Synthesis of cordiaquinone J and K via B-alkyl Suzuki-Miyaura coupling as a key step and determination of the absolute configuration of natural products

Article abstract of DOI:10.1016/j.tet.2005.06.115

A versatile methodology for the synthesis of various terpenoids via B-alkyl Suzuki-Miyaura coupling as a key step is established. Synthesis of cordiaquinone J and K, new antifungal and larvicidal meroterpenoids, was achieved by using this methodology. The

Full text of DOI:10.1016/j.tet.2005.06.115

Tetrahedron 61 (2005) 9164–9172
Synthesis of cordiaquinone J and K via B-alkyl Suzuki–Miyaura
coupling as a key step and determination of the absolute
configuration of natural products
Arata Yajima, Fumihiro Saitou, Mayu Sekimoto, Shoichiro Maetoko, Tomoo Nukada and
*
Goro Yabuta
Department of Fermentation Science, Faculty of Applied Biological Science, Tokyo University of Agriculture, Sakuragaoka 1-1-1,
Setagaya-ku, Tokyo 156-8502, Japan
Received 31 May 2005; accepted 27 June 2005
Available online 28 July 2005
Abstract—A versatile methodology for the synthesis of various terpenoids via B-alkyl Suzuki–Miyaura coupling as a key step is established.
Synthesis of cordiaquinone J and K, new antifungal and larvicidal meroterpenoids, was achieved by using this methodology. The absolute
configurations of cordiaquinone J and K were confirmed by the synthesis.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
(Fig. 1).4 These compounds exhibit antifungal activities
against phytopathogenic fungus such as Cladosporium
cucumerinum and larvicidal activity against the larvae of
the yellow fever-transmitting mosquito Aedes aegypti. The
structures of cordiaquinone J and K were established on the
basis of HRMS, UV and 1D and 2D NMR spectra. In
connection with our synthetic studies of biologically active
natural terpenoids,5 we became interested in clarifying the
absolute configuration of cordiaquinones. The synthesis and
absolute configuration of cordiaquinone B were reported by
Cordiaquinones are antifungal and larvicidal meroterpe-
noids isolated from Panamanian plants such as Cordia
linnaei. In 1990, Messana and co-workers reported the
isolation and structures of cordiaquinones A (1) and B (2)
(Fig. 1).1 After their identification of cordiaquinones from
the plant, several cordiaquinones have been isolated.2,3 In
2000, Hostettmann and co-workers reported the structures of
cordiaquinones J (3) and K (4) isolated from C. curassavica
Figure 1. Structures of cordiaquinones.
Keywords: Synthesis; B-Alkyl Suzuki–Miyaura coupling; Cordiaquinones; Absolute configuration.
*
Corresponding author. Tel.: 81 3 5477 2542; fax: 81 3 5477 2622; e-mail: yabta@nodai.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.115

A. Yajima et al. / Tetrahedron 61 (2005) 9164–9172
9165
Asaoka and his co-workers.6 In previous communications,
we reported the synthesis of (R)-(C)-cordiaquinone K
employing one-pot B-alkyl Suzuki–Miyaura coupling as a
key step and the determination of the absolute configuration
of the natural product.7 Although the absolute configuration
of cordiaquinone K was determined to be S as shown in
Figure 1, the absolute configuration of cordiaquinone J
remained unknown. In recent structural studies of natural
products, NOE studies are a powerful tool, especially for
relative stereochemistry determination. However, Hostett-
mann provided no clear information on the relative
stereochemistry of cordiaquinone J, including NOE exper-
iment.4 To clarify the stereochemistry, we decided to
synthesize cordiaquinone J. This paper describes details of
the synthesis of (R)-(C)-cordiaquinone K, (11R,13S,16R)-
and (11S,13R,16S)-cordiaquinone J employing one-pot
B-alkyl Suzuki–Miyaura coupling8 as a key step. This
paper also describes the determination of the relative and
absolute configuration of the natural products.
Figure 2. Structures of natural products with related structure of
cordiaquinones.
diketone. Naphtoquinone derivative C would be synthesized
from known 6-bromonaphtoquinone.13
As our target, we first chose (G)-13-deoxocordiaquinone K
(5), since there was an urgent need to establish the
appropriate conditions of the coupling reaction. Scheme 2
summarizes our synthesis of (G)-13-deoxocordiaquinone K
(5). 6-Bromonaphtoquinone13 (6) and (G)-g-cyclohomo-
geranyl iodide5a,14 (8) were selected as the starting
materials. 6-Bromonaphtoquinone (6) was first hydrogen-
ated with PtO2 followed by methylation of the resulting
hydroxyl groups to give 7. (G)-g-Cyclohomogeranyl iodide
(8) was derived from the corresponding alcohol.15 To
connect the g-cyclohomogeranyl unit (8) and the naphto-
quinone derivative (7), we examined one-pot B-alkyl
Suzuki–Miyaura coupling reaction. As a preliminary
experiment for the coupling of 8 with 7, the conditions
reported by Marshall and Johns16 {PdCl2(dppf) as a
catalyst} were examined to give the desired product (9) in
only 10% yield based on 8. Then we examined various
conditions. Table 1 summarizes reaction conditions and
yields of 9. Although PdCl2(dppf) was not an effective
catalyst (entries 1–3), Pd(PPh3)4 was superior in yield
(entry 4). Moreover, by heating the reaction mixture to
2. Results and discussion
Our synthetic plans for the synthesis of cordiaquinone J and
K are shown in Scheme 1. Appropriate transformations of
the oxygen functionality at C-13 led to hydroxyolefines A
and B, respectively. Disconnection between C-6 and C-9
gave g-cyclohomogeranyl units D and E, respectively, and
naphtoquinone derivative C. We planned to apply B-alkyl
Suzuki–Miyaura coupling reaction to connect these units.
This methodology would be useful for not only the synthesis
of cordiaquinones but also various terpenoids such as
ambrein,9 luffarin W,10 penlanpallescensin.11 (Fig. 2),
because these compounds have a common structural
feature with cordiaquinones, namely, a g-cyclohomo-
geranyl unit connecting with an aryl or a vinyl unit.
Optically active g-cyclohomogeranyl units could be derived
12
from known hydroxyketone F, obtained by yeast-
mediated asymmetric reduction of the corresponding
Scheme 1. Retrosynthetic analyses of cordiaquinone J and K.

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A. Yajima et al. / Tetrahedron 61 (2005) 9164–9172
80 8C, 50% yield of 9 was obtained (entry 6). This indicates
that the yield based on 7 was quantitative. Increasing the
stoichiometry of 7, however, showed only a slight
improvement (55%, entry 7). Other palladium catalysts
such as Pd2(dba)3, PdCl2(dppe), PdCl2(dppp), Pd(PEt3)2Cl2,
Pd(OAc)2C2Cy3P and allylpalladium chloride dimer or
other bases such as Ba(OH)2, TlOEt and Cs2CO3 were also
examined, but we found Pd(PPh3)4 with K3PO4 is the best
choice for the coupling reaction. With the desired product
(9) in hand (Scheme 2), the aromatic ring of 9 was oxidized
with ceric ammonium nitrate (CAN) to afford (G)-13-
deoxocordiaquinone K (5). The spectroscopic data of
synthetic 5 are in perfect accordance with the structure of 5.
By using this established methodology as described above,
the synthesis of optically active cordiaquinone K was
investigated (Scheme 3). The known alcohol (11)17 derived
from the known hydroxyketone (10)12 was selected as the
starting material. Alcohol 11 was converted to the correspond-
ing iodide 12(ZE)intwosteps(68%). Theresultingiodide12
was coupled with 7 by using the optimized conditions
described above to give coupled product 13 (50%). In the 1H
NMR spectrum of the crude product, we observed the signals
of side products with the terminal ethyl group. The yield of
the product was estimated to be 20–35%. Although the
Scheme 2. Synthesis of (G)-13-deoxocordiaquinone K. Reagents,
conditions and yields. (a) (1) H2, PtO2, EtOAc; (2) NaH, MeI, DMF
(89%, two steps); (b) (i) 2 equiv t-BuLi, ether, K78 8C; (ii) 2.5 equiv
B-MeO-9-BBN, hexane, THF; (iii) 2.5 equiv base; (iv) 5 mol% Pd catalyst,
7, DMF (see Table 1); (c) CAN, CH3CN, 0 8C (73%).
Table 1. Reaction conditions and yields of 9
Entry
Pd catalysta
Equiv of 7
Temp. (8C)
Time (h)
Yield based on 8
(%)
Yield based on 7
(%)
1
2
3
4
5
6
7
8
PdCl2(dppf)
0.5
0.5
0.5
0.5
0.5
0.5
1
rt
rt
80
rt
rt
80
80
80
16
120
16
16
72
16
16
16
10
13
12
24
22
50
55
50
20
26
24
48
Pd(PPh3)4
44
Quant.
55
25
2
a Five mole percent of catalysts with 2.5 equiv of K3PO4 were used.
Scheme 3. Synthesis of (C)-cordiaquinone K. Reagents, conditions and yields. (a) TsCl, Py.; (b) NaI, acetone, reflux (68%, two steps); (c) (i) 2 equiv t-BuLi,
ether, K78 8C; (ii) 2.5 equiv B-MeO-9-BBN, hexane, THF; (iii) 3 M K3PO4; (iv) 5 mol% Pd(PPh3)4, 7, DMF, 80 8C, 16 h (50%); (d) TBAF, THF, 60 8C
(90%); (e) PCC, MS4A, CH2Cl2 (63%); (f) CAN, CH3CN, 0 8C (quant.).

A. Yajima et al. / Tetrahedron 61 (2005) 9164–9172
9167
Scheme 4. Synthesis of (11R,13S,16R)-cordiaquinone J. Reagents, conditions and yields. (a) TsCl, Py.; (b) NaI, acetone, reflux (77%, two steps); (c) (i) 2 equiv
t-BuLi, ether, K78 8C; (ii) 2.5 equiv B-MeO-9-BBN, hexane, THF; (iii) 3 M K3PO4; (iv) 5 mol% Pd(PPh3)4, 7, DMF, 80 8C, 16 h (43%); (d) TBAF, THF,
60 8C (93%); (e) NIS, CH3CN, (75%); (f) n-Bu3SnH, AIBN, benzene, reflux (84%); (g) CAN, CH3CN, 0 8C (72%).
isolation of this compound was unsuccessful due to other
side products, this compound was presumed to be
compound 14, which might be produced by protonation of
lithiated 12. This result indicates that optimization of the
lithium–boron exchange procedure could improve the yield
of this step.18 The obtained coupling product 13 was treated
with TBAF at 60 8C to give alcohol 15 (ZB) (90%).
Finally, the resulting hydroxyl group was oxidized with
PCC (63%) and subsequent oxidation of the aromatic ring
with CAN at 0 8C gave (R)-(C)-cordiaquinone K (4) as a
pale yellow gum in quantitative yield. The overall yield of
(C)-4 was 19% in six steps from known alcohol (11). The
1H and 13C NMR and MS spectra are identical with those of
reported data4. Synthetic cordiaquinone K (4) shows [a]2D6
C45 (c 0.35, acetone), while natural cordiaquinone K
shows [a]D K46.4 (c 0.35, acetone)4. This means that our
synthetic cordiaquinone K is the antipode of the natural
product. The absolute configuration of natural cordiaqui-
none K is, therefore, determined to be S.
construction of an oxabicyclo ring system. Namely,
intermolecular iodo-etherification by treatment with
N-iodosuccinimide (NIS) gave 17 (75%), then radical
reduction of 17 by tri-n-butyltinhydride afforded 18 with
the desired oxabicyclo ring system (84%). Finally,
oxidation of the aromatic ring with CAN gave
(11R,13S,16R)-cordiaquinone J (3) in 72% yield. The
overall yield of (11R,13S,16R)-3 was 14% in seven steps
1
from known alcohol 110. The H NMR and IR spectra of
synthetic (11R,13S,16R)-cordiaquinone J (3) are in good
accordance with those of the natural product. But the 13C
NMR spectrum of synthetic 3 is not identical with those of
the natural product. Table 2 summarizes selected 13C NMR
chemical shift values of synthetic and natural cordiaquinone
J. Remarkable differences are observed at C-10, C-12 and
C-18, which are located around the oxabicyclo ring system.
So, we concluded that our synthetic 3 is a diastereomer of
the natural cordiaquinone J.
To prove this hypothesis, we decided to synthesize a
diastereomer of 3. Since we have already synthesized
compound 15 as an intermediate of (R)-(C)-cordiaquinone
K (Scheme 1), we chose 15 as starting material for the
In order to determine the relative and absolute configur-
ation, we set out to synthesize cordiaquinone J (Scheme 4).
We first choose (11R,13S,16R)-3 as a candidate of the
natural product. This compound possesses a cis naphtoqui-
none-substituted side chain at C-11 and a methyl group at
C-16 as originally indicated by Hostettmann (Fig. 1).4 The
absolute configuration at C-11 of 3 was presumed to be the
same as that of natural (S)-(K)-cordiaquinone K, because
cordiaquinones could be biosynthesized from a common
intermediate. For the synthesis of 3, we selected known
alcohol 110, diastereomer of the intermediate of our
synthesis of cordiaquinone K (4), as a starting material.
Alcohol 110 was converted to the corresponding iodide 120
(ZD) as described above (77%, in two steps). The iodide
120 was coupled with 7 using one-pot B-alkyl Suzuki–
Miyaura coupling strategy to give 130 (43%). Removal of
the TBS group to give 150 (93%) was followed by
Table 2. 100 MHz 13C NMR chemical shifts of synthetic (11R,13S,16R)-
and natural cordiaquinone J
Carbon number
Synthetic (ppm)
Natural (ppm)
9
29.6
27.3
57.6
42.5
86.5
29.5
36.5
88.2
20.0
32.8
21.8
36.8
30.3
56.2
46.0
86.4
26.3
39.7
86.9
19.2
26.2
23.6
10
11
12
13
14
15
16
17
18
19

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KBr plates for solids on a Shimadzu IR-470 spectrometer.
1H NMR spectra were taken with Jeol JNM-A400
(400 MHz) spectrometer using CDCl3 at dZ7.24 or
acetone-d6 at dZ2.04 as an internal standard. 13C NMR
spectra were taken with Jeol JNM-A400 (100 MHz)
spectrometer using CDCl3 at dZ77.0 or acetone-d6 at dZ
29.8 as an internal standard. HRMS spectra were measured
on a Jeol-MS700 spectrometer and Jeol-HX110/110A
spectrometer. Elemental compositions were analyzed on a
J-Science MICROCORDER JM10. Column chromato-
graphy was performed with silica gel Wakogel-C200.
4.1.1. 6-Bromo-1,4-dimethoxynaphthalene (7). To a
solution of 6 (700 mg, 2.95 mmol) in EtOAc (10 ml),
PtO2 (15 mg) was added. The stirred suspension was
degassed by evacuating, and filled with H2. After stirring
for 3 h, the suspension was filtered through Celite pad and
concentrated in vacuo. The residue was dissolved in DMF
(10 ml), and added MeI (460 ml, 11.8 mmol) and 60% NaH
in oil (443 mg, ca. 12 mmol) to the solution. After stirring
overnight, the mixture was poured into water and extracted
with EtOAc three times. The combined organic extracts
were washed with water and dried with MgSO4. After
concentration in vacuo, the residue was purified by column
chromatography (hexane/EtOAcZ100:1) to afford 700 mg
(89%) of 7 as a colorless amorphous solid. IR (KBr) nmax
(cmK1)Z3000 (w, H–C]C), 2950 (m, C–H), 1625 (m),
1590 (s), 1460 (s), 1420 (s), 1365 (s), 1330 (m), 1150 (m),
1100 (s), 1080 (s), 960 (m), 860 (m), 830 (m), 800 (s), 760
(m), 720 (m), 440 (s); 1H NMR (400 MHz, CDCl3): dZ3.92
(s, 6H, 1, 4-OCH3), 6.66 (d, JZ8.3 Hz, 1H, 2-H), 6.69 (d,
JZ8.3 Hz, 1H, 3-H), 7.54 (dd, JZ2.4, 8.8 Hz, 1H, 7-H),
8.05 (d, JZ8.8 Hz, 1H, 8-H), 8.35 (d, JZ2.4 Hz, 1H, 5-H).
Found C, 53.95%; H, 4.15%. Calcd for C12H11BrO2: C,
53.96%; H, 4.15%.
Scheme 5. Synthesis of (11S,13S,16R)-cordiaquinone J. Reagents,
conditions and yields. (a) NIS, CH3CN, 0 8C (74%); (b) n-Bu3SnH,
AIBN, benzene, reflux (quant.); (c) CAN, CH3CN (70%).
synthesis of (11S,13S,16R)-cordiaquinone J (30). Scheme 5
summarizes the synthesis of (11S,13S,16R)-cordiaquinone J
(30). In the same manner of the synthesis of (11R,13S,16R)-
isomer, 15 was converted to 30 in three steps. All spectral
1
13
data such as IR and H and C NMR of synthetic 30 are
identical with those of the natural product. Synthetic 30 shows
[a]2D1 C34 (c 0.21, acetone), while the natural cordiaquinone J
shows [a]D K37 (c 0.2, acetone)4. This means that our
synthetic cordiaquinone J is the antipode of the natural
product. The absoluteconfigurationof natural cordiaquinone J
is, therefore, determined to be 11R,13R,16S.
4.1.2. B-Alkyl Suzuki–Miyaura coupling reaction of
iodide (8, 12 and 120) and bromonaphthoquinone
derivative (7). General procedure. To a stirred and cooled
(K78 8C) solution of iodide in dry ether was added
dropwise tert-BuLi in pentane (2.5 equiv) under Ar. After
stirring for 30 min, B-methoxy-9-borabicyclo[3.3.1]nonane
in hexane (1.5 equiv) was added dropwise, followed by
addition of dry THF. After stirring for 10 min at the same
temperature, the resulting solution was allowed to warm to
rt for 75 min To the mixture, aqueous 3 M K3PO4 solution
(2.5 equiv) was added, followed by a solution of 7 (1 equiv)
in DMF. After addition of Pd(PPh3)4 (0.05 equiv), the
mixture was stirred at 80 8C for 16 h. After cooling to rt, the
mixture was diluted with ether. The organic layer was
washed with water and brine, and the combined aqueous
layers were extracted with ether three times. The combined
organic layers were dried with Na2SO4. After concentration
in vacuo, the residue was purified by column chromato-
graphy (hexane) to afford 9, 12 or 120 as a colorless oil or
amorphous solid.
3. Conclusion
A versatile methodology for terpenoid synthesis was estab-
lished by using one-pot B-alkyl Suzuki–Miyaura coupling
reaction. With this methodology, synthesis of (R)-cordiaqui-
none K was achieved. The absolute configuration of the natural
cordiaquinone K (4) was determined to be S by a comparison of
optical rotations of the synthetic and natural products. We also
synthesized (11R,13S,16R)- and (11S,13S,16R)-cordiaquinone
J (3 and 30). The absolute stereochemistry of natural
cordiaquinone J was determined to be 11R,13R,16S. Both the
natural cordiaquinone K and J possess the same stereochemical
feature at C-11. This suggests that cordiaquinones would be
biosynthesized from a common intermediate.
4.1.3. (G)-6-[20-(600,600-Dimethyl-200-methylenecyclo-
hexyl)-ethyl]-1,4-dimethoxynaphthalene (9). Yield:
55%; amorphous solid; IR (KBr) nmax (cmK1)Z3080 (m,
H–C]C), 2920 (s, C–H), 1645 (m), 1635 (m), 1610 (s, Ar–
O–CH3), 1460 (s), 1390 (s), 1345 (m), 1270 (s), 1165 (m),
1090 (m), 1000 (m), 970 (m), 895 (s), 825 (s), 795 (s), 715
4. Experimental
4.1. General
Optical rotations were measured on a Jasco DIP-140. IR
spectra were measured for samples as films for oils or as

A. Yajima et al. / Tetrahedron 61 (2005) 9164–9172
9169
(m); 1H NMR (400 MHz, CDCl3): dZ0.81 (s, 3H, 600-CH3),
0.89 (s, 3H, 600-CH3), 1.71–1.99 (m, 7H, 20, 400, 500-CH2),
2.05 (m, 1H, 300-CHH), 2.06 (m, 1H, 300-CHH), 2.50 (m, 1H,
10-CHH), 2.75 (m, 1H, 10-CHH), 3.93, 3.94 (2!s, 6H, 2!
CH3–O), 4.64 (br s, 1H, H–C]C), 4.83 (br s, 1H, H–C]C),
6.60, 6.66 (d, JZ8.6 Hz, 2H, 2,3-H), 7.29 (dd, JZ2.0,
8.8 Hz, 1H, 7-H), 7.94 (d, JZ2.9 Hz, 1H, 5-H), 8.07 (d, JZ
8.8 Hz, 1H, 8-H); 13C NMR (100 MHz, CDCl3): dZ23.7,
26.4, 28.3, 28.7, 32.4, 34.88, 34.93, 36.1, 53.9, 55.70, 55.70,
102.3, 103.2, 109.3, 120.2, 121.7, 124.7, 126.4, 127.3,
141.0, 149.19, 149.23, 149.6; HRFABMS: Calcd for
C23H30O2 [M]C: 338.2246, found: 338.2243.
C]O), 1600 (s), 1450 (m), 1390 (w), 1370 (m), 1305 (s),
1140 (w), 1045 (m), 890 (m), 835 (m), 735 (m); H NMR
1
(400 MHz, CDCl3): dZ0.82 (s, 3H, 19-CH3), 0.89 (s, 3H,
18-CH3), 1.22–1.80 (m, 7H, 10,13,14-CH2, 11-H), 2.05 (m,
2H, 15-CH2), 2.50 (m, 1H, 9-CHH), 2.14 (m, 1H, 9-CHH),
4.60 (br s, 1H, H–C]C), 4.84 (br s, 1H, H–C]C), 6.93 (s,
2H, 2,3-H), 7.52 (dd, JZ1.5, 8.3 Hz, 1H, 7-H), 7.86 (d, JZ
1.5 Hz, 1H, 5-H), 7.97 (d, JZ8.3 Hz, 1H, 8-H); 13C NMR
(100 MHz, CDCl3): dZ23.6, 26.5, 28.1, 28.3, 32.2, 34.8,
34.9, 35.9, 53.8, 109.7, 126.1, 126.7, 129.9, 131.2, 134.1,
138.5, 138.8, 148.7, 150.5, 184.9, 185.5; HRFABMS: Calcd
for C21H24O2 [M]C: 308.1777, found: 308.1810.
4.1.4. (100R,300S)-6-[20-(300-tert-Butyldimethylsilyloxy-200,
200-dimethyl-600-methlenecyclohexyl)-ethyl]-1,4-
4.2. Synthesis of (R)-(D)-cordiaquinone K (4)
dimethoxynaphthalene (13). Yield: 50%; oil; [a]2D5 C3.98
(cZ0.98, CHCl3); IR (film) nmax (cmK1)Z3080 (w, H–
C]C), 2950 (s, C–H), 2850 (s, C–H), 1645 (m), 1635 (s),
1605 (s), 1460 (s), 1385 (s), 1270 (s), 1240 (s), 1210 (w),
1190 (w), 1140 (w), 1030 (w), 1000 (m), 985 (s), 845 (s),
4.2.1. (10R,30S)-2-(30-tert-Butyldimethylsilyloxy-20,20-
dimethyl-60-methylenecyclohexyl)iodoethane (12). To a
stirred and ice-cooled solution of 11 (990 mg, 3.32 mmol) in
dry pyridine (10 ml), p-TsCl (769 mg, 4.03 mmol) was
added in one portion. The mixture was stirred overnight at
4 8C, then poured into water. The aqueous layer was
extracted with ether three times. The combined extracts
were washed with satd CuSO4 aq, water and brine, and dried
with MgSO4. After concentration in vacuo, the residue was
dissolved in dry acetone (15 ml). To the solution, NaI
(970 mg, 6.47 mmol) was added, and the mixture was
refluxed for 4 h. After being cooled to rt, the mixture was
poured into water, and extracted with pentane three times.
The combined extracts were washed with satd NaHCO3 aq,
satd Na2S2O3 aq, water and brine, and dried with Na2SO4.
After concentration in vacuo, the residue was purified by
column chromatography (pentane) to give 923 mg of 12
(68%) as a colorless oil; IR (film) nmax (cmK1)Z2950 (s,
C–H), 2850 (s, C–H), 1645 (m), 1470 (s), 1385 (m), 1360
(m), 1250 (s), 1080 (s), 1000 (m), 990 (m), 935 (s), 875 (s),
670 (w); 1H NMR (400 MHz, CDCl3): dZ0.01 [s, 6H,
Si(CH3)2], 0.82 (s, 3H, 20-CH3), 0.87 [s, 9H, SiC(CH3)3],
0.89 (s, 3H, 20-CH3), 1.46 (m, 1H, 40-CHH), 1.72 (m, 1H,
400-CHH), 1.82 (dd, JZ2.4, 11.7 Hz, 1H, 10-H), 1.95 (m, 2H,
5 -CH2), 2.18 (m, 1H, 2-CHH), 2.31 (m, 1H, 2-CHH), 2.91
(ddd, JZ7.3, 9.3, 16.6 Hz, 1H, 1-CHHI), 3.26 (ddd, JZ3.9,
8.8, 16.6 Hz, 1H, 1-CHHI), 3.50 (dd, JZ3.9, 5.9 Hz, 1H,
30-H), 4.62 (br s, 1H, H–C]C), 4.81 (br s, 1H, H–C]C).
This was employed in the next step without further
purification.
1
795 (m), 770 (s), 720 (m), 670 (w); H NMR (400 MHz,
CDCl3): dZ0.00 (s, 3H, SiCH3), 0.01 (s, 3H, Si–CH3), 0.76
(s, 3H, 200-CH3), 0.87 [s, 9H, SiC(CH3)3], 0.89 (s, 3H,
200-CH3), 1.48–2.08 (m, 6H, 20, 500-CH2, 100-H, 400-CHH),
2.39 (m, 1H, 400-CHH), 2.51 (m, 1H, 10-CHH), 2.87 (m, 1H,
10-CHH), 3.41 (dd, JZ3.7, 7.6 Hz, 1H, 300-H), 3.94 (s, 6H,
1, 4-CH3O), 4.69 (br s, 1H, H–C]C), 4.89 (br s, 1H,
H–C]C), 6.61 (d, JZ8.3 Hz, 1H, 2-H), 6.68 (d, JZ8.3 Hz,
1H, 3-H), 7.33 (dd, JZ1.3, 8.8 Hz, 1H, 7-H), 7.95 (d, JZ
1.3 Hz, 1H, 5-H), 8.09 (d, JZ8.8 Hz, 1H, 8-H); 13C NMR
(100 MHz, CDCl3): dZK5.0, K4.2, 18.0, 18.8, 25.8, 26.9,
28.1, 29.7, 30.8, 32.2, 37.1, 40.5, 52.1, 55.6, 102.2, 103.1,
108.7, 120.2, 121.6, 124.6, 126.4, 127.3, 140.9, 148.1,
149.2, 149.5.
4.1.5. (100S,300S)-6-[20-(300-tert-Butyldimethylsilyloxy-200,
200-dimethyl-600-methlenecyclohexyl)-ethyl]-1,4-
dimethoxynaphthalene (130). Yield: 40%; oil; [a]2D1
C14.48 (c 0.202, CHCl3); IR (film) nmax (cmK1)Z3080
(w, C]C–H), 2950 (s, C–H), 2850 (s, C–H), 1645 (m,
C]C), 1600 (s, C]C); 1H NMR (400 MHz, CDCl3):
dZK0.02 [s, 6H, Si(CH3)2], 0.84 [s, 9H, SiC(CH3)3], 0.85
[s, 6H, 200-(CH3)2], 1.48–2.08 (m, 6H, 20, 500-CH2, 100-H,
400-CHH), 2.39 (m, 1H, 400-CHH), 2.51 (m, 1H, 10-CHH),
2.87 (m, 1H, 10-CHH), 3.56 (dd, JZ4.2, 9.0 Hz, 1H, 300-H),
3.93 (s, 3H, CH3O), 3.95 (s, 3H, CH3O), 4.66 (br s, 1H,
H–C]C), 4.86 (br s, 1H, H–C]C), 6.62 (d, JZ8.3 Hz, 1H,
2-H), 6.66 (d, JZ8.3 Hz, 1H, 3-H), 7.33 (dd, JZ1.3, 8.8 Hz,
1H, 7-H), 7.95 (d, JZ1.3 Hz, 1H, 5-H), 8.11 (d, JZ8.8 Hz,
1H, 8-H). Found C, 74.47%; H, 9.21%. Calcd for
C29H44SiO3: C, 74.31%; H, 9.46%.
4.2.2. (100R,300S)-6-[20-(300-Hydroxy-200,200-dimethyl-600-
methlenecyclohexyl)-ethyl]-1,4-dimethoxynaphthalene.
(15). A solution of 6 (235 mg, 503 mmol) and TBAF (1 ml,
1 mmol, 1.0 M in THF) in dry THF (2 ml) was stirred at
50–60 8C for 6 h under Ar. After being cooled to rt, water
was added, and the mixture was extracted with ether three
times. The organic extracts were washed with water and
brine, then dried with MgSO4. After concentration in vacuo,
the residue was purified by column chromatography
(AcOEt/hexaneZ1:10) to furnish 70 (160 mg, 90%) as a
colorless oil; [a]D21 K218 (c 0.56, CHCl3); IR (film) nmax
(cmK1)Z3450 (br m, O–H), 3080 (w H–C]C), 2950 (s,
C–H), 2850 (s, C–H), 1645 (m), 1610 (s) 1460 (s), 1370 (s),
1275 (s), 1240 (s), 1210 (m), 1195 (m), 1160 (w), 1095 (s),
1020 (m), 1005 (m), 990 (m), 930 (m), 900 (s), 820 (m); 1H
NMR (400 MHz, CDCl3): dZ0.71 (s, 3H, 200-CH3), 1.00 (s,
3H, 200-CH3), 1.53 (m, 1H, 400-CHH), 1.75 (br d, JZ11.7 Hz,
4.1.6. (G)-13-Deoxocordiaquinone K (5). To a stirred
solution of 9 (100 mg, 300 mmol) in MeCN/waterZ4:1
(15 ml) at 0 8C was added ceric ammonium nitrate (329 mg,
600 mmol) in several portions and the mixture was stirred
for 30 min Then, the mixture was poured into water and
extracted with ether three times. The extract was washed
with water and brine, then dried with MgSO4. After
concentration in vacuo, the residue was purified by column
chromatography (AcOEt/hexaneZ1:50) to afford 5 (65 mg,
73%) as a pale yellow gum; IR (film) nmax (cmK1)Z3070
(w, H–C]C), 2930 (s, C–H), 2860 (m, C–H), 1670 (s,

9170
A. Yajima et al. / Tetrahedron 61 (2005) 9164–9172
1H, 100-H), 1.81–1.95 (m, 3H, 20-CH2, 400-CHH), 2.03 (ddd,
JZ4.9, 11.7, 1030 .2 Hz, 1H, 500-CHH), 2.36 (ddd, JZ4.9, 4.9
13.2 Hz, 1H, 5 -CHH), 2.56 (ddd, JZ7.3, 9.3, 14.20Hz, 1H,
10-CHH), 2.93 (ddd, JZ4.9, 9.080 , 14.2 Hz, 1H, 1 -CHH),
3.39 (dd, JZ4.4, 9.8 Hz, 1H, 3 -H), 3.94 (s, 3H, CH3O),
3.95 (s, 3H, CH3O), 4.77 (br s, 1H, H–C]C), 4.98 (br s, 1H,
H–C]C), 6.62 (d, JZ8.3 Hz, 1H, 2-H), 6.66 (d, JZ8.3 Hz,
1H, 3-H), 7.34 (dd, JZ1.7, 8.3 Hz, 1H, 7-H), 7.96 (d, JZ
1.7 Hz, 1H, 5-H), 8.11 (d, JZ8.3 Hz, 1H, 8-H); 13C NMR
(100 MHz, CDCl3): dZ15.6, 25.9, 27.5, 32.1, 32.9, 35.2,
40.5, 51.1, 55.7, 102.3, 103.2, 108.7, 120.2, 121.8, 124.7,
126.4, 127.2, 140.6, 147.1, 149.1, 149.5. Found: C, 77.96%;
H, 8.47%. Calcd for C23H30O3: C, 77.93%; H, 8.53%.
322.1581; 1H and 13C NMR spectra are identical with those
of reported natural product.
4.3. Synthesis of (11R,13S,16R)-cordiaquinone J (3)
4.3.1. (10S,30S)-2-(30-tert-Butyldimethylsilyloxy-20,20-
dimethyl-60-methylenecyclohexyl)-iodoethane0 (120). In
the same manner as described above for (10R,3 S)-isomer,
5.28 g (18.8 mmol) of 110 was converted to 120 to give
5.91 g (77%, two steps); IR (film) nmax (cmK1)Z3080 (w,
H–C]C), 2950 (s, C–H), 2850 (s, C–H), 1645 (m, C]C),
1600 (s, C]C), 1485 (s, Si–CH3), 1385 (s, Si–CH3), 1285
(s, Si–CH3), 1240 (s, C–I), 1100 (s, Si–O), 680 (w, C–I); 1H
NMR (400 MHz, CDCl3): dZ0.01 [s, 6H, Si(CH3)2], 0.82
(s, 3H, 20-CH3), 0.86 [s, 12H, 20-CH3, SiC(CH3)3], 1.45 (m,
1H, 40-C0HH), 1.63 (m, 1H, 40-CHH), 1.80–2.05 (m, 3H,
2-CH2, 5 -CHH), 2.08 (dd, JZ3.2, 11.5 Hz, 1H, 10-H), 2.19
(ddd, JZ5.4, 5.4, 13.7 Hz, 1H, 50-CHH), 2.92 (dd, JZ8.3,
17.6 Hz, 1H, 1-CHHI), 3.22 (ddd, JZ3.9, 8.8, 17.6 Hz, 1H,
1-CHHI), 3.49 (dd, JZ3.9, 8.8 Hz, 1H, 30-H), 4.63 (br s, 1H,
H–C]C), 4.82 (br s, 1H, H–C]C). This was employed in
the next step without further purification.
4.2.3. (R)-6-[20-(200,200-Dimethyl-600-methylen-300-oxocy-
clohexyl)ethyl]-1,4-dimethoxynaphthalene (16). To a
stirred solution of 15 (65 mg, 0.18 mmol) in dry CH2Cl2
(1.5 ml), powdered MS 4A (24 mg) and PCC (80 mg,
0.37 mmol) were added, respectively, at rt. After stirring for
30 min, the mixture was filtered through Celite pad, and the
filtrate was concentrated in vacuo. The residue was purified
by column chromatography (AcOEt/hexaneZ50:1) to give
16 (41 mg, 63%) as a colorless oil; [a]2D4 C55.08 (c 0.34,
CHCl3); IR (film) nmax (cmK1)Z3080 (w, H–C]C), 2950
(s, C–H), 2850 (s, C–H), 1710 (s, C]O), 1610 (s), 1460 (s),
4.3.2. (100S,300S)-6-[20-(300-hydroxy-200,200-dimethyl-600-
methlenecyclohexyl)-ethyl]-1,4-dimethoxynaphthalene
(150). In the same manner as described above for (10R,30S)-
isomer, 117 mg (244 mmol) of 130 was converted to 150
(83 mg, 93%) as a colorless oil; [a]2D1 K15.78 (c 0.328,
CHCl3); IR (film) nmax (cmK1)Z3450 (br m, O–H), 3080
(w, H–C]C), 2950 (s, C–H), 2850 (s, C–H), 1645 (m,
1
1370 (s), 1270 (s), 1100 (s), 900 (s), 800 (s), 720 (s); H
NMR (400 MHz, CDCl3): dZ0.97 (s, 3H, 200-CH3), 1.13 (s,
3H, 200-CH3), 1.51 (m, 1H, 20-CHH), 1.85 (m, 1H, 20-CHH),
2.16 (dd, JZ3.4, 8.3 Hz, 1H, 100-H), 2.27 (m, 1H, 400-CHH),
2.43–2.60 (m, 4H, 10,500-CH2), 2.73 (m, 1H, 400-CHH), 3.88,
3.89 (2!s, 6H, 2!CH3O), 4.86 (br s, 1H, H–C]C), 5.05
(br s, 1H, H–C]C), 6.57 (d, JZ8.8 Hz, 1H, 2-H), 6.62 (d,
JZ8.3 Hz, 1H, 3-H), 7.24 (dd, JZ1.5, 6.8 Hz, 1H, 7-H),
7.84 (d, JZ1.5 Hz, 1H, 5-H), 8.05 (d, JZ8.3 Hz, 1H, 8-H).
This was employed in the next step without further
purification.
1
C]C), 1610 (s, C]C); H NMR (400 MHz, CDCl3): dZ
0.88 (s, 3H, 200-CH3), 0.97 (s, 3H, 200-CH3), 1.45–1.91 (m,
4H, 20, 400-CH2), 2.00 (dd, JZ3.0, 12.2 Hz, 1H, 100-H), 2.25
(m, 2H, 500-CH2), 2.49 (ddd, JZ6.3, 10.7, 14.2 Hz, 1H,
10-CHH), 2.72 (ddd, JZ4.4, 10.7, 14.2 Hz, 1H, 10-CHH),
3.63 (dd, JZ4.4, 10.3 Hz, 1H, 300-H), 3.93 (s, 3H, CH3O),
3.94 (s, 3H, CH3O), 4.69 (br s, 1H, H–C]C), 4.88 (br s, 1H,
H–C]C), 6.62 (d, JZ8.3 Hz, 1H, 2-H), 6.66 (d, JZ8.3 Hz,
1H, 3-H), 7.31 (d, JZ8.3 Hz, 1H, 7-H), 7.94 (s, 1H, 5-H),
8.09 (d, JZ8.3 Hz, 1H, 8-H). Found: C, 78.00%, H, 8.48%.
Calcd for C23H30O3: C, 77.93%, H, 8.53%.
4.2.4. (R)-(D)-Cordiaquinone K (4). To a stirred solution
of 16 (37 mg, 106 mmol) in MeCN/waterZ4:1 (0.5 ml) at
0 8C was added ceric ammonium nitrate (126 mg,
229 mmol) in several portions and the mixture was stirred
for 2.5 h. Then, the mixture was poured into water and
extracted with ether three times. The extract was washed
with water and brine, then dried with MgSO4. After
concentration in vacuo, the residue was purified by column
chromatography (AcOEt/hexaneZ1:40) to afford 4 (36 mg,
quant.) as a pale yellow gum; [a]2D6 C44.9 (c 0.35, acetone),
lit.4: [a]D K46.48 (c 0.35, acetone); IR (film) nmax (cmK1)Z
3080 (w, H–C]C), 2950 (s, C–H), 2850 (s, C–H), 1710 (s,
C]O), 1670 (m), 1600 (s), 1420 (s), 1310 (m), 935 (m), 900
(m); 1H NMR (400 MHz, acetone-d6): dZ0.99 (s, 3H,
19-CH3), 1.18 (s, 3H, 18-CH3), 1.49 (m, 1H, 10-CHH), 1.94
(m, 1H, 10-CHH), 2.24 (m, 1H, 14-CHH), 2.34 (dd, JZ3.7,
12.0 Hz, 1H, 11-H), 2.55–2.98 (m, 5H, 9, 15-CH2, 14-CHH),
4.94 (br s, 1H, H–C]C), 5.13 (br s, 1H, H–C]C), 6.88 (s,
2H, 2, 3-H), 7.58 (dd, JZ1.8, 6.4 Hz, 1H, 7-H), 7.71 (d, JZ
1.8 Hz, 1H, 5-H), 7.82 (d, JZ7.8 Hz, 1H, 8-H); 13C NMR
(100 MHz, acetone-d6): dZ21.6 (C-19), 27.4 (C-18), 29.9
(C-10), 31.1 (C-15), 34.6 (C-9), 38.0 (C-14), 49.4 (C-12),
56.7 (C-11), 113.9 (C-17), 126.5 (C-5), 127.0 (C-8), 130.9
(C-8a), 132.9 (C-4a), 134.9 (C-7), 139.3 (C-3), 139.5 (C-2),
150.2 (C-6), 185.4 (C-4), 185.7 (C-1), 213.6 (C-13);
HREIMS: Calcd for C21H22O3 [M]C: 322.1569, found:
4.3.3. (1R,2S,4S)-2-[20-(500,800-Dimethoxynaphthalene-200-
yl)-ethyl]-1-iodomethyl-3,3,-dimethyl-7-oxabicy-
clo[2.2.1]heptane (17). A solution of 15 (253 mg,
0.72 mmol) and N-iodosuccinimide (290 mg, 1.28 mmol)
in dry MeCN (3 ml) was stirred at rt in the dark overnight.
The resulting mixture was poured into water and extracted
with ether. The extract was washed successively with
Na2S2O4 aq, water, satd NaHCO3 and brine, then dried with
MgSO4. After concentration in vacuo, the residue was
purified by column chromatography (AcOEt/hexaneZ1:40)
to afford 284 mg of 17 (83%) as a colorless oil; [a]D21
K36.28 (c 0.302, CHCl3); IR (film) ymax (cmK1)Z2950 (s,
C–H), 1635 (m), 1600 (s), 1465 (s), 1425 (m), 1365 (s),
1340 (w), 1270 (s), 1245 (s), 1215 (m), 1195 (s), 1160 (w),
1095 (s), 1000 (m), 980 (m), 965 (w), 950 (m), 820 (m), 795
1
(s), 715 (s); H NMR (400 MHz, CDCl3): dZ1.00 (s, 3H,
3-CH3), 1.15 (s, 3H, 3-CH3), 1.52 (m, 2H, 10-CH2), 1.68 (m,
4H, 6-CH2, 5-CHH, 2-CH), 1.95 (m, 1H, 5-CHH), 2.68 (m,
1H, 20-CHH), 2.82 (ddd, JZ4.0, 9.2, 9.2 Hz, 1H, 20-CHH),
3.48 (d, JZ10.7 Hz, 1H, CHH-I), 3.53 (d, JZ10.7 Hz, 1H,
CHH-I), 3.85 (d, JZ4.9 Hz, 1H, 4-H), 3.93, 3.95 (2!s, 3H,

A. Yajima et al. / Tetrahedron 61 (2005) 9164–9172
9171
2!CH3O), 6.63 (d, JZ8.3 Hz, 1H, 600-H), 6.68 (d, JZ
8.3 Hz0,0 1H, 700-H), 7.32 (d, JZ8.3 Hz, 1H, 300-H), 7.95 (s,
1H, 1 -H), 8.12 (d, JZ8.3 Hz, 1H, 400-H). Found: C,
57.52%; H, 6.04%. Calcd for C23H29O3I: C, 57.51%; H,
6.08%.
4.4. Synthesis of (11S,13S,16R)-(D)-cordiaquinone J (30)
4.4.1. (1R,2R,4S)-2-[20-(500,800-Dimethoxynaphthalene-200-
yl)-ethyl]-1-iodomethyl-3,3,-dimethyl-7-oxabicy-
clo[2.2.1]heptane (170). In the same manner as described
above for (1R,2S,4S)-isomer, 160 mg (452 mmol) of 150 was
converted to 170 (160 mg, 74%) as a colorless oil; [a]2D1
C48.88 (c 0.81, CHCl3); IR (film) nmax (cmK1)Z2950 (s,
C–H), 1635 (s), 1600 (s), 1460 (br s), 1365 (s), 1270 (s),
1240 (s), 1210 (m), 1195 (m), 1160 (m), 1095 (s), 1000 (s),
970 (m), 955 (m), 900 (w), 860 (w), 830 (m), 800 (s), 720
4.3.4. (1R,2S,4S)-2-[20-(500,800-Dimethoxynaphthalene-200-
yl)-ethyl]-1,3,3-trimethyl-7-oxabicyclo[2.2.1]heptane
(18). To a stirred solution of 16 (57 mg, 119 mmol) in dry
benzene (1.5 ml) was added n-Bu3SnH (80 ml, 297 mmol)
and AIBN (32 mg, 196 mmol) under Ar. Then the mixture
was stirred at reflux for 5 h. After cooling to rt, the mixture
was poured into water and extracted with ether. The extract
was washed with water, satd NaHCO3 and brine, then dried
with MgSO4. After concentration in vacuo, the residue was
purified by column chromatography (AcOEt/hexaneZ1:50)
to afford 18 (98 mg, 84%) as a colorless oil; [a]2D1 K9.38 (c
0.33, CHCl3); IR (film) nmax (cmK1)Z2950 (s, C–H), 1635
(s), 1605 (s), 1465 (s), 1425 (s), 1370 (s), 1340 (m), 1270 (s),
1245 (s), 1215 (s), 1195 (s), 1160 (m), 1140 (w), 1095 (s),
1000 (s), 980 (m), 965 (w), 950 (m), 895 (w), 860 (w), 820
(m), 795 (s), 715 (s); 1H NMR (400 MHz, CDCl3): dZ0.98
(s, 3H, 3-CH3), 1.11 (s, 3H, 3-CH3), 1.14–1.24 (m, 2H, 2-H,
6-CHH), 1.35 (m, 1H, 6-CHH), 1.39 (s, 3H, 1-CH3), 1.50–
1.70 (m, 3H, 5-CHH, 10-CH2), 1.80 (m, 1H, 5-CHH), 2.68
(ddd, JZ6.3, 10.7, 13.7 Hz, 1H, 20-CHH), 2.78 (ddd, JZ
4.9, 11.2, 13.7 Hz, 1H, 20-CHH), 3.80 (d, JZ5.9 Hz, 1H,
4-H), 3.93 (s, 3H, CH3O), 3.95 (s, 3H, CH3O), 6.62 (d, JZ
8.3 Hz, 1H, 600-H), 6.67 (d, JZ8.3 Hz, 1H, 700-H), 7.33 (dd,
JZ2.0, 8.8 Hz, 1H, 300-H), 7.95 (d, JZ2.0 Hz, 1H, 100-H),
8.15 (d, JZ8.8 Hz, 1H, 400-H). Found: C, 77.96%; H,
8.46%. Calcd for C23H30O3: C, 77.93%; H, 8.53%.
1
(s); H NMR (400 MHz, CDCl3): dZ1.12 (s, 3H, 3-CH3),
1.15 (s, 3H, 3-CH3), 1.50–1.75 (m, 5H, 6, 10-CH2, 5-CHH),
1.85 (m, 1H, 5-CHH), 1.88 (dd, JZ1.9,0 11.2 Hz, 1H, 2-H),
2.63 (ddd, JZ6.4, 9.8, 13.7 Hz, 1H, 2 -CHH), 2.80 (ddd,
JZ4.9, 10.7, 13.7 Hz, 1H, 20-CHH), 3.26 (d, JZ10.3 Hz,
1H, 1-CHH), 3.47 (d, JZ10.3 Hz, 1H, 1-CHH), 3.86 (d, JZ
4.4 Hz, 1H, 4-H), 3.88, 3.89 (2!s, 6H, 2!CH3O), 6.58 (d,
00
JZ8.3 Hz, 1H, 600-H), 6.62 (d, JZ8.3 Hz, 1H, 7 -H), 7.30
00
(dd, JZ1.9, 8.3 Hz, 1H, 300-H), 7.91 (br s, 1H, 1 -H), 8.06
(d, JZ8.3 Hz, 1H, 400-H); 13C NMR (100 MHz, CDCl3):
dZ8.00, 23.5, 25.6, 26.4, 29.3, 36.2, 38.0, 46.0, 54.3, 55.7,
86.7, 87.3, 102.5, 103.3, 120.2, 122.0, 124.8, 126.4, 127.0,
139.7, 149.1, 149.5. Found: C, 57.58%; H, 6.13%. Calcd for
C23H29O3I: C, 57.51%; H, 6.08%.
4.4.2. (1R,2R,4S)-2-[20-(500,800-Dimethoxynaphthalene-200-
yl)-ethyl]-1,3,3-trimethyl-7-oxabicyclo[2.2.1]heptane
(180). In the same manner as described above for (1R,2S,4S)-
isomer, 160 mg (452 mmol) of 170 was converted to 180
(106 mg, quant.) as a colorless oil; [a]2D1 C27.88 (c 0.63,
CHCl3); IR (film) nmax (cmK1)Z2950 (s, C–H), 1600 (s),
1460 (s), 1425 (m), 1365 (s), 1270 (s), 1240 (m), 1195 (m),
1095 (s), 1000 (w), 990 (m), 985 (w), 830 (w), 800 (s), 720
4.3.5. (11R,13S,16R)-Cordiaquinone J (3). To a stirred
solution of 17 (60 mg, 169 mmol) in MeCN/waterZ4:1
(1 ml) at 0 8C was added CAN (187 mg, 341 mmol) in
several portions and the mixture was stirred for 2 h. Then,
the mixture was poured into water and extracted with ether
three times. The extract was washed with water and brine,
then dried with MgSO4. After concentration in vacuo, the
residue was purified by column chromatography (AcOEt/
hexaneZ1:40) to afford 3 (39 mg, 72%) as a pale yellow
gum; [a]2D1 –208 (c 0.05, acetone); IR (film) nmax (cmK1)Z
3080 (w, H–C]C), 2950 (s, C–H), 2855 (m, C–H), 1665 (s,
C]C–C]O), 1600 (s, C]C–C]O), 1465 (m), 1385 (m),
1340 (w), 1335 (m), 1305 (s), 1190 (w), 1135 (w), 1080 (w),
1
(m); H NMR (400 MHz, CDCl3): dZ1.10 (s, 6H, 2!3-
CH3), 1.30 (dd, JZ5.9, 8.3 Hz, 1H, 2-H), 1.39–1.53 (m, 2H,
5, 6-CHH), 1.68 (m, 3H, 6-CHH, 10-CH2), 1.91 (ddd, JZ
4.9, 8.5, 12.50Hz, 1H, 5-CHH), 2.69 (ddd, JZ6.3, 9.8,
13.7 Hz, 1H, 2 -CHH), 2.78 (ddd, JZ5.9, 10.2, 13.7 Hz, 1H,
20-CHH), 3.80 (d, JZ5.9 Hz, 1H, 4-H), 3.93, 3.95 (2!s,
6H, 2!CH3O) 6.62 (d, JZ8.3, 1H, 600-H), 6.67 (d, JZ8.3,
1H, 700-H) 7.34 (dd, JZ2.0, 8.8 Hz, 1H, 300-H), 7.95 (d, JZ
2.0 Hz, 1H, 100-H), 8.15 (d, JZ8.8 Hz, 1H, 400-H); 13C NMR
(100 MHz, CDCl3): dZ19.0, 23.5, 25.7, 26.1, 29.9, 36.4,
36.5, 39.0, 45.3, 55.5, 55.7, 86.1, 86.7, 102.4, 103.3, 120.1,
121.9, 124.7, 126.4, 127.0, 140.4, 149.1, 149.5. Found: C,
77.93%; H, 8.41%. Calcd for C23H30O3: C, 77.93%; H,
8.53%.
1
1045 (m), 995 (m), 870 (m), 835 (s); H NMR (400 MHz,
acetone-d6): dZ1.00 (s, 3H, 19-CH3), 1.07 (s, 3H, 18-CH3),
1.12 (ddd, JZ2.0, 3.9, 12.2 Hz, 1H, 15-CHH), 1.31 (ddd,
JZ1.9, 4.4, 9.3 Hz, 1H, 14-CHH), 1.50 (dddd, JZ5.4, 5.4,
12.7, 12.7 Hz, 1H, 10-CHH), 1.54–1.74 (m, 3H, 11-H, 10,
15-CHH), 1.83 (dddd, JZ3.9, 4.9, 8.8, 12.2 Hz, 1H,
14-CHH), 2.75 (ddd, JZ6.8, 11.3, 13.7 Hz, 1H, 9-CHH),
2.85 (dd, JZ4.9, 10.3, 13.7 Hz, 1H, 9-CHH), 3.72 (d, JZ
4.9 Hz, 1H, 13-H), 7.00 (s, 2H, 2, 3-H), 7.66 (dd, JZ2.0,
7.8 Hz, 1H, 7-H), 7.83 (d, JZ2.0 Hz, 1H, 5-H), 7.88 (d, JZ
7.8 Hz, 1H, 8-H); 13C NMR (100 MHz, acetone-d6): dZ
20.0 (C-17), 21.8 (C-19), 27.3 (C-14), 30.3 (C-10), 30.4
(C-9), 32.9 (C-18), 36.6 (C-15), 42.6 (C-12), 57.6 (C-11),
86.6 (C-13), 88.3 (C-16), 126.4 (C-5), 127.1 (C-8), 130.9
(C-8a), 132.9 (C-4a), 134.8 (C-7), 139.4 (C-3), 139.5 (C-2),
150.6 (C-6), 185.3 (C-2), 185.7 (C-1). Found: C, 77.77%, H,
7.40%. Calcd for C21H24O3: C, 77.75%, H, 7.46%.
4.4.3. (11S,13S,16R)-(D)-Cordiaquinone J (30). In the
same manner as described above for (11R,13S,16R)-isomer,
79 mg (309 mmol) of 170 was converted to 30 (71 mg, 70%)
as a pale yellow gum; [a]D21 C34.18 (c 0.205, acetone), lit.4;
[a]D K378 (c 0.2, acetone); IR (film) nmax (cmK1)Z3080
(w, H–C]C), 2995 (s, C–H), 2975 (m, C–H), 1665 (s,
C]C–C]O), 1600 (s, C]C–C]O), 1460 (m), 1380 (m),
1345 (w), 1310 (s), 1190 (w), 1180 (w), 1135 (m), 1045 (m),
995 (m), 875 (m), 835 (s); 1H NMR (400 MHz, acetone-d6):
dZ1.08 (s, 3H, 19-CH3), 1.12 (s, 3H, 18-CH3), 1.32 (s, 3H,
17-CH3), 1.33–1.4 (m, 2H, 11-H, 15-CHH), 1.51–1.6 (m, 1H,
15-CHH), 1.55–1.67 (m, 2H, 10, 14-CHH), 1.72 (m, 1H, 10-
CHH), 1.93 (ddd, JZ4.9, 8.5, 12.2 Hz, 1H, 14-CHH), 2.80
(m, 2H, 9-CH2), 3.67 (d, JZ5.4 Hz, 1H, 13-H), 7.00 (s, 2H,

9172
A. Yajima et al. / Tetrahedron 61 (2005) 9164–9172
5. (a) Yajima, A.; Takikawa, H.; Mori, K. Liebigs Ann. 1996,
891. (b) Yajima, A.; Mori, K. Eur. J. Org. Chem. 2000, 4079.
6. Kuramochi, T.; Asaoka, M.; Ohkubo, T.; Takei, H. Tetra-
hedron Lett. 1996, 37, 7075.
2, 3-H), 7.72 (br d, JZ7.8 Hz, 1H, 7-H), 7.85 (s, 1H, 5-H),
7.95 (d, JZ7.8 Hz, 1H, 8-H); 13C NMR (100 MHz, acetone-
d6): dZ19.2 (C-17), 23.6 (C-19), 26.1 (C-18), 26.3 (C-14),
30.3 (C-10), 36.8 (C-9), 39.7 (C-15), 46.0 (C-12), 56.3
(C-11), 86.4 (C-13), 86.9 (C-16), 126.3 (C-5), 127.1 (C-8),
130.9 (C-8a), 132.9 (C-4a), 134.7 (C-7), 139.3 (C-3), 139.5
(C-2), 150.7 (C-6), 185.3 (C-4), 185.7 (C-1). Found: C,
77.71%; H, 7.42%. Calcd for C21H24O3: C, 77.75%; H
7.46%; 1H and 13C NMR spectra are identical with those of
reported natural product.
7. (a) Yajima, A.; Saitou, F.; Sekimoto, M.; Maetoko, S.; Yabuta,
G. Tetrahedron Lett. 2003, 44, 6915. (b) Yajima, A.; Saitou,
F.; Sekimoto, M.; Maetoko, S.; Yabuta, G. Tetrahedron Lett.
2004, 45, 6087.
8. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (b)
Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew. Chem.,
Int. Ed. 2001, 40, 4544.
9. (a) Ruzicka, L.; Lardon, L. Helv. Chim. Acta 1946, 29, 912.
ˆ
(b) Lederer, E.; Marx, F.; Mercier, D.; Perot, G. Helv. Chim.
Acta 1946, 29, 1354.
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12. Mori, K.; Mori, H. Organic Syntheses, Wiley Sons, New York,
1993, Collect. Vol. VIII, 312.
We thank Dr. Shingo Kakita (Kyowa Hakko Kogyo Co.) for
the measurements of MS spectra.
13. Cameron, D. W.; Feutrill, G. I.; Patti, A. F. Aust. J. Chem.
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References and notes
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J. Chem. Soc., Chem. Commun. 1995, 403. (b) Crombie, B. S.;
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