Asymmetric synthesis of abietane diterpenoids via B-alkyl Suzuki-Miyaura coupling. Formal total asymmetric synthesis of 12-deoxyroyleanone and cryptoquinone

Article abstract of DOI:10.1016/j.tet.2006.11.072

A convergent synthetic strategy for abietane diterpenoids via B-alkyl Suzuki-Miyaura coupling and Lewis acid-mediated cyclization reactions is established. Asymmetric total synthesis of 12-deoxyroyleanone, an antileishmanial diterpene, is described.

Full text of DOI:10.1016/j.tet.2006.11.072

Tetrahedron 63 (2007) 1080–1084
Asymmetric synthesis of abietane diterpenoids via B-alkyl
Suzuki–Miyaura coupling. Formal total asymmetric
synthesis of 12-deoxyroyleanone and cryptoquinone
*
Arata Yajima, Ayumi Yamaguchi, Fumihiro Saitou, Tomoo Nukada and Goro Yabuta
Department of Fermentation Science, Faculty of Applied Biological Science, Tokyo University of Agriculture (NODAI),
Sakuragaoka 1-1-1, Setagaya-ku, Tokyo 156-8502, Japan
Received 23 October 2006; revised 22 November 2006; accepted 27 November 2006
Available online 12 December 2006
Abstract—A convergent synthetic strategy for abietane diterpenoids via B-alkyl Suzuki–Miyaura coupling and Lewis acid-mediated cycli-
zation reactions is established. Asymmetric total synthesis of 12-deoxyroyleanone, an antileishmanial diterpene, is described.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
reaction was reported by Harring and Livinghouse in
1994.6 They also reported that BF3$OEt2 in MeNO2 is
equally effective in the total synthesis of (ꢀ)-taxodione via
the biomimetic cationic cyclization. Although the reason
for the effectiveness is not clear, the combination of BF3
with MeNO2 as the solvent is advantageous in terms of yield
and seems to avoid a rearrangement of the carbocation inter-
mediate than any other Lewis acids.
Abietane diterpenoids are widely distributed in nature, and
many of them are found as biologically active natural
products. Due to their interesting biological activities and
relatively simple structures, abietane diterpenoids are good
synthetic targets and many synthetic studies have been
reported.1 One classical methodology for the construction
of the tricyclic skeleton is an acid-promoted B-ring closure
by intramolecular Friedel–Crafts alkylation between C-9
and C-10 (Fig. 1). Since the applied acids were such strong
acids as H2SO4,2 P2O5,3 or AlCl3,4 which often cause drastic
rearrangement of the resulting carbocation intermediate, the
yield of the B-ring closure was relatively low. Furthermore,
since the rearrangement of the carbocation from C-10 to C-5
destroys the asymmetric center, this strategy has been
avoided for enantioselective synthesis. In 2001, Yamamoto
and co-workers reported Lewis acid-assisted chiral Brønsted
acid-catalyzed enantioselective biomimetic cyclization of
homo(polyprenyl)arenes (Fig. 1).5 The products, obtained
in good yields and moderate enantiomeric purities, are use-
ful intermediates for various diterpenoid synthesis. But the
main product was partially cyclized, a bicyclic compound
with about 10% of the target tricyclic compound. They
also reported Lewis acid-promoted B-ring closure of the
bicyclic product without loss of the enantiomeric purity by
using BF3$OEt2 in MeNO2. Originally, the effectiveness of
gaseous BF3 in MeNO2 to promote cationic cyclization
Recently we reported the synthesis of antifungal meroterpe-
noids, cordiaquinones J7,8 and K,8 via B-alkyl Suzuki–
Miyaura coupling9 as a key step. This synthetic methodology
requires an easily available chiral homocyclogeranyl
Keywords: Abietane diterpenes; B-Alkyl Suzuki–Miyaura coupling reac-
tion; 12-Deoxyroyleanone; Cryptoquinone.
* Corresponding author. Tel.: +81 3 5477 2264; fax: +81 3 5477 2622;
e-mail: ayaji@nodai.ac.jp
Figure 1. General synthetic method for abietane diterpenes and the Lewis
acid-assisted chiral Brønsted acid-catalyzed enantioselective biomimetic
cyclization of homo(polyprenyl)arenes reported by Yamamoto.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.072

A. Yajima et al. / Tetrahedron 63 (2007) 1080–1084
1081
enzymatic enantioselective hydrolysis of the corresponding
acetate. Because both of the enantiomers of E are available,
this strategy would be useful for the enantioselective synthe-
sis of various tricyclic diterpenes.
Scheme 2 summarizes our asymmetric synthesis of 12-
deoxyroyleanone (1) and cryptoquinone (2). According to
Meyers’ method,15 the regioselective bromination of com-
mercially available 2-isopropylphenol (3) with N-bromosuc-
cinimide (NBS) at room temperature gave 4a in good yield.
In the same manner, 3 was treated with N-iodosuccinimide
(NIS) to give iodide 4b in only 16% yield with 40–50% of
the starting material recovery. At lower temperature, the
yield of iodide was slightly improved but the formation of
the 4-iodo-isomer was observed. The halogenated phenol
derivatives were converted to the corresponding acetates
(5a and 5b). According to Mori’s method,14 the optically ac-
tive alcohol 7 was prepared in the reported manner (90% ee).
Alcohol 7 was halogenated in two steps to give optically ac-
tive b-cyclohomogeranyl iodide16 [(S)-8]. To connect (S)-b-
cyclohomogeranyl iodide (8) and the phenol derivatives,
one-pot B-alkyl Suzuki–Miyaura coupling reaction was un-
dertaken under the established conditions.7,8 The reaction
with bromide 5a gave a complex mixture and the desired
coupling product (9) was isolated in <10% yield. But,
with iodide 5b, the reaction proceeded smoothly to give
the coupling product (9) in 76% yield. The other key reaction
of this synthesis, BF3$OEt2 in CH3NO2-promoted cationic
cyclization without loss of the enantiomerical purity, was
attempted with 9 to obtain the tricyclic compound (10).
The mild exothermic reaction was observed and the desired
product was obtained in 91% yield. The enantiomeric purity
of 10 was estimated to be 87–88% ee by the HPLC analysis
(Daicel CHIRALPAK IA, hexane/EtOAc¼30:1, flow rate:
0.3 ml/min, at 0 ꢁC). This result indicates that the racemiza-
tion at the next position (C-5) of the resulting carbocation
(C-9) is almost suppressed (1–1.5%). Fortunately, enan-
tiomerically pure (>99% ee by HPLC analysis) 10 was
obtained by simple recrystallization. Deacetylation of 10
gave the known compound 11,17 the common synthetic in-
termediate of 12-deoxyroyleanone (1) and cryptoquinone
(2) in Alvarez-Manzaneda’s and Matsushita’s syntheses.12,13
The physical properties, NMR spectra, and [a]D, of our syn-
thetic 11 were compared with the reported data. Although 1H
and 13C NMR spectra of our synthetic 11 and those reported
by Matsushita were in good accord, we found that the re-
ported 1H and 13C NMR data of compound 11 by Alvarez-
Manzaneda and Matsushita were different. The selected
chemical shifts of 11 reported by Alvarez-Manzaneda and
Matsushita and our synthetic 11 are shown in Table 1. Obvi-
ously, the observed 13C NMR spectrum of our synthetic 11
agrees with Matsushita’s data but does not agree with
Alvarez-Manzaneda’s data. Our synthetic 11 shows [a]D
+27.9 (c 0.96, CHCl3), and Matsushita’s 11 was reported
to show [a]D +52.9 (c 0.507, CHCl3).13a Since the [a]D value
of Alvarez-Manzaneda’s 11 was not reported, a strict com-
parison of the [a]D values is difficult. Our synthetic 11 is
proved to be enantiomerically pure by the HPLC analysis
of the precursor 10, and Matsushita synthesized 11 from
naturally occurring dehydroabietic acid. The phenomenon
might arise from air oxidation of phenolic hydroxy group.
In any case the reason for the disagreement is obscure.
We turned to attempt further transformation with 11 to
Figure 2. Structures of 12-deoxyroyleanone and cryptoquinone.
fragment and an aryl fragment, and it is possible to
provide various synthetic intermediates of biologically
active terpenoids by a slight modification of either/both of
the fragment(s). So we became interested in applying the
methodology to the synthesis of tricyclic terpenoids. To dem-
onstrate the versatility of the methodology, the biologically
active abietane diterpenoids, 12-deoxyroyleanone (1) and
cryptoquinone (2), were selected as the synthetic targets.
12-Deoxyroyleanone (1) with antileishmanial activity was
isolated from the root extracts of the Lamiaceae plant, Salvia
cilicica Boiss and Kotschy, by Kolodziej et al.,10 and crypto-
quinone (2) with antifungal and cytotoxic activities was iso-
lated from the bark of the Sugi plant, Cryptomeria japonica
D. Don, by Kofujita et al.11 (Fig. 2). Although synthetic stud-
ies toward these two biologically active diterpenes have been
reported by Alvarez-Manzaneda12 and Matsushita,13 respec-
tively, their methods were partial syntheses starting from
naturally occurring abietic acid or dehydroabietic acid.
This paper describes asymmetric formal total synthesis of
12-deoxyroyleanone and cryptoquinone via B-alkyl Suzuki–
Miyaura coupling followed by BF3$OEt2 in MeNO2-pro-
moted cationic B-ring formation. The 13C NMR assignments
of a synthetic intermediate of 1 are also discussed.
2. Results and discussion
Our synthetic strategy for the synthesis of abietane diter-
penes is shown in Scheme 1. BF3$OEt2 in MeNO2-promoted
B-ring closure of B between C-9 and C-10 directly gave the
abietane skeleton A. The B-alkyl Suzuki–Miyaura coupling
reaction of the aryl fragment C and the optically active frag-
ment D gave the intermediate B. This methodology would be
useful for the synthesis of not only abietane diterpenoids but
also various tricyclic terpenoids because it is easy to modify
the functionalities and positions of the functionalities of the
fragments. Optically active b-cyclohomogeranyl fragment D
could be derived from known14 alcohol E, obtained by the
Scheme 1. Retrosynthetic analyses of abietane diterpenes.

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A. Yajima et al. / Tetrahedron 63 (2007) 1080–1084
Scheme 2. Synthesis of 12-deoxyroyleanone (1). Reagents, conditions, and yields: (a) for 4a:15 NBS, CS2, rt (85%), for 4b: NIS, CS2, rt (16%, 32% based on
recovered starting material); (b) Ac2O, Py (95% for 5a, 98% for 5b); (c) lit.16 (i) MeC(OEt)3, EtCOOH, 140 ꢁC (76%); (ii) LAH, ether (91%); (d) (i) TsCl, Py;
(ii) NaI, acetone (66% in two steps); (e) (i) t-BuLi, ether, ꢂ78 ꢁC; (ii) B-MeO-9-BBN, hexane, THF; (iii) 3 M K3PO4; (iv) Pd(PPh3)4, 5b, DMF, 80 ꢁC (76%); (f)
(i) BF3$OEt2, MeNO2 (91%); (ii) recrystallization from MeOH (78%); (g) K2CO3, MeOH (94%); (h) CAN, MeCN, THF, H2O (68%).
Table 1. 13C NMR chemical shifts of 10
synthesis of an antileishmanial diterpene, 12-deoxyroylea-
none (1), and an antifungal/cytotoxic diterpene, cryptoqui-
none (2), was achieved. Disagreements of the physical and
chemical properties of the synthetic intermediate (11) be-
tween our synthetic product and the reported data were ob-
served. The reason for the disagreement is obscure, but
since the conversion of synthetic 11 to 12-deoxyroyleanone
(1) was successful, the structure of our synthetic 11 should
be correct. This established synthetic methodology would
be a novel methodology of asymmetric synthesis of tricyclic
diterpenes.
Carbon
number
This worka
(ppm)
Matsushitab
(ppm)
Alvarez-Manzanedac
(ppm)
8
9
11
12
13
14
123.20
149.04
116.34
120.55
129.88
150.16
123.24
149.05
116.38
120.62
129.96
150.20
130.9
149.1
116.5
123.3
130.9
150.3
a
100 MHz.
63 MHz.
75 MHz.
b
c
4. Experimental
4.1. General
12-deoxyroyleanone (1). Although the details of the reaction
condition were not reported, phenol derivative 11 was
treated with excess amount of potassium nitrosodisulfonate
(Fremy’s salt) in MeOH according to Alvarez-Manzaneda’s
procedure. But we could not obtain 12-deoxyroyleanone (1),
and no reaction was observed. We suspected that this might
be due to the low solubility of Fremy’s salt in MeOH. Heat-
ing the reaction mixture and addition of water as a co-solvent
were undertaken but in vain. On the other hand, Matsushita’s
procedure of the oxidation of 11 with H2O2 catalyzed by
RuCl3 succeeded in giving 12-deoxyroyleanone (1) in 73%
yield. An alternative procedure to oxidize 11 with ceric am-
monium nitrate (CAN) gave 1 in 68% yield. The spectro-
scopic data of synthetic 1 are in perfect accordance with
those of the natural product. Since the conversion of 12-
deoxyroyleanone (1) to cryptoquinone (2) was reported by
Matsushita, this synthesis is also a formal asymmetric total
synthesis of 2.
Optical rotations were measured on a Jasco DIP-140. IR
spectra were measured for samples as films for oils or as
KBr plates for solids on a Jasco IR-4100 spectrometer. H
1
NMR spectra were taken with Jeol JNM-A400 (400 MHz)
spectrometer using TMS at d¼0.00 as an internal standard.
13C NMR spectra were taken with Jeol JNM-A400
(100 MHz) spectrometer using CDCl3 at d¼77.0 as an inter-
nal standard. Elemental compositions were analyzed on a
J-Science MICROCORDER JM10. HPLC analyses were
performed with Jasco 880-PU as a pump and UV-2075 as
a detector. Column chromatography was performed with
silica gel Wakogel-C200.
4.1.1. 2-Iodo-6-isopropylphenol (4b). To a solution of
3 (1.00 g, 7.35 mmol) in CS2 (20 ml), NIS (1.65 g,
7.35 mmol) was added at room temperature. After stirring
overnight, the solvent was concentrated invacuo and the resi-
due was dissolved in ether. The organic layer was washed
with 10% aq Na2S2O3 and brine, and dried with MgSO4.
After concentration in vacuo, the residue was purified by
column chromatography (hexane/EtOAc¼60:1) to afford
300 mg (16%) of 4b as a colorless oil. IR (film) nmax
(cmꢂ1)¼3490 (m, O–H), 2960, 2920, 2865 (m, C–H),
1590 (m), 1470 (s), 1435 (s), 1325 (s), 1235 (s), 1205 (s),
3. Conclusion
A simple and versatile methodology for enantioselective
synthesis of tricyclic abietane diterpenoid was established
by using one-pot B-alkyl Suzuki–Miyaura coupling reaction
and BF3$OEt2 in MeNO2-promoted cationic cyclization.
With this synthetic sequence, formal total asymmetric

A. Yajima et al. / Tetrahedron 63 (2007) 1080–1084
1083
1175 (s), 1150 (s), 895 (s), 825 (s), 770 (s), 550 (s); 1H NMR
(400 MHz, CDCl3): d¼1.23 (d, J¼6.8 Hz, 6H, 2ꢃCH3),
3.31 (sep, J¼6.8 Hz, 1H, CH–Ar), 5.29 (s, 1H, H–O), 6.66
(dd, J¼8.0, 8.0 Hz, 1H, 4-H), 7.16 (d, J¼8.0 Hz, 1H, 5-H),
7.49 (dd, J¼1.6, 8.0 Hz, 1H, 3-H). This compound was im-
mediately used in the next step without further purification.
4.1.4. (S)-20-Isopropyl-60-[200-(2000,6000,6000-trimethyl-2000-
cyclohexenyl)ethyl]phenyl acetate (9). To a stirred and
cooled (ꢂ78 ꢁC) solution of
8 (90% ee, 777 mg,
2.80 mmol) in dry ether (8 ml) was added dropwise
1.47 M t-BuLi in pentane (4.19 ml, 6.16 mmol) under Ar.
After stirring for 30 min, 1.0 M B-methoxy-9-borabicy-
clo[3.3.1]nonane in hexane (6.44 ml, 6.44 mmol) was added
dropwise, followed by addition of dry THF (8 ml). After
stirring for 10 min at the same temperature, the resulting
solution was allowed to warm to room temperature for
75 min. To the mixture, aq 3 M K3PO4 solution (1.87 ml,
5.60 mmol) was added, followed by a solution of 4b
(850 mg, 2.80 mmol) in DMF (10 ml). After addition of
Pd(PPh3)4 (162 mg, 0.14 mmol), the mixture was stirred at
80 ꢁC for 16 h. After cooling to room temperature, the mix-
ture 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/EtOAc¼250:1) to afford 9 (694 mg, 76%)
as a colorless oil. [a]D25 ꢂ30.8 (c 0.31, CHCl3); IR (film)
nmax (cmꢂ1)¼3030 (w, H–C]C), 2965 (s, C–H), 2870 (s,
C–H), 1765 (s, C]O), 1455 (s), 1165 (s), 1210 (s), 1045
(s), 1095 (m), 1045 (w), 1010 (m), 910 (m), 790 (m), 750
4.1.2. Acetylation of 4a and 4b. To a stirred solution of 4a
or 4b in dry pyridine was added dropwise acetic anhydride
(1.2 equiv). After stirring for 1 h, the mixture was diluted
with ether. The organic layer was washed with dil HCl, water
and brine, and the organic layer was dried with MgSO4.
After concentration in vacuo, the residue was purified by
column chromatography (hexane/EtOAc¼100:1) to afford
5a or 5b as a colorless oil.
4.1.2.1. 2-Bromo-6-isopropylphenyl acetate (5a).
Yield: 95%; IR (film) nmax (cmꢂ1)¼3070 (w, H–C]C),
2965 (s, C–H), 2870 (m), 1770 (s, C]O), 1565 (w), 1470
(m), 1440 (s), 1370 (s), 1195 (s), 1085 (m), 1010 (m), 910
(s), 780 (s), 735 (w), 675 (w), 610 (w); 1H NMR
(400 MHz, CDCl3): d¼1.20 (d, J¼7.2 Hz, 6H, 2ꢃCH3),
2.40 (s, 3H, CH3–C]O), 2.97 (sep, J¼7.2 Hz, 1H, CH–
Ar), 6.97 (dd, J¼8.0, 8.0 Hz, 1H, 4-H), 7.29 (d, J¼8.0 Hz,
1H, 5-H), 7.66 (dd, J¼1.6, 8.0 Hz, 1H, 3-H). Found C,
51.38%; H, 5.09%. Calcd for C11H13BrO2: C, 51.38%; H,
5.09%.
1
(m), 700 (w), 600 (w); H NMR (400 MHz, CDCl3): d¼
0.88 (s, 3H, CH3), 0.98 (s, 3H, CH3), 1.19 (d, J¼7.2 Hz,
6H, CH3–CH), 1.2–1.5 (m, 5H, 200,5000-CH2, 1000-H), 1.96
(m, 2H, 4000-CH2), 2.33 (s, 3H, CH3–C]O), 2.49 (m, 2H,
100-CH2), 2.91 (sep, J¼7.2 Hz, 1H, CH–CH3), 5.31 (br s,
1H, 3000-H), 7.08 (dd, J¼4.8, 4.8 Hz, 1H, 40-H), 7.16 (d,
J¼4.8 Hz, 2H, 30,50-H). This compound was employed in
the next step without further purification.
4.1.2.2. 2-Iodo-6-isopropylphenyl acetate (5b). Yield:
99%; IR (film) nmax (cmꢂ1)¼3060 (w, H–C]C), 2965 (s,
C–H), 2870 (m), 1765 (s, C]O), 1560 (w), 1465 (m),
1430 (s), 1370 (s), 1190 (s), 1080 (m), 1010 (m), 905 (s),
780 (s); 1H NMR (400 MHz, CDCl3): d¼1.19 (d,
J¼7.2 Hz, 6H, 2ꢃCH3), 2.40 (s, 3H, CH3–C]O), 2.97
(sep, J¼7.2 Hz, 1H, CH–Ar), 6.97 (dd, J¼8.0, 8.0 Hz, 1H,
4-H), 7.29 (d, J¼8.0 Hz, 1H, 5-H), 7.66 (dd, J¼1.6,
8.0 Hz, 1H, 3-H). Found C, 43.44%; H, 4.30%. Calcd for
C11H13IO2: C, 43.44%; H, 4.31%.
4.1.5. (5S,10S)-14-Acetoxyabieta-8,11,13-triene (10). To
a stirred solution of 9 (45 mg, 0.14 mmol) in dry MeNO2
(1 ml) was added dropwise BF3$OEt2 (67 ml, 0.55 mmol)
under Ar. After stirring for 3 h, the solution was poured
into satd NaHCO3 aq and extracted with ether. The com-
bined organic phases were dried with MgSO4 and concen-
trated in vacuo. The residue was purified by column
chromatography (hexane/EtOAc¼1000:1) to give 41 mg
(91%) of 10 as a colorless solid. The enantiomeric purity
was estimated to be 87–88% ee by HPLC [Daicel CHIRAL-
PAK IA column, hexane/EtOAc¼30:1, flow rate¼0.3 ml/
min, 0 ꢁC; tR¼14.9 (5S,10S), 21.0 (5R,10R)]. Recrystalliza-
tion from MeOH gave 32 mg (78%) of pure 10 (colorless
needles, >99% ee by HPLC). Mp 100–101 ꢁC; [a]D25 +42.5
(c 0.69, CHCl3); IR (KBr) nmax (cmꢂ1)¼2925 (s, C–H),
2865 (s, C–H), 1760 (s, C]O), 1460 (m), 1365 (m), 1215
4.1.3. (S)-b-Cyclohomogeranyl iodide (8). To a stirred and
ice-cooled solution of 714b (11.0 g, 65.5 mmol) in dry
pyridine (80 ml) was added portionwise p-toluenesulfonyl
chloride (15.0 g, 78.6 mmol). After stirring overnight, the
reaction mixture was poured into water, and extracted with
ether. The combined organic extracts were washed with
satd CuSO4 aq, water, and brine. After concentration in va-
cuo, the residue was dissolved in dry acetone (100 ml). To
the solution NaI (14.7 g, 98.2 mmol) was added, and the re-
sulting suspension was heated under reflux. After stirring for
2 h, the reaction mixture was concentrated in vacuo, and the
residue was diluted with pentane. The organic phase was
washed with water and brine, and dried with Na2SO4. After
concentration in vacuo, the residue was purified with column
chromatography (pentane) to give 8 (12.0 g, 66% in two
steps) as a colorless oil. [a]2D5 ꢂ120 (c 1.01, pentane); IR
(film) nmax (cmꢂ1)¼2955, 2920 (s, C–H), 1460 (m), 1385
(w), 1165 (m), 1025 (s), 820 (s), 765 (s), 590 (s); 1H NMR
(400 MHz, CDCl3): d¼0.88 (s, 3H, 5-CH3), 0.91 (s, 3H, 5-
CH3), 1.18 (m, 1H, 4-CHH), 1.37 (m, 1H, 4-CHH), 1.45
(m, 1H, 6-H), 1.70 (br d, J¼1.4 Hz, 3H, CH3–C]C),
1.85–2.10 (m, 4H, 3,10-CH2), 3.23 (t, J¼7.8 Hz, 2H,
CH2I), 5.33 (br s, 1H, H–C]C). This compound was
employed in the next step without further purification.
1
(s), 1205 (s), 1170 (m), 1140 (w), 1015 (m), 815 (m); H
NMR (400 MHz, CDCl3): d¼0.91 (s, 3H, CH3), 0.92 (s,
3H, CH3), 1.16 (d, J¼7.0 Hz, 3H, CH3–CH), 1.18 (s, 3H,
CH3), 1.19 (d, J¼7.0 Hz, 3H, CH3–CH), 1.1–1.8 (m, 8H,
1,2,3-CH2, 6-CHH, 5-H), 1.86 (br dd, J¼6.8, 13.2 Hz, 1H,
6-CHH), 2.25 (br d, J¼12.4 Hz, 1H, 7-CHH), 2.33 (s, 3H,
CH3–C]O), 2.4–2.8 (br m, 1H, 7-CHH), 2.88 (sep,
J¼7.0 Hz, 1H, CH–CH3), 7.09 (d, J¼8.0 Hz, 1H, Ar–H),
7.14 (d, J¼8.0 Hz, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): d¼18.3, 19.3, 20.6, 21.6, 23.2 (br), 24.8, 27.2,
33.2, 33.3, 37.6, 38.7, 41.5, 49.6, 122.4, 123.4, 127.5,
136.5, 146.2, 149.3, 169.3. Found C, 80.43%; H, 9.82%.
Calcd for C22H32O2: C, 80.43%; H, 9.81%.

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A. Yajima et al. / Tetrahedron 63 (2007) 1080–1084
4.1.6. (5S,10S)-Abieta-8,11,13-trien-14-ol (11). A suspen-
sion of 10 (180 mg, 0.55 mmol) and K2CO3 (152 mg,
1.10 mmol) in MeOH/THF (2:1, 3 ml) was stirred at room
temperature for 3 h. The suspension was poured into dil
HCl and extracted with ether. The organic extracts were
washed with water and brine, then dried with MgSO4. After
concentration in vacuo, the residue was purified by column
chromatography (hexane/EtOAc¼1000:1) to furnish 11
(147 mg, 94%) as a colorless oil; [a]2D5 +27.9 (c 0.96,
CHCl3); IR (film) nmax (cmꢂ1)¼3615, 3565 (br m, O–H),
2960 (s, C–H), 2865 (s, C–H), 1580 (w), 1455 (s), 1420
for C20H28O2: C, 79.95%; H, 9.39%. 1H and 13C NMR spec-
tra are identical with those of reported natural product.
Acknowledgements
We wish to acknowledge the valuable discussions on
compound 11 with Professor Y. Matsushita (Miyazaki
University). This work was financially supported by the
Agricultural Chemical Research Foundation (33rd Grant
No. 1-278) and the NODAI (Tokyo University of Agricul-
ture) Research Institute (Grant for Faculty Research Project
and Grant for Support Program for Young Scientists).
1
(s), 1375 (m), 1290 (w), 1205 (s), 1175 (s), 810 (s); H
NMR (400 MHz, CDCl3): d¼0.93 (s, 3H, CH3), 0.95 (s,
3H, CH3), 1.19 (s, 3H, CH3), 1.22 (d, J¼7.0 Hz, 3H, CH3–
CH), 1.25 (d, J¼7.0 Hz, 3H, CH3–CH), 1.2–1.8 (m, 7H,
1,2,3-CH2, 5-H), 1.98 (br dd, J¼8.0, 13.4 Hz, 1H,
6-CHH), 2.27 (m, 1H, 6-CHH), 2.60 (ddd, J¼7.6, 11.2,
16.2 Hz, 1H, 7-CHH), 2.81 (dd, J¼7.0, 16.2 Hz, 1H, 7-
CHH), 3.14 (sep, J¼7.0 Hz, 1H, CH–CH3), 4.63 (br s, 1H,
H–O), 6.85 (d, J¼8.0 Hz, 1H, Ar–H), 7.01 (d, J¼8.0 Hz,
1H, Ar–H); 13C NMR (100 MHz, CDCl3): d¼18.36, 19.28,
21.57, 22.47, 22.75, 24.28, 24.82, 26.80, 33.27, 33.35,
37.46, 38.88, 41.57, 49.64, 116.34, 120.55, 123.20,
129.88, 149.04, 150.16. Found: C, 83.85%; H, 10.56%.
Calcd for C20H30O: C, 83.85%; H, 10.55%.
References and notes
1. Goldsmith, D. The Total Synthesis of Natural Products;
ApSimon, J., Ed.; Wiley-Interscience, 1992; Vol. 8, pp 5–101.
2. Haworth, R. D.; Barker, R. L. J. Chem. Soc. 1939, 1299.
3. King, F. E.; King, T. J.; Topliss, J. G. J. Chem. Soc. 1957, 573.
4. (a) Matsumoto, T.; Usui, S.; Morimoto, T. Bull. Chem. Soc. Jpn.
1977, 50, 1575; (b) Matsumoto, T.; Usui, S. Bull. Chem. Soc.
Jpn. 1979, 52, 212.
5. (a) Ishihara, K.; Ishibashi, H.; Yamamoto, H. J. Am. Chem. Soc.
2001, 123, 1505; (b) Ishihara, K.; Ishibashi, H.; Yamamoto, H.
J. Am. Chem. Soc. 2002, 124, 3647; (c) Ishibashi, H.; Ishihara,
K.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 11122.
6. Harring, S. R.; Livinghouse, T. Tetrahedron 1994, 50, 9229.
7. Yajima, A.; Saitou, F.; Sekimoto, M.; Maetoko, S.; Nukada, T.;
Yabuta, G. Tetrahedron 2005, 61, 9164.
8. (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.
9. (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.
4.1.7. 12-Deoxyroyleanone (1). To a stirred solution of 11
(70 mg, 0.24 mmol) in THF/MeCN/H2O (2:2:1, 10 ml),
CAN (1.34 g, 2.4 mmol) was added portionwise. After
stirring for 48 h, the mixture was poured into water and
extracted with EtOAc. The organic extracts were washed
with water and brine, then dried with MgSO4. After concen-
tration in vacuo, the residue was filtered through short silica
gel column to give crude 1. Recrystallization from EtOH
gave pure 1 (50 mg, 68%) as pale yellow needles. Mp 75–
76 ꢁC (lit.:13a yellow plate, 83.8–84.8 ꢁC); [a]2D4 ꢂ71.0
(c 0.20, CHCl3) [lit.:9 [a]D20 ꢂ60.0 (c 0.05, CHCl3), lit.:13a
[a]2D4 ꢂ65.3 (c 0.407, CHCl3)]; IR (KBr) nmax (cmꢂ1)¼
2955 (s, C–H), 2925 (s, C–H), 2855 (m, C–H), 1648
(s, C]O), 1595 (m), 1455 (w), 1370 (w), 1285 (w), 1240
(m), 900 (m); 1H NMR (400 MHz, CDCl3): d¼0.90 (s, 3H,
19-CH3), 0.93 (s, 3H, 18-CH3), 1.09 (d, J¼7.0 Hz, 3H, 16-
CH3), 1.10 (d, J¼7.0 Hz, 3H, 17-CH3), 1.08–1.54 (m, 6H,
1,2,6-CHH, 3-CH2, 5-H), 1.72 (ddd, 3.6, 3.6, 13.6 Hz, 1H,
2-CHH), 1.86 (dd, J¼13.6, 7.6 Hz, 6-CHH), 2.30 (ddd,
J¼7.6, 12.0, 20.2 Hz, 1H, 7-CHH), 2.68 (dd, J¼20.2,
5.6 Hz, 1H, 7-CHH), 2.72 (m, 1H, 1-CHH), 2.98 (sep,
J¼7.0 Hz, 1H, 15-H), 6.31 (br s, 1H, 12-H); 13C NMR
(100 MHz, CDCl3): d¼17.4 (C-6), 18.9 (C-2), 20.2 (C-20),
21.4 (C-16,17), 21.8 (C-19), 25.9 (C-7), 26.2 (C-15), 33.5
(C-18), 33.6 (C-19), 36.4 (C-1), 38.5 (C-10), 41.4 (C-3),
51.6 (C-5), 131.9 (C-12), 142.7 (C-8), 150.9 (C-9), 152.7
(C-13), 188.1 (C-14). Found C, 79.95%; H, 9.39%. Calcd
¨
10. Tan, N.; Kaloga, M.; Radtke, O. A.; Kiderlen, A. F.; Oks€uz, S.;
Ulubelen, A.; Kolodziej, H. Phytochemistry 2002, 61, 881.
11. Kofujita, H.; Ota, M.; Takahashi, K.; Kawai, Y.; Hayashi, Y.
Phytochemistry 2002, 61, 895.
12. Alvarez-Manzaneda, E. J.; Chahboun, R.; Bentaleb, F.; Torres,
E. C.; Alvarez, E.; Haidour, A.; Ramos, J. M.; Alvarez-
Manzaneda, R.; Houssame, S. Synlett 2004, 2701.
13. (a) Matsushita, Y.; Iwakiri, Y.; Yoshida, S.; Sugamoto, K.;
Matsui, T. Tetrahedron Lett. 2005, 46, 3629; (b) Matsushita,
Y.; Matsui, T. Jpn. Kokai Tokkyo Koho A2 20051104, 2005.
14. (a) Mori, K.; Puapoomchareon, P. Liebigs Ann. Chem. 1991,
1053; (b) Mori, K.; Aki, S. Acta Chem. Scand. 1992, 46, 625.
15. Basil, L. F.; Nakano, H.; Frutos, R.; Kopach, M.; Meyers, A. I.
Synthesis 2002, 2064.
16. Yajima, A.; Takikawa, H.; Mori, K. Liebigs Ann. 1996, 891.
17. Akita, H.; Oishi, T. Chem. Pharm. Bull. 1981, 29, 1567.