Confirmation of the structure of ventiloquinone J through synthesis

Article abstract of DOI:10.1055/s-2004-822370

An unambiguous route has been developed for the synthesis of rac ventiloquinones J and E as well as their diastereoisomers, rac isoventiloquinones J and E by using a mercury(II) mediated ring closure as a key step.

Full text of DOI:10.1055/s-2004-822370

PAPER
1601
Confirmation of the Structure of Ventiloquinone J through Synthesis
Confirmation of
t
o
he Structure
b
of
V
entiloqu
i
inone
J
through SynthesisG. F. Giles,a Ivan R. Green,*b Nestor van Eedenb
a
Department of Chemistry, Murdoch University, Murdoch, WA 6150, Australia
b
Department of Chemistry, University of the Western Cape, Private Bag X17, Bellville, 7530, South Africa
Fax +27(21)9593055; E-mail: igreen@uwc.ac.za
Received 16 March 2004
For various reasons we were interested in the synthesis of
the 6,9- rather than the corresponding isomeric 5,10-
quinones. Some early successful syntheses of ventilagone
3 and ventiloquinone H, 4 were accomplished by Brassard
et al.5 via an elegant Diels–Alder methodology. Following
on this, Giles et al.6 described their syntheses of ventilo-
quinones E, 5 and G, 6 and the regioisomer of ventilo-
quinone J, viz., 2. This latter finding clearly suggested that
by default, the correct structure of ventiloquinone J is 1.
Cameron et al.7 subsequently described a synthesis of
ventilagone 3, the last step of which involved the intro-
duction of the C8 methyl group via a radical C-methyla-
tion protocol. In a further extention of their earlier work,
Brassard et al.8 described the syntheses of ventiloquinones
C, D, E and G. In the same year the Cameron group also
reported on the synthesis of ventiloquinone E, 5 but using
a new strategy.9 These ventiloquinones all possess the
1R,3S absolute stereochemistry for these cis-1,3-dimeth-
ylnaphthopyrans.
Abstract: An unambiguous route has been developed for the syn-
thesis of rac ventiloquinones J and E as well as their diastereoiso-
mers, rac isoventiloquinones J and E by using a mercury(II)
mediated ring closure as a key step.
Key Words: natural product synthesis, naphthopyranquinones,
mercury(II)-mediated cyclizations, stereochemistry
Some time ago Thomson et al.1 reported the isolation and
structural elucidation of eleven new ventiloquinones
found in the root bark of Ventilago maderaspatana and V.
calyculata. This work, which focused on the (1R,3S)-1,3-
dimethylnaphtho[2,3-c]-pyran-5,10- and -6,9-quinones
supported and expanded earlier isolations in which Thom-
son et al.2 focused on isofuranonaphthoquinones. Subse-
quent to these investigations, Thomson et al.3 described
the isolation of ventiloquinones L, M, N and O from V.
goughii, while ventiloquinones G, L and M were reported
to be isolated from the root bark of Fijian V. vitiensis.4 Al-
though the Thomson group were able to assign structures
to most of the ventiloquinones isolated, they were unable
to unambiguously assign the structure of ventiloquinone J
as either 1 or 2.1 This paper describes a protocol for the
unambiguous synthesis of ventiloquinone J to confirm its
structure as 1. (Figure 1).
Our approach to this first synthesis of ventiloquinone J
was based on the premise that we would be able to
chemoselectively differentiate between groups attached to
the C5- and C10-oxygen atoms of the naphthopyran nu-
cleus by the judicious choice of protecting groups placed
on these oxygens. The group at the C10-oxygen had to ad-
ditionally enable sufficient (1R,3S)-1,3-dimethylnaphtho-
pyran to form during the mercury(II) mediated ring
closure reaction (vide infra).
Consequently, naphthalene 76 was pyrolyzed at 160 °C
under nitrogen and the subsequent phenolic product de-
rived by the Claisen rearrangement was not isolated but
immediately methylated with 5 molar equivalents of
K2CO3 and MeI in boiling acetone to afford naphthalene
8 in 76% yield for the two steps (Scheme 1). Reduction of
the ketone group in 8 was effected by treatment with
LiAlH4 in Et2O at 25 °C to produce alcohol 9 in 83%
yield. Mercury(II) mediated intramolecular ring
closure10,11 of the ortho-allyl alcohol 9 produced an insep-
arable mixture of the (1R,3S)- and (1R,3R)-1,3-dimethyl-
naphthopyrans 10 and 11 in an overall yield of 75% but in
a disappointing ratio, as determined by 1H NMR spectros-
copy, of 1:2 respectively that favored the unwanted trans
1
isomer. The diagnostic signal in the H NMR spectrum
Figure 1
used to make the assignments is H-3 which appeared at
3.63 ppm for the 1,3-cis isomer 10 and at 4.14 ppm for
1,3-trans-isomer 11.12
SYNTHESIS 2004, No. 10, pp 1601–1608
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Advanced online publication: 18.05.2004
DOI: 10.1055/s-2004-822370; Art ID: P02904SS
© Georg Thieme Verlag Stuttgart · New York
Oxidative demethylation of the mixture of naphthopyrans
10 and 11 in aqueous CH3CN and cerium(IV) ammonium

1602
R. G. F. Giles et al.
PAPER
Scheme 1 i) 160 °C, N2; ii) K2CO3, CH3I, acetone reflux; iii) LiAlH4, Et2O, 25 °C; iv) Hg(OAc)2, THF, NaOH, NaBH4; v) Ce(NH4)2(NO3)6,
CH3CN, H2O
nitrate13 afforded a crude mixture of the corresponding By an analogous series of transformations naphthol 146
quinones 12 and 13 which were successfully separated on was treated with MOM-chloride15 to afford the MOM-
a long slow column to afford the pure isomers but in low ether 19 (60%), and then transformed into the 4-O-allyl-
yields viz. 12 (12%) and 13 (24%). In the latter two cases, naphthalene 20 (99%), followed by transformation into
the signal due to H-3 in the 1H NMR spectra appeared at the tetramethoxynaphthalene 21 (79%) and finally re-
3.49 ppm for 12 while at 4.05 ppm for 13. This result dem- duced to the naphthyl alcohol 22 (100%) using similar
onstrated that the benzyl group at the Cl0-oxygen is suffi- methods to those described earlier as shown in Scheme 2.
ciently large to retard good formation of the 1R,3S-isomer
With both naphthyl alcohols 18 and 22 in hand we pro-
during the ring closure6 and thus alternative protecting
ceeded with their conversions into the corresponding
groups were sought.
naphthopyrans. Thus treatment of the MEM-naphthalene
Treatment of naphthol 146 with MEM-chloride14 with vig- 18 under the same mercury(II) mediated conditions de-
orous stirring in the presence of K2CO3 in boiling acetone scribed earlier10,11 did not lead to the desired products. The
afforded a quantitative yield of the corresponding MEM- only identifiable products comprised an inseparable mix-
ether 15 after purification by chromatography ture of the 1R,3S- and 1R,3R-1,3-dimethyl-10-hydroxy-
1
(Scheme 2). We discovered that it is necessary to add tri- naphthopyrans 23 and 24 in a ratio of 1:1 (by H NMR)
methylamine (1% by volume) to the eluent to inhibit hy- and a total yield of 25% (Scheme 3). Typical three-proton
drolysis of the MEM group during chromatography. doublets in the region of 1.36 and 1.56 ppm; complex one-
Hydrolysis of the acetate functionality of the MEM-ether proton multiplets at 2.44 and 2.90 ppm, the absence of the
15 in methanolic KOH produced the expected 4-naphthol signals for the MEM-group in the 1H NMR spectrum sup-
derivative which was transformed without purification ported the assignment of structures 23 and 24 to the rather
into the 4-O-allylnaphthalene 16 in a yield of 46% for the unstable mixture. Quite evidently the MEM protecting
two steps. Pyrolysis of naphthalene 16 at 135 °C caused group is too sensitive under the conditions of cyclization.
the molecule to undergo the expected Claisen rearrange-
ment and the corresponding naphthol was converted into
the tetramethoxynaphthalene 17 as described earlier in a
By contrast, treatment of the corresponding MOM-naph-
thalene 22 under the same conditions produced a mixture
of the desired naphthopyrans 25 and 26 in a 1:1 ratio (by
yield of 89% for the two steps. As expected, there are five
1H NMR) and a total yield of 85%. Separation of the mix-
1
methoxy signals in the H NMR spectrum viz., 3.37
ture by PLC afforded the 1R,3S-racemate 25 (39%) and
(MEM methoxy), 3.75, 3.78, 3.96 and 4.01 ppm. Finally,
the 1R,3R-racemate 26 (40%). Assignment of the struc-
tures was made on the basis of the chemical shifts of the
the ketone function of naphthalene 17 was reduced with
LiAlH4 in Et2O at 25 °C to afford the expected naphthyl
protons H-3 in the 1H NMR spectrum viz., 3.70 ppm (for
alcohol 18 in 80% yield.
Synthesis 2004, No. 10, 1601–1608 © Thieme Stuttgart · New York

PAPER
Confirmation of the Structure of Ventiloquinone J through Synthesis
1603
Scheme 2 i) R-Cl, K2CO3, acetone reflux; ii) KOH, MeOH; CH2=CHCH2Br, K2CO3, acetone reflux; iii) 135 °C, CH3I, K2CO3, acetone reflux;
iv) LiAlH4, Et2O, 25 °C
25) and 4.05 ppm (for 26). It is also interesting to note that ing recrystallized tosic acid in aqueous dioxane at 55 °C
the signals due to the methylenedioxy group are diaste- for 18 h. In this way the MOM-protected 1R,3R-naphtho-
reotopic appearing as two one-proton doublets at 4.83 and pyranquinone 28 was converted into racemic isoventilo-
5.09 ppm (J = 6.6 Hz) for 25 and at 4.86 and 5.11 ppm quinone J 30 (67%) and the corresponding 1R,3S-
(J = 6.2 Hz) for 26.
naphthopyranquinone 29 was converted into racemic ven-
tiloquinone J 1 (56%), the spectral data for which are
identical to those published by Thomson et al.1
It was hoped that oxidation of the naphthopyran 26 would
occur either preferentially or exclusively at the terminal,
more highly oxygenated, more electron-rich aromatic ring Thus, an unambiguous protocol has been established for
to give the required 6,9-quinone. In practice, however, ox- the first synthesis of the racemate of 1, thereby establish-
idation with ceric ammonium nitrate afforded two differ- ing the correct structure for ventiloquinone J. By employ-
ent quinonoid products. After careful PLC separation of ing a mercury(II)-mediated ring closure as the key step,
these compounds the following assignments were made. the protocol has also lead to the synthesis of ventiloquino-
The compound 27 we now name isoventiloquinone E was ne E 5, isoventiloquinone E 27 and isoventiloquinone J 30
isolated in 56% yield from the faster moving band and from a common precursor viz., naphthyl alcohol 22.
was identical to that reported earlier.6 The compound iso-
lated from the slower moving band was assigned the
1H and 13C NMR spectra were recorded on a Varian 200 MHz spec-
trometer in CDCl3 using the residual CHCl3 as internal standard
(d = 2.73 and 77.1, respectively). IR spectra were recorded on a Per-
kin Elmer Fourier Transform spectrometer 2000. Liquid samples
were recorded as films while solids were recorded as sodium bro-
mide pressed discs. HRMS were recorded on a modified AEI 902
mass spectrometer at 70 eV and a source temperature of 180 °C. El-
emental analyses were performed on a Carlo Erba 1500 NA analy-
quinonoid structure 28 (43%) and is based inter alia on the
1
following signals in the H NMR spectrum: three three-
proton signals at 3.57, 3.83 and 3.97 ppm; two one-proton
doublets (J = 6.4 Hz) at 4.81 and 5.07 ppm for the diaste-
reotopic protons of the methylenedioxy group and a one-
proton multiplet at 4.02 ppm for H-3a.
Similar oxidative demethylation of the 1R,3S-isomer 25 ser. Melting points were obtained on a Fischer-Johns melting point
afforded the racemate of ventiloquinone E1,6 5 (59%) in
apparatus and are uncorrected. All solvents used for reactions and
which H-3a appeared as a multiplet at 3.54 ppm in the 1H
chromatography were distilled prior to use. Hexane refers to that
fraction boiling between 65–70 °C. Column chromatography was
NMR spectrum followed by the desired 1R,3S-naphtho-
carried out on dry packed columns using Merck Silica Gel 60 (75–
230 mesh) as stationary phase. PLC (Preparative Thin Layer Chro-
pyranquinone 29 (39%) in which H-3a appeared as a mul-
tiplet at 3.58 ppm in the 1H NMR spectrum.
matography) was conducted on glass plates measuring 20 × 20 cm
with a 1 mm layer of silica gel (Aldrich Z26,582-9). The term ‘res-
The final step, the removal of the MOM group from the
idue obtained upon workup’ refers to the organic phase being dried
Cl0-oxygen atom proved problematic owing to the sensi-
over MgSO4, filtered and the solvent removed by rotatory evapora-
tive nature of the product to the applied conditions, with
tion.
decomposition occurring. Best results were obtained us-
Synthesis 2004, No. 10, 1601–1608 © Thieme Stuttgart · New York

1604
R. G. F. Giles et al.
PAPER
Scheme 3 i) Hg(OAc)2, THF, KOH, NaBH4; ii) Ce(NH4)2(NO3)6, CH3CN, H2O; iii) Tosic acid, dioxane, 55 °C
2-Acetyl-1-benzyloxy-4,5,6,8-tetramethoxy-3-prop-2¢-enyl-
naphthalene (8); Typical Procedure
Hz, 1 H, trans H-3¢), 5.04 (dt, J3¢,2¢ = 10.0 Hz, J3¢,1¢ = 1.4 Hz, 1 H, cis
H-3¢), 5.97 (m, 1 H, H-2¢), 6.73 (s, 1 H, H-7), 7.40 (m, 5 H, Ph).
Allyloxy ketone 76 (270 mg, 0.64 mmol) was pyrolyzed under ni-
trogen at 160 °C for 6 h to afford a dark residue. This was dissolved
in acetone (50 mL) and then treated with K2CO3 (532 mg, 3.86
mmol) and MeI (548 mg, 3.86 mmol) and vigorously stirred under
reflux for 12 h. The cooled reaction mixture was filtered and the res-
idue obtained upon removal of volatiles was chromatographed us-
ing EtOAc–hexane (3:7) as eluent to afford ketone 8 as a light
yellow oil; yield: 213 mg (76%).
13C NMR (50 MHz): d = 30.5, 33.5, 56.5, 56.8, 62.2, 62.9, 78.6,
96.8, 116.2, 120.1, 126.4, 127.1, 128.1, 128.3 (2 ×), 128.6 (2 ×),
133.5, 137.2, 137.6, 148.1, 149.8, 150.7, 151.0, 153.7, 206.3.
Anal. Calcd for C26H28O6: C, 71.56; H, 6.42. Found: C, 71.26; H,
6.59.
MS: m/z [M+] calcd for C26H28O6: 436; found: 436 (68).
IR (film): 1695 cm–1.
1-Benzyloxy-2-(1¢-hydroxyethyl)-4,5,6,8-tetramethoxy-3-prop-
2¢¢-enylnaphthalene (9); Typical Procedure
To a slurry of LiAlH4 (38 mg, 1.0 mmol) in Et2O (15 mL) as 25 °C
was dripped ketone 8 (205 mg, 0.47 mmol) in Et2O (15 mL) over 10
min. The reaction mixture was stirred for an additional 1 h,
1H NMR (200 MHz): d = 2.56 (s, 3 H, COCH3), 3.56 (dt, J1¢,2¢ = 5.4
Hz, J1¢,3¢ = 1.4 Hz, 2 H, H-1¢), 3.79, 3.80, 3.89, 4.02 (4 × s, 12 H,
OCH3), 4.82 (s, 2 H, PhCH2O), 4.96 (dt, J3¢,2¢ = 17.0 Hz, J3¢,1¢ = 1.4
Synthesis 2004, No. 10, 1601–1608 © Thieme Stuttgart · New York

PAPER
Confirmation of the Structure of Ventiloquinone J through Synthesis
IR (NaBr): 1666 cm–1.
1605
quenched with aq NH4Cl (8 drops), then water (5 mL) and finally
additional Et2O (30 mL) was added. The residue obtained upon
workup afforded the crude alcohol 9 as a white solid which was not
purified. Yield: 171 mg (83% crude), waxy white material.
1H NMR (200 MHz): d = 1.60 (d, J2¢,1¢ = 6.8 Hz, 3 H, H-2¢), 1.90 (br
s, 1 H, D2O exchangeable, 1¢-OH), 3.80 (m, 2 H, H-1¢¢), 3.77, 3.80,
3.83, 4.00 (4 × s, 12 H, OCH3), 5.00 (m, 5 H, H-1¢, H-3¢¢, CH2Ph),
6.05 (m, 1 H, H-2¢¢), 6.73 (s, 1 H, H-7), 7.42 (m, 5 H, Ph).
1H NMR (200 MHz): d = 1.36 (d, JC3-methyl,H-3 = 6.2 Hz, 3 H, C3-
CH3), 1.58 (d, JCl–methyl,H–1 = 6.6 Hz, 3 H, Cl–CH3), 2.43 (dd,
JH-4a,H-4e = 18.0 Hz, JH-4a,H-3a = 11.0, 1 H, 4-Ha), 2.93 (dd, JH-4e,H-4a =
18.0 Hz, JH-4e,H-3a = 3.5 Hz, 1 H, H-4e), 3.83, 3.86 (2 × s, 6 H,
OCH3), 4.05 (m, 1 H, H-3a), 4.78 (d, JCH2Ph = 11.0 Hz, 1 H, CH2Ph),
4.93 (d, JCH2Ph = 11.0 Hz, 1 H, CH2Ph), 5.08 (q, JH–1,Cl–methyl = 6.6
Hz, 1 H, H-1), 5.93 (s, 1 H, H-8), 7.40 (m, 5 H, Ph).
HRMS: m/z [M+] calcd for C26H30O6: 438.2042; found: 438.2038.
13C NMR (50 MHz): d = 20.2, 21.8, 30.3, 57.0, 61.5, 62.3, 68.9,
77.3, 102.9, 121.3, 122.5, 127.7 (2 ×), 128.4, 128.9 (2 ×), 135.5,
136.9, 145.1, 150.0, 150.7, 158.2, 179.7, 183.1.
Rac-(1R,3S)- and (1R,3R)-10-Benzyloxy-3,4-dihydro-5,6,7,9-
tetramethoxy-1,3-dimethyl-1H-naphtho [2,3-c]pyrans (10) and
(11); General Procedure
HRMS: m/z [M+] calcd for C24H24O6: 408.1573; found: 408.1573.
To a solution of the crude alcohol 9 (171 mg, 0.39 mmol) in THF (5
mL) and water (5 mL) was added mercury(II) acetate (175 mg, 0.55
mmol) and the solution was stirred for 1 h after which time NaOH
(4 mL of a 3 M solution) was added and the milky white mixture
was stirred for another 1 h. A mixture of NaBH4 (216 mg, 5.85
mmol) and NaOH (4.0 mL of a 3 M solution) was then added to the
reaction mixture and stirring was continued for a further 1 h. The re-
action mixture was extracted with EtOAc (5 × 40 mL) and the resi-
due obtained from upon workup was chromatographed using
EtOAc–hexane (3:7) as eluent to afford a mixture of the two pyrans
10 and 11 as an oil. Yield: 120 mg (75%) as an olive colored oil.
4-Acetoxy-2-acetyl-5,6,8-trimethoxy-1-(2¢-methoxyethoxyme-
thyleneoxy)naphthalene (15); Typical Procedure
To a solution of phenol 146 (346 mg, 1.04 mmol) in acetone (100
mL) and K2CO3 (414 mg; 3.0 mmol) was added 1-chloromethoxy-
2-methoxyethane (327 mg, 3.0 mmol) and the resulting mixture was
vigorously stirred under reflux under nitrogen for 48 h. The cooled
mixture was filtered and volatile material removed under rotatory
evaporation to afford a residue that was chromatographed using
EtOAc–hexane–Et3N (60:39:1) as eluent to provide the ether 15 as
an orange solid recrystallized from hexane–EtOAc. Yield: 497 mg
(100% crude); orange cubes; mp 83–85 °C.
1H NMR (200 MHz): d = 1.40, 1.39 (2 × d, 6 H, JC3-methyl,H-3 = 6.2
Hz, C3-CH3), 1.65, 1.66 (2 × d, 6 H, JC1-methyl,H-1 = 6.2 Hz, C1-CH3),
2.60 (m, 2 H, H-4a), 3.13 (dm, JH-4e,H-4a = 17.0 Hz, 2 H, H-4e), 3.63
(m, 1 H, H-3a for 10), 3.80, 3.82, 3.84, 3.85, 3.98, 4.00 (6 × s, 18 H,
OCH3), 4.14 (m, 1 H, H-3a, of 11), 4.70 (d, 2 H, J = 10.6, CH2Ph),
4.98 (d, J = 10.6 Hz, 2 H, CH2Ph), 5.13, 5.33 (2 × q,
JH-1,C1-methyl = 6.2 Hz, 2 H, H-1), 6.69 (br s, 2 H, H-7 for both iso-
mers), 7.36 (m, 10 H, Ph).
IR (NaBr): 1735, 1659 cm–1.
1H NMR (200 MHz): d = 2.33 (s, 3 H, C4-OAc), 2.73 (s, 3 H, C2-
COCH3), 3.33 (s, 3 H, CH2OCH3), 3.46 (m, 2 H, OCH2CH2O), 3.69
(m, 2 H, OCH2CH2O), 3.78, 3.98, 3.99 (3 × s, 9 H, OCH3), 5.15 (s,
2 H, OCH2O), 6.74 (s, 1 H, H-7), 7.26 (s, 1 H, H-3).
13C NMR (50 MHz): d = 20.7, 31.6, 56.7, 56.8, 59.1, 62.0, 70.4,
71.8, 97.6, 101.1, 116.4, 120.1, 126.8, 129.2, 136.3, 141.6, 152.1
(2 ×), 154.8, 170.0, 200.4.
HRMS: m/z [M+] calcd for C26H30O6: 438.2042; found: 438.2036.
MS: m/z (%) = 422 (19), 380 (10), 334 (16), 304 (24), 292 (46), 277
(100), 262 (84), 247 (29), 89 (79), 59 (83), 43 (69).
HRMS: m/z [M+] calcd for C21H26O9: 422.4310; found: 422.4319.
Rac-(1R,3S),- and (1R,3R)-10-Benzyloxy-3,4-dihydro-5,7-
dimethoxy-1,3-dimethyl-1H-naphtho [2,3-c]pyran-6,9-diones
(12) and (13); General Procedure
Anal. Calcd for C21H26O9: C, 59.72; H, 6.16. Found: C, 59.99; H,
6.51.
To a solution of a mixture of pyrans 10 and 11 (120 mg, 0.27 mmol)
in CH3CN (5 mL) and water (1.0 mL) was added dropwise a solu-
tion of cerium(IV) ammonium nitrate (330 mg, 0.60 mmol) in wa-
ter. After stirring for 15 min, water (50 mL) was added and the
solution was extracted with CH2Cl2 (3 × 50 mL). The residue ob-
tained upon workup was chromatographed using EtOAc–hexane
(2:3) as eluent to afford the rac-1R,3S-naphthopyran 12. Yield: 14
mg (12%) as a light red oil.
4-Acetoxy-2-acetyl-5,6,8-trimethoxy-1-methoxymethyleneoxy-
naphthalene (19); Typical Procedure
To a solution of phenol 146 (580 mg, 1.74 mmol) in acetone (80 mL)
and K2CO3 (1198 mg, 8.7 mmol) was added chloromethyl methyl
ether (695 mg; 8.7 mmol) and the resulting mixture was vigorously
stirred under reflux under nitrogen for 12 h. The cooled mixture was
filtered and the residue remaining after removal of volatile material
on the rotatory evaporator was chromatographed using EtOAc–hex-
ane–Et3N (49:49:2) as eluent to afford ether 19 as a white solid re-
crystallized from MeOH. Yield: 397 mg (60%); off-white needles;
mp 132–134 °C.
IR (film): 1665 cm–1.
1H NMR (200 MHz): d = 1.36 (d, JC3-methyl,H-3 = 6.1 Hz, 3 H,
C3-CH3), 1.59 (d, JC1-methyl,H-1 = 6.6 Hz, 3 H, C1–CH3), 2.44
(dd, JH-4a,H-4e = 17.9 Hz, JH-4a,H-3a = 11.0 Hz, 1 H, 4-Ha), 2.95 (dd,
J
H-4e,H-4a = 17.9 Hz, JH4e, H-3a = 3.5 Hz, 1 H, H-4e), 3.49 (m, 1 H,
H-3a), 3.86, 3.89 (2 × s, 6 H, OCH3), 4.76 (d, JCH2Ph = 11.2 Hz, 1 H,
CH2Ph), 4.91 (d, JCH2Ph = 11.2 Hz, 1 H, CH2Ph), 5.08 (q,
IR (NaBr): 1755, 1659 cm–1.
1H NMR (200 MHz): d = 2.34 (s, 3 H, C4-OAc), 2.73 (s, 3 H,
C2-COCH3), 3.45 (s, 3 H, OCHOCH3), 3.79, 3.99, 4.00 (3 × s, 9 H,
OCH3), 5.04 (s, 2 H, OCH2OCH3), 6.75 (s, 1 H, H-7), 7.26 (s, 1 H,
H-3).
13C NMR (50 MHz): d = 20.7, 31.5, 56.7, 56.9, 58.6, 62.0, 97.6,
102.3, 116.8, 120.1, 126.4, 126.8, 129.3, 141.6, 152. 0 (2 ×), 154.8,
170.1, 200.5.
JH–1, Cl–methyl = 6.6 Hz, 1 H, H-1), 5.93 (s, 1 H, H-8), 7.40 (m, 5 H,
Ph).
13C NMR (50 MHz): d = 20.2, 21.8, 30.3, 57.0, 61.5, 62.3, 68.9,
77.3, 102.9, 121.3, 122.5, 127.7 (2 ×), 128.4, 128.9 (2 ×), 135.5,
136.9, 145.1, 150.0, 150.7, 158.2, 179.7, 183.1.
Anal. Calcd for C24H24O6: C, 70.59; H, 5.88. Found: C, 70.35; H,
5.60.
MS: m/z [M+] calcd for C19H22O8: 378.13; found: 378.13.
Further elution afforded the rac-1R,3R-naphthopyran 13 as a red
solid which was recrystallized from EtOAc–hexane. Yield: 28 mg
(24%); red rosettes; mp 195–196 °C.
Anal. Calcd for C19H22O8: C, 76.19; H, 5.82. Found: C, 76.31; H,
6.05.
Synthesis 2004, No. 10, 1601–1608 © Thieme Stuttgart · New York

1606
R. G. F. Giles et al.
PAPER
2-Acetyl-5,6,8-trimethoxy-1-(2¢-methoxyethoxymethyleneoxy)-
4-prop-2¢¢-enyloxynaphthalene (16); Typical Procedure
3.76 (m, 2 H, OCH2CH2O), 3.78, 3.96, 4.01 (3 × s, 9 H, OCH3), 4.94
(dt, JH-3¢¢,H-2¢¢ = 17.0 Hz, JH-3¢¢,H-1¢¢ = 1.4 Hz, 1 H, trans H-3¢¢), 5.03
(dq, JH-3¢¢,H-2¢¢ = 10.4 Hz, JH-3¢¢,H-1¢¢ = 1.4 Hz, 1 H cis-H-3¢¢), 5.05 (s, 2
H, OCH2O), 5.90 (m, 1 H, H-2¢¢), 6.72 (s, 1 H, H-7).
MEM-acetate 15 (327 mg, 0.77 mmol) was dissolved with warming
in MeOH (70 mL). The solution at 25 °C was then treated with a
methanolic solution of KOH (4.3 mL of a 5% m/v solution, 3.85
mmol) and the resulting solution was stirred at 25 °C for 20 min, af-
ter which H2O (120 mL) and CH2Cl2 (200 mL) were added. The
mixture was carefully acidified with dilute aq HCl (0.1 M). The
naphthol was extracted into the CH2Cl2 and the residue obtained
upon workup was dissolved in acetone (100 mL) and treated with
K2CO3 (531 mg, 3.58 mmol) and allyl bromide (433 mg, 3.58
mmol) and the resulting mixture was vigorously stirred and heated
under reflux under nitrogen for 48 h. The oily residue obtained upon
filtration and removal of the volatile material was chromatographed
using EtOAc–hexane–Et3N (60:39:1) as eluent to afford the MEM-
allyl ether 16. Yield: 150 mg (46%); thick olive colored oil.
Anal. Calcd for C23H30O8: C, 63.59; H, 6.91. Found: C, 63.50; H,
7.00.
2-Acetyl-4,5,6,8-tetramethoxy-1-methoxymethyleneoxy-3-
prop-2¢-enylnaphthalene (21); Typical Procedure
Pyrolysis of the MOM-allyl ether 20 (134 mg, 0.36 mmol) in an oil
bath at 160 °C under nitrogen for 2 h and treatment of the phenolic
intermediate as described for the tetramethoxynaphthalene 17, gave
after chromatography using EtOAc–hexane–Et3N (29:69:2) as elu-
ent the MOM-allylnaphthalene 21 as an orange solid recrystallized
from hexane–EtOAc. Yield: 111 mg (79%); light orange cubes; mp
87–89 °C.
IR (film): 1680 cm–1.
IR (NaBr): 1700 cm–1.
1H NMR (200 MHz): d = 2.75 (s, 3 H, C2-COCH3), 3.32 (s, 3 H,
CH2OCH3), 3.46 (m, 2 H, OCH2CH2O), 3.64 (m, 2 H, OCH2CH2O).
3.79, 3.97, 4.00 (3 × s, 9 H, OCH3), 4.62 (dt, JH-1¢¢,H-2¢¢ = 5.2 Hz,
JH-1¢¢,H-3¢¢ = 1.2 Hz, 2 H, H-1¢¢), 5.10 (s, 2 H, OCH2O), 5.30 (dt,
JH-3¢¢,H-2¢¢ = 10.4 Hz, JH-3¢¢,H-1¢¢ = 1.4 Hz, 1 H, cis-H-3¢¢), 5.54 (dt,
1H NMR (200 MHz): d = 2.61 (s, 3 H, C2-OAc), 3.50 (s, 3 H,
CH2OCH3), 3.57 (dt, JH-1¢,H-2¢ = 6.0 Hz, JH-1¢,H-3¢ = 1.6 Hz, 2 H, H-1¢),
3.75, 3.78, 3.97, 4.00 (3 × s, 12 H, OCH3), 4.94 (dt, JH-3¢,H-2¢ = 17.6
Hz, JH-3¢,H-1¢ = 1.6 Hz, 1 H, trans-H-3¢), 4.95 (s, 2 H, OCH2OCH3),
5.03 (dt, JH-3¢,H-2¢ = 10.4 Hz, JH-3¢,H-1¢ = 1.6 Hz, 1 H, cis-H-3¢), 5.93
(m, 1 H, H-2¢), 6.72 (s, 1 H, H-7).
13C NMR (50 MHz): d = 29.7, 33.7, 56.6, 56.8, 58.1, 62.1, 62.8,
96.9, 101.8, 115.7, 116.2, 126.3, 127.1, 133.4, 136.8, 137.3, 145.8,
149.9, 151.0, 153.5, 205.5.
J
H-3¢¢,H-2¢¢ = 17.0 Hz, JH-3¢¢,H-1¢¢ = 1.4 Hz, 1 H, trans H-3¢¢), 6.16 (m, 1
H, H-2¢¢), 6.76 (s, 1 H, H-7), 7.01 (s, 1 H, H-3).
HRMS: m/z [M+] calcd for C22H28O3: 420.1784; found: 420.1768.
Anal. Calcd for C22H28O8: C, 62.86; H, 6.67. Found: C, 62.49; H,
6.95.
MS: m/z (%) [M+] = 390 (66), 345 (32), 315 (71), 301 (100), 288
(43), 273 (85).
2-Acetyl-5,6,8-trimethoxy-1-methoxymethyleneoxy-4-prop-2¢-
enyloxynaphthalene (20)
By an analogous procedure described for the MEM-allyl ether 16,
the MOM-acetate 19 (280 mg, 0.74 mmol) was transformed into the
MOM-allyl ether 20 as a yellow solid recrystallized from hexane.
Yield: 274 mg (99% crude); olive yellow rods; mp 70–72 °C.
IR (NaBr): 1650 cm–1.
1H NMR (200 MHz): d = 2.76 (s, 3 H, C2-COCH3), 3.42 (s, 3 H,
Anal. Calcd for C21H26O7: C, 64.62; H, 6.67. Found: C, 64.99; H,
6.98.
2-(1¢¢-Hydroxyethyl)-4,5,6,8-tetramethoxy-1-(2¢-methoxyeth-
oxyethyleneoxy)-3-prop-2¢¢¢-enylnaphthalene (18); Typical Pro-
cedure
Into a stirred slurry of LiAlH4 (38 mg, 1.0 mmol) in Et2O (15 mL)
was dripped a solution of the MEM-ketone 17 (240 mg, 0.56 mmol)
in Et2O (15 mL) and stirring was continued at 25 °C until reduction
was complete (TLC). Careful addition of a sat. aq solution of NH4Cl
(3–4 drops) destroyed the excess of LiAlH4. Water (5 mL) and Et2O
(30 mL) were added and the Et2O layer upon workup yielded the
MEM-alcohol 18 which was used in the next step without further
purification. Yield: 200 mg (80% crude); thick oil.
1H NMR (200 MHz): d = 1.20 (d, JH-2¢¢,H-1¢¢ = 6.4 Hz, 3 H, H-2¢¢),
3.37 (s, 3 H, CH2OCH3), 3.58 (dt, JH-1¢¢¢,H-2¢¢¢ = 5.2 Hz, JH-1¢¢¢,H-3¢¢¢ = 1.4
Hz, 2 H, H-1¢¢¢), 3.74, 3.77 (2 × s, 9 H, OCH3), 3.80 (m, 4 H,
OCH2CH2O), 3.94, 4.00 (2 × s, 6 H, OCH3), 4.90 (dt, JH-3¢¢¢,H-2¢¢¢
17.0 Hz, JH-3¢¢¢,H-1¢¢¢ = 1.4 Hz, 1 H, trans-H-3¢¢¢), 5.05 (dt, JH-3¢¢¢,H-2¢¢¢
CH2OCH3), 3.79, 3.98, 4.00 (3 × s, 9 H, OCH3), 4.62 (dt, JH-1¢,H-2¢
=
5.4 Hz, JH-1¢,H-3¢ = 1.4 Hz, 2 H, H-1¢), 5.00 (s, 2 H, CH2OCH3), 5.30
(dt, JH-3¢,H-2¢ = 10.6 Hz, JH-3¢,H-1¢ = 1.4 Hz, 1 H, cis-H-3¢), 5.54 (dt,
J
H-3¢,H-2¢ = 17.4 Hz, JH-3¢,H-1¢ = 1.4 Hz, 1 H, trans-H-3¢), 6.16 (m, 1 H,
H-2¢), 6.77 (s, 1 H, H-7), 7.00 (s, 1 H, H-3).
13C NMR (50 MHz): d = 31.8, 56.8, 57.0, 58.5, 61.2, 71.0, 98.1,
102.0, 107.8, 116.5, 117.7, 126.4, 129.4, 133.4, 138.3, 147.8, 151.2,
152.0, 154.1, 201.7.
MS: m/z [M+] = 376 (28), 331 (29), 316 (23), 301 (81), 287 (100),
273 (41).
=
=
Anal. Calcd for C20H24O7: C, 63.83; H, 6.43. Found: C, 63.51; H,
6.30.
10.4 Hz, JH-3¢¢¢,H-1¢¢¢ = 1.4 Hz, 1 H, cis-H-3¢¢¢), 5.10 (q, JH-1¢¢,H-2¢¢ = 6.4
Hz, 1 H, H-1¢¢), 5.18 (br s, 1 H, D2O exchangeable, Cl¢¢-OH), 6.12
(m, 1 H, H-2¢¢¢), 6.70 (s, 1 H, H-7).
2-Acetyl-4,5,6,8-tetramethoxy-1-(2¢-methoxyethoxymethylene-
oxy)-3-prop-2¢¢-enylnaphthalene (17); Typical Procedure
Pyrolysis of the MEM-allyl ether 16 (261 mg, 0.62 mmol) in an oil
bath at 135 °C under nitrogen for 4 h produced a dark product which
was dissolved in acetone (100 mL) and then K2CO3 (425 mg; 3.1
mmol) and MeI (440 mg; 3.1 mmol) were added. The resulting mix-
ture was vigorously stirred and heated under reflux under nitrogen
for 12 h. The residue obtained upon filtration and removal of vola-
tile material was chromatographed using EtOAc–hexane–Et2N
(60:39:1) as eluent to afford the tetramethoxynaphthalene 17. Yield:
240 mg (89%); clear oil.
2-(1¢-Hydroxyethyl)-4,5,6,8-tetramethoxy-1-methoxymethyl-
eneoxy-3-prop-2¢¢-enylnaphthalene (22); Typical Procedure
Into a stirred slurry of LiAlH4 (36.5 mg, 0.96 mmol) in Et2O (12
mL) was dripped a solution of the MOM-ketone 21 (189 mg, 0.96
mmol) and the reaction was conducted as described for the MEM-
ketone 17 above. The residue obtained upon workup was chromato-
graphed using EtOAc–hexane–Et3N (59:39:2) as eluent to afford
the MOM-alcohol 22 as a white solid recrystallized from hexane–
CH2Cl2. Yield: 190 mg (100% crude); white flakes; mp 113–115
°C.
IR (film): 1679 cm–1.
IR (NaBr): 3430 cm–1.
1H NMR (200 MHz): d = 2.59 (s, 3 H, C2-OAc), 3.37 (s, 3 H,
CH2OCH3), 3.56 (m, 4 H, OCH2CH2O, H-1¢¢), 3.75 (s, 3 H, OCH3),
1H NMR (200 Hz): d = 1.68 (d, JH-2¢,H-1¢ = 7.0 Hz, 3 H, H-2¢), 3.57
(s, 3 H, CH2OCH3), 3.73 (sharp m, 2 H, H-1¢¢), 3.74, 3.77, 3.94, 3.99
Synthesis 2004, No. 10, 1601–1608 © Thieme Stuttgart · New York

PAPER
Confirmation of the Structure of Ventiloquinone J through Synthesis
1607
(4 × s, 12 H, OCH3), 4.35 (br s, 1 H, D2O exchangeable, C1¢-OH),
4.86 (dt, JH-3¢¢,H-2¢¢ = 17.4 Hz, JH-3¢¢,H-1¢¢ = 1.4 Hz, 1 H, trans-H-3¢¢),
4.95 (d, JGem = 8.0 Hz, 1 H, OCH2O), 5.05 (dt, JH-3¢¢,H-2¢¢ = 10.4 Hz,
The slower moving band afforded the MOM-pyran 26. Yield: 46
mg (40%) as a yellow oil
IR (film): 1388 cm–1.
1H NMR (200 MHz): d = 1.38 (d, JC3–methyl,H–3 = 6.2 Hz, 3 H,
C3-CH3), 1.65 (d, JC3–methyl,H–1 = 6.6 Hz, 3 H, C1–CH3), 2.58 (dd,
JH-4a,H-4e = 17.2 Hz, JH-4a,H-3a = 11.0 Hz, 1 H, H-4a), 3.11 (dd,
JH-4e,H-4a = 17.2 Hz, JH-4e,H-3a = 3.4 Hz, 1 H, H-4e), 3.60 (s, 3 H,
CH2OCH3), 3.77, 3.80, 3.95, 3.99 (4 × s, 12 H, OCH3), 4.05 (m, 1
H, H-3a), 4.86 (d, JGem = 6.2 Hz, 1 H, OCH2), 5.11 (d, JGem = 6.2 Hz,
1 H, OCH2O), 5.46 (q, JH–1,Cl–methyl = 6.6 Hz, 1 H, H-1), 6.67 (s, 1 H,
H-8).
J
H-3¢¢,H-1¢¢ = 1.4 Hz, 1 H, cis-H-3¢¢), 5.15 (m, 2 H, OCH2O, H-1¢), 6.10
(m, 1 H, H-2¢¢), 6.70 (s, 1 H, H-7).
13C NMR (200 MHz): d = 23.6, 30.4, 56.9 (2 ×), 57.8, 62.0, 62.6,
66.1, 97.3, 101.6, 115.6, 116.1, 125.3, 129.7, 132.6, 136.8, 137.8,
148.5, 149.6, 149.9, 152.7.
MS: m/z [M+] = 392 (23), 330 (82), 315 (100).
Anal. Calcd for C21H28O7: C, 64.29; H, 7.14. Found: C, 64.51; H,
7.38.
13C NMR (50 MHz): d = 20.4, 22.2, 30.7, 56.7, 57.0, 57.6, 61.3,
62.0, 62.6, 69.1, 96.7, 101.5, 115.7, 124.7, 126.4, 128.9, 136.8,
146.4, 148.4, 149.4, 152.7.
Rac-(1R,3S)- and (1R,3R)-10-Hydroxy-3,4-dihydro-5,6,7,9-tet-
ramethoxy-1,3-dimethyl-1H-naphtho[2,3-c]pyrans (23) and
(24); General Procedure
Anal. Calcd for C21H28O7: C, 64.29; H, 7.14. Found: C, 64.35; H,
7.30.
HRMS: m/z [M+] calcd for C21H28O7: 392.1835; found: 392.1832.
To a solution of the crude MEM-alcohol 18 (200 mg, 0.46 mmol) in
THF (5 mL) and water (5 mL) at 25 °C was added mercury(II) ace-
tate (207 mg, 0.65 mmol) and the resultant mixture was stirred for
1 h. Aqueous NaOH (4.6 mL of 3 M) was added and stirring of the
milky solution was continued for a further 1 h. To this was then add-
ed a mixture of NaBH4 (255 mg; 6.9 mmol) in aq NaOH (4.6 mL of
3 M) and stirring was continued for a further 1 h. The resulting so-
lution was extracted with EtOAc (4 × 30 mL) and the residue ob-
tained upon workup was chromatographed using EtOAc–hexane–
Et3N (59:39:2) as eluent to give an inseparable mixture of the two
naphthopyrans 23 and 24 in the ratio of 1:1 as determined by NMR
spectroscopy. Yield: 50 mg (25%); thick oil.
1H NMR (200 MHz): d = 1.36 (m, 6 H, C3-CH3), 1.56 (m, 6 H,
C1-CH3), 2.44 (m, 2 H, H-4a), 2.90 (m, 2 H, H-4e), 3.70 (m, 1 H,
H-3), 3.82, 3.85, 3.87, 3.98 (4 × br s, 24 H, OCH3), 4.02 (m, 1 H,
H-3), 4.85, 5.05 (2 × q, 2 H, JH–1,Cl–Cl3 = 6.4 Hz, H-1), 6.68 (br s, 2
H, H-7).
Rac-(1R,3R)-3,4-Dihydro-6,7,9-trimethoxy-1,3-dimethyl-1H-
naphtho[2,3-c]pyran-5,10-dione (27) and (1R,3R)-3,4-Dihydro-
5,7-dimethoxy-10-methoxymethyleneoxy-1,3-dimethyl-1H-
naphtho[2,3-c]pyran-6,9-dione (28); General Procedure
To a solution of pyran 26 (20 mg; 0.051 mmol) in CH3CN (2 mL)
and water (0.5 mL) was added dropwise a solution of cerium(IV)
ammonium nitrate (60 mg, 0.110 mmol) in water (1 mL) at 25 °C
and stirring was maintained for 15 min after which water (20 mL)
was added and the resulting aqueous solution was extracted with
CH2Cl2 (3 × 30 mL). The residue obtained upon workup was chro-
matographed by PLC using EtOAc–hexane (1:4) as eluent to yield
a faster band identified as isoventiloquinone E 27 as a brown solid
recrystallized from hexane. Yield: 9.5 mg (56%); brown/yellow
crystals; mp 169–171 °C (lit.6 mp 177.5–178.5 °C).
HRMS: m/z [M+] calcd for C19H24O6: 348.1573; found: 348.1565.
IR (NaBr): 1660 cm–1.
1H NMR (200 MHz): d = 1.33 (d, JC3–CH3,H–3a = 6.2 Hz, 3 H,
C3-CH3), 1.51 (d, JC3–CH3,H–1 = 6.6 Hz, 3 H, C1–CH3), 2.21
(ddd, JH-4a,H-4e = 18.6 Hz, JH-4a,H-3a = 9.8 Hz, JH-4a,H-1 = 1.8 Hz, 1 H,
Rac-(1R,3S)- and (1R,3R)-3,4-Dihydro-5,6,7,9-tetramethoxy-
10-methoxymethyleneoxy-1,3-dimethyl-1H-naphtho[2,3-c]pyr-
an (25) and its Diastereoisomer 26; General Procedure
To a solution of the MOM-alcohol 22 (115 mg; 0.29 mmol) in THF
(5 mL) and water (5 mL) at 25 °C was added mercury(II) acetate (94
mg; 0.30 mmol) and the resultant mixture stirred for 1 h. Aqueous
NaOH (4.5 mL of 3 M) was added and stirring continued for a fur-
ther 1 h after which a mixture of NaBH4 (159 mg; 4.2 mmol) and aq
NaOH (4.5 mL of 3 M) were added. After a further 1 h of stirring
water (50 mL) was added to the mixture which was extracted with
EtOAc (4 × 30 mL). The residue obtained after workup (97 mg,
85%) was purified by PLC using EtOAc–hexane (1:4) as eluent and
the faster running band afforded the MOM-pyran 25. Yield: 45 mg
(39%); olive-colored oil.
H-4a), 2.65 (ddd, JH-4e,H-4a = 18.6 Hz, JH-4e,H-3a = 3.6 Hz, JH-4e,H-1
=
1.0 Hz, 1 H, H-4e), 3.87, 3.98, 3.99 (3 × s, 9 H, OCH3), 3.97 (m, 1
H, H-3a), 4.98 (dq, JH–1,Cl–CH3 = 6.6 Hz, JH-1,H-4a = 1.8 Hz, 1 H), 6.74
(s, 1 H, H-8).
13C NMR (50 MHz): d = 19.8, 21.6, 29.7, 56.3, 56.8, 61.4, 62.7,
67.3, 101.4, 114.0, 126.6, 140.4, 143.6, 146.8, 158.2, 159.7, 181.7,
184.2.
Anal. Calcd for C18H20O6: C, 65.06; H, 6.02. Found: C, 65.18; H,
6.12.
HRMS: m/z [M+] calcd for C18H20O6: 332. 1260; found: 332.1259.
IR (film): 1390 cm–1.
The slower moving band afforded the MOM–quinone 28 as a yel-
low solid material recrystallized from hexane. Yield: 8 mg (43%);
yellow crystals; mp 130–132 °C.
IR (NaBr): 1652 cm–1.
1H NMR (200 MHz): d = 1.37 (d, JC3–methyl,H–3a = 5.8 Hz, 3 H,
C3-CH3), 1.60 (d, JCl–methyl,H–1 = 6.6 Hz, 3 H, C1–CH3), 2.42
(dd, JH-4a,H-4e = 17.6 Hz, JH-4a,H-3a = 10.6 Hz, 1 H, H-4a), 2.92
(dd, JH-4e,H-4a = 17.6 Hz, JH-4e,H-3a = 3.4 Hz, 1 H, H-4e), 3.57 (s, 3 H,
CH2OCH3), 3.83, 3.97 (2 × s, 6 H, OCH3), 4.02 (m, 1 H, H-3a), 4.81
(d, J = 6.4 Hz, 1 H, OCH2OCH3), 5.07 (d, J = 6.4 Hz, 1 H,
OCH2OCH3), 5.28 (q, J = 6.6 Hz, 1 H, H-1), 5.94 (s, 1 H, H-8).
13C NMR (50 MHz): d = 19.8, 21.8, 30.4, 57.1, 57.9, 61.5, 62.2,
69.0, 102.6, 102.9, 121.1, 125.6, 135.2, 145.1, 149.4, 150.6, 158.2,
170.1, 179.5.
1H NMR (200 MHz): d = 1.40 (d, JC3–methyl,H–3 = 5.8 Hz, 3 H,
C3-CH3), 1.68 (d, JC3–methyl,H–1 = 6.2 Hz, 3 H, Cl-CH3), 2.55 (dd,
JH-4e,H-4a = 15.6 Hz, JH-4e,H-3a = 10.6 Hz, 1 H, H-4a), 3.11 (ddd,
JH-4e,H-4a = 15.6 Hz, JH-4e,H-3a = 3.4 Hz, JH-4e,H-1a = 1.0 Hz, 1 H, H-4e),
3.59 (s, 3 H, CH2OCH3), 3.70 (m, 1 H, H-3a), 3.79, 3.81, 3.94, 4.00
(4 × s, 12 H, OCH3), 4.83 (d, JGem = 6.6 Hz, 1 H, OCH2O), 5.09 (d,
JGem = 6.6 Hz, 1 H, OCH2O), 5.29 (dq, JH–1a,C3–methyl = 6.2 Hz,
JH-1a,H-4e = 1.0 Hz, 1 H, H-1a), 6.67 (s, 1 H, H-8).
13C NMR (50 MHz): d = 21.9, 22.8, 31.7, 56.9, 57.0, 57.8, 61.7,
62.1, 69.5, 71.7, 96.9, 101.5, 116.0, 124.7, 128.0, 129.6, 136.5,
146.5, 147.7, 149.4, 152.8.
Anal. Calcd for C21H28O7: C, 64.29; H, 7.14. Found: C, 64.31; H,
7.24.
HRMS: m/z [M+] calcd for C21H28O7: 392.1835; found: 392.1829.
Anal. Calcd for C19H22O7: C, 62.98; H, 6.08. Found: C, 63.05; H,
6.13.
Synthesis 2004, No. 10, 1601–1608 © Thieme Stuttgart · New York

1608
R. G. F. Giles et al.
PAPER
HRMS: m/z [M+] calcd for C19H22O7: 362.1366; found: 362.1359.
13C NMR (50 MHz): d = 21.4, 21.6, 31.1, 57.0, 57.9, 61.5, 69.0,
71.7, 102.4, 102.8, 121.1, 129.8, 136.4, 141.6, 145.4, 150.4, 157.4,
170.1, 179.5.
Rac-(1R,3R)-3,4-Dihydro-10-hydroxy-5,7-dimethoxy-1,3-dime-
thyl-1H-naphtho[2,3-c]pyran-6,9-dione (30) (Isoventiloquinone
J); Typical Procedure
Anal. Calcd for C19H22O7: C, 62.98; H, 6.08. Found: C, 63.10; H,
6.15.
Tosic acid (1.5 mg; 0.009 mmol) was added to a solution of quinone
28 (10 mg, 0.028 mmol) in dioxane (10 mL) and water (4 mL) at 55
°C and stirring was maintained at this temperature for 18 h after
which water (80 mL) was added and the aqueous solution was ex-
tracted with CH2Cl2 (4 × 30 mL). The residue obtained upon work-
up was purified by PLC using EtOAc–hexane (1:4) as eluent to
afford ventiloquinone 30 as a red solid recrystallized from i-PrOH.
Yield: 6 mg (67%); red crystals; mp 140–142 °C.
HRMS: m/z [M+] calcd for C19H22O7: 362.1366; found: 362.1362.
Rac-(1R,3S)-3,4-Dihydro-10-hydroxy-5,7-dimethoxy-1,3-dime-
thyl-1H-naphtho[2,3-c]pyran-6,9-dione 1 (Ventiloquinone J)
In an analogues protocol applied to quinone 28, deprotection of
quinone 29 (10 mg; 0.028 mmol) afforded ventiloquinone J 1 as red
crystals recrystallized from i-PrOH and having spectral data identi-
cal to those published in the literature.1 Yield: 5 mg (56%); red crys-
tals; mp 140–142 °C (lit.1 mp 141 °C).
IR (NaBr): 3368, 1660 cm–1.
1H NMR (200 MHz): d = 1.40 (d, JC3–CH3,H–3a = 6.2 Hz, 3 H,
C3-CH3), 1.61 (d, JC3–CH3,H–1 = 6.6 Hz, 3 H, C1–CH3), 2.44
(dd, JH-4a,H-4e = 17.6 Hz, JH-4a,H-3a = 10.6 Hz, 1 H, H-4a), 2.93
(dd, JH-4e,H-4a = 17.6 Hz, JH-4e,H-3a = 3.5 Hz, 1 H, H-4e), 3.84, 3.99 (2
× s, 6 H, OCH3), 4.03 (m, 1 H, H-3a), 5.09 (q, J = 6.6 Hz, 1 H,
H-1), 6.10 (s, 1 H, H-8), 13.40 (s, 1 H, D2O exchangeable, 10-OH).
References
(1) Hanumaiah, T.; Marshall, D. S.; Rao, B. K.; Rao, C. P.; Rao,
G. S. R.; Rao, J. U. M.; Rao, K. V. J.; Thomson, R. H.
Phytochemistry 1985, 24, 2373.
(2) Hanumaiah, T.; Rao, G. S. R.; Rao, C. P.; Rao, K. V. J.;
Cowe, H. J.; Cox, P. J.; Howie, R. A.; Marshall, D. S.;
Thomson, R. H. Tetrahedron 1985, 41, 635.
(3) Jammula, S. R.; Pepalla, S. B.; Telikepalli, H.; Rao, K. V. J.;
Thomson, R. H. Phytochemistry 1991, 30, 3741.
(4) Ali, S.; Read, R. W.; Sotheeswaran, S. Phytochemistry 1994,
35, 1029.
HRMS: m/z [M+] calcd for C17H18O6: 318.1103; found: 318.1109.
Rac-(1R,3S)-3,4-Dihydro-6,7,9-trimethoxy-1,3-dimethyl-1H-
naphtho[2,3-c]pyran-5,10-dione (5) (Ventiloquinone E) and
(1R,3S)-3,4-Dihydro-5,7-dimethoxy-10-methoxymethyleneoxy-
1,3-dimethyl-1H-naphtho[2,3-c] pyran-6,9-dione (29); General
Procedure
To a solution of pyran 25 (17 mg; 0.043 mmol) in CH3CN (2 mL)
and water (0.5 mL) was added dropwise a solution of cerium(IV)
ammonium nitrate (52 mg, 0.095 mmol) in water (1 mL) at 25 °C
and stirring was maintained for 15 min. Similar workup as de-
scribed earlier afforded ventiloquinone E 5 as the front band as a
yellow solid recrystallized from hexane. All spectral data are con-
sistent with those published.1,6 Yield: 8.5 mg (59%); yellow flakes;
mp 130–132 °C (lit.6 mp 129–130 °C, lit.8 mp 127–128 °C).
(5) Blouin, M.; Béland, M.-C.; Brassard, P. J. Org. Chem. 1990,
55, 1466.
(6) De Koning, C. B.; Giles, R. G. F.; Green, I. R. J. Chem. Soc.,
Perkin Trans. 1 1991, 2743.
(7) Cameron, D. W.; Crosby, I. T.; Feutrill, G. I. Aust. J. Chem.
1992, 45, 2025.
(8) Bergeron, D.; Brassard, P. Heterocycles 1992, 34, 1835.
(9) Cameron, D. W.; Crosby, I. T.; Feutrill, G. I.; Pietersz, G. A.
Aust. J. Chem. 1992, 45, 2003.
(10) Uno, H. J. Org. Chem. 1986, 51, 350.
(11) Naruta, Y.; Uno, H.; Maruyama, K. J. Chem. Soc., Chem.
Commun. 1981, 1277.
(12) Giles, R. G. F.; Green, I. R.; Hugo, V. I.; Mitchell, P. R. K.;
Yorke, S. C. J. Chem. Soc., Perkin Trans. 1 1983, 2309.
(13) Green, I. R.; Hugo, V. I.; Oosthuizen, F. J.; van Eeden, N.;
Giles, R. G. F. S. Afr. J. Chem. 1995, 48, 15.
(14) Corey, E. J.; Gras, J.-L.; Ulrich, P. Tetrahedron Lett. 1976,
809.
The slower moving band afforded the MOM-quinone 29 as a yellow
solid recrystallized from hexane. Yield: 6.0 mg (39%); yellow crys-
tals; mp 134–135 °C.
IR (NaBr): 1653 cm–1.
1H NMR (200 MHz): d = 1.38 (d, JC3–methyl,H–3a = 6.2 Hz, 3 H,
C3-CH3), 1.60 (d, JC3–CH3,H–1 = 6.2 Hz, 3 H, C1–CH3), 2.42
(ddd, JH-4a,H-4e = 17.2 Hz, JH-4a,H-3a = 10.2 Hz, JH-4a,H-1 = 2.2 Hz, 1 H,
H-4a), 2.92 (ddd, JH-4e,H-4a = 17.2 Hz, JH-4e,H-3a = 3.6 Hz, JH4e,H-1 = 1.8
Hz, 1 H, H-4e), 3.56 (s, 3 H, CH2OCH3), 3.58 (m, 1 H, H-3a), 3.85,
3.97 (2 × s, 6 H, OCH3), 4.77 (d, J = 6.2 Hz, 1 H, OCH2OCH3), 5.04
(d, J = 6.2 Hz, 1 H, OCH2OCH3), 5.07 (qdd, JH–1,Cl–CH3 = 6.2 Hz,
JH-1,H-4a = 2.2 Hz, JH1,H-4e = 1.8 Hz, 1 H, H-1), 5.94 (s, 1 H, H-8).
(15) Kluge, A. F.; Untch, K. G.; Fried, J. H. J. Am. Chem. Soc.
1972, 94, 7827.
Synthesis 2004, No. 10, 1601–1608 © Thieme Stuttgart · New York