphthalene gave both the corresponding spirofuran and benzocydohexa[1,2-b]furan under the same oxidation conditions. The acid-catalyzed ring-opening reaction of the spirofurans and benzocycloalka[1,2-b]furans was also investigated.

Full text of DOI:10.1055/s-2005-861807

PAPER
731
One-Pot Synthesis of Spirofuran and Benzocycloalka[1,2-b]furan Derivatives
Using Manganese(III)-Mediated Oxidative Radical Cyclization
Spirofuran and
B
e
enzocycloa
i
lka[1, 2
k
-
b
]furanUsi
a
ngManganese(III
F
)-Mediated
R
a
u
dical Cycliz
j
ation ino,a Hiroshi Nishino*b
a
Department of Materials and Life Science, Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1,
Kumamoto 860-8555, Japan
b
Department of Chemistry, Faculty of Science, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan
Fax +81(96)3423374; E-mail: nishino@sci.kumamoto-u.ac.jp
Received 28 September 2004; revised 24 November 2004
new types of spiro[furan-2(3H),1¢-(benzocycloalkane)]
derivatives and benzocycloalka[1,2-b]furan derivatives
using the manganese(III)-mediated oxidation of methyl-
enebenzocycloalkanes and/or benzocycloalkenes in the
Abstract: New spiro[furan-2(3H),1¢-(benzocycloalkane)] deriva-
tives were obtained by the oxidation of methylenebenzocycloal-
kanes with manganese(III) acetate in the presence of 1,3-dicarbonyl
compounds. A similar oxidation of the benzocycloalkene deriva-
tives produced the functionalized benzocycloalka[1,2-b]furans in presence of various 1,3-dicarbonyl compounds.
good yields. However, 1-benzyl-3,4-dihydronaphthalene gave both
the corresponding spirofuran and benzocyclohexa[1,2-b]furan un-
der the same oxidation conditions. The acid-catalyzed ring-opening
reaction of the spirofurans and benzocycloalka[1,2-b]furans was
also investigated.
Key words: oxidations, radicals, cyclizations, spiro compounds,
furans, manganese
The construction of polyfunctionalized furans,1 spiro-
furans, and furan-fused cycloalkanes is important from
the standpoint of the synthesis of biologically active natu-
ral products, such as aflatoxin, asteltoxin, monensin, pan-
acene, and so on,2 which consist of furan rings.3
Especially, the 4,5-dihydrofurans are convenient synthet-
ic starting materials since the dihydrofurans can be easily
transformed by dehydrogenation or reduction into the cor-
responding furans or tetrahydrofurans. In recent years,
Snider developed the oxidative cyclization reaction using
Scheme 1
manganese(III) acetate in the presence of copper(II) ace-
tate as a co-oxidant,4 and applied it to the total synthesis
of many natural products.5 This technique was also ap-
plied to some natural product syntheses by other groups.6,7
We previously reported the convenient synthesis of the
5,5-diaryl-4,5-dihydrofurans using the oxidation of 1,1-
We first investigated the reaction of 1-methylenetetralin
(1b) with 2,4-pentanedione in the presence of manga-
nese(III) acetate. In order to predominantly undergo the
oxidative radical reaction, the mixture was heated in ace-
tic acid, and then manganese(III) acetate dihydrate was
added just before refluxing.8e,g,10 The mixture was heated
under reflux, and the reaction was over in 3 min. After
work-up, contrary to our expectations, 3-acetyl-2,9b-di-
methyl-3a,4,5,9b-tetrahydronaphtho[1,2-b]furan (4c) was
obtained in 74% yield instead of the desired spiro[furan-
2,1¢-tetrahydronaphthalene] 2b (Scheme 2). It was postu-
lated that the exo-endo isomerization of 1b occurred under
the acidic conditions since the endo isomer 3c is ca. 5
kcal/mol more stable than the exo isomer 1b,11 and then
the endo isomer 3c preferentially reacted with 2,4-pen-
tanedione to form 4c. Therefore, the desired 4-acetyl-5-
methylspiro[furan-2(3H),1¢-(1¢,2¢,3¢,4¢-tetrahydronaph-
thalene)] (2b) was finally obtained in 68% yield by the si-
multaneous heating of the exo isomer 1b, 2,4-
pentanedione, and manganese(III) acetate in acetic acid
before the exo-endo isomerization.
diarylethenes
with
tris(2,4-pentanedionato)manga-
nese(III) or manganese(III) acetate in the presence of 1,3-
dicarbonyl compounds in boiling acetic acid (Scheme 1).8
Our manganese(III)-based dihydrofuran synthesis does
not necessarily require a co-oxidant because of the selec-
tion of the starting alkenes and relatively high-tempera-
ture reaction conditions.7,8 It is also well-known that a
similar reaction is carried out at ambient temperature in
air in the absence of a co-oxidant, such as copper(II) ace-
tate, to quantitatively give the 6,6-diaryl-1,2-dioxan-3-ols
(Scheme 1).9 In connection with our study of the oxidative
radical cyclization, we herein report the facile synthesis of
SYNTHESIS 2005, No. 5, pp 0731–0740
Advanced online publication: 09.02.2005
DOI: 10.1055/s-2005-861807; Art ID: F14004SS
© Georg Thieme Verlag Stuttgart · New York
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x
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732
R. Fujino, H. Nishino
PAPER
in the yields shown in Table 1. When 1-phenylbutane-1,3-
dione was used in the reaction of 1b, two types of spirofu-
ran were produced (Table 1, entry 5). One was a 4-acetyl-
5-phenylspirofuran 2e cyclized at the benzoyl oxygen,
and the other was a 4-benzoyl-5-methylspirofuran 2f an-
nulated at the acetyl oxygen. The trisubstituted alkene
such as 9-benzylidene-9H-xanthene (1d) also gave the
corresponding spirofuran derivatives 2h and 2i, however,
the yields were moderate to fair (entries 7 and 8).8a The
structure of the obtained spirofurans 2a–i was determined
by spectroscopic methods and elemental analysis. The
spirofuran skeleton was so interesting that the exact struc-
tures of 2b, 2g, and 2h were elucidated by X-ray crystal-
lography. The single crystals of 2b, 2g, and 2h were
successfully grown as a racemic mixture from diethyl
ether–hexane, and each ORTEP diagram was obtained af-
ter crystallographic analysis (Figures 1, 2, and 3). The
bond angles of O1–C10–C6, O1–C10–C9, and O1–C10–
C11 in 2b appeared as 105.9(1)°, 106.3(1)°, and
103.6(1)°, respectively, while those of C6–C10–C9, C6–
C10–C11, and C9–C10–C11 were 112.2(1)°, 114.4(2)°,
and 113.5(2)°, respectively.
Scheme 2
Table 1 Reaction of Methylenebenzocycloalkanes 1a–d with Vari-
ous 1,3-Dicarbonyl Compounds in the Presence of Manganese(III)
Acetatea
Entry
Methylenebenzo-
cycloalkane
1,3-Dicarbonyl
compound
Product
(yield %)b
R1
R2
1
2
3
4
5
1a
1b
1b
1b
1b
n = 1
n = 2
n = 2
n = 2
n = 2
Me
Me
Me
Me
Ph
Ac
2a (72)
2b (68)
2c (70)
2d (71)
2e (39)
2f (18)
2g (75)
2h (19)
2i (39)
Ac
CO2Me
CO2Et
Ac
Me
Me
Me
Me
Bz
6
7
8
1c
1d
1d
n = 3
Ac
Ac
CO2Me
a The reaction was carried out in boiling AcOH (50 mL) at the molar
ratio of methylenebenzocycloalkane 1–1,3-dicarbonyl compound–
Mn(OAc)3 = 1:3.5:3.
b Isolated yield based on the methylenebenzocycloalkane 1 used.
In order to construct a consecutive ring system including
the furan ring, we applied the current reaction to benzene-
fused cycloalkenes 3a–g. The reaction of 3-phenyl-1H-in-
dene (3a) with 2,4-pentanedione was conducted in the
presence of manganese(III) acetate under similar condi-
tions used in the case of the methylenebenzoalkanes 1. Af-
ter the usual work-up, the desired 4,8b-dihydro-3aH-
indeno[1,2-b]furan 4a was produced in 67% yield
(Scheme 4 and Table 2, entry 1). Other benzocycloal-
kenes 3b–f also gave the corresponding benzocycloal-
Scheme 3
We next investigated the synthesis of spiro[furan-
2(3H),1¢-(2-benzocycloalkane)] derivatives 2a–j. Since
we found the reaction conditions for the formation of
spirofuran 2b, a similar oxidation of other methyleneben-
zocycloalkanes 1a,c,d was carried out in the presence of
various 1,3-dicarbonyl compounds (Scheme 3). As a re-
sult, the corresponding spirofurans 2a,c–i were obtained
Synthesis 2005, No. 5, 731–740 © Thieme Stuttgart · New York

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Spirofuran and Benzocycloalka[1,2-b]furan Using Manganese(III)-Mediated Radical Cyclization
733
Figure 3 ORTEP Drawing of 2h (R1 = Me, R2 = Ac)
Figure 1 ORTEP Drawing of 2b (R1 = Me, R2 = Ac, n = 2)
3c. In fact, the formation energy of the endo-alkene 3g
(49.1 kcal/mol) was similar to that of the exo isomer (49.4
kcal/mol) based on PM3 calculations.11 The structures of
the benzocycloalka[1,2-b]furans 4a–g were characterized
by spectroscopic methods and elemental analysis. Espe-
cially, the exact structure of 4d was ascertained by X-ray
crystallography, and it was confirmed that the stereo-
chemistry of the ring junction of 4d was a cis-fused con-
figuration (Figure 4).
Scheme 4
Figure 2 ORTEP Drawing of 2g (R1 = Me, R2 = Ac, n = 3)
ka[1,2-b]furan derivatives 4b–f in good yields (Entries 2–
6). When 4-benzyl-1,2-dihydronaphthalene (3g) was used
in the oxidation with 2,4-pentanedione, the desired benzo-
cyclohexa[1,2-b]furan 4g was obtained in 36% yield
along with spirofuran 2j in 25% yield (Scheme 5 and En-
try 7). This phenomenon was also explained by the endo–
exo isomerization of 3g similar to the case between 1b and
Scheme 5
Synthesis 2005, No. 5, 731–740 © Thieme Stuttgart · New York

734
R. Fujino, H. Nishino
PAPER
Table 2 Reaction of Benzocycloalkenes 3a–g with 2,4-Pentanedi-
However, the dihydronaphthalenes 5d and 5e having a 2-
oxo-4-hydroxy-3-penten-3-yl functionality were obtained
by the acid-catalyzed decomposition of the benzocyclo-
hexa[1,2-b]furans 4d and 4e, respectively (Scheme 7).
one in the Presence of Manganese(III) Acetatea
Entry
Benzocycloalkene
Product (yield %)b
4a (67)
1
2
3
4
5
6
7
3a
3b
3c
3d
3e
3f
R = Ph
n = 1
n = 1
n = 2
n = 2
n = 2
n = 3
n = 2
R = 1-Naphthyl
R = Me
4b (52)
4c (74)
R = Ph
4d (56)
R = 1-Naphthyl
R = Ph
4e (82)
4f (92)
3g
R = Bn
2j (25)
4g (36)
a The reaction was carried out in boiling AcOH (50 mL) at the molar
ratio of benzocycloalkene 3–2,4-pentanedione–Mn(III) = 1:3.5:3.
b Isolated yield based on the benzocycloalkene 3 used.
Scheme 6
Figure 4 ORTEP Drawing of 4d (R = Ph, n = 2)
Scheme 7
We also investigated the acid-catalyzed reaction of the
spirofurans and benzocycloalka[1,2-b]furans. Recently,
we reported the acid-catalyzed decomposition of the dihy-
drofuran derivatives giving the corresponding 4-hydroxy-
3-penten-2-ones.12 Therefore, in order to transform the di-
hydrofuran ring of the spirofurans 2 or benzocycloal-
ka[1,2-b]furans 4 into a 2-oxo-4-hydroxy-3-penten-3-yl
functionality, we carried out the acid-catalyzed reaction of
spirofuran 2b in anhydrous benzene at reflux temperature
(Scheme 6). Contrary to our expectation, the methylenete-
tralin 5b was not obtained, but benzoindene 6 was isolated
in 48% yield. Probably, the dihydrofuran ring of 2b was
opened once to give the corresponding tetralin 5b, which
would be then recyclized under acidic conditions to pro-
duce benzoindene 6.
Very surprisingly, a similar reaction of benzocyclohep-
ta[1,2-b]furan 4f gave benzocyclohepta[a]naphthalene 7
probably through the ring-opening A, retro-Claisen
deacetylation B, followed by recyclization (Scheme 8).
These obtained aromatic condensed-ring compounds 6
and 7 are interesting from the standpoint of the construc-
tion of the natural product scaffold.
In conclusion, a convenient one-pot synthesis of new
functionalized spirofuran derivatives 2a–i and benzocy-
cloalka[1,2-b]furans 4a–g was demonstrated using the
manganese(III)-mediated oxidative radical cyclization. In
addition, ring assembly could be achieved by the manipu-
lative use of the acid-catalyzed reaction of spirofuran 2b
and benzocyclohepta[1,2-b]furan 4f.
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Spirofuran and Benzocycloalka[1,2-b]furan Using Manganese(III)-Mediated Radical Cyclization
735
1H NMR (CDCl3): d = 7.37–7.19 (4 H, m, arom H), 3.34 (1 H, dq,
J = 14.5, 1.47 Hz, CHaHb), 3.12 (1 H, dq, J = 14.7, 1.47 Hz,
CHaHb), 3.07 (1 H, dd, J = 15.8, 7.92 Hz, CHcHd), 2.88 (1 H, dq,
J = 16.0, 3.86 Hz, CHeHf), 2.51 (1 H, dq, J = 13.6, 3.86 Hz, CHeHf),
2.26–2.14 (1 H, m, CHcHd), 2.24 (3 H, s, COCH3), 2.22 (3 H, t,
J = 1.47 Hz, CH3).
13C NMR (CDCl3): d = 194.3 (C=O), 166.5 (C-5), 144.1, 143.7
(arom C), 129.2, 127.2, 124.9, 122.9 (arom CH), 111.8 (C-4), 96.1
[C-2(1¢)], 41.5 (C-3), 40.8 (C-2¢), 29.6 (C-3¢), 29.4 (COCH3), 15.3
(CH3).
MS: m/z (%) = 228 (M+, 67), 210 (28), 195 (19), 167 (100), 141
(38), 128 (41), 113 (79), 43 (98).
HRMS (FAB): m/z calcd for C15H17O2 (M + 1): 229.1229; found:
229.1229.
4-Acetyl-5-methylspiro[furan-2(3H),1¢-(1¢,2¢,3¢,4¢-tetrahydro-
naphthalene)] (2b)
Rf = 0.70 (Et2O–hexane, 8:2); colorless plates (from Et2O); mp
62.0–64.0 °C.
IR (CHCl3): 1663 (C=O) cm–1.
Scheme 8
1H NMR (CDCl3): d = 7.39–7.04 (4 H, m, arom H), 3.13 (2 H, ddq,
J = 54.8, 14.3, 1.47 Hz, CH2), 2.92–2.72 (2 H, m, CH2), 2.30 (3 H,
t, J = 1.47 Hz, CH3), 2.22 (3 H, s, COCH3), 2.16–1.77 (4 H, m,
CH2 × 2).
13C NMR (CDCl3): d = 194.5 (C=O), 166.8 (C-5), 139.5, 136.4
(arom C), 128.8, 127.9, 126.7, 126.2 (arom CH), 111.2 (C-4), 87.2
[C-2(1¢)], 45.7 (C-3), 36.7 (C-2¢), 29.5 (COCH3), 29.3 (C-4¢), 19.8
(C-3¢), 15.3 (CH3).
All the mps were determined using a Yanaco micro mp apparatus
MP-J3 and were uncorrected. All of the NMR spectra were recorded
on a JNM-AL 300 FT NMR spectrometer (300 MHz for 1H and 75
MHz for 13C) with tetramethylsilane as the internal standard. The
chemical shifts are shown in d (ppm) and the coupling constants in
Hz. The IR spectra were measured using a Shimadzu FTIR-8400
spectrometer. The IR spectral data are expressed in cm–1. The MS
were measured on a Shimadzu GCMS-QP5050A at an ionizing
voltage of 70 eV. High resolution MS were recorded using a JMS-
HX110A mass spectrometer. Elemental analyses were performed at
the Center of Instrumental Analysis Center, Kumamoto University,
Kumamoto, Japan.
MS: m/z (%) = 242 (M+, 24), 224 (12), 199 (14), 182 (33), 181 (59),
167 (15), 141 (11), 128 (23), 115 (18), 43 (100).
Anal. Calcd for C16H18O2: C, 79.31; H, 7.49. Found: C, 79.38; H,
7.50.
X-Ray Crystallographic Data of 2b
Empirical formula C32H36O4; formula weight 484.63; colorless,
platelet; crystal dimensions 0.30 × 0.40 × 0.10 mm; monoclinic;
primitive; space group P21/c (# 14); lattice parameters
a = 9.2579(4) Å, b = 17.3043(9) Å, c = 16.2643(8) Å,
b = 101.235(1)°, V = 2555.6(2) Å3, Z = 4; rcalcd = 1.259 g cm–3;
F000 = 1040.00; m (Mo Ka) = 0.81 cm–1; 2qmax = 55.0°; no. of reflec-
tions measured total: 17591, unique: 5768 (Rint = 0.057); no. obser-
vations [I > 3.00s (I)] 3297; no. variables 470; reflection/parameter
ratio 7.01; R1 = 0.040; wR2 = 0.047. The X-ray crystallographic
data have been deposited as supplementary publication number
CCDC249340. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ,
UK [fax: +44(0)1223336033 or e-mail: deposit@ccdc.cam.ac.uk.
Manganese(III) acetate dihydrate, Mn(OAc)3·2 H2O, was prepared
according to the literature method.13 The alkenes were prepared by
the Wittig reaction of the corresponding carbonyl compounds with
methyltriphenyl phosphonium bromide. Acetylacetone, methyl ac-
etoacetate, and ethyl acetoacetate were purchased from Wako Pure
Chemical Ind., Ltd., and were used as received. Benzoylacetone
was purchased from Tokyo-Kasei Co., Ltd., and was used as re-
ceived.
Manganese(III)-Mediated Oxidative Radical Cyclization of
Alkenes with 1,3-Dicarbonyl Compounds
A mixture of methylenebenzocycloalkane 1 or benzocycloalkene 3
(1 mmol), 1,3-dicarbonyl compound (3.5 mmol), and manga-
nese(III) acetate dihydrate (3 mmol) was heated under reflux in
AcOH (50 mL) with stirring until the dark-brown color of Mn(III)
disappeared (normally within 3 min). The solvent was removed in
vacuo and the residue was treated with HCl (2 M; 50 mL), followed
by extraction with CH2Cl2 (20 × 3 mL). The combined extract was
washed with H2O, followed by sat. aq NaHCO3, and dried (MgSO4).
The products were separated by silica gel TLC (Wakogel B-10) us-
ing CHCl3 or Et2O–hexane (4:6–8:2 v/v) as the developing solvent.
The yields are summarized in Table 1 and Table 2. The analytical
samples were further purified by recrystallization from the appro-
priate solvent mentioned below, except for the liquid products.
4-Methoxycarbonyl-5-methylspiro[furan-2(3H),1¢-(1¢,2¢,3¢,4-
tetrahydronaphthalene)] (2c)
Rf = 0.64 (Et2O–hexane, 5:5); colorless plates (from hexane), mp
74.0–76.0 °C.
IR (CHCl3): 1687 cm–1 (C=O).
1H NMR (CDCl3): d = 7.38–7.01 (4H, m, arom H), 3.70 (3 H, s,
COOCH3), 3.06 (2 H, ddq, J = 55.9, 14.7, 1.47 Hz, CH2), 2.87–2.68
(2 H, m, CH2), 2.26 (3 H, t, J = 1.47 Hz, CH3), 2.15–1.72 (4 H, m,
CH2 × 2).
13C NMR (CDCl3): d = 167.2 (C=O), 166.5 (C-5), 139.7, 136.4
(arom C), 128.8, 127.8, 126.7, 126.3 (arom CH), 100.5 (C-4), 87.1
[C-2(1¢)], 50.7 (COOCH3), 44.9 (C-3), 36.7 (C-2¢), 29.3 (C-4¢), 19.8
(C-3¢), 14.3 (CH3).
4-Acetyl-5-methylspiro[furan-2(3H),1¢-(2¢,3¢-dihydroindene)]
(2a)
Rf = 0.52 (7:3 Et2O–hexane); yellow liquid.
IR (neat): 1593 (C=O) cm–1.
MS: m/z (%) = 258 (M+, 34), 226 (89), 211 (69), 208 (19), 183 (66),
155 (74), 153 (27), 128 (55), 115 (37), 43 (100).
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R. Fujino, H. Nishino
PAPER
Anal. Calcd for C16H18O3: C, 74.39; H, 7.02. Found: C, 74.25; H,
7.10.
s, COCH3), 2.10–1.89 (5 H, m, 2 CH2, CHa2Hb2), 1.50–1.29 (1 H, m,
CHa2Hb2).
13C NMR (CDCl3): d = 194.1 (C=O), 165.2 (C-5¢), 145.1, 139.0
(arom C), 130.8, 127.3, 126.1, 123.8 (arom CH), 111.9 (C-4¢), 92.1
[C-5(2¢)], 40.2 (C-3¢), 38.3 (C-4), 36.3 (C-2), 29.2 (COCH3), 27.5
(C-1), 25.8 (C-3), 15.0 (CH3).
MS: m/z (%) = 256 (M+, 6), 238 (10), 214 (26), 196 (21), 195 (32),
169 (23), 167 (10), 141 (21), 128 (24), 115 (20), 91 (10), 43 (100).
4-Ethoxycarbonyl-5-methylspiro[furan-2(3H),1¢-(1¢,2¢,3¢,4¢-tet-
rahydronaphthalene)] (2d)
Rf = 0.63 (Et2O–hexane, 5:5); colorless liquid.
IR (CHCl3): 1682 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.39–7.02 (4 H, m, arom H), 4.18 (2 H, q,
J = 7.17 Hz, COOCH2CH3), 3.07 (2 H, ddq, J = 54.0, 14.7, 1.47 Hz,
CH2), 2.89–2.66 (2 H, m, CH2), 2.26 (3 H, t, J = 1.47 Hz, CH3),
2.12–1.74 (4 H, m, 2 CH2), 1.28 (3 H, t, J = 7.17 Hz, COOCH2CH3).
Anal. Calcd for C17H20O2: C, 79.65; H, 7.86. Found: C, 79.63; H,
8.01.
13C NMR (CDCl3): d = 166.9 (C=O), 166.1 (C-5), 139.8, 136.3
(arom C), 128.7, 127.8, 126.6, 126.3 (arom CH), 100.7 (C-4), 86.9
[C-2(1¢)], 59.4 (COOCH2CH3), 45.0 (C-3), 36.7 (C-2¢), 29.3 (C-4¢),
19.8 (C-3¢), 14.5 (CH3), 14.3 (COOCH2CH3).
MS: m/z (%) = 272 (M+, 22), 226 (72), 211 (51), 183 (50), 155 (53),
153 (19), 128 (40), 115 (29), 43 (100).
X-Ray Crystallographic Data of 2g
Empirical formula C16H18O2; formula weight 242.32; colorless,
prism; crystal dimensions 0.50 × 0.40 × 0.03 mm; orthorhombic;
primitive; space group Pbca (# 61); lattice parameters a = 8.4382(2)
Å, b = 16.0661(5) Å, c = 20.4929(4) Å, V = 2778.2(1) Å3, Z = 8;
r
calcd = 1.159 g cm–3; F000 = 1040.00; m (Mo Ka) = 0.75 cm–1;
2qmax = 54.6°; no. of reflections measured total: 25293, unique:
3134 (Rint = 0.040); no. observations [I > 3.00s (I)] 2152; no. vari-
ables 252; reflection/parameter ratio 8.54; R1 = 0.035;
wR2 = 0.046. The X-ray crystallographic data have been deposited
as supplementary publication number CCDC249341. Copies of the
data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK [fax: +44(0)1223336033 or
e-mail: deposit@ccdc.cam.ac.uk.
HRMS (FAB): m/z calcd for C17H21O3 (M + 1): 273.1491; found:
273.1513.
4-Acethyl-5-phenylspiro[furan-2(3H),1¢-(1¢,2¢,3¢,4¢-tetrahydro-
naphthalene)] (2e)
Rf = 0.30 (Et2O–hexane, 2:8); light yellow liquid.
IR (CHCl3): 1618 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.64–7.06 (9 H, m, arom H), 3.33 (2 H, dd,
J = 55.4, 15.2 Hz, CH2), 2.92–2.73 (2 H, m, CH2), 2.29–1.78 (4 H,
m, 2 CH2), 2.01 (3 H, s, COCH3).
13C NMR (CDCl3): d = 194.4 (C=O), 165.2 (C-5), 139.4, 136.5,
131.1 (arom C), 130.5, 129.2 (2 C), 128.8, 128.2 (2 C), 127.9, 126.7,
126.3 (arom CH), 113.7 (C-4), 87.1 [C-2(1¢)], 46.4 (C-3), 36.6 (C-
2¢), 29.3 (C-4¢), 29.0 (COCH3), 19.6 (C-3¢).
4-Acetyl-5-methyl-3-phenylspiro[furan-2(3H),9¢-xanthene]
(2h)8a
Rf = 0.51 (Et2O–hexane, 5:5); colorless prisms (from EtOH); mp
142.5–143.5 °C (Lit.8a 141 °C).
IR (CHCl3): 1669 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.51–6.67 (13 H, m, arom H), 4.43 (1 H, q,
J = 1.47 Hz, CH), 2.69 (3 H, d, J = 1.47 Hz, CH3) 1.78 (3 H, s,
COCH3).
13C NMR (CDCl3): d = 196.0 (C=O), 169.1 (C-5), 150.2, 149.3,
138.3 (2 C), 121.4 (arom C), 129.2, 128.8, 128.3, 128.0 (2 C), 127.1,
126.8 (2 C), 124.1, 123.9, 122.5, 116.9, 115.7 (arom CH), 112.1 (C-
4), 86.3 [C-2(9¢)], 65.2 (C-3), 29.6 (COCH3), 14.8 (CH3).
MS: m/z (%) = 304 (M+, 12), 286 (14), 244 (26), 128 (15), 115 (22),
105 (100), 77 (41), 43 (37).
HRMS (FAB): m/z calcd for C21H21O2 (M + 1): 305.1542; found:
305.1543.
4-Benzoyl-5-methylspiro[furan-2(3H),1¢-(1¢,2¢,3¢,4¢-tetrahydro-
naphthalene)] (2f)
Rf = 0.45 (Et2O–hexane, 2:8); colorless liquid.
MS: m/z (%) = 368 (M+, 9), 350 (7), 325 (100), 310 (17), 281 (33),
197 (24), 181 (43), 152 (9), 129 (27), 77 (10), 43 (44).
IR (CHCl3): 1599 cm–1 (C=O) .
X-ray Crystallographic Data of 2h
1H NMR (CDCl3): d = 7.64–7.05 (9 H, m, arom H), 3.28 (2 H, ddq,
J = 65.7, 14.7, 1.47 Hz, CH2), 2.94–2.69 (2 H, m, CH2), 2.20–1.75
(4 H, m, CH2 × 2), 1.91 (3 H, t, J = 1.47 Hz, CH3).
13C NMR (CDCl3): d = 193.0 (C=O), 168.0 (C-5), 141.1, 139.4,
136.5 (arom C), 130.8, 128.8, 128.2 (2 C), 127.9, 127.7 (2 C), 126.7,
126.3 (arom CH), 111.5 (C-4), 87.4 [C-2(1¢)], 46.1 (C-3), 36.5 (C-
2¢), 29.2 (C-4¢), 19.8 (C-3¢), 15.8 (CH3).
Empirical formula C25H20O3; formula weight 368.43; colorless,
prism; crystal dimensions 0.30 × 0.40 × 0.10 mm; monoclinic;
primitive; space group P21/n (# 14); lattice parameters
a = 11.0904(4) Å, b = 10.9721(4) Å, c = 15.6705(5) Å,
b = 93.0893(8)°, V = 1904.1(1) Å3, Z = 4; rcalcd = 1.285 g cm–3;
F000 = 776.00; m (Mo Ka) = 0.83 cm–1; 2qmax = 55.0°; no. of reflec-
tions measured total: 16107, unique: 4357 (Rint = 0.030); no. obser-
vations [I > 3.00s (I)] 3627; no. variables 334; reflection/parameter
ratio 10.86; R1 = 0.042; wR2 = 0.065. The X-ray crystallographic
data have been deposited as supplementary publication number
CCDC249342. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ,
UK [fax: +44(0)1223336033 or e-mail: deposit@ccdc.cam.ac.uk.
MS: m/z (%) = 304 (M+, 12), 286 (14), 244 (32), 128 (18), 115 (14),
105 (100), 91 (14), 77 (44), 43 (23).
HRMS (FAB): m/z calcd for C21H21O2 (M + 1): 305.1542; found:
305.1543.
4-Acetyl-5-methylspiro[furan-2(3H),1¢-(1¢,2¢,3¢,4¢,5¢-penta-
hydrobenzocycloheptane) (2g)
Rf = 0.32 (Et2O–hexane, 5:5); colorless prisms (from hexane); mp
74.0–75.5 °C.
4-Methoxycarbonyl-5-methyl-3-phenylspiro[furan-2(3H),9¢-
xanthene] (2i)
Rf = 0.61 (Et2O–hexane, 5:5); colorless microcrystals (from EtOH);
mp 151.0–152.5 °C.
IR (CHCl3): 1669 cm–1 (C=O) .
IR (CHCl3): 1697 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.42–7.35 (1 H, m, arom H), 7.22–7.08 (3 H,
m, arom H), 3.48 (1 H, dq, J = 14.13, 1.47 Hz, CHa1Hb1), 2.95–2.72
(3 H, m, CH2, CHa1Hb1), 2.37 (3 H, t, J = 1.47 Hz, CH3), 2.19 (3 H,
1H NMR (CDCl3): d = 7.50–6.64 (13 H, m, arom H), 4.41 (1 H, q,
J = 1.47 Hz, CH), 3.48 (3 H, s, COOCH3), 2.66 (3 H, d, J = 1.47 Hz,
CH3).
Synthesis 2005, No. 5, 731–740 © Thieme Stuttgart · New York

PAPER
Spirofuran and Benzocycloalka[1,2-b]furan Using Manganese(III)-Mediated Radical Cyclization
737
13C NMR (CDCl3): d = 169.2 (C=O), 166.1 (C-5), 150.2, 149.2,
138.5, 126.8, 121.5 (arom C), 129.1, 128.6, 127.9 (2 C), 127.6 (2 C),
126.9, 126.5, 124.2, 123.8, 122.4, 116.7, 115.6 (arom CH), 103.0
(C-4), 86.1 [C-2(9¢)], 64.2 (C-3), 50.9 (COOCH3), 14.2 (CH3).
3-Acetyl-2,9b-dimethyl-3aH-benzo[e]cyclohexa[1,2-b]furan
(4c)
Rf = 0.28 (Et2O–hexane, 5:5); colorless plates (from Et2O); mp
61.0–62.5 °C.
IR (CHCl3): 1612 cm–1 (C=O) .
MS: m/z (%) = 384 (M+, 17), 366 (12), 341 (24), 309 (13), 281
(100), 205 (12), 180 (15), 152 (14), 128 (18), 43 (13).
1H NMR (CDCl3): d = 7.59–7.50 (1 H, m, arom H), 7.33–7.07 (3 H,
m, arom H), 3.12 (1 H, dd, J = 10.84, 5.14 Hz, CH), 2.77–2.48 (2 H,
m, CH2), 2.37–2.15 (1 H, m, CHaHb), 2.33 (3 H, s, COCH3), 2.30 (3
H, s, CH3), 1.55 (3 H, s, CH3), 1.44–1.24 (1 H, m, CHaHb).
13C NMR (CDCl3): d = 194.4 (C=O), 166.5 (C-2), 137.7, 137.4
(arom C), 128.1, 127.6, 127.3, 126.7 (arom CH), 117.6 (C-3), 85.9
(C-9b), 49.4 (C-3a), 29.6 (COCH3), 29.3 (CH3), 28.4 (C-5), 27.9 (C-
4), 15.8 (CH3).
4-Acetyl-5-methyl-3-phenylspiro[furan-2(3H),1¢-(1¢,2¢,3¢,4¢-tet-
rahydronaphthalene)] (2j)
Rf = 0.33 (Et2O–hexane, 2:8); colorless needles (from EtOH); mp
111.0–112.0 °C.
IR (CHCl3): 1665 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.64–7.57 (1 H, m, arom H), 7.41–7.00 (8 H,
m, arom H), 4.68 (1 H, q, J = 1.10 Hz, CH), 2.79–2.56 (2 H, m,
CH2), 2.41 (3 H, d, J = 1.10 Hz, CH3), 1.85 (3 H, s, COCH3), 1.77–
1.60 (2 H, m, CH2), 1.57–1.42 (2 H, m, CH2).
13C NMR (CDCl3): d = 195.1 (C=O), 168.4 (C-5), 140.5, 139.8,
136.7 (arom C), 130.2 129.1, 128.4 (2 C), 128.3 (2 C), 127.3, 127.0,
125.5 (arom) CH, 115.8 (C-4), 89.5 [C-2(1¢)], 60.3 (C-3), 33.3 (C-
4¢), 29.6 (COCH3), 29.3 (C-2¢), 19.4 (C-3¢), 15.3 (CH3).
MS: m/z (%) = 242 (M+, 24), 227 (9), 209 (15), 181 (27), 165 (12),
142 (86), 128 (18), 115 (17), 43 (100).
Anal. Calcd for C16H18O2: C, 79.31; H, 7.49. Found: C, 79.24; H,
7.48.
3-Acetyl-2-methyl-9b-phenyl-3aH-benzo[e]cyclohexa[1,2-b]fu-
ran (4d)
Rf = 0.33 (Et2O–hexane, 5:5); colorless prisms (from EtOH); mp
MS: m/z (%) = 318 (M+, 20), 300 (17), 275 (22), 258 (48), 147 (16),
129 (47), 115 (14), 91 (23), 43 (100).
160.0–160.5 °C.
Anal. Calcd for C22H22O2: C, 82.99; H, 6.96. Found: C, 83.23; H,
7.08.
IR (CHCl3): 1619 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.32–7.05 (9 H, m, arom H), 3.50 (1 H, ddd,
J = 10.09, 5.32, 0.92 Hz, CH), 2.87–2.80 (2 H, m, CH2), 2.43–2.32
(1 H, m, CHaHb), 2.40 (3 H, d, J = 0.92 Hz, CH3), 2.24 (3 H, s,
COCH3), 1.72–1.57 (1 H, m, CHaHb).
13C NMR (CDCl3): d = 194.2 (C=O), 166.8 (C-2), 146.9, 138.2,
137.3 (arom C), 129.9, 128.2 (2 C), 128.1, 127.8, 127.1, 126.8,
124.8 (2 C) (arom CH), 117.3 (C-3), 89.2 (C-9b), 52.0 (C-3a), 29.4
(COCH3), 28.2 (C-5), 27.9 (C-4), 15.5 (CH3).
3-Acetyl-2-methyl-8b-phenyl-3aH-benzo[d]cyclopenta[1,2-
b]furan (4a)
Rf = 0.42 (Et2O–hexane, 5:5); yellow prisms (from EtOH); mp
74.5–76.0 °C.
IR (neat): 1620 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.35–7.13 (9 H, m, arom H), 4.01 (1 H, dsex,
J = 8.27, 1.29 Hz, CH), 3.57 (1 H, q, J = 8.45 Hz, CHaHb), 3.15 (1
H, dd, J = 16.9, 2.57 Hz, CHaHb), 2.28 (3 H, d, J = 1.29 Hz, CH3),
2.22 (3 H, s, COCH3).
13C NMR (CDCl3): d = 194.1 (C=O), 166.5 (C-2), 143.7, 143.5,
143.0 (arom C), 129.4, 128.4 (2 C), 127.5, 127.4, 125.6, 125.2,
124.9 (2 C) (arom CH), 117.1 (C-3), 100.6 (C-8b), 55.5 (C-3a), 39.1
(C-4), 29.4 (COCH3), 15.4 (CH3).
MS: m/z (%) = 304 (M+, 46), 262 (12), 243 (19), 228 (18), 217 (18),
204 (65), 91 (12), 43 (100).
Anal. Calcd for C21H20O2: C, 82.86; H, 6.62. Found: C, 82.82; H,
6.65.
X-ray Crystallographic Data of 4d
Empirical formula C21H20O2; formula weight 304.39; colorless,
prism; crystal dimensions 0.15 × 0.40 × 0.40 mm; orthorhombic;
primitive; space group Pbca (# 61); lattice parameters
a = 13.9736(3) Å, b = 28.6550(8) Å, c = 8.0136(2) Å,
V = 3208.8(1) Å3, Z = 8; rcalcd = 1.260 g cm–3; F000 = 1296.00; m
(Mo Ka) = 0.79 cm–1; 2qmax = 55.0°; no. of reflections measured to-
tal: 23073, unique: 3630 (Rint = 0.041); no. observations [I > 2s (I)]
2884; no. variables 289; reflection/parameter ratio 9.98;
R1 = 0.066; wR2 = 0.188. The X-ray crystallographic data have
been deposited as supplementary publication number
CCDC249343. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ,
UK [fax: +44(0)1223336033 or e-mail: deposit@ccdc.cam.ac.uk.
MS: m/z (%) = 290 (M+, 97), 271 (10), 247 (24), 229 (65), 215 (19),
202 (58), 189 (15), 115 (15), 77 (14), 43 (100).
Anal. Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.72; H,
6.21.
3-Acetyl-2-methyl-8b-(1-naphthyl)-3aH-benzo[d]cyclopen-
ta[1,2-b]furan (4b)
Rf = 0.54 (Et2O–hexane, 7:3); colorless prisms (from EtOH); mp
202.0–204.0 °C.
IR (neat): 1614 cm–1 (C=O) .
1H NMR (CDCl3): d = 8.20–6.85 (11 H, m, arom H), 4.33 (1 H, d,
J = 7.34 Hz, CH), 3.83 (1 H, br s, CHaHb), 3.27 (1 H, dd, J = 17.1,
2.20 Hz, CHaHb), 2.34 (3 H, s, COCH3), 2.22 (3 H, s, CH3).
13C NMR (CDCl3): d = 194.4 (C=O), 166.2 (C-2), 143.0, 134.6
(arom C), 129.5 (2 C), 129.4, 129.2 (2 C), 127.4, 126.0, 125.6,
125.3, 124.7, 124.3 (arom CH), 118.2 (C-3), 101.5 (C-8b), 53.9 (C-
3a), 40.3 (C-4), 29.5 (COCH3), 15.5 (CH3).
3-Acetyl-2-methyl-9b-(1-naphthyl)-3aH-benzo[e]cyclo-
hexa[1,2-b]furan (4e)
Rf = 0.61 (Et2O–hexane, 8:2); yellow prisms (from EtOH); mp
182.0–184.0 °C.
IR (neat): 1587 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.81 (2 H, t, J = 6.98 Hz, arom H), 7.72 (1 H,
d, J = 6.98 Hz, arom H), 7.53–7.15 (6 H, m, arom H), 6.93 (1 H, t,
J = 7.72 Hz, arom H), 6.74 (1 H, d, J = 7.72 Hz, arom H), 3.88 (1
H, br s, CH), 3.00–2.82 (2 H, m, CH2), 2.43 (3 H, s, CH3), 2.39–2.24
(1 H, m, CHaHb), 2.22–2.05 (1 H, m, CHaHb), 2.16 (3 H, s, COCH3).
MS: m/z (%) = 340 (M+, 18), 298 (17), 253 (47), 212 (7), 170 (7),
43 (100).
Anal. Calcd for C24H20O2: C, 84.68; H, 5.92. Found: C, 84.64; H,
5.94.
Synthesis 2005, No. 5, 731–740 © Thieme Stuttgart · New York

738
R. Fujino, H. Nishino
PAPER
13C NMR (CDCl3): d = 194.1 (C=O), 167.4 (C-2), 139.8, 139.2,
136.7, 134.7, 129.6 (arom C), 129.2, 129.0, 128.8, 128.4, 128.2,
126.7, 125.6, 125.3, 125.2, 124.8, 122.9 (arom CH), 117.1 (C-3),
90.4 (C-9b), 49.6 (C-3a), 29.2 (COCH3), 27.7 (C-5), 27.0 (C-4),
15.3 (CH3).
2-(4-Hydroxy-2-oxo-3-penten-3-yl)-1-phenyl-3,4-dihydronaph-
thalene (5d)
Rf = 0.56 (Et2O–hexane, 2:8); colorless prisms (from EtOH); mp
108.0–109.0 °C.
IR (CHCl3): 1597 cm–1 (C=O) .
MS: m/z (%) = 355 (M + 1, 33), 281 (16), 221 (9), 147 (24), 73
(100), 43 (22).
1H NMR (CDCl3): d = 16.3 (1 H, s, OH), 7.38–7.04 (8 H, m, arom
H), 6.77 (1 H, d, J = 7.54 Hz, arom H), 3.01 (2 H, t, J = 7.54 Hz,
CH2), 2.60–2.52 (2 H, m, CH2), 2.07 (6 H, s, 2 CH3).
13C NMR (CDCl3): d = 189.8 (2 C) (C=O), 139.6 (C-1), 139.2,
135.6, 131.9 (arom C), 136.2 (C-2), 129.1 (2 C), 128.2 (2 C), 127.3,
127.2, 127.1, 126.4 (2 C) (arom CH), 115.1 (C-3¢), 30.5 (C-3), 28.9
(C-4), 23.9 (2 C) (CH3).
Anal. Calcd for C25H22O2: C, 84.72; H, 6.26. Found: C, 84.53; H,
6.19.
3-Acetyl-2-methyl-10b-phenyl-3aH-benzo[e]cyclo-
hepta[1,2-b]furan (4f)
Rf = 0.35 (Et2O–hexane, 5:5); light yellow prisms (from hexane);
mp 123.5–125.0 °C.
MS: m/z (%) = 304 (M+, 68), 262 (34), 243 (20), 228 (20), 215 (27),
204 (52), 115 (12), 91 (19), 43 (100).
IR (CHCl3): 1627 cm–1 (C=O) .
Anal. Calcd for C21H20O2: C, 82.86; H, 6.62. Found: C, 82.88; H,
6.63.
1H NMR (CDCl3): d = 7.69–7.61 (1 H, m, arom H), 7.35–7.08 (8 H,
m, arom H), 3.70 (1 H, dt, J = 11.21, 1.10 Hz, CH), 2.62–2.43 (2 H,
m, CH2), 2.34 (3 H, d, J = 1.10 Hz, CH3), 2.32 (3 H, s, COCH3),
1.93–1.73 (2 H, m, CH2), 1.65–1.48 (1 H, m, CHaHb), 1.36–1.17 (1
H, m, CHaHb).
13C NMR (CDCl3): d = 193.6 (C=O), 165.1 (C-2), 144.8, 139.4,
136.7 (arom C), 129.1, 128.4 (2 C), 128.3, 128.3, 126.9, 126.6,
125.7 (2 C) (arom CH), 118.4 (C-3), 95.0 (C-10b), 51.8 (C-3a), 31.6
(C-6), 29.3 (COCH3), 27.8 (C-4), 25.0 (C-5), 15.7 (CH3).
2-(4-Hydroxy-2-oxo-3-penten-3-yl)-1-(1-naphthyl)-3,4-dihy-
dronaphthalene (5e)
A mixture of keto and enol form (keto–enol, 1:2); Rf = 0.59/0.76
(CHCl3); colorless liquid.
IR (neat): 1593 cm–1 (C=O) .
MS: m/z (%) = 354 (M+, 11), 312 (17), 293 (12), 269 (30), 252 (28),
141 (18), 117 (31), 43 (100).
HRMS (FAB): m/z calcd for C25H22O2 (M+): 354.1620; found:
354.1622.
MS: m/z (%) = 318 (M+, 4), 276 (12), 218 (100), 203 (23), 165 (10),
115 (15), 91 (13), 77 (10), 43 (88).
Anal. Calcd for C22H22O2: C, 82.99; H, 6.96. Found: C, 82.89; H,
6.99.
Keto Form
1H NMR (CDCl3): d = 7.90–6.43 (11 H, m, arom H), 4.24 (1 H, s,
CH), 3.28–3.13 (2 H, m, CH2), 2.84–2.70 (2 H, m, CH2), 2.07 (3 H,
s, CH3), 1.80 (3 H, s, CH3).
3-Acetyl-9b-benzyl-2-methyl-3aH-benzo[e]cyclohexa[1,2-b]fu-
ran (4g)
Rf = 0.25 (Et2O–hexane, 2:8); colorless needles (from hexane), mp
79.0–81.0 °C.
13C NMR (CDCl3): d = 204.0 (C=O), 203.9 (C=O), 137.9, 136.1,
135.5, 135.5, 132.2 (arom C), 133.8 (C-1), 132.0 (C-2), 128.4,
128.2, 127.4, 127.3, 126.8, 126.4, 126.3, 126.3, 126.2, 125.6, 125.6
(arom CH), 70.7 (C-3¢), 30.2 (CH3), 29.9 (CH3), 28.3 (C-3), 25.5
(C-4).
IR (CHCl3): 1614 cm–1 (C=O) .
1H NMR (CDCl3): d = 7.60 (1 H, dd, J = 7.72, 1.10 Hz, arom H),
7.34–6.97 (6 H, m, arom H), 6.84–6.78 (2 H, m, arom H), 3.35 (1
H, ddd, J = 11.76, 5.33, 0.92 Hz, CH), 3.06 (2 H, dd, J = 23.33,
13.05 Hz, CH2), 2.46 (1 H, dt, J = 15.25, 3.31 Hz, CHa1Hb1), 2.30–
2.19 (1 H, m, CHa1Hb1), 2.18 (3 H, d, J = 0.92 Hz, CH3), 2.16 (3 H,
s, COCH3), 2.02–1.88 (1 H, m, CHa2Hb2), 1.12 (1 H, ddd, J = 24.80,
12.68, 3.12 Hz, CHa2Hb2).
Enol Form
1H NMR (CDCl3): d = 16.25 (1 H, s, OH), 7.90–6.43 (11 H, m,
arom H), 3.10–2.98 (2 H, m, CH2), 2.62–2.47 (2 H, m, CH2), 2.20
(3 H, s, CH3), 1.85 (3 H, s, CH3).
13C NMR (CDCl3): d = 193.9 (C=O), 166.1 (C-2), 138.9, 136.5,
135.0 (arom C), 130.3 (2 C), 127.8, 127.7 (2 C), 127.7, 127.5, 126.7,
126.5 (arom CH), 117.9 (C-3), 88.2 (C-9b), 48.7 (CH2), 46.0 (C-3a),
29.2 (COCH3), 28.4 (C-5), 27.8 (C-4), 15.6 (CH3).
13C NMR (CDCl3): d = 190.5 (C=O), 189.0 (COH), 138.6, 136.2,
136.2, 134.8, 133.8 (arom C), 133.9 (C-1), 131.3 (C-2), 128.5,
127.8, 127.3, 127.3, 126.9, 126.6, 126.3, 126.2, 125.6, 125.5, 125.4
(arom CH), 115.0 (C-3¢), 30.8 (C-3), 28.9 (C-4), 24.3 (CH3), 23.9
(CH3).
MS: m/z (%) = 227 (100), 91 (25), 43 (92).
Anal. Calcd for C22H22O2: C, 82.99; H, 6.96. Found: C, 83.10; H,
7.04.
2-Acetyl-3-methyl-4,5-dihydro-1H-benzo[g]indene (6)
Rf = 0.30 (Et2O–hexane, 2:8); yellow liquid.
IR (CHCl3): 1639 cm–1 (C=O) .
Acid-Catalyzed Reaction of the Spirofurans and Benzocycloal-
ka[1,2-b]furans
1H NMR (CDCl3): d = 7.31–7.14 (4 H, m, arom H), 3.62 (2 H, sex,
J = 2.30 Hz, CH2), 2.95 (2 H, t, J = 8.27 Hz, CH2), 2.55 (2 H, tt,
J = 8.27, 1.84 Hz, CH2), 2.39 (3 H, s, COCH3), 2.36 (3 H, t, J = 2.30
Hz, CH3).
13C NMR (CDCl3): d = 194.6 (C=O), 154.7 (C-3), 144.2, 143.3
(arom C), 136.6 (C-3a), 135.8 (C-9b), 132.4 (C-2), 127.9, 127.7,
126.9, 123.1 (arom CH), 39.2 (C-1), 29.6 (C-5), 28.5 (COCH3),
20.7 (C-4), 14.0 (CH3).
A spirofuran or benzocycloalkafuran (0.2 mmol) was placed in a 30
mL flask. Anhyd benzene (10 mL) containing TsOH (2 mmol) was
added to the flask equipped with a reflux condenser and a gas inlet
tube. The mixture was heated under reflux in an argon atmosphere
for 18–36 h. The reaction was quenched by H2O (50 mL). The aq
mixture was extracted with CH2Cl2 (20 × 3 mL). The combined ex-
tract was washed with H2O and a sat. aq NaHCO3, dried (MgSO4),
filtered, and then concentrated to dryness. The residue was separat-
ed by silica gel TLC (Wakogel B-10) with Et2O–hexane (2:8–5:5
v/v) as the developing solvent. The dihydronaphthalenes 5d and 5e
were further purified by recrystallization from EtOH.
MS: m/z (%) = 224 (M+, 67), 182 (58), 181 (100), 165 (92), 89 (26),
43 (59).
HRMS (FAB): m/z calcd for C16H17O (M + 1): 225.1279; found:
225.1282.
Synthesis 2005, No. 5, 731–740 © Thieme Stuttgart · New York

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Spirofuran and Benzocycloalka[1,2-b]furan Using Manganese(III)-Mediated Radical Cyclization
739
5-Methyl-8,9,9a,13a-tetrahydro-7H-benzo[f]cyclohep-
ta[a]naphthalene (7)
Rf = 0.72 (Et2O–hexane, 2:8); light yellow liquid.
72; Herz, W.; Falk, H.; Kirby, G. W., Eds.; Springer: New
York, 1997. (b) The Chemistry of Heterocycles, 2nd ed.;
Eicher, T.; Hauptmann, S., Eds.; Wiley: New York, 2003.
(c) Merino, P.; Franco, S.; Merchan, F. L.; Tejero, T. In
Recent Research Developments in Synthetic Organic
Chemistry, Vol. 3; Transworld Research Network: Kerala,
2000, 65–74. (d) Garofalo, A. W.; Litvak, J.; Wang, L.;
Dubenko, L. G.; Cooper, R.; Bierer, D. E. J. Org. Chem.
1999, 64, 3369. (e) Schoop, A.; Greiving, H.; Gohrt, A.
Tetrahedron Lett. 2000, 41, 1913. (f) Matsui, K.;
1H NMR (CDCl3): d = 8.08–7.98 (2 H, m, arom H), 7.48–7.14 (7 H,
m, arom H), 2.71 (3 H, s, CH3), 2.60–2.33 (4 H, m, 2 CH2), 2.19–
2.07 (2 H, m, CH2).
13C NMR (CDCl3): d = 140.9, 138.2, 136.4, 134.1, 133.7, 132.0,
131.3 (arom C), 130.8, 128.4, 128.3, 127.2, 126.4, 125.5, 125.4,
124.6, 124.2 (arom CH), 33.5 (C-8), 31.6 (C-7), 31.1 (C-9), 19.5
(CH3).
Fukuyama, K.; Tsukihara, K.; Tsukihara, T.; Katsube, Y.;
Munakata, K. Bull. Chem. Soc. Jpn. 1976, 49, 62.
MS: m/z (%) = 258 (M+, 100), 243 (43), 228 (51), 215 (32), 114
(g) Kajikawa, S.; Nishino, H.; Kurosawa, K. Heterocycles
2001, 54, 171. (h) Jogo, S.; Nishino, H.; Yasutake, M.;
Shinmyozu, T. Tetrahedron Lett. 2002, 43, 9031.
(28), 108 (27).
HRMS (FAB): m/z calcd for C20H18 (M+): 258.1409; found:
258.1444.
(4) Snider, B. B. Chem. Rev. 1996, 96, 339.
(5) (a) Snider, B. B.; Mohan, R.; Kates, S. A. J. Org. Chem.
1985, 50, 3661. (b) Dombroski, M. A.; Kates, S. A.; Snider,
B. B. J. Am. Chem. Soc. 1990, 112, 2759. (c) Snider, B. B.;
Zhang, Q. J. Org. Chem. 1993, 58, 3185. (d) Vo, N. H.;
Snider, B. B. J. Org. Chem. 1994, 59, 5419. (e) Snider, B.
B.; Han, L.; Xie, C. J. Org. Chem. 1997, 62, 6978.
(6) (a) Toyao, A.; Chikaoka, S.; Takeda, Y.; Tamaru, O.;
Muraoka, O.; Tanabe, G.; Ishibashi, H. Tetrahedron Lett.
2001, 42, 1729. (b) Yang, D.; Ye, X.-Y.; Xu, M.; Pang, K.-
W.; Cheung, K.-K. J. Am. Chem. Soc. 2000, 122, 1658.
(c) Yang, D.; Ye, X.-Y.; Xu, M. J. Org. Chem. 2000, 65,
2208. (d) Bar, G.; Parsons, A. F.; Thomas, C. B.
X-Ray Crystallography of 2b,g,h, and 4d
All measurements were made using a Rigaku RAXIS-RAPID Im-
aging Plate diffractometer with graphite monochromated Mo-Ka
radiation (l = 0.71069 Å). Indexing was performed from 2 oscilla-
tions, which were exposed for 1.7–3.3 min. The camera radius was
127.40 mm. The readout was performed in the 0.100 mm pixel
mode. The data were collected at a temperature of –180 1 °C to a
maximum 2q value of 55.0° and anode power of 50 kV × 32 mA.
The crystallographic data and details of the data collections and re-
finements are available from the authors. Data reduction was car-
ried out using the program ABSCOR, and Lorentz and polarization
corrections were performed. A correction for secondary extinction
was applied. The structures were solved by direct methods and were
refined on SIR-92.14 The refinements were followed by a least-
squares full matrix method with anisotropic displacement parame-
ters for all non-hydrogen atoms. The hydrogen atoms were included
but not refined. All calculations were performed using the teXsan15
crystallographic software package from Molecular Structure Cor-
poration.
Tetrahedron Lett. 2000, 41, 7751. (e) Paquette, L. A.;
Schaefer, A. G.; Springer, J. P. Tetrahedron 1987, 43, 5567.
(f) Iwasawa, N.; Funahashi, M.; Hayakawa, S.; Ikeno, T.;
Narasaka, K. Bull. Chem. Soc. Jpn. 1999, 72, 85.
(7) For recent reviews, see: (a) Melikyan, G. G. Synthesis 1993,
833. (b) Iqbal, J.; Bhatia, B.; Nayyar, N. K. Chem. Rev.
1994, 94, 519. (c) Melikyan, G. G. Org. React. 1997, 49,
427. (d) Melikyan, G. G. Aldrichimica Acta 1998, 31, 50.
(e) Nishino, H. Oleoscience 2001, 1, 491.
(8) (a) Nishino, H. Bull. Chem. Soc. Jpn. 1985, 58, 1922.
(b) Nishino, H.; Yoshida, T.; Kurosawa, K. Bull. Chem. Soc.
Jpn. 1991, 64, 1097. (c) Qian, C.-Y.; Nishino, H.;
Kurosawa, K. J. Heterocycl. Chem. 1993, 30, 209.
(d) Ouyang, J.; Nishino, H.; Kurosawa, K. J. Heterocycl.
Chem. 1995, 32, 1783. (e) Nguyen, V.-H.; Nishino, H.;
Kurosawa, K. Tetrahedron Lett. 1996, 37, 4949.
Acknowledgment
This research was supported by Grants-in-Aid for Scientific Re-
search on Priority Areas (A) ‘Exploitation of Multi-Element Cyclic
Molecules’ No. 13029088 and No.14044078, from the Ministry of
Education, Culture, Sports, Science and Technology, Japan, and
also by Grants-in-Aid for Scientific Research, No. 13640539 and
No. 15550039, from the Japan Society for the Promotion of Sci-
ence. We gratefully acknowledge Professor Teruo Shinmyozu and
Dr. Mikio Yasutake, Institute for Materials Chemistry and Enginee-
ring, Kyushu University, Japan, for their crystallographic assi-
stance.
(f) Nishino, H.; Nguyen, V.-H.; Yoshinaga, S.; Kurosawa,
K. J. Org. Chem. 1996, 61, 8264. (g) Nguyen, V.-H.;
Nishino, H.; Kurosawa, K. Synthesis 1997, 899.
(h) Yoshinaga, T.; Nishino, H.; Kurosawa, K. Tetrahedron
Lett. 1998, 39, 9197. (i) Chowdhury, F. A.; Nishino, H.;
Kurosawa, K. Heterocycl. Commun. 1999, 5, 111.
(j) Kajikawa, S.; Nishino, H.; Kurosawa, K. Heterocycles
2001, 54, 171. (k) Nguyen, V.-H.; Nishino, H. Tetrahedron
Lett. 2004, 45, 3373. (l) Kumabe, R.; Nishino, H.
References
(1) (a) Onitsuka, S.; Nishino, H.; Kurosawa, K. Tetrahedron
Lett. 2000, 41, 3149. (b) Onitsuka, S.; Nishino, H.;
Kurosawa, K. Heterocycl. Commun. 2000, 6, 529.
(c) Onitsuka, S.; Nishino, H.; Kurosawa, K. Tetrahedron
2001, 57, 6003. (d) Onitsuka, S.; Nishno, H. Tetrahedron
2003, 59, 755.
(2) (a) Corey, E. J.; Cheng, X.-M. The Logic of Chemical
Synthesis; Wiley: New York, 1989. (b) Nicolaou, K. C.;
Sorensen, E. J. Classics in Total Synthesis; VCH: Weinheim,
1996.
Heterocycl. Commun. 2004, 10, 135.
(9) (a) Tategami, S.; Yamada, T.; Nishino, H.; Korp, J. D.;
Kurosawa, K. Tetrahedron Lett. 1990, 31, 6371.
(b) Nishino, H.; Tategami, S.; Yamada, T.; Korp, J. D.;
Kurosawa, K. Bull. Chem. Soc. Jpn. 1991, 64, 1800.
(c) Qian, C.-Y.; Yamada, T.; Nishino, H.; Kurosawa, K.
Bull. Chem. Soc. Jpn. 1992, 65, 1371. (d) Yamada, T.;
Iwahara, Y.; Nishino, H.; Kurosawa, K. J. Chem. Soc.,
Perkin. Trans. 1 1993, 609. (e) Nguyen, V.-H.; Nishino, H.;
Kurosawa, K. Heterocycles 1998, 48, 465. (f) Chowdhury,
F. A.; Nishino, H.; Kurosawa, K. Heterocycles 1999, 51,
(3) (a) Fortschritte der Chemie Organischer Naturstoffe–
Progress in the Chemistry of Organic Natural Product, Vol.
Synthesis 2005, No. 5, 731–740 © Thieme Stuttgart · New York

740
R. Fujino, H. Nishino
PAPER
575. (g) Sakata, M.; Shirakawa, Y.; Kamata, N.; Sakaguchi,
M.; Nishino, H.; Ouyang, J.; Kurosawa, K. J. Heterocycl.
Chem. 2000, 37, 269. (h) Kumabe, R.; Nishino, H.;
Yasutake, M.; Nguyen, V.-H.; Kurosawa, K. Tetrahedron
Lett. 2001, 42, 69. (i) Kumabe, R.; Nishino, H. Tetrahedron
Lett. 2004, 45, 703.
(12) Kajikawa, S.; Nishino, H.; Kurosawa, K. Tetrahedron Lett.
2001, 42, 3351.
(13) Heiba, E. I.; Dessau, R. M.; Koehl, W. J. Jr. J. Am. Chem.
Soc. 1969, 91, 138.
(14) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, M.;
Giacovazzo, C.; Guagliardi, A.; Polidori, G. J. Appl.
Crystallogr. 1994, 27, 435.
(15) Crystal Structure Analysis Package, Molecular Structure
Corporation: 1985 and 1992.
(10) Nishino, H.; Kamachi, H.; Baba, H.; Kurosawa, K. J. Org.
Chem. 1992, 57, 3551.
(11) PM3 calculation was performed by CAChe version 4.9.3.
Synthesis 2005, No. 5, 731–740 © Thieme Stuttgart · New York