A novel bis-Lactonisation of naphtho- and phenanthro-1,2-dioxines with malonate nucleophiles

Article abstract of DOI:10.1055/s-2003-38073

Malonate nucleophiles add in a conjugate fashion to substituted naphtho- and phenanthro-1,2-dioxines to furnish functionalised bis-lactones in high yield and with high de. The basicity of the malonate nucleophile is sufficiently mild to rearrange the 1,2-dioxines to yield the transient cis-δhydroxy enone species with no further Kornblum-DeLaMare rearrangement. The cis-δhydroxy enones readily undergo conjugate addition by malonate nucleophiles in a highly diastereoselective fashion. An intramolecular domino cyclisation then ensues yielding the observed bis-lactones. The relative configuration of the bis-lactone series was established by 1- and 2-D ¹H, ¹³C NMR techniques and further confirmed by single crystal X-ray analysis.

Full text of DOI:10.1055/s-2003-38073

6
68
PAPER
A Novel bis-Lactonisation of Naphtho- and Phenanthro-1,2-Dioxines with
Malonate Nucleophiles
a
a
a
a
a
b
A
B
N
ovel bis-Lact
e
onisation o
n
f
Naphtho- and Phe
G
nanthro-1, 2-Dioxi
r
nes with
e
M
alonate
a
N
ucleophile
t
s
rex, Martyn Jevric, Marc C. Kimber, Sara J. Krivickas, Dennis K. Taylor,* Edward R. T. Tiekink
a
Department of Chemistry, University of Adelaide, South Australia, Australia, 5005.
Fax +61(8)83034358; E-mail: dennis.taylor@adelaide.edu.au
b
Department of Chemistry, National University of Singapore, Singapore, 117543.
Received 21 October 2002; revised 28 January 2003
Furthermore, these cis-γ-hydroxy enones have been effi-
ciently transformed into a range of biologically important
substrates by the addition of stabilised nucleophiles.1
Abstract: Malonate nucleophiles add in a conjugate fashion to sub-
stituted naphtho- and phenanthro-1,2-dioxines to furnish functiona-
lised bis-lactones in high yield and with high de. The basicity of the
b,4
malonate nucleophile is sufficiently mild to rearrange the 1,2-diox- Naphtho- and phenanthro-1,2-dioxines 5 and 6 have pre-
ines to yield the transient cis-γ-hydroxy enone species with no fur- viously been shown to rearrange to their isomeric cis-γ-
ther Kornblum–DeLaMare rearrangement. The cis-γ-hydroxy
hydroxy enones 8, in the presence of mildly basic stabi-
enones readily undergo conjugate addition by malonate nucleo-
philes in a highly diastereoselective fashion. An intramolecular
domino cyclisation then ensues yielding the observed bis-lactones.
The relative configuration of the bis-lactone series was established
6,7
lised ylides 7. These cis-γ-hydroxy enones have then
undergone 1,4-conjugate addition by 7 followed by con-
comitant expulsion of triphenylphosphine oxide from the
6
1
13
intermediate 9 to generate 1,2-dihydronaphthyl- 10 and
by 1- and 2-D H, C NMR techniques and further confirmed by
single crystal X-ray analysis.
7
1,2-dihydrophenanthrylfurans 11 in good to excellent
yields (Scheme 2).
Key words: bis-lactones, peroxides, cis-γ-Hydroxy enones, domi-
no reactions, michael additions
R1
H
R1
H
Ph3P
R2
O
OH
1
7
R3
The reported base-catalysed rearrangement of 1,2-diox-
O
H
O
ines 1, to afford their isomeric cis-γ-hydroxy enones 2, has
been a difficult transformation to control due to the inher-
ent instability of the enones. They readily undergo dehy-
2
dration to generate furans 3 in the presence of acid or
5
and 6
8
readily undergo a Kornblum–DeLaMare rearrangement to
furnish 1,4-diketones 4, under excessively basic condi-
tions (Scheme 1).
1
,4-addition
of ylide
2
,3
R2
excess
acid
3
Ph P
O
H
R1
R2
R3
R1
H
R1
R3
R1
H
R1
R2
O
base
O
3
O
O
OH
-OPPh3
O
or
Co(II)
OH
R1
R2
R2
R2
H
H
excess
base
1
2
O
O
4
10 and 11
9
Scheme 1
Scheme 2
In this connection, our group has been interested in the use In this study we wished to further extend the methodology
of 1,2-dioxines as masked cis-γ-hydroxy enones and the by the addition of highly stabilised malonate nucleophiles.
transformation of these enones into biologically interest- Consequently, not only would the basic nature of the ma-
ing species. This research has subsequently shown that lonate induce ring-opening of the parent 1,2-dioxines to
1
,2-dioxines can be transformed into the reactive cis-γ-hy- their isomeric cis-γ-hydroxy enones as seen with stabi-
1
b,4
droxy enone moiety under mildly basic conditions or lised ylides, conjugate addition by the malonate to 8 fol-
with the use of Co(II) mediated homolytic ring cleavage, lowed by a double cyclisation via structure 12 could occur
5
without significant decomposition of the transient enones. to yield the novel bis-lactone series 13 (Scheme 3). Herein
we report a novel diastereoselective route to highly substi-
tuted cis-fused bis-lactones from a range of substituted
naphtho- and phenanthro-1,2-dioxines and malonate.
Synthesis 2003, No. 5, Print: 01 04 2003.
Art Id.1437-210X,E;2003,0,05,0668,0672,ftx,en;T11302SS.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
©

PAPER
A Novel bis-Lactonisation of Naphtho- and Phenanthro-1,2-Dioxines with Malonate Nucleophiles
669
EtO2C
R1 R2
The naphtho-1,2-dioxines 5a–d were each treated with so-
dio-diethyl malonate to yield the novel bis-lactones 18a–
d in good yields of 76–87% and with excellent de (>98%
by H NMR). The phenanthro-1,2-dioxines 6a–d, were
EtO2C
OH
OH
sodio-diethylmalonate
,4-addition
8
1
1
similarly treated with sodio-diethyl malonate to furnish
bis-lactones 19a and 19b in comparable yields and de
12
(
Scheme 5). However, the gem-dimethylphenanthro-1,2-
dioxine 6c, and parent phenanthro-1,2-dioxine 6d failed
to yield the desired bis-lactones. While an explanation for
the failure of 6c to yield the bis-lactone does not readily
present itself, it must be noted that the parent phenanthro-
tandem cyclisation
O
O
1
,2-dioxine 6d undergoes facile polymerisation at ambi-
R2
O
7,8b
1
ent temperature.
R
O
13
Scheme 3
The 1,2-dioxines chosen for this study are depicted in
Scheme 4. Wittig olefination of aldehydes 14 and 16 with
various ylides furnished the olefins 15 and 17 respective-
ly, in excellent yields. The olefins were then
1
a,6,8,9
photolysed
in the presence of the photosensitiser,
rose bengal bis(triethylammonium) salt and oxygen, con-
6
,8a
sequently affording the naphtho-1,2-dioxines 5a–d,
8
b
and phenanthro-1,2-dioxines 6a–d, respectively. 1,2-
Dioxines 5b and 5d have not been previously reported and
were fully characterized and the relative configuration as-
signed by 1- and 2-D H NMR and C NMR spectrosco-
py.
1
13
Scheme 5 (a) Diethyl malonate, NaOEt, THF, 16 h, r.t.
The relative configuration of the series 18 and 19, was de-
1
13
termined via 1-D and 2-D H and C NMR techniques. Of
note, was the ROESY correlations observed for H /H and
a
b
H /H (Figure 1). This ROESY correlation was observed
b
c
for all the bis-lactones and supported the proposed config-
uration of the fused ring system; namely a cis-fused ring
system and H /H being syn. Further confirmation of the
b
c
configuration was via single crystal X-ray analysis of 18a
(
Figure 2) and 18d.10
O
O
Ha
O
ROESY Correlation
O
Hb
Ha - Hb cis-fused ring system
Hb - Hc syn
R
Hc
R = Me, Ph, 4-MeO-Ph, cyclohexyl
1
2
1
Scheme 4 (a) Ph P=CR R , CH Cl ; (b) O , hυ, rose Bengal,
3
2
2
2
CH Cl2
2
Figure 1 ROESY Correlations for the bis-lactone series 18 and 19.
Synthesis 2003, No. 5, 668–672 ISSN 0039-7881 © Thieme Stuttgart · New York

6
70
B. Greatrex et al.
PAPER
hydroxyl to generate the thermodynamically stable mono-
γ-lactone 23. This species then undergoes further lactoni-
sation via the phenolic hydroxyl to furnish the observed
bis fused cis-γ,δ-lactones 18 and 19.
EtO2C
EtO2C
H
R
1,4-addition
OH
OH
8
cis-γ-hydroxy enone
22
cyclisation
O
O
O
H
O
R
R
O
H
CO2Et
OH
H
H
H
O
cyclisation
18 and 19
23
Figure 2 Molecular structure of 18a.
Scheme 7
The mechanism of the double cyclisation deserves further
discussion. While the formation of the 5-membered lac-
tone ring is thermodynamically more favourable, the cy-
clisation to yield the 6-membered lactone would involve
the participation of the more nucleophilic phenolic hy-
droxyl. To investigate which ring formed first, 1,2-diox-
ine 6a was treated with the enolate of the sulfonyl ester
nucleophile 20. This stabilised nucleophile was chosen
since only one cyclisation could occur and hence this may
elucidate some insights into which ring is formed first
and/or which ring is more thermodynamically favoured.
Exposure of 1,2-dioxine 6a to 20, furnished the mono-lac-
tone 21 in a good yield of 60% (Scheme 6), showing that
the 5-membered lactone was formed first.
In conclusion, the methodology described here provides a
novel one-pot route to bis-fused lactones of types 18 and
1
9 in good overall yields and further expands the synthetic
utility of the under-utilised cis-γ-hydroxy enone function-
ality. The use of the 1,2-dioxine moiety as a masking
group for the sensitive cis-γ-hydroxy enones is a topic of
interest within our group and further synthetic uses are
currently being pursed and will be reported on in due
course.
1H and 13C NMR was performed using a Varian Gemini-200, Bruk-
er ACP-300 or a Varian Innova-600 spectrometer operating at 200
1
MHz, 300 MHz and 600 MHz respectively for H and 50 MHz, 75
13
1
MHz and 150 MHz for C in CDCl . H NMR were referenced to
3
3
1
internal trimethylsilane (δ 0.00). C NMR were referenced to
CDCl (δ 77.0). Multiplicities are assigned as s: singlet, d: doublet,
3
t: triplet, q: quartet, p: pentet, and br: broad denotes broadened sig-
nals. Infrared Spectra were recorded using a Perkin Elmer spectrum
BX FT-IR system as either nujol mulls or in the neat form as denot-
ed. Melting points were detemined on a Reichert hot stage apparatus
and are uncorrected. Mass spectra were acquired using a VG ZAB
2
HF spectrometer and HRMS were performed by the Organic Mass
Spectrometry Facility, Central Science Laboratory, University of
Tasmania. Microanalysis were performed at the University of Ota-
go. Thin layer chromatography were performed using Merck silica
gel 60 F254 aluminium backed silica sheets. Flash chromatography
were performed using Merck silica gel 60 (230–400 mesh). All re-
agents were of analytical grade and purchased from Aldrich and
used without further purification. THF was distilled from sodium/
benzophenone ketyl and CH Cl was distilled from P O prior to
Scheme 6 (a) 20, NaOMe, THF; (b) 1 M HCl
We therefore propose the following mechanism for the
generation of the bis-fused lactones (Scheme 7). The ma-
lonate anion induces ring opening of the 1,2-dioxines to
initially generate the isomeric cis-γ-hydroxy enones. The
2
2
2
5
use.
Synthesis of Substituted 1,2-Dioxines 5a–d and 6a–d; General
intermediate cis-γ-hydroxy enones 8 then readily undergo Procedure
syn-1,4-conjugate addition by the ester nucleophile to All 1,2-dioxines were prepared by the Rose Bengal, bis(triethylam-
monium) salt sensitised [4π + 2π] cycloaddition of singlet oxygen
generate intermediate 22. The first cyclisation is by the γ-
Synthesis 2003, No. 5, 668–672 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A Novel bis-Lactonisation of Naphtho- and Phenanthro-1,2-Dioxines with Malonate Nucleophiles
671
+
and to the corresponding substituted vinylic naphthalenes 15a–d,
and phenanthrolenes 17a–d, detailed in previous work. All yields
MS: m/z (%) = 268 (M , 18), 196 (68), 168 (49), 139 (35), 97 (30),
6
,8
81 (36), 69 (95), 43 (100).
reported were based upon recovered starting materials. 1,2-Diox-
ines 5a, 5c, and 6a–d, have been previously reported, however,
HRMS: m/z calcd for C H O , 268.0736; found, 268.0732.
8a
8a
8b
16 12
4
the following have not been characterised.
Crystal data for 18a
C H O , M = 268.3, T = 223(2) K, monoclinic, P2 /c,
1
6
12
4
1
2
-Cyclohexyl-2,4a-dihydronaphtho[2,1-c][1,2]dioxine (5b)
a = 9.9053(10), b = 18.0747(17), c = 7.1622(7) Å, b = 99.262(2)°,
Yield 49%; R 0.35 (25% CH Cl –hexanes).
3
f
2
2
V = 1265.6(2) Å , Z = 4, D = 1.408, F(000) = 560, m = 0.102
x
1
–1
H NMR (600 MHz, CDCl ): δ = 0.83–0.89 (m, 1 H), 1.00–1.38 (m,
mm , no. of unique data (Bruker AXS SMART CCD using Mo Ka
3
5
(
H), 1.67 (br d, J = 12.4 Hz, 1 H), 1.70–1.72 (m, 2 H), 1.90–1.98
m, 1 H), 2.11 (br d, J = 12.9 Hz, 1 H), 4.12 (ddd, J = 3.0, 3.0, 7.7
Hz, 1 H), 5.76 (ddd, J = 0.8, 2.3, 9.9 Hz, 1 H), 5.86 (dddd, J = 2.3,
.0, 3.0, 4.0 Hz, 1 H), 6.14 (ddd, J = 0.8, 3.0, 4.0 Hz, 1 H), 6.40–
.42 (m, 1 H), 7.02 (dd, J = 1.9, 7.2 Hz, 1 H), 7.18–7.22 (m, 2 H),
.41 (dd, J = 2.1, 6.6 Hz, 1 H).
radiation so that qmax = 30.0°) = 3662, no. of parameters = 181, R
–
3
(all data) = 0.077, wR (all data) = 0.128, r = 0.34 e Å . CCDC dep-
osition number = 190919. Selected bond distances [A] and angles
[o]: C1–O2 1.4644(16), C3–O2 1.3453(16), C3–O3 1.1987(16),
C4–O4 1.1949(16), C4–O5 1.3547(16), C5a–O5 1.4011(16), C1–
O2–C3 111.55(10), C3–C3a–C4 110.18(10) and C4–O5–O5a
122.41(10).
3
6
7
1
3
C NMR (CDCl , 300MHz): δ = 25.8, 25.9, 26.3, 29.3, 29.7, 42.7,
3
7
1
8.7, 84.9, 121.0, 123.7, 123.8, 127.2, 128.3, 128.6, 129.0, 131.3,
31.9, 134.8.
1
-Cyclohexyl-1,3a,4,11c-tetrahydro-3H-benzo[f]furo[3,4-c]-
chromen-3,4-dione (18b)
Yield: 79%, mp 257–259 °C (CH Cl –hexanes).
+
MS: m/z (%) = 268 (M , 50), 171 (97), 157 (91), 128 (35), 83 (100).
2
2
HRMS: m/z calcd for C H O , 268.1463; found, 268.1464.
IR (nujol): 1786, 1748, 1625, 1338, 1271, 1215, 1165 cm–1.
1
8
20
2
1
H NMR (600 MHz, CDCl ): δ = 0.70–0.92 (m, 7 H), 1.12–1.18 (m,
3
2
(
-(4-Methoxyphenyl)-2,4a-dihydronaphtho[2,1-c][1,2]dioxine
5d)
Yield 25%, mp 136–138 °C; R 0.43 (50% CH Cl –hexanes).
1
3
H), 1.27–1.30 (m, 1 H), 1.35–1.38 (m, 1 H), 1.50–1.54 (m, 1 H),
.80 (d, J = 11.4 Hz, 1 H), 4.68 (dd, J = 9.0, 11.4 Hz, 1 H), 4.92 (dd,
f
2
2
J = 6.6, 9.0 Hz, 1 H), 7.21 (d, J = 9.0 Hz, 1 H), 7.50–7.47 (m, 1 H),
7.61–7.58 (m, 1 H), 7.72 (d, J = 9.0 Hz, 1 H), 7.82 (d, J = 9.0 Hz, 1
H), 7.85–7.83 (m, 1 H).
1
H NMR (600 MHz, CDCl ): δ = 3.79 (s, 3 H), 5.49 (dd, J = 2.7 Hz,
3
1
3
H), 5.80 (dd, J = 1.8, 10.2 Hz, 1 H), 6.00 (dddd, J = 1.8, 2.7, 2.7,
.0 Hz, 1 H), 6.16 (dd, J = 2.7, 2.7 Hz, 1 H), 6.46 (dd, J = 3.0, 10.2
1
3
C NMR (150 MHz, CDCl ): δ = 25.2, 25.4, 25.5, 26.8, 30.2, 37.4,
3
Hz, 1 H), 6.88–6.90 (m, 2 H), 7.07 (dd, J = 1.2, 7.8 Hz, 1 H), 7.20–
.28 (m, 2 H), 7.40–7.43 (m, 2 H), 7.47 (d, J = 7.8 Hz, 1 H).
3
1
9.4, 42.3, 86.1, 110.0, 117.4, 122.4, 125.9, 128.5, 129.3, 130.9,
31.1, 131.5, 149.3, 159.7, 168.8.
7
1
3
C NMR (CDCl , 300MHz): δ 55.3, 79.0, 81.3, 113.8, 120.2,
3
+
MS: m/z (%) = 336 (M , 10), 197 (15), 196 (100), 168 (25), 139
1
1
24.0, 124.1, 127.4, 128.5, 128.9, 129.1, 130.1, 131.2, 131.7, 132.2,
35.7, 159.8.
(12).
Anal. Calcd for C21H O : C, 74.98; H, 5.99. Found: C, 74.83; H,
20 4
+
MS: m/z (%) = (M , 274), 259 (48), 231 (18), 202 (14), 135 (100).
5
.92%.
+
HRMS: m/z calcd for C H O [M + H] , 293.1178; found,
1
9
17
3
2
93.1161.
1
-Phenyl-1,3a,4,11c-tetrahydro-3H-benzo[f]furo[3,4-c]chrom-
en-3,4-dione (18c)
Yield: 84%; mp 209–211 °C (CH Cl –hexanes).
bis-Lactonisation of Naphtho- and Phenanthro-1,2-Dioxines 5
and 6; General Procedure
To a solution of sodio-diethyl malonate, prepared from NaOEt (0.5
M, 2.2 mL) and diethyl malonate (0.17 g, 1.1 mmol), in anhyd THF
2
2
–
1
IR (nujol): 1786, 1750, 1715, 1221, 1162 cm .
1
H NMR (600 MHz, CDCl ): δ = 3.83 (d, J = 10.2 Hz, 1 H), 4.87
3
(
4 mL) was added a solution of the 1,2-dioxine, 5 or 6 (1 mmol) in
(dd, J = 7.8, 10.2 Hz, 1 H), 6.16 (d, J = 7.8 Hz, 1 H), 6.54–6.55 (m,
2 H), 6.83 (d, J = 9.0 Hz, 1 H), 6.88–6.91 (m, 2 H), 7.00–7.03 (m, 1
H), 7.50–7.53 (m, 1 H), 7.65 (d, J = 9.0 Hz, 1 H), 7.68–7.71 (m, 1
H), 7.82 (d, J = 8.4 Hz, 1 H), 7.99 (d, J = 8.4 Hz, 1 H).
13
anhyd THF (1 mL) and the reaction left to stir for 16 h under N . Af-
ter this period the reaction was quenched by the addition of 1M HCl
(
1
CH Cl (3 × 50 mL) and the organic layers dried (MgSO ), filtered
and the solvent removed under reduced pressure. Each bis-lactone
was purified by crystallisation from CH Cl –hexanes or acetone–
hexanes. By this method the following bis-lactones were obtained.
2
2 mL) and the mixture partitioned between CH Cl (50 mL) and
2 2
M HCl (50 mL). The aqueous layer was then extracted with
C NMR (150 MHz, CDCl ): δ = 39.7, 41.6, 82.0, 109.4, 117.0,
3
2
2
4
1
1
22.1, 124.7, 125.8, 126.1, 128.2, 128.5, 128.8, 129.4, 130.8, 150.8,
57.7, 168.6 (two aromatic signals masked).
2
2
+
MS: m/z (%) = 330 (M , 35), 286 (15), 262 (18), 244 (19), 221 (25),
1
96 (35), 105 (30), 43 (100).
1
-Methyl-1,3a,4,11c-tetrahydro-3H-benzo[f]furo[3,4-c]chrom-
HRMS: m/z calcd for C H O , 330.0892; found, 330.0892.
2
1
14
4
en-3,4-dione (18a)
Yield: 76%; mp 234–236 °C (acetone–hexanes).
1
-(4-Methoxyphenyl)-1,3a,4,11c-tetrahydro-3H-benzo[f]furo-
–
1
[3,4-c]chromen-3,4-dione (18d)
Yield: 87%; mp 229–231 °C (acetone–hexanes).
IR (nujol): 1788, 1749, 1625, 1515, 1337, 1269, 1214, 1168 cm .
1
H NMR (600 MHz, CDCl ): δ = 0.91 (d, J = 6.6 Hz, 3 H), 3.84 (d,
3
–
1
IR (nujol): 1787, 1748, 1621, 1516, 1263, 1156 cm .
J = 10.8 Hz, 1 H), 4.65 (dd, J = 7.8, 10.8 Hz, 1 H), 5.30 (dt, J = 6.6,
7
7
7
.8 Hz, 1 H), 7.22 (d, J = 9.0 Hz, 1 H), 7.50–7.47 (m, 1 H), 7.60–
.57 (m, 1 H), 7.74 (d, J = 9.0 Hz, 1 H), 7.82 (d, J = 9.0 Hz, 1 H),
.86–7.84 (m, 1 H).
1
H NMR (600 MHz, CDCl ): δ = 3.58 (s, 3 H), 3.81 (d, J = 10.2 Hz,
3
1
6
H), 4.82 (dd, J = 7.8, 10.2 Hz, 1 H), 6.12 (d, J = 7.8 Hz, 1 H),
.40–6.46 (m, 4 H), 6.85 (d, J = 9.0 Hz, 1 H), 7.50–7.53 (m, 1 H),
1
3
7.66 (d, J = 9.0 Hz, 1 H), 7.67–7.70 (m, 1 H), 7.82 (d, J = 8.4 Hz, 1
H), 7.98 (d, J = 8.4 Hz, 1 H).
C NMR (150 MHz, CDCl ): δ = 17.2, 37.9, 41.9, 78.6, 110.8,
3
1
1
17.5, 122.0, 126.0, 128.4, 129.3, 130.9, 131.0, 131.1, 149.5, 159.8,
68.6.
Synthesis 2003, No. 5, 668–672 ISSN 0039-7881 © Thieme Stuttgart · New York

6
72
B. Greatrex et al.
PAPER
1
3
C NMR (150 MHz, CDCl ): δ = 39.8, 41.6, 55.1, 81.9, 109.4,
8.1 Hz, 1 H), 7.50–7.75 (m, 7 H), 7.95–7.99 (m, 2 H), 8.05–8.08 (m,
3
1
1
13.6, 117.1, 122.1, 125.8, 125.9, 126.0, 128.4, 129.4, 130.8, 130.9,
45.2, 158.5, 169.5 (two aromatic signals masked).
1 H), 8.27–8.29 (m, 1 H), 8.77–8.83 (m, 2 H), 10.20 (br s, 1 H).
13
C NMR (75 MHz, DMSO-d ): δ 16.5, 71.9, 78.3, 83.5, 113.7,
6
+
MS: m/z (%) = 360 (M , 20), 274 (15), 197 (20), 196 (100), 168
122.4, 123.0, 123.3, 124.2, 125.8, 126.1, 127.5, 129.0, 129.4, 130.7,
131.7, 134.6, 136.9, 149.7, 168.4 (three aromatic signals masked).
(
35), 135 (34), 97 (32), 57 (67).
+
HRMS: m/z calcd for C H O , 360.0998; found, 360.1001.
MS: m/z (%) = 432 (M , 10), 415 (10), 388 (30), 319 (38), 291 (42),
2
2
16
5
2
18 (78), 105 (74), 47 (100).
1
3-Methyl-10a,11,13,13a-tetrahydro-10H-dibenzo[f,h]furo[3,4-
HRMS: m/z calcd for of C H O S, 432.1048; found, 432.1024.
2
5
20
5
c]chromen-10,11-dione (19a)
Yield: 65%; mp 270–273 °C (acetone–hexanes).
–
1
Acknowledgements
IR (nujol): 1789, 1748, 1496, 1322, 1172, 1159 cm .
1
H NMR (600 MHz, CDCl ): δ = 1.04 (d, J = 6.6 Hz, 3 H), 3.97 (d,
This work was supported by the Australian Research Council
(ARC). B. G., M. J. and S. J. K. thank The University of Adelaide,
Faculty of Science for their Postgraduate Awards.
3
J = 10.2 Hz, 1 H), 4.72 (dd, J = 8.4, 10.2 Hz, 1 H), 5.41 (dq, J = 6.6,
8
1
.4 Hz, 1 H), 7.68–7.73 (m, 3 H), 7.76–7.78 (m, 1 H), 7.79–7.84 (m,
H), 8.40–8.42 (m, 1 H), 8.70–8.74 (m, 2 H).
1
3
C NMR (150 MHz, CDCl ): δ = 17.3, 38.3, 42.1, 78.7, 106.9,
3
References
1
1
22.4, 122.7, 122.8, 123.2, 123.7, 126.7, 127.7, 128.3, 128.4, 128.6,
28.9, 131.3, 145.8, 159.6, 168.6.
(1) (a) Clennan, E. L. Tetrahedron 1991, 47, 1343; and
references cited therein. (b) Avery, T. A.; Taylor, D. K.;
Tiekink, E. R. T. J. Org. Chem. 2000, 65, 5531; and
references cited therein.
(2) (a) Cormier, R. A.; Grosshans, C. A.; Skibbe, S. L. Synth.
Commun. 1988, 18, 677. (b) Friedrich, L. E.; Cormier, R. A.
J. Org. Chem. 1971, 36, 3011. (c) Sammond, D. M.;
Sammakia, T. Tetrahedron Lett. 1996, 37, 6065. (d)Nishio,
T.; Omote, Y. Chem. Lett. 1976, 103.
+
MS: m/z (%) = 318 (M , 48), 246 (100), 218 (78), 189 (55), 69 (71),
4
3 (58).
Anal. Calcd for C H O : C, 75.46; H, 4.43. Found: C, 75.60; H,
20
14
4
4
.51.
1
3-Phenyl-10a,11,13,13a-tetrahydro-10H-dibenzo[f,h]furo[3,4-
c]chromen-10,11-dione (19b)
Yield: 67%, mp 280–284 °C (CH Cl –hexanes).
2
2
(3) (a) Kornblum, N.; De La Mare, H. J. Am. Chem. Soc. 1951,
73, 881. (b) Sengül, M. E.; Ceylan, Z.; Balci, M.
Tetrahedron 1997, 10401.
–
1
IR (nujol): 1808, 1790, 1748, 1608, 1189, 1156 cm .
1
H NMR (600 MHz, DMSO-d ): δ = 4.63 (d, J = 10.8 Hz, 1 H), 5.23
dd, J = 8.4, 10.8 Hz, 1 H), 6.53 (d, J = 8.4 Hz, 1 H), 6.57–6.59 (m,
H), 6.89–6.95 (m, 3 H), 7.59–7.61 (m, 1 H), 7.68–7.75 (m, 2 H),
.82–7.85 (m, 1 H), 7.87–7.89 (m, 1 H), 8.41 (d, J = 7.8 Hz, 1 H),
.79 (d, J = 8.4 Hz, 1 H), 8.83 (d, J = 7.8 Hz, 1 H).
6
(
4) (a) Avery, T. A.; Haselgrove, T. D.; Rathbone, T. J.; Taylor,
(
D. K.; Tiekink, E. R. T. Chem. Commun. 1998, 333.
2
7
8
(
b) Avery, T. A.; Greatrex, B. W.; Taylor, D. K.; Tiekink, E.
R. T. J. Chem. Soc., Perkin Trans. 1 2000, 1319. (c) Avery,
T. A.; Fallon, G.; Greatrex, B. W.; Pyke, S. M.; Taylor, D.
K.; Tiekink, E. R. T. J. Org. Chem. 2001, 66, 7955.
(d) Greatrex, B. W.; Kimber, M. C.; Taylor, D. K.; Fallon,
G.; Tiekink, E. R. T. J. Org. Chem. 2002, 67, 5307.
(e) Kimber, M. C.; Taylor, D. K. J. Org. Chem. 2002, 67,
3142.
1
3
C NMR (150 MHz, DMSO-d ): δ 38.6, 41.3, 81.5, 108.2, 121.1,
22.2, 123.1, 123.6, 124.4, 126.5, 127.7, 127.5, 127.9, 128.1, 128.3,
28.3, 129.2, 130.9, 135.2, 144.4, 160.3, 170.2 (one aromatic car-
bon masked).
MS: m/z (%) = 380 (M , 18), 246 (100), 218 (80), 189 (61), 149
15), 105 (25), 57 (52), 43 (58).
HRMS: m/z calcd for of C H O , 380.1049; found, 380.1049.
6
1
1
+
(
(
5) (a) Avery, T. A.; Jenkins, N. F.; Kimber, M. C.; Lupton, D.
W.; Taylor, D. K. Chem. Commun. 2002, 22. (b) Boyd, J.
D.; Foote, C. S.; Imagawa, D. K. J. Am. Chem. Soc. 1980,
(
2
5
16
4
102, 3641. (c) Balci, M.; Aklbulut, N. Tetrahedron 1985,
41, 1315. (d) O’Shea, K. E.; Foote, S. C. J. Org. Chem.
1989, 54, 3475. (e) Sengül, M. E.; Simsek, N.; Balci, M.
Preparation of 5-Methyl-4-(9-phenanthryl)-3-(phenylsulfonyl)-
tetrahydro-2-furanone (21)
To a solution of sodio-methyl phenylsulfonyl acetate, prepared
from NaOMe (0.5 M, 2.2 mL) and methyl phenylsulfonyl acetate 20
0.236 g, 1.1 mmol), in anhyd THF (4 mL) was added a solution of
the 1,2-dioxine, 6a (0.256 g, 1.0 mmol) in anhyd THF (2 mL) and
the reaction left to stir for 16 h under N . After this period the reac-
tion was quenched by the addition of 1 M HCl (2 mL) and the mix-
ture partitioned between CH Cl (50 mL) and 1 M HCl (50 mL).
The aqueous layer was then extracted further with CH Cl (3 × 50
mL) and the organic layers dried (MgSO ), filtered and the solvent
Eur. J. Org. Chem. 2000, 1359. (f) Harter, R. V.; Weymuth,
C.; Scheffold, R. Helv. Chim. Acta 1993, 76, 353.
(
6) Haselgrove, T. D.; Jevric, M.; Taylor, D. K.; Tiekink, E. R.
T. Tetrahedron 1999, 55, 14739.
2
(
(
7) Krivickas, S. J.; Taylor, D. K. 2001, unpublished results.
8) (a) Matsumoto, M.; Kondo, K. Tetrahedron Lett. 1975, 45,
2
2
3935. (b) Matsumoto, M.; Dobashi, S.; Kondo, K. Bull.
2
2
Chem. Soc. Jpn. 1978, 51, 185.
4
(
9) (a) Matsumoto, M.; Dobashi, S.; Kuroda, K.; Kondo, K.
Tetrahedron 1985, 41, 2147. (b) Motoyoshiya, J.; Okuda,
Y.; Matsuoka, I.; Hayashi, S.; Takaguchi, Y.; Aoyama, H. J.
Org. Chem. 1999, 64, 493. (c) Matsumoto, M.; Nasu, S.;
Takeda, M.; Murakami, H.; Watanabe, N. Chem. Commun.
2000, 821. (d) Takahashi, Y.; Wakamatsu, K.; Morishima,
S.; Miyashi, T. J. Chem. Soc., Perkin Trans. 2 1993, 243.
removed under reduced pressure. The title compound was purified
by recrystallisation from acetone–hexanes, to yield pale pink crys-
tals.
Yield: 60%; mp 263–266 °C.
–
1
IR (nujol): 3434, 1758, 1600, 1502, 1448, 1308, 1211, 1147 cm .
1
H NMR (300 MHz, DMSO-d ): δ = 0.97 (d, J = 6.6 Hz, 3 H), 4.96
d, J = 2.4 Hz, 1 H), 5.16 (dd, J = 2.4, 8.1 Hz, 1 H), 5.28 (dq, J = 6.6,
6
(10) Greatrex, B.; Jevric, M.; Kimber, M. C.; Krivickas, S. J.;
(
Taylor, D. K.; Tiekink, E. R. T. Z. Kristallogr. 2002, 217,
587.
Synthesis 2003, No. 5, 668–672 ISSN 0039-7881 © Thieme Stuttgart · New York