DDQ induced oxidative cyclisations of 1,2-dihydronaptho[2,1-b]furans

Article abstract of DOI:10.1016/j.tet.2004.12.010

The DDQ mediated oxidative cyclisation reactions of a series of dihydronaptho[2,1-b]furans were examined. In the presence of an acid catalyst, the reaction yielded polycyclic ethers and lactones in good to excellent yields.

Full text of DOI:10.1016/j.tet.2004.12.010

Tetrahedron 61 (2005) 1885–1891
DDQ induced oxidative cyclisations of
1,2-dihydronaptho[2,1-b]furans
a
b
Martyn Jevric,a Dennis K. Taylor,a, Ben W. Greatrex and Edward R. T. Tiekink
*
aDepartment of Chemistry, University of Adelaide, Adelaide 5005, Australia
bDepartment of Chemistry, National University of Singapore, Singapore, Singapore 117543
Received 30 July 2004; revised 1 November 2004; accepted 2 December 2004
Available online 12 January 2005
Abstract—The DDQ mediated oxidative cyclisation reactions of a series of dihydronaptho[2,1-b]furans were examined. In the presence of
an acid catalyst, the reaction yielded polycyclic ethers and lactones in good to excellent yields.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
2,3-Dichloro-5,6-dicyanobenzoquinone (DDQ) is a com-
mon oxidant used in dehydrogenation reactions leading to
aromatised products1–3 and in the oxidation of aromatic and
allylic alcohols to aldehydes and ketones.4–6 DDQ can be
used to generate benzylic and napthylic cations on suitably
activated systems via hydride abstraction. The cations thus
generated can undergo nucleophilic addition and intra-
molecular cyclisation reactions leading to oxygen contain-
ing heterocycles when the substrates are substituted with
suitable latent nucleophiles.7–9
The synthesis of the starting dihydronapthofurans 3a–d
was achieved using our previously published procedure,
Scheme 1.10 Thus, Rose Bengal bis(triethylammonium) salt
sensitised photooxidation of 1-vinylnapthalenes gave the
1,2-dioxines 1a–d. These 1,2-dioxines underwent
rearrangement when allowed to react with DABCO to
afford the 1-(b-keto)-2-napthols 2a–d in excellent yield.
Reaction of the napthols 2a–d with methyl(triphenyl-
phosphoranylidene)acetate afforded the requisite dihydro-
napthofurans 3a–d via a Wittig/oxy-Michael sequence.
Further functional group modifications were made on the
dihydronapthofurans 3a–d such that the scope of the
oxidative cyclisation could be examined. Saponification of
the esters 3a–c afforded the acids 4a–c and LiAlH4
reduction of 3b and 3d gave the alcohols 5b and 5d,
respectively. To the best of our knowledge, electrophilic
aromatic substitution has not been examined on 1,2-
dihydronaptho[2,1-b]furans, although the dehydrogenated
naptho[2,1-b]furans are known to react primarily at the C6
position.14 When 3b was exposed to standard nitration
conditions, electrophilic substitution occurred at both the C7
and C9 positions on the naphthalene skeleton to afford 6 and
7 in good overall yield. The identity of these isomers was
determined using both COSY and ROESY 2D NMR
techniques.
We have recently developed a route to 1,2-dihydro-
naptho[2,1-b]furans 3 utilising 1,2-dioxines 1 and stabilised
phosphorus ylides.10 We considered these products to be
ideal substrates for DDQ induced oxidation due to the
stabilising effect of the furan ring on the intermediate
napthylic cation. The products generated in this previous
study also contained an ester group that could act as the
nucleophile for the intramolecular trapping of the napthylic
cation. It was hypothesised that this ester or derivative
thereof could participate in the reaction and give rise to
novel cyclisation products. Some aryl-fused furofurans are
found in nature such as psorofebrin11,12 and platypod-
antherone13 and we believed that by investigating DDQ
induced oxidative cyclisations on dihydronapthofurans, we
could develop a route to these types of compounds. We now
report on the oxidative cyclisation reactions of a series of
substituted 1,2-dihydronapthofurans facilitated by DDQ.
With a range of substrates in hand, the DDQ facilitated
oxidative cyclisation reactions of napthofurans 3, 4, 5, 7 and
8 were examined, Scheme 2 and Table 1. Initially, when the
ester 3a was heated to 50 8C in dry benzene in the presence
of 1.1 equivalents of DDQ, no reaction was observed. To
Keywords: DDQ; Dihydronapthofuran; Cyclisation.
* Corresponding author. Tel.: C61 8 8303 5494; fax: C61 8 8303 4358;
e-mail: dennis.taylor@adelaide.edu.au
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.12.010

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M. Jevric et al. / Tetrahedron 61 (2005) 1885–1891
Scheme 1. Key: (a) DABCO; (b) Ph3P]CHCO2Me; (c) KOH, MeOH/H2O, 16 h; (d) LiAlH4, THF, 16 h; (e) HNO3, AcOH, 1 h.
Scheme 2.
enhance the reactivity of the DDQ, addition of an acid
catalyst to the reaction medium was examined. In the
presence of p-toluenesulfonic acid, the esters 3a–d and 7
reacted with DDQ affording the furofuranones 9a–e in good
yield, entries 1–5. The dihydronapthofuran acids 4a–c and 8
underwent smooth reaction to give the furofuranones 9a–c,e
without the need for an acid catalyst, entries 6–9. The
yields obtained from the acids 4a–c and 8 were virtually
identical to the yields seen in the corresponding ester series
3a–c and 7.
requirement for the acid catalyst in the ester series may be
due to the reduced ability of the ester group, relative to the
acid and alcohol groups, to stabilise the cation in the rate-
determining cation-forming step. Oxidations involving
DDQ are often performed in acidic solvents to activate
DDQ towards hydride abstraction.15
The 1H NMR data for the furolactones were consistent with
the proposed structures. Each lactone exhibited a singlet at
ca. d 6.20 ppm due to the napthylic proton and an AB
quartet at ca. d 3.00 ppm. The lactone products exhibited
characteristic IR absorptions at 1785 cmK1 and the stereo-
chemistry of the products were confirmed when the X-ray
structures of 9b and 9e were obtained, Figure 1.16 The
Cyclisation of the alcohols 5b and 5d also proceeded
smoothly to afford the furofurans 10b and 10d in the
absence of an acid catalyst in excellent yield. The
Table 1. Oxidative cyclisations of 1,2-dihydronaptho[2,1-b]furans
Entrya
Starting
material
R
R1
R2
R3
Product
Yield (%)
1b
2b
3b
4b
5b,c
6
3a
3b
3c
3d
7
4a
4b
4c
8
H
Me
Ph
4-ClPh
Me
H
Me
Ph
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2H
CO2H
CO2H
CO2H
CH2OH
CH2OH
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
NO2
H
H
H
NO2
H
9a
9b
9c
9d
9e
9a
9b
9c
40
64
80
85
88
38
81
71
91
81
87
7
8
9c
10
11
Me
Me
4-ClPh
9e
10b
10d
5b
5d
H
a Reactions were performed in dry benzene at 50 8C for 1 h.
b Performed in the presence of a catalytic amount (2 mg) of p-toluenesulfonic acid.
c Reaction heated to reflux for 16 h.

M. Jevric et al. / Tetrahedron 61 (2005) 1885–1891
1887
DDQ for the reaction to achieve completion. This result
suggests an oxygen transfer mechanism as depicted with a
faster second hydride abstraction due to the stabilising effect
of the a-oxygen atom. Nitrile 12 exhibited a resonance in
1
the H NMR attributed to the C1 carbonyl carbon at d
197.3 ppm and an IR absorption at 2258 cmK1 correspond-
ing to the nitrile moiety confirming the assigned structure.
The oxidative cyclisation of dihydronapthofurans is a useful
method for the construction of aryl furofuran ring systems, a
ring structure found in natural products such as platypo-
dantherone and psorofebrin. The naphthalene ring serves as
a rigid template for the ether or lactone construction while
stabilising the carbocation formation. Ring closures of this
type could be used in the construction of arylfurofuranone
natural products.
3. Experimental
3.1. General experimental
Solvents were dried by appropriate methods wherever
needed. Benzene was dried by distillation over calcium
hydride prior to use. Thin-layer chromatography (TLC) was
performed using aluminium sheets silica gel 60 F254 (40!
80 mm) from Merck. Melting points were taken on a
Reichert Thermovar Kofler apparatus and are uncorrected.
Infrared spectra were recorded on an ATI Mattson Genesis
Series FTIR spectrophotometer as nujol mulls unless
Figure 1. X-ray structures of 9b and 9e.
1
otherwise indicated. H NMR and 13C NMR spectra were
structure of 9e also confirmed the substitution pattern
obtained from the electrophilic aromatic substitution
reaction of 3b.
recorded in CDCl3 solution on a Varian INOVA (600 MHz)
or on a Varian Gemini 2000 instrument, TMS (0 ppm) and
CDCl3 (77.0 ppm) as internal standards unless otherwise
specified. Dihydrofurans 3a–d and compounds 1d and 2d
were prepared according to our previously reported
procedure.10
Mechanistically, the reaction proceeds via a two-step
sequence with initial hydride abstraction by DDQ to give
the napthyl cation and the DDQHK anion. The napthylic
cation is trapped by the oxygen of the alcohol, acid or ester
and then the DDQHK anion abstracts either a proton or
methyl to yield the reduced DDQH2 or DDQH(Me),
respectively and the cyclisation product.
3.1.1. (G) (2R,4aR)-2-(4-Chlorophenyl)-2,4a-dihydro-
naphtho[2,1-c][1,2]dioxine 1d. Light yellow solid; mp
78–82 8C; Rf 0.32 (30:70 CH2Cl2/hexane); 1H NMR
(CDCl3, 600 MHz) d 5.52 (dd, JZ3.0, 3.0 Hz, 1H) 5.78
(dd, JZ10.2, 2.4 Hz, 1H), 6.02 (dddd, JZ3.0, 3.0, 3.0,
2.4 Hz, 1H), 6.15 (ddd, JZ3.0, 3.0, 1.2 Hz, 1H), 6.45
(dd, JZ10.2, 3.0 Hz, 1H), 7.08 (dd, JZ7.8, 1.2 Hz, 1H),
The oxidative cyclisation of a dihydrofuran with a nitrogen
bearing arm was also examined, Scheme 3. The reaction of
amide 11 afforded nitrile 12 and required two equivalents of
Scheme 3.

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M. Jevric et al. / Tetrahedron 61 (2005) 1885–1891
7.22–7.28 (m, 2H), 7.32–7.34 (m, 2H), 7.38–7.48 (m, 3H);
13C NMR (CDCl3, 150 MHz) d 80.9, 82.0, 119.3, 123.6,
124.1, 127.4, 128.6, 128.6, 129.2, 129.3, 129.9, 130.9,
132.2, 134.4, 136.3, 138.0; MS m/z (%) 296 (MC, 20), 278
(57), 265 (32), 139 (100), 111 (31); HRMS calcd for
C18H13O325Cl: 296.0604; found: 296.0610.
6.9, 9.6 Hz, 1H), 7.11–7.14 (m, 1H), 7.30–7.35 (m, 1H),
7.45–7.51 (m, 1H), 7.57–7.60 (m, 1H), 7.68–7.71 (m, 1H),
7.80–7.83 (m, 1H); 13C NMR (CDCl3, 50 MHz) d 34.3,
40.6, 79.1, 112.1, 117.6, 122.7, 123.1, 126.8, 128.8, 129.3,
129.4, 130.7, 156.4, 175.1; EIMS m/z 228 (MC, 9), 168
(39), 69 (54), 55 (56), 41 (100); Anal. Calcd for C14H12O3:
C, 73.67; H, 5.30; Found C, 73.40; H, 5.03.
3.1.2. 1-(4-Chlorophenyl)-2-(2-hydroxy-1-naphthal-
enyl)-1-ethanone 2d. White solid; mp 212–220 8C
(decomposes); IR (Nujol) 3421, 1674, 1630, 1587, 1570,
1518 cmK1; 1H NMR (CDCl3/d6-DMSO, 300 MHz) d 4.70
(s, 2H), 7.20–7.27 (m, 2H), 7.37–7.44 (m, 3H), 7.64–7.75
(m, 3H), 8.09–8.11 (m, 1H), 9.18 (s, 1H); 13C NMR (CDCl3/
d6-DMSO, 75 MHz) d 35.9, 112.7, 117.9, 122.2, 122.4,
126.1, 128.1, 128.3, 128.4, 129.6, 133.6, 135.0, 138.8,
152.3, 197.3, (1 masked aromatic); MS m/z (%) 296 (MC,
32), 157 (100), 139 (67), 128 (45); Anal. Calcd for
C18H13ClO2: C, 72.85; H, 4.42; Cl, 11.95; Found C,
72.64; H, 4.34; Cl, 12.18.
3.2.2. 2-(2-Methyl-1,2-dihydronaphtho[2,1-b]furan-2-
yl)acetic acid 4b. Recrystallised from n-heptane/dichloro-
methane; mp 124–126 8C; IR (Nujol) 1711, 1633, 1574,
1
1603, 2670 cmK1; H NMR (CDCl3, 300 MHz) d 1.68 (s,
3H), 2.91 (s, 2H), 3.33 (d, JZ15.9 Hz, 1H), 3.61 (d, JZ
15.9 Hz, 1H), 7.07–7.10 (m, 1H), 7.27–7.33 (m, 1H), 7.45–
7.49 (m, 1H), 7.56–7.59 (m, 1H), 7.67–7.70 (m, 1H), 7.79–
7.82 (m, 1H); 13C NMR (CDCl3, 200 MHz) d 26.6, 40.4,
45.0, 86.7, 112.3, 117.8, 122.7, 122.9, 126.7, 128.7, 129.2,
129.3, 130.9, 155.5, 175.4; EIMS m/z 242 (MC, 39), 144
(100), 105 (98), 77 (53); Anal. Calcd for C15H14O3: C,
74.36; H, 5.82; Found C, 74.15; H, 5.74.
3.1.3. Methyl 2-[2-phenyl-1,2-dihydronaphtho[2,1-
b]furan-2-yl]acetate 3c. Colorless oil; Rf 0.46 (80:20
hexane/ethyl acetate); IR (CH2Cl2) 1738, 1633, 1601,
3.2.3. 2-(2-Phenyl-1,2-dihydronaphtho[2,1-b]furan-2-
yl)acetic acid 4c. Recrystallised from hot dichloro-
methane/hexane (1:1); mp 154.5–155.5 8C; IR (Nujol)
1
1579, 1522, 1494 cmK1; H NMR (CDCl3, 300 MHz) d
3.13 (d, JZ14.6 Hz, 1H), 3.16 (d, JZ14.6 Hz, 1H), 3.48 (s,
3H), 3.77 (d, JZ15.7 Hz, 1H), 4.14 (d, JZ15.7 Hz, 1H),
7.26–7.50 (m, 6H), 7.58–7.62 (m, 3H), 7.72–7.75 (m, 1H),
7.81–7.83 (m, 1H); 13C NMR (CDCl3, 50 MHz) d 41.2,
46.4, 51.6, 89.1, 112.0, 117.7, 122.7, 123.0, 124.8, 126.6,
127.5, 128.4, 128.7, 129.2, 129.4, 130.7, 144.8, 155.9,
169.9; EIMS m/z 318 (MC, 32), 286 (22), 257 (2), 244
(100), 181 (11); HRMS calcd for C21H18O3: 318.1256;
found 318.1255.
1722, 1657, 1603, 1577, 1521, 1496 cmK1 1H NMR
;
(CDCl3, 300 MHz) d 3.17 (d, JZ15.5 Hz, 1H), 3.18 (d,
JZ15.5 Hz, 1H), 3.74 (d, JZ15.9 Hz, 1H), 4.03 (d, JZ
15.9 Hz, 1H), 7.24–7.37 (m, 5H), 7.44–7.47 (m, 1H), 7.53–
7.56 (m, 3H), 7.70–7.73 (m, 1H), 7.78–7.81 (m, 1H); 13C
NMR (CDCl3, 50 MHz) d 41.7, 45.9, 89.4, 112.1, 117.6,
122.7, 123.2, 124.8, 126.8, 127.7, 128.5, 128.7, 129.4,
129.6, 130.7, 144.2, 155.7, 173.6; EIMS m/z 304 (MC, 64),
257 (28), 244 (100), 181 (15); Anal. Calcd for C20H16O3: C,
78.93; H, 5.30; Found C, 78.77; H, 5.44.
3.1.4. Methyl 2-[2-(4-chlorophenyl)-1,2-dihydro-
naphtho[2,1-b]furan-2-yl]acetate 3d. Pale yellow viscous
oil; Rf 0.49 (80:20 hexane/ethyl acetate); IR (neat) 1738,
1633, 1601, 1579, 1521 cmK1; 1H NMR (CDCl3, 300 MHz)
d 3.11 (d, JZ14.9 Hz, 1H), 3.14 (d, JZ14.9 Hz, 1H), 3.51
(s, 3H), 3.73 (d, JZ15.6 Hz, 1H), 4.11 (d, JZ15.6 Hz, 1H),
7.21–7.24 (m, 1H), 7.29–7.36 (m, 3H), 7.44–7.52 (m, 3H),
7.56–7.59 (m, 1H), 7.71–7.74 (m, 1H), 7.79–7.82 (m, 1H);
13C NMR (CDCl3, 300 MHz) d 41.4, 46.2, 51.6, 89.2, 112.0,
117.4, 122.6, 123.1, 126.4, 126.8, 128.5, 128.7, 129.4,
129.5, 130.6, 133.4, 143.2, 155.7, 169.7; EIMS m/z 352
(MC, 19), 291 (22), 278 (100), 181 (20); HRMS calcd for
C21H17O335Cl: 352.0866; found 352.0860.
3.3. General procedure for the reduction of esters 3b,d
3.3.1. 2-(2-Methyl-1,2-dihydronaphtho[2,1-b]furan-2-
yl)-1-ethanol 5b. To a stirred solution of dihydrofuran 3b
(206 mg, 0.805 mmol) in anhydrous THF (5 ml) was added
LiAlH4 (30 mg, 0.790 mmol) at ambient temperature. After
16 h the reaction was quenched with ethyl acetate (1 ml) and
1 N HCl (10 ml) added. The mixture was extracted with
CH2Cl2 (2!20 ml), dried (Na2SO4), filtered and concen-
trated in vacuo. Purification by flash chromatography
afforded a colorless oil (169 mg, 92%); Rf 0.24 (90:10
CH2Cl2/ethyl acetate); IR (CH2Cl2) 3614, 3566, 1632, 1599,
1
1586, 1522 cmK1; H NMR (CDCl3, 600 MHz) d 1.56 (s,
3.2. General procedure for the hydrolysis of esters 3a–c
and 7
3H), 1.71 (br s, 1H), 2.09 (ddd, JZ5.4, 6.2, 14.5 Hz, 1H),
2.19 (ddd, JZ5.6, 7.4, 14.5 Hz, 1H), 3.28 (d, JZ15.3 Hz,
1H), 3.43 (d, JZ15.3 Hz, 1H), 3.86 (ddd, JZ5.6, 6.2,
11.5 Hz, 1H), 3.95 (ddd, JZ5.4, 7.4, 11.5 Hz, 1H) 7.06–
7.07 (m, 1H), 7.29–7.32 (m, 1H), 7.45–7.48 (m, 1H), 7.55–
7.57 (m, 1H), 7.68–7.69 (m, 1H), 7.80–7.81 (m, 1H); 13C
NMR (CDCl3, 150 MHz) d 28.9, 41.2, 43.4, 59.5, 89.8,
112.4, 118.1, 122.8, 123.0, 126.9, 128.9, 129.3, 129.4,
131.2, 155.9; EIMS m/z 228 (100), 209 (12), 195 (54), 183
(45); HRMS calcd for C15H16O2: 228.1150; found
228.1158.
3.2.1. 2-(1,2-Dihydronaphtho[2,1-b]furan-2-yl)acetic
acid 4a. A solution of dihydrofuran 3a (138 mg,
0.57 mmol) and potassium hydroxide (400 mg, excess) in
methanol (10 ml) was stirred for 16 h. The solution was
acidified with 1 N HCl and then extracted with CH2Cl2 (2!
20 ml), dried (Na2SO4), filtered and concentrated in vacuo.
The crude acid was recrystallised from chloroform to give a
white solid (110 mg, 85%); mp 138.5–139.5 8C; IR
1
(CH2Cl2) 2760, 1693, 1631, 1599, 1577, 1520 cmK1; H
NMR (CDCl3, 300 MHz) d 2.83 (dd, JZ6.0, 16.2 Hz, 1H),
3.01 (dd, JZ16.2, 7.2 Hz, 1H), 3.23 (dd, JZ15.4, 6.9 Hz,
1H), 3.74 (dd, JZ15.4, 9.6 Hz, 1H), 5.40 (dddd, JZ6.0, 7.2,
3.3.2. 2-[2-(4-Chlorophenyl)-1,2-dihydronaphtho[2,1-
b]furan-2-yl]-1-ethanol 5d. Gummy colorless oil; Rf 0.25
(95:5 CH2Cl2/ethyl acetate); IR (CH2Cl2) 3683, 3608, 1633,

M. Jevric et al. / Tetrahedron 61 (2005) 1885–1891
1889
1603, 1579, 1522, 1491 cmK1; 1H NMR (CDCl3, 600 MHz)
d 1.94 (br s, 1H), 2.37 (ddd, JZ5.6, 5.6, 14.7 Hz, 1H), 2.50
(ddd, JZ6.0, 7.6, 14.7 Hz, 1H), 3.63–3.67 (m, 2H), 3.73
(ddd, JZ5.6, 7.4, 11.4 Hz, 1H), 3.79 (d, JZ15.2 Hz, 1H),
7.20–7.22 (m, 1H), 7.30–7.34 (m, 3H), 7.43–7.46 (m, 3H),
7.51–7.53 (m, 1H), 7.72–7.74 (m, 1H), 7.80–7.81 (m, 1H);
13C NMR (CDCl3, 75 MHz) d 43.3, 44.2, 59.0, 91.7, 111.8,
117.2, 122.5, 123.1, 126.1, 126.7, 128.5, 128.6, 129.3,
129.4, 130.5, 133.0, 143.6, 155.5; EIMS m/z 324 (MC, 100),
291 (81), 279 (49), 215 (27); Anal. Calcd for C20H17O2Cl:
C, 73.96; H, 5.28; Found C, 73.88; H, 5.33.
8.8 Hz, 1H), 7.99 (dd, JZ8.0, 1.1 Hz, 1H); 13C NMR
(CDCl3, 300 MHz) d 26.4, 41.1, 44.6, 87.1, 114.4, 114.7,
121.0, 122.7, 123.1, 130.6, 130.8, 133.5, 146.1, 159.0,
174.0; EIMS m/z 287 (MC, 53), 270 (57), 253 (53), 227
(85), 181 (100), 152 (72), 45 (90); Anal. Calcd for
C15H13NO5: C, 62.72; H, 4.56; N, 4.88; Found C, 63.26;
H, 4.69; N, 4.98.
3.5. General procedure for the reaction of esters 3a–d
and 7 with DDQ
To a stirred solution of dihydronapthofuran (0.11 mmol)
and DDQ (29 mg, 0.12 mmol) in dry benzene (8 ml) was
added p-toluenesulphonic acid (2 mg, 0.01 mmol) dissolved
in benzene (0.5 ml). The solution was heated to 50 8C for
1 h and then cooled and concentrated in vacuo to ca. 1 ml.
The solution was filtered through a plug of cotton wool and
the residue purified by flash chromatography.
3.4. Reaction of methyl 2-(2-methyl-1,2-dihydro-
naphtho[2,1-b]furan-2-yl)acetate 3b with nitric acid
To a stirred solution of dihydronapthofuran 3b (325 mg,
1.27 mmol) in glacial acetic acid (20 ml) cooled in an ice
water bath was added nitric acid (4 ml, 50% in glacial acetic
acid). The vessel was warmed to 30 8C and left to stir for 1 h
at ambient temperature. The solution was poured onto ice
water and the mixture extracted with dichloromethane (2!
20 ml). The organic phase was dried (Na2SO4), filtered and
the solvent removed in vacuo. The crude residue was
purified by flash chromatography (80:20 hexane/ethyl
acetate) to give 6 (120 mg, 31%) and 7 (150 mg, 39%).
3.6. General procedure for the reaction of acids 4a–c, 8
and alcohols 5b,d with DDQ
A stirred solution of dihydronapthofuran (0.11 mmol) and
DDQ (29 mg, 0.12 mmol) in dry benzene (8 ml) was heated
to 50 8C for 1 h and then cooled and concentrated in vacuo
to ca. 1 ml. The solution was filtered through a plug of
cotton wool and the residue purified by flash
chromatography.
3.4.1. Methyl 2-(2-methyl-7-nitro-1,2-dihydronaphtho-
[2,1-b]furan-2-yl)acetate 6. Yellow oil; Rf 0.33 (80:20
hexane/ethyl acetate); IR (CH2Cl2) 1738, 1626, 1603, 1537,
1
1506, 1338 cmK1; H NMR (CDCl3, 600 MHz) d 1.67 (s,
3.6.1. (G) (7aR,10aR)-7a,8,9,10a-Tetrahydrofuro[3,2-
b]naphtho[2,1-d]furan-9-one 9a. White solid; mp 205–
207 8C (lit. 207–208 8C)17; Rf 0.58 (40:60 ethyl acetate/
3H), 2.86 (d, JZ15.3 Hz, 1H), 2.89 (d, JZ15.3 Hz, 1H),
3.33 (d, JZ16.2 Hz, 1H), 3.66 (d, JZ16.2 Hz, 1H), 3.66 (s,
3H), 7.19 (d, JZ8.7 Hz, 1H), 7.60 (d, JZ9.1 Hz, 1H), 7.85
(d, JZ8.7 Hz, 1H), 8.21 (dd, JZ9.1, 2.4 Hz, 1H), 8.74 (d,
JZ2.4 Hz, 1H); 13C NMR (CDCl3, 50 MHz) d 26.9, 39.6,
44.8, 51.6, 88.1, 114.3, 119.0, 120.1, 123.7, 125.6, 127.2,
131.7, 133.6, 143.0, 159.1, 170.1; EIMS m/z 301 (MC, 17),
227 (100), 181 (38), 152 (22); HRMS calcd for C16H15NO5:
301.0950; found 301.0941.
1
hexane); H NMR (CDCl3, 300 MHz) d 3.05 (dd, JZ19.0,
2.0 Hz, 1H), 3.17 (dd, JZ19.0, 6.6 Hz, 1H), 5.56 (ddd, JZ
2.0, 6.6, 6.6 Hz, 1H), 6.46 (d, JZ6.6 Hz, 1H), 7.12–7.15 (m,
1H), 7.38–7.43 (m, 1H), 7.55–7.60 (m, 1H), 7.83–7.89 (m,
3H); 13C NMR (CDCl3, 75 MHz) d 35.5, 81.5, 83.4, 112.1,
115.1, 122.1, 124.1, 128.1, 128.7, 129.6, 130.6, 133.4,
159.2, 174.7.
3.4.2. Methyl 2-(2-methyl-9-nitro-1,2-dihydronaphtho-
[2,1-b]furan-2-yl)acetate 7. Yellow orange oil; Rf 0.41
(80:20 hexane/ethyl acetate); IR (CH2Cl2) 1738, 1636,
1599, 1579, 1525, 1352 cmK1; 1H NMR (C6D6, 600 MHz) d
1.27 (s, 3H), 2.37 (d, JZ15.0 Hz, 1H), 2.39 (d, JZ15.0 Hz,
1H), 3.09 (d, JZ16.2 Hz, 1H), 3.18 (s, 3H), 3.48 (d, JZ
16.2 Hz, 1H), 6.60 (dd, JZ8.2, 7.6 Hz, 1H), 6.93 (d, JZ
8.8 Hz, 1H), 7.17 (d, JZ8.8 Hz, 1H), 7.25 (dd, JZ7.6,
1.2 Hz, 1H), 7.31 (dd, JZ8.2, 1.2 Hz, 1H); 13C NMR
(CDCl3, 75 MHz) d 26.6, 40.8, 44.8, 51.6, 87.3, 114.2,
114.7, 120.8, 122.6, 122.9, 130.4, 130.6, 133.4, 146.0,
159.0, 170.0; EIMS m/z 301 (MC, 25), 284 (22), 267 (28),
227 (100), 181 (79), 152 (47). HRMS calcd for C16H15NO5:
301.0950; found 301.0941.
3.6.2. (G) (7aR,10aR)-7a-Methyl-7a,8,9,10a-tetrahydro-
furo[3,2-b]naphtho[2,1-d]furan-9-one 9b. White crystal-
line solid; mp 147–149 8C (CH2Cl2/hexane); Rf 0.39 (70:30
hexane/ethyl acetate); IR (CH2Cl2) 1780, 1635, 1601, 1585,
1
1525 cmK1; H NMR (CDCl3, 300 MHz) d 1.73 (s, 3H),
2.93 (d, JZ18.9 Hz, 1H), 3.22 (d, JZ18.9 Hz, 1H), 6.06 (s,
1H), 7.09–7.12 (m, 1H), 7.37–7.42 (m, 1H); 7.54–7.59 (m,
1H), 7.83–7.88 (m, 3H); 13C NMR (CDCl3, 75 MHz) d 23.5,
41.2, 88.0, 90.1, 112.4, 114.6, 122.2, 123.9, 128.0, 128.7,
129.5, 131.0, 133.4, 158.5, 174.4; EIMS m/z 240 (MC, 12),
195 (17), 181 (39), 115 (23), 44 (100); Anal. Calcd for
C15H12O3: C, 74.99; H, 5.03. Found C, 75.08; H, 5.07.
3.6.3. (G) (7aS,10aR)-7a-Phenyl-7a,8,9,10a-tetrahydro-
furo[3,2-b]naphtho[2,1-d]furan-9-one 9c. White solid; mp
171–172 8C; Rf 0.65 (70:30 hexane/ethyl acetate); IR
3.4.3. 2-(2-Methyl-9-nitro-1,2-dihydronaphtho[2,1-
b]furan-2-yl)acetic acid 8. Yellow solid recrystallised
from hot aqueous ethanol; mp 160–162 8C; IR (Nujol)
1709, 1624, 1595, 1576, 1522, 1500, 1331 cmK1; 1H NMR
(CDCl3, 300 MHz) d 1.64 (s, 3H), 2.82 (d, JZ15.3 Hz, 1H),
2.84 (d, JZ15.3 Hz, 1H), 3.17 (d, JZ16.2 Hz, 1H), 3.41 (d,
JZ16.2 Hz, 1H), 7.23 (d, JZ8.8 Hz, 1H), 7.32 (dd, JZ8.0,
8.0 Hz, 1H), 7.80 (dd, JZ8.0, 1.1 Hz, 1H), 7.81 (d, JZ
1
(CH2Cl2) 1784, 1635, 1603, 1583, 1525, 1496 cmK1; H
NMR (CDCl3, 300 MHz) d 3.38 (d, JZ18.9 Hz, 1H), 3.53
(d, JZ18.9 Hz, 1H), 6.35 (s, 1H), 7.26–7.29 (m, 1H), 7.36–
7.45 (m, 4H), 7.52–7.57 (m, 3H), 7.80–7.85 (m, 2H), 7.90–
7.93 (m, 1H); 13C NMR (CDCl3, 50 MHz) d 43.4, 89.7,
93.2, 112.1, 114.6, 122.2, 124.1, 124.5, 128.1, 128.7, 128.8,
129.0, 129.8, 130.8, 133.6, 139.6, 158.9, 174.0; EIMS m/z

1890
M. Jevric et al. / Tetrahedron 61 (2005) 1885–1891
302 (MC, 14), 257 (100), 181 (49), 115 (42), 77 (60); Anal.
Calcd for C20H14O3: C, 79.46; H, 4.67; Found C, 79.14; H,
4.83.
3.6.8. 2-(2-Phenyl-1,2-dihydronaphtho[2,1-b]furan-2-
yl)acetamide 11. To a stirred solution of acid 4c (492 mg,
1.62 mmol) in dry CH2Cl2 (10 ml) was added thionyl
chloride (1 ml). After 4 h the volatiles were removed under
a stream of nitrogen. The residue was taken up in dry ether
(25 ml), the vessel cooled to K78 8C and dry ammonia was
condensed into the vessel for 5 min before the contents of
the reaction were allowed to reach room temperature.
Saturated NaCl (10 ml) was added to the mixture and the
aqueous phase extracted with CH2Cl2 (2!20 ml). The
organic phase was dried (Na2SO4), filtered and the solvent
removed in vacuo. Purification by flash chromatography
(florisilw, 70:30 CH2Cl2/ethyl acetate) gave a cream colored
solid (352 mg, 76%); mp 155–158 8C; Rf 0.30 (70:30
CH2Cl2/ethyl acetate); IR (CH2Cl2) 3510, 3398, 1685, 1633,
3.6.4. (G) (7aS,10aR)-7a-(4-Chlorophenyl)-7a,8,9,10a-
tetrahydrofuro[3,2-b]naphtho[1,2-d]furan-9-one 9d.
White solid; mp 200–208 8C (decomposes); Rf 0.42 (80:20
hexane/ethyl acetate); IR (Nujol) 1785, 1636, 1582, 1526,
1
1494 cmK1; H NMR (CDCl3, 300 MHz) d 3.33 (d, JZ
19.2 Hz, 1H), 3.53 (d, JZ19.2 Hz, 1H), 6.31 (s, 1H), 7.25–
7.28 (m, 1H), 7.37–7.43 (m, 3H), 7.47–7.58 (m, 3H), 7.80–
7.86 (m, 2H), 7.91–7.93 (m, 1H); 13C NMR (CDCl3,
50 MHz) d 43.2, 89.5, 92.7, 112.0, 114.4, 122.2, 124.3,
125.9, 128.2, 128.8, 129.2, 129.9, 130.7, 133.7, 134.7,
138.1, 158.7, 173.6; EIMS m/z 336 (MC, 46), 307 (59), 291
(100), 278 (38), 226 (26); Anal. Calcd for C20H13O3Cl: C,
71.33; H, 3.89, Cl, 10.53. Found C, 71.05; H, 3.85; Cl, 10.27.
1
1589, 1495 cmK1; H NMR (CDCl3, 300 MHz) d 3.15 (s,
2H), 3.70 (d, JZ15.6 Hz, 1H), 3.90 (d, JZ15.6 Hz, 1H),
5.28 (br s, 1H), 6.27 (br s, 1H), 7.24–7.57 (m, 9H), 7.75–
7.83 (m, 2H); 13C NMR (CDCl3, 50 MHz) d 42.9, 48.2,
89.9, 111.7, 117.7, 122.8, 123.4, 124.6, 126.9, 127.7, 128.7,
129.5, 129.7, 130.7, 144.1, 155.2, 171.2, (one masked
aromatic); EIMS m/z 303 (MC, 21), 278 (13), 244 (100),
215 (14); Anal. Calcd for C20H17O2N: C, 79.19; H, 5.65; N,
4.62; Found C, 78.88; H, 5.75; N, 4.84.
3.6.5. (G) (7aR,10aR)-7a-Methyl-1-nitro-7a,8,9,10a-
tetrahydrofuro[3,2-b]naphtho[2,1-d]furan-9-one 9e. The
general procedure was employed, however, the reaction
mixture was refluxed overnight to give a yellow solid; mp
190–195 8C (sealed tube, decomposes); Rf 0.58 (40:60 ethyl
acetate/hexane); IR (CH2Cl2) 1784, 1628, 1599, 1579,
1
1529 cmK1; H NMR (CDCl3, 600 MHz) d 1.78 (s, 3H)
2.89 (d, JZ19.2 Hz, 1H), 3.11 (d, JZ19.2 Hz, 1H), 6.12 (s,
1H), 7.25 (d, JZ8.7 Hz, 1H), 7.44 (dd, JZ7.8, 7.8 Hz, 1H),
7.98 (d, JZ8.7 Hz, 1H), 7.99 (dd, JZ7.8, 1.2 Hz, 1H), 8.07
(dd, JZ8.7, 1.2 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d
23.5, 41.0, 88.6, 90.1, 112.2, 114.7, 122.3, 122.9, 125.3,
131.1, 134.2, 134.6, 145.8, 161.6, 173.5; MS m/z (%): 285
(MC, 100), 240 (8), 226 (64), 201 (48), 145 (65). HRMS,
C15H11NO5Na: calcd, 308.0535; found 308.0531.
3.6.9. (1-Oxo-2-phenyl-1,2-dihydronaphtho[2,1-b]furan-
2-yl)methyl cyanide 12. Colorless oil; Rf 0.25 (25:75 ethyl
acetate/hexane); IR (Nujol) 2258, 1704, 1632, 1586, 1529,
1
1496 cmK1; H NMR (CDCl3, 300 MHz) d 3.20 (d, JZ
16.8 Hz, 1H), 3.35 (d, JZ16.8 Hz, 1H) 7.39–7.54 (m, 5H),
7.68–7.73 (m, 3H), 7.85–7.89 (m, 1H), 8.17–8.22 (m, 1H),
8.64–8.69 (m, 1H); 13C NMR (CDCl3, 50 MHz) d 27.6,
87.1, 111.3, 113.5, 114.7, 123.2, 124.6, 125.9, 128.7, 129.0,
129.2, 129.3, 129.8, 130.3, 134.4, 141.2, 174.0, 197.3;
EIMS m/z 299 (57), 259 (100), 231 (14), 126 (33); HRMS
calcd for C20H13O2N: 299.0946; found: 299.0954.
3.6.6. (G) (7aR,10aR)-7a-Methyl-7a,8,9,10a-tetrahydro-
furo[3,2-b]naphtho[1,2-d]furan 10b. White solid; mp 63–
65 8C; Rf 0.56 (80:20 hexane/ethyl acetate); IR (CH2Cl2)
1633, 1601, 1585, 1523 cmK1; 1H NMR (CDCl3, 600 MHz)
d 1.67 (s, 3H), 2.11 (ddd, JZ13.2, 11.1, 7.5 Hz, 1H), 2.37
(ddd, JZ1.9, 4.9, 13.2 Hz, 1H), 3.59 (ddd, JZ4.9, 7.5,
11.1 Hz, 1H), 3.98 (ddd, JZ1.9, 7.5, 7.5 Hz, 1H), 5.64 (s,
1H), 7.05–7.06 (m, 1H), 7.31–7.34 (m, 1H), 7.49–7.52 (m,
1H), 7.76–7.81 (m, 2H), 7.88–7.90 (m, 1H); 13C NMR
(CDCl3, 150 MHz) d 23.4, 40.8, 66.5, 87.4, 96.0, 112.1,
116.2, 122.3, 123.2, 127.3, 128.6, 129.4, 131.4, 131.7,
158.4; EIMS m/z 226 (MC, 100), 195 (57), 181 (60), 171
(20); Anal. Calcd for C15H14O2: C, 79.62; H, 6.24; Found C,
79.52; H, 6.46.
Acknowledgements
We are grateful for financial support from the Australian
Research Council. MJ thanks the University of Adelaide,
Faculty of Science for a postgraduate scholarship. The
National University of Singapore is thanked for a research
grant (R-143-000-186-112) in support of this research.
3.6.7. (G) (7aS,10aR)-7a-(4-Chlorophenyl)-7a,8,9,10a-
tetrahydrofuro[3,2-b]naphtho[1,2-d]furan 10d. Gummy
colorless oil; Rf 0.48 (15:85 ethyl acetate/hexane); IR
References and notes
1
(CH2Cl2) 3055, 1635, 1603, 1581, 1522, 1493 cmK1; H
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(ddd, JZ4.8, 7.5, 8.0 Hz, 1H), 4.21 (ddd, JZ1.3, 7.5,
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3H), 7.49–7.52 (m, 3H), 7.80–7.83 (m, 2H), 7.86–7.87 (m,
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111.6, 115.7, 122.3, 123.5, 126.2, 127.5, 128.7, 128.7,
129.8, 131.2, 132.1, 133.6, 140.2, 158.6; EIMS m/z 323
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