Total synthesis of (-)-dendrobine via α-carbonyl radical cyclization

Article abstract of DOI:10.1021/ja9643432

An efficient total synthesis of enantiomerically pure (-)-dendrobine (1) is accomplished based on an α-carbonyl radical cyclization reaction. (S)- carvotanacetone (6) was convened to bicyclic acetal-enone 4 in five steps. Cul-mediated conjugate addition o

Full text of DOI:10.1021/ja9643432

4130
J. Am. Chem. Soc. 1997, 119, 4130-4135
Total Synthesis of (-)-Dendrobine via R-Carbonyl Radical
Cyclization
Chin-Kang Sha,* Rei-Torng Chiu, Cheng-Fen Yang, Nai-Tung Yao,
Wei-Hong Tseng, Fen-Ling Liao, and Sue-Lein Wang
Contribution from the Department of Chemistry, National Tsing Hua UniVersity,
Hsinchu 300, Taiwan, R.O.C.
ReceiVed December 17, 1996X
Abstract: An efficient total synthesis of enantiomerically pure (-)-dendrobine (1) is accomplished based on an
R-carbonyl radical cyclization reaction. (S)-carvotanacetone (6) was converted to bicyclic acetal-enone 4 in five
steps. CuI-mediated conjugate addition of 4-(trimethylsilyl)-3-butynylmagnesium chloride to 4 followed by treatment
with TMSCl afforded trimethylsilyl enol ether 10. Iodination of 10 with NaI and m-CPBA gave iodoketone 3.
Intramolecular radical cyclization of 3, effected with Bu3SnH and AIBN, furnished tricyclic ketone 2. Removal of
the TMS group of 2 and oxidation of the resulting cyclic acetal 12 with m-CPBA and BF3 etherate gave peroxy
compound 13. Compound 13 was treated with DBU to yield lactone 14. Hydroboration of 14 with basic H2O2
oxidation gave diol 17. Conversion of 17 to the corresponding azido alcohol 19 followed by Jones oxidation furnished
azido ketone 20. Treatment of 20 with PPh3 followed by reduction with NaBH3CN afforded amine 21. Crude
amine 21 was methylated to give enantiomerically pure (-)-dendrobine (1).
(-)-Dendrobine (1) is the major alkaloid isolated from an
Scheme 1
ornamental orchid “Jinchai Shihu” (Dendrodium nobile Lindl)
that is used in traditional Chinese herbal medicine as a tonic.1
Due to its interesting physiological activity and intricate
molecular structure, dendrobine is a challenging target for total
synthesis. Several successful total syntheses2 and formal
syntheses3 of dendrobine have been reported. Among these,
only two formal syntheses3c-f were asymmetric syntheses. In
our previous report, we described an R-carbonyl radical cy-
clization reaction for synthesis of fused-bicyclic ketones with
a cis-ring juncture.4 Herein, we report an application of this
method to asymmetric total synthesis of enantiomerically pure
(-)-dendrobine (1). The retro-synthetic analysis is outlined in
Scheme 1. The cis-ring juncture of (-)-dendrobine (1) might
be established by an R-carbonyl radical cyclization (3 f 2).
Iodoketone 3 would be generated from 4 according to our
method.4 Conjugate addition of Grignard reagent 5 to the less
hindered â-face of bicyclic acetal-enone 4 might give the desired
stereochemistry in 3. Chiral bicyclic acetal-enone 4 would be
prepared from (S)-carvotanacetone (6).5
Thus our synthesis started from the chiral starting material
6. According to the method of Takazawa,6 compound 6 was
treated sequentially with methylmagnesium chloride, ferric
chloride, and chlorotrimethylsilane and then a mixture of
trimethyl orthoformate and boron trifluoride etherate to give
acetal 7 (55%), Scheme 2. Reaction of 7 with lithium
diisopropylamide (LDA) and chlorotrimethylsilane generated
the corresponding trimethylsilyl enol ether, which without
purification was reacted with m-chloroperoxybenzoic acid (m-
CPBA) to give siloxyenone 8 (71%).7 Compound 8 was then
treated with p-toluenesulfonic acid (PTSA) to effect cyclization
to afford bicyclic acetal-enones 4 (79%) and 9 (14%). The latter
was isolated and converted to 4 on treatment with PTSA in
refluxing dichloromethane (55% yield with 25% 9 recovered).
Cuprous iodide-mediated conjugate addition of Grignard reagent
5 to 4 followed by trapping the resulting enolate with chloro-
trimethylsilane yielded 10 with desired stereochemistry which
was confirmed in the next step of the synthesis, Scheme 3. At
this point, the addition of Grignard reagent 5 to the enone moiety
of 4 was expected to proceed from the less hindered â-face of
X Abstract published in AdVance ACS Abstracts, April 1, 1997.
(1) Susuki, H.; Keimatsu, I. J. Pharm. Soc. Jpn. 1932, 52, 1049.
(2) (a) Yamada, K.; Susuki, M.; Hayakawa, Y.; Aoki, K.; Nakamura,
H.; Nagase, H.; Hirata, Y. J. Am. Chem. Soc. 1972, 94, 8278. (b) Inubushi,
Y.; Kikushi, T.; Ibuka, T.; Tanaka, K.; Saji, I.; Tokane, K. J. Chem. Soc.,
Chem. Commun. 1972, 1252. (c) Inubushi, Y.; Kikushi, T.; Ibuka, T.;
Tanaka, K.; Saji, I.; Tokane, K. Chem. Pharm. Bull. 1974, 22, 349. (d)
Kende, A. S.; Benthy, T. J.; Mader, R. A.; Ridge, D. J. Am. Chem. Soc.
1974, 96, 4332. (e) Roush, W. R. J. Am. Chem. Soc. 1978, 100, 3599. (f)
Roush, W. R. J. Am. Chem. Soc. 1980, 102, 1390. (g) Lee, C. H.; Westling,
M.; Livinghouse, T.; Williams, A. C. J. Am. Chem. Soc. 1992, 114, 4089.
(3) (a) Martin, S. F.; Li, W. J. Org. Chem. 1989, 54, 265. (b) Martin, S.
F.; Li, W. J. Org. Chem. 1991, 56, 642. (c) Trost, B. M.; Tasker, A. S.;
Ruther, G.; Brandes, A. J. Am. Chem. Soc. 1991, 113, 670. (d) Mori, M.;
Uesaka, N.; Shibasaki, M. J. Org. Chem. 1992, 57, 3519. (e) Mori, M.;
Uesaka, N.; Shibasaki, M.; Saitoh, F. Chem. Lett. 1993, 213. (f) Mori, M.;
Uesaka, N.; Shibasaki, M.; Saitoh, F.; Okamura, K.; Date, T. J. Org. Chem.
1994, 59, 5633.
(4) Sha, C.-K.; Jean, T.-S.; Wang, D.-C. Tetrahedron Lett. 1990, 31,
3745.
(5) Ireland, R. E.; Bey, P. Organic Syntheses; Wiley: New York, 1988;
Collect. Vol. VI, p 459.
(6) Takazawa, O.; Tamura, H.; Kogami, K.; Hayashi, K. Bull. Chem.
Soc. Jpn. 1982, 55, 1907.
(7) Rubottom, G. M.; Gruber, J. M.; Juve, H. D., Jr. Org. Synth. 1985,
64, 118.
S0002-7863(96)04343-0 CCC: $14.00 © 1997 American Chemical Society

Synthesis of (-)-Dendrobine
J. Am. Chem. Soc., Vol. 119, No. 18, 1997 4131
Scheme 2
Figure 1. Molecular drawing of compound 11 generated by SHELXTL
PLUS.
of 2 is believed to be the same as that of 11. The trimethylsilyl
group was then removed from 2 by treatment with trifluoroacetic
acid to give 12 (84%).
Scheme 3
In order to convert the cyclic acetal group in 12 to a lactone,
compound 12 was oxidized with m-CPBA in the presence of
boron trifluoride etherate according to Grieco’s method,10
Scheme 4. However a labile peroxy compound 13 was obtained
instead of the desired lactone 14. The expected spontaneous
elimination of carboxylic acid from 13 occurred very slowly at
room temperature. Apparently intramolecular abstraction of the
peroxy-acetal proton by the carbonyl oxygen in 13, through a
six-membered transition state,10 is difficult due to the steric
hinderance. Thus, peroxy compound 13 was treated with a base,
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), to effect elimination
and produced lactone 14 (62% from 12). Stereoselective
hydroboration of 14 with borane dimethyl sulfide complex
followed by basic hydrogen peroxide oxidation afforded diol
17. It is noteworthy that hydroboration occurred from the less
hindered R-face to give 15 that was followed by internal delivery
of hydride11 from the â-face Via intermediate 16 to afford diol
17 after oxidation by basic hydrogen peroxide. Diol 17 was
then treated with methanesulfonyl chloride and triethylamine
to give mesylate 18. Crude product 18 was further reacted with
sodium azide and 18-crown-6 in DMF to afford azido alcohol
19 (80% from 17). Compound 19 was oxidized by Jones
reagent12 to afford azido ketone 20 (94%). Treatment of 20
with triphenylphosphine followed by reduction of the imine
moiety with sodium cyanoborohydride from the less hindered
R-face afforded amine 21. The crude amine 21 was immediately
methylated with paraformaldehyde and formic acid to give
enantiomerically pure (-)-dendrobine (1) (42% from 20). 1H
NMR, 13C NMR, and MS spectra of 1 were identical to the
spectra provided by Professor Livinghouse.2g The optical
rotation13 of 1 is in satisfactory agreement with those reported.14
In summary, we have demonstrated that the combination of
conjugate addition and R-carbonyl radical cyclization is a
4, as the bulky isopropyl group was locked at the axial position
in the bicyclic structure of 4 and shielded the R face. Reaction
of crude 10 with an iodination reagent, generated by mixing
sodium iodide and m-CPBA in THF,8 gave iodoketone 3 (82%
from 4). Compound 3 was then treated with tributyltin hydride
and AIBN by slow addition to effect radical cyclization. The
tricyclic ketone 2 (E:Z, 1:9) was obtained as a viscous liquid in
69% yield with a minor amount (25%) of the uncyclized
reduction product.
In order to determine the stereochemistry of 2, iodoketone 3
was also cyclized with atom transfer cyclization method9 to
produce a crystalline product 11. The stereochemistry of 11
was determined by single-crystal X-ray analysis, Figure 1.
Compounds 2 and 11 presumably were formed via similar
radical cyclization mechanisms.9 Hence, the stereochemistry
(9) (a) Curran, D. P.; Chen. M.-H.; Kim, D. J. Am. Chem. Soc. 1986,
108, 2489. (b) Curran, D. P.; Chen, M.-H.; Kim, D. J. Am. Chem. Soc.
1989, 111, 6265.
(10) Grieco, P. A.; Oguri, T.; Yokoyama, Y. Tetrahedron Lett. 1978,
419.
(11) For a closely related intramolecular hydride delivery reaction, see:
Iio, H.; Isobe, M.; Kawai, T.; Goto, T. J. Am. Chem. Soc. 1979, 101, 6076.
(12) Djerassi, C.; Engle, R. R.; Bowers, E. J. Org. Chem. 1956, 21, 1547.
(13) Inubushi, Y.; Sasaki, Y.; Tsuda, Y.; Yasui, B.; Konita, T.;
Matsumoto, J.; Katarao, E.; Nakano, J. Tetrahedron 1964, 20, 2007.
(14) An authentic sample was not available for comparison.
(8) Sha, C.-K.; Young, J.-J.; Jean, T.-S. J. Org. Chem. 1987, 52, 3919.

4132 J. Am. Chem. Soc., Vol. 119, No. 18, 1997
Sha et al.
Scheme 4
mmol) in THF (40 mL) at -20 °C was added methylmagnesium
chloride (20% in THF, 7 mL, 19.3 mmol) dropwise. After stirring for
15 min, a solution of 6 (10 g, 66.3 mmol) in THF (130 mL) was added
over 2 h and stirred at -20 °C for 30 min. To this reaction mixture,
another portion of methylmagnesium chloride (20% in THF, 25 mL,
68.8 mmol) was added over 1 h. After stirring for 30 min, chlorotri-
methylsilane (11.5 mL, 91.1 mmol) and triethylamine (12.6 mL, 91.1
mmol) were added. The mixture was poured into a saturated NaHCO3
solution (150 mL) at 0 °C. The resulting mixture was filtered through
a short pad of Celite. The aqueous layer was extracted with hexane (3
× 100 mL). The combined organic layer was washed with brine and
dried (K2CO3). Concentration gave a residue (14.7 g). To the residue
(14.7 g) was added a solution of trimethyl orthoformate (11 mL, 100.7
mmol) in CH2Cl2 (130 mL). After cooling to -78 °C, BF3‚OEt2 (11
mL, 87.5 mmol) was added dropwise. After stirring for 1 h at -78
°C, the reaction mixture was quenched with saturated NaHCO3 (100
mL) and allowed to warm to room temperature. The organic layer
was separated. The aqueous layer was extracted with CH2Cl2 (2 ×
100 mL). The combined organic layer was dried (MgSO4). Concentra-
tion and silica-gel chromatography (ethyl acetate-hexane, 1:20) gave
7 (8.2 g, 55%): 1H NMR (400 MHz, CDCl3) δ 6.74-6.69 (m, 1 H),
4.39 (d, J ) 4.9 Hz, 1 H), 3.38 (s, 6 H), 2.63-2.57 (m, 1 H), 2.47 (dd,
J ) 16.4, 4.7 Hz, 1 H), 2.22 (dd, J ) 16.4, 8.9 Hz, 1 H), 2.02-1.95
(m, 1 H), 1.86-1.76 (m, 1 H), 1.73 (s, 3 H), 0.87 (d, J ) 6.9 Hz, 3 H),
straightforward and highly efficient method for synthesis of a
complex natural product. Total synthesis of enantiomerically
pure (-)-dendrobine (1) from (S)-carvotanacetone (6) has been
accomplished. In this synthesis six stereogenic centers were
induced, each in a stereoselective manner, from a single chiral
center of the starting material. Stereoselective hydroboration
(14 to 17) is highly efficient, in which an internal hydride
delivery mechanism was proposed. The formation of peroxy
compound 13 from the oxidation of the cyclic acetal moiety of
12 was unexpected. However this provides proof for the
oxidation mechanism proposed by Grieco.10 Applications of
this sequence of conjugate addition and R-carbonyl radical
cyclization to total syntheses of other natural products are
currently under investigation in our laboratories.
Experimental Section
General Methods. 1H and 13C NMR were recorded on a Varian
Gemini-300, Varian Unity-400, or a Bruker AM-400 spectrometer. Mass
spectra were recorded on a JEOL SX-102A or HX-110 mass spec-
trometer. IR spectra were recorded on a Bomem MB-100 FT
spectrometer. Melting points were determined with a Bu¨chi 530
melting-point apparatus and were uncorrected. Optical rotations were
measured on a JASCO DIP-360 polarimeter. Single crystal X-ray
analysis was performed on a Siemens SMART CCD diffractometer.
Elemental analyses were performed by the Southern Regional Instru-
ment Center of National Science Council at National Cheng Kung
University, Tainan, Taiwan.
0.83 (d, J ) 6.6 Hz, 3 H);
13C NMR (100.6 MHz, CDCl3) δ 200.0,
144.0, 136.1, 105.5, 56.0, 54.6, 42.4, 41.4, 37.3, 28.3, 20.9, 17.8, 15.8;
IR (neat) 1674 cm-1; HRMS calcd for C13H22O3 226.1569, found
226.1561. Anal. Calcd for C13H22O3: C, 68.99; H, 9.8. Found: C,
68.76; H, 9.76. [R]25 -109 (c 0.95, CHCl3).
D
(4R,5S)-4-(Dimethoxymethyl)-5-isopropyl-2-methyl-2-cyclohexen-
1-one (7). To a suspension of anhydrous ferric chloride (1.68 g, 10.4
(4R,5S,6R)-4-(Dimethoxymethyl)-5-isopropyl-2-methyl-6-(tri-
methylsiloxy)-2-cyclohexen-1-one (8). To a solution of diisopropyl-

Synthesis of (-)-Dendrobine
J. Am. Chem. Soc., Vol. 119, No. 18, 1997 4133
amine (2.7 mL, 19.3 mmol) in THF (20 mL) was added n-BuLi (1.6
M in hexane, 12 mL, 19.2 mmol) at -20 °C. After warming to 0 °C,
the solution was stirred for 30 min and then cooled to -78 °C. To
this mixture a solution of 7 (3.34 g, 14.8 mmol) in THF (20 mL) was
added dropwise at -78 °C. After stirring for 30 min chlorotrimeth-
ylsilane (2.1 mL, 16.6 mmol) and triethylamine (2.2 mL, 15.9 mmol)
were added. The reaction mixture was allowed to warm to room
temperature and poured into a saturated NaHCO3 solution (100 mL) at
0 °C. The aqueous layer was extracted with hexane (3 × 70 mL). The
combined organic layer was washed with brine and dried (K2CO3).
Concentration gave a crude silyl enol ether (4.41 g). The crude silyl
enol ether (4.41 g) was then dissolved in CH2Cl2 (50 mL). To the
resulting solution was added NaHCO3 (6.22 g, 17.4 mmol) at room
temperature and a solution of m-CPBA (3.06 g, 17.8 mmol) in CH2Cl2
(20 mL) at -20 °C. After stirring for 20 min, a saturated Na2S2O3
solution (20 mL) was added. The mixture was extracted with CH2Cl2
(3 × 50 mL). The combined organic layer was washed with a saturated
NaHCO3 solution and dried (MgSO4). Concentration and silica-gel
chromatography (ethyl acetate-hexane, 1:30) gave 8 (3.29 g, 71%):
1H NMR (400 MHz, CDCl3) δ 6.59 (d, J ) 4.0 Hz, 1 H), 4.61 (d, J )
6.3 Hz, 1 H), 3.98 (d, J ) 6.2 Hz, 1 H), 3.38 (s, 3 H), 3.35 (s, 3 H),
2.56-2.50 (m, 1 H), 2.05-2.00 (m, 1 H), 1.75-1.68 (m, 1 H), 1.73
(s, 3 H), 0.91 (t, J ) 6.6 Hz, 6 H), 0.09 (s, 9 H); 13C NMR (100.6
MHz, CDCl3) δ 198.1, 143.4, 133.8, 106.6, 74.7, 55.01, 54.95, 47.5,
42.1, 28.5, 21.2, 20.0, 16.0, 0.2; IR (CHCl3) 1678 cm-1; HRMS calcd
for C16H30O4Si 314.1913, found 314.1904. Anal. Calcd for C16H30O4-
(1.0 mL, 7.6 mmol), and triethylamine (1.1 mL, 8.0 mmol) were added
dropwise in sequence. The reaction mixture was allowed to warm to
room temperature and stirred for 12 h and was then poured into a
saturated NaHCO3 solution (30 mL). The mixture was stirred and
filtered with Celite to remove black solid. The Celite with filtered
solid was washed with hexane (100 mL). After separating the organic
layer, the aqueous layer was extracted with hexane (2 × 60 mL). The
combined organic layer was washed with brine and dried (K2CO3).
Concentration gave crude product 10 (4.8 g) that was used for the next
step without purification. A small sample of crude 10 was purified by
silica-gel chromatography (ethyl acetate-hexane, 1:50) gave 10 as a
pale yellow liquid: 1H NMR (400 MHz, CDCl3) δ 4.74 (s, 1H), 4.02
(d, 1H, J ) 4.4 Hz), 3.35 (s, 3 H), 2.51-2.21 (m, 5H), 2.04-1.91 (m,
2H), 1.55-1.39 (m, 1 H), 1.51 (s, 3 H), 1.00 (d, J ) 6.7 Hz, 3 H),
0.92 (d, J ) 6.5 Hz, 3H), 0.20 (s, 9 H), 0.14 (s, 9 H); 13C NMR (75
MHz, CDCl3) δ 146.4, 113.9. 106.0, 105.0, 85.5, 79.4, 55.0, 49.2,
43.6, 35.3, 27.4, 24.7, 22.0, 21.5, 17.2, 12.2, 0.0, -0.2; IR (neat) 2170
cm-1; HRMS calcd for C22H40O3Si2: 408.2516, found 408.2513.
(1S,2S,5R,7R,8S)-3-Iodo-8-isopropyl-7-methoxy-3-methyl-2-(4-
(trimethylsilyl)-3-butynyl)-6-oxabicyclo[3.2.1]octan-4-one (3). To a
solution of crude product 10 (4.6 g) and NaI (4.62 g, 30 mmol) in
THF (100 mL) was added a solution of m-CPBA (87%, 5.63 g, 28
mmol) in THF (50 mL) dropwise at 0 °C. After warming to room
temperature and stirring for 20 min, the reaction mixture was diluted
with Et2O (150 mL) and quenched with a saturated Na2S2O3 solution
(150 mL). The organic layer was separated, washed with a saturated
NaHCO3 solution and brine, and dried (MgSO4). Concentration and
silica-gel chromatography (ethyl acetate-hexane, 1:50) gave 3 (3.54
g, 82% from 4) as a brown liquid: 1H NMR (400 MHz, CDCl3) δ
5.28 (s, 1 H), 4.47 (d, J ) 5.6 Hz, 1 H), 3.38 (s, 3H), 2.50-2.41 (m,
2 H), 2.36-2.24 (m, 2 H), 2.05 (s, 3 H), 1.95-1.85 (m, 1 H), 1.80-
1.70 (m, 1 H), 1.31-1.21 (m, 1 H), 1.12-1.01 (m, 1 H), 0.97 (d, J )
6.4 Hz, 3 H), 0.91 (d, J ) 6.0 Hz, 3 H), 0.09 (s, 9 H); 13C NMR (100.6
MHz, CDCl3) δ 204.8, 105.3, 103.0, 87.3, 83.2, 55.0, 50.6, 46.0, 43.9,
Si: C, 61.11; H, 9.61. Found: C, 61.09; H, 9.58. [R]22 -87.0 (c
D
1.22, CHCl3).
(1R,5R,7R,8S)-8-Isopropyl-7-methoxy-3-methyl-6-oxabicyclo-
[3.2.1]oct-2-en-4-one (4) and (1R,5R,7S,8S)-8-Isopropyl-7-methoxy-
3-methyl-6-oxabicyclo[3.2.1]oct-2-en-4-one (9). To a solution of 8
(3.29 g, 10.5 mmol) in CHCl3 (60 mL) was added PTSA monohydrate
(5 mg, 0.03 mmol). The reaction mixture was stirred for 6 h at room
temperature and diluted with CH2Cl2 (100 mL). The organic solution
was washed with a NaHCO3 solution (20 mL) and dried (MgSO4).
Concentration and silica-gel chromatography (ethyl acetate-hexane,
1:20) gave 4 (1.73 g, 79%) and 9 (0.31 g, 14%) as white solids.
Recrystallization (hexane-CH2Cl2) of 4 and 9 both gave colorless
crystals. Data of 4: mp 56.0-56.5 °C; 1H NMR (400 MHz, CDCl3) δ
6.71-6.68 (m, 1 H), 4.75 (s, 1 H), 4.30 (d, J ) 6.0 Hz, 1 H), 3.41 (s,
3 H), 2.81 (dd, J ) 6.4, 3.6 Hz, 1 H), 2.57-2.49 (m, 1 H), 1.73 (d, J
) 1.2 Hz, 3 H), 1.59-1.49 (m, 1 H), 0.91 (d, J ) 6.4 Hz, 3 H), 0.89
(d, J ) 6.8 Hz, 3 H); 13C NMR (100.6 MHz, CDCl3) δ 196.1, 139.9,
136.9, 106.9, 84.0, 56.7, 55.2, 46.1, 23.8, 21.7, 21.2, 14.5; IR (CHCl3)
1691 cm-1; HRMS calcd for C12H18O3 210.1256, found 210.1269. Anal.
Calcd for C12H18O3: C, 68.55; H, 8.63. Found: C, 68.60; H, 8.60.
[R]22D -220.2 (c 0.95, CHCl3). Data of 9: mp 73.5-74.0 °C; 1H NMR
(300 MHz, CDCl3) δ 6.66-6.60 (m, 1 H), 5.26 (d, J ) 4.3 Hz, 1 H),
4.20 (d, J ) 6.6 Hz, 1 H), 3.38 (s, 3 H), 3.02 (dt, J ) 9.1, 4.5 Hz, 1
H), 2.23-2.14 (m, 1 H), 1.83 (s, 3 H), 1.60-1.47 (m, 1 H), 0.85 (d, J
) 8.8 Hz, 6 H); 13C NMR (100.6 MHz, CDCl3) δ 197.1, 140.8, 137.5,
108.6, 84.6, 58.9, 57.0, 43.6, 24.2, 21.7, 20.7, 14.9; IR (CHCl3) 1684
cm-1; HRMS calcd for C12H18O3 210.1256, found 210.1265. Anal.
Calcd for C12H18O3: C, 68.55; H, 8.63. Found: C, 68.56; H, 8.70.
40.5, 34.8, 30.8, 25.0, 21.0, 18.2, 0.1; IR (neat) 2173, 1716 cm-1
HRMS calcd for C19H31IO3Si 462.1089, found 462.1082.
;
(1R,2S,6R,8R,10R,11S)-11-Isopropyl-10-methoxy-6-methyl-5-
[(Z and E)-1-(trimethylsilyl)methylidene]-9-oxatricyclo[6.2.1.02,6]-
undecan-7-one (2). To a solution of 3 (3.07 g, 6.65 mmol) in refluxing
benzene (333 mL) was added a solution of tributyltin hydride (2.16 g,
7.44 mmol) and AIBN (87 mg, 0.53 mmol) in benzene (93 mL) with
a syringe pump over 6 h. After the addition, the reaction mixture was
heated at reflux for 1 h, then cooled to room temperature, and
concentrated. The residue was dissolved into ethyl acetate (70 mL).
A KF solution (2.88 g, 49.7 mmol) in water (5 mL) was added. The
resulting solution was stirred for 10 h and filtered to remove white
solid. The filtrate was washed with saturated NaHCO3 solution (2 ×
50 mL). The organic layer was dried (MgSO4). Concentration and
silica-gel chromatography (ethyl acetate-hexane, 1:40) gave the
uncyclized reduction product (555 mg, 25%) and cyclized product 2
(1.55 g, 69%) as a mixture of E and Z isomers (E:Z ) 1:9): 1H NMR
(300 MHz, CDCl3) δ 5.30 (t, J ) 2.0 Hz, 0.9 H), 5.15 (t, J ) 2.4 Hz,
0.1 H), 4.89 (s, 0.9 H), 4.77 (s, 0.1 H), 4.22 (d, J ) 6.2 Hz, 0.9 H),
4.12 (d, J ) 6.0 Hz, 0.1 H), 3.33 (s, 2.7 H), 3.29 (s, 0.3 H), 2.88-2.52
(m, 2 H), 2.46-2.36 (m, 1 H), 2.28-2.10 (m, 3 H), 1.85-1.62 (m, 1
H), 1.35-1.10 (m, 1 H), 1.19 (s, 2.7 H), 1.13 (s, 0.3 H), 0.92 (d, J )
6.5 Hz, 3 H), 0.88 (d, J ) 6.4 Hz, 3 H), 0.05 (s, 8.1 H), 0.04 (s, 0.9
H); 13C NMR (75 MHz, CDCl3) of Z isomer: δ 210.3, 163.6, 121.2,
105.3, 84.3, 58.8, 54.7, 53.5, 49.3, 48.6, 37.7, 26.0, 25.4, 24.5 , 21.1,
20.8, 0.9; IR (neat) 1715 cm-1; HRMS calcd for C19H32O3Si 336.2121,
found 336.2126. Anal. Calcd for C19H32O3Si: C, 67.81; H, 9.58.
Found: C, 67.73; H, 9.53.
[R]20 -216.4 (c 1.21, CHCl3).
D
Conversion of 9 to 4. To a solution of 9 (75 mg, 0.36 mmol) in
dichloromethane (7 mL) was added PTSA monohydrate (7 mg, 0.04
mmol). The reaction mixture was heated to reflux for 1 h. After
cooling to room temperature, a saturated NaHCO3 solution was added.
The organic layer was separated. The aqueous layer was extracted
with CH2Cl2 (2 × 10 mL). The combined organic layer was dried
(MgSO4). Concentration and silica-gel chromatography (ethyl acetate-
hexane, 1:5) gave 4 (41 mg, 55%) and 9 (18 mg, 25%).
(1R,2S,5R,7R,8S)-8-Isopropyl-7-methoxy-3-methyl-4-(trimethyl-
siloxy)-2-(4-(trimethylsilyl)-3-butynyl)-6-oxabicyclo[3.2.1]oct-3-
ene (10). To a suspension of magnesium (820 mg, 34.2 mmol) in
refluxing THF (10 mL) was added a solution of 4-chloro-1-(trimeth-
ylsilyl)-1-butyne (3.84 g, 23.9 mmol) and 1,2-dibromoethane (0.2 mL,
2.32 mmol) in THF (34 mL) dropwise over a period of 4 h. The
reaction mixture was heated for 30 min and cooled to -78 °C. CuI
(1.93 g, 10.1 mmol) was added. After stirring at -78 °C for 30 min,
compound 4 (1.95 g, 9.28 mmol) in THF (31 mL), chlorotrimethylsilane
(1R,2S,6R,8R,10R,11S)-5-[(E)-1-Iodo-1-(trimethylsilyl)methylidene]-
11-isopropyl-10-methoxy-6-methyl-9-oxatricyclo[6.2.1.02,6]undecan-
7-one (11). To a solution of 3 (302 mg, 0.65 mmol) and iodoethane
(0.2 mL) in benzene (5 mL) was added bis(tributyltin) (208 mg, 0.36
mmol) and AIBN (5 mg, 0.03 mmol). The reaction mixture was
irradiated with a sun lamp (300 W) to reflux for 1 h. Et2O (50 mL)
and a solution of KF (189 mg, 3.25 mmol) in water (10 mL) was added.
The mixture was stirred for 30 min, then filtered, and extracted with
Et2O (3 × 50 mL). The combined organic layer was dried (MgSO4).
Concentration and silica-gel chromatography (ethyl acetate-hexane,

4134 J. Am. Chem. Soc., Vol. 119, No. 18, 1997
Sha et al.
1:40) gave 11 (220 mg, 73%). Recrystallization (ethyl acetate-hexane)
gave colorless crystals, mp 128.0-129.0 °C: 1H NMR (400 MHz,
CDCl3) δ 4.87 (s, 1 H), 4.29 (d, J ) 6.3 Hz, 1 H), 3.37 (s, 3 H), 3.04-
2.81 (m, 2 H), 2.50-2.40 (m, 2 H), 2.31-2.14 (m, 2 H), 1.77-1.69
(m,1 H), 1.24 (s, 3 H), 1.24-1.12 (m, 1 H), 0.91 (d, 6 H, J ) 7.2 Hz),
0.28 (s, 9 H); 13C NMR (75 MHz, CDCl3) δ 210.4, 164.8, 107.1, 105.2,
84.4, 60.3, 54.8, 53.9, 51.5, 50.7, 49.1, 25.7, 24.22, 24.18, 20.7, 20.5,
3.7; IR (CHCl3) 1710 cm-1; MS (EI) m/z 462 (M+, 13), 335 (100),
305 (24), 193 (30), 175 (34). Anal. Calcd for C19H31IO3Si: C, 49.35;
H, 6.76. Found: C, 49.39; H, 6.78. Single-crystal X-ray analysis of
11 was performed. All crystallographic calculation were carried out
with Siemens SHELXTL PLUS-VMS system. Crystal data of 11:
C19H31IO3Si, MW ) 462.4 g/mol, orthorombic crystal system, space
group P21212, Z ) 8, a ) 16.377(2) Å, b ) 29.029(2) Å, c 8.932(2)
Å, V ) 4234(1) Å3, Dc ) 1.451 Mg/m3. A total of 7468 independent
reflections were collected of which 6746 were considered observed [I
> 3.0σ(I), (R ) 6.09%)]. The structure was solved by direct methods
and refined to an R value 0.0448. Absolute structure was determined
with η ) 0.98(4).
(1R,2S,6R,8R,10R,11S)-11-Isopropyl-10-methoxy-6-methyl-5-
methylene-9-oxatricyclo[6.2.1.02,6]undecan-7-one (12). To a solution
of 2 (219 mg, 0.65 mmol) in benzene (5 mL) was added CF3CO2H
(0.25 mL, 3.3 mmol). The reaction mixture was stirred for 20 min
and then concentrated to give a residue. Silica-gel chromatography
(ethyl acetate-hexane, 1:15) gave 12 (144 mg, 84%) as a white solid.
Recrystallization (CH2Cl2) gave colorless crystals, mp 94-94.5 °C: 1H
NMR (300 MHz, CDCl3) δ 4.89 (s, 1 H), 4.83 (t, J ) 2.2 Hz, 1 H),
4.73 (t, J ) 2.6 Hz, 1 H), 4.19 (d, J ) 6.0 Hz, 1 H), 3.35 (s, 3 H),
2.79-2.54 (m, 2 H), 2.45 (ddd, J ) 11.8, 6.0, 3.8 Hz, 1 H), 2.31-
2.14 (m, 3 H), 1.86-1.73 (m, 1 H), 1.42-1.24 (m, 1 H), 1.21 (s, 3 H),
0.98 (d, J ) 6.5 Hz, 3 H), 0.91 (d, J ) 6.3 Hz, 3 H); 13C NMR (100.6
MHz, CDCl3) δ 208.7, 154.6, 106.0, 105.3, 83.5, 57.2, 54.8, 52.6, 48.8,
45.9, 31.7, 26.8, 26.4, 24.5, 21.3, 21.0; IR (neat) 1716 cm-1; HRMS
calcd for C16H24O3 264.1725, found 264.1729. Anal. Calcd for
C16H24O3: C, 72.69; H, 9.15. Found: C, 72.70; H, 9.15. [R]19D -50.9
(c 0.99, CHCl3).
C15H20O3 248.1412, found 248.1414. Anal. Calcd for C15H20O3: C
72.55, H 8.12. Found: C, 72.57; H, 8.13. [R]29 +55.9 (c 1.34,
D
CHCl3).
(1R,2S,5S,6R,7R,8R,11S)-7-Hydroxy-5-(hydroxymethyl)-11-iso-
propyl-6-methyl-9-oxatricyclo[6.2.1.02,6]undecan-10-one (17). To a
solution of 14 (45 mg, 0.18 mmol) in THF (5 mL) was added BH3‚S-
(CH3)2 (1.38 M in THF, 1.30 mL, 1.79 mmol) dropwise at room
temperature. The reaction mixture was stirred at room temperature,
stirred for 4.5 h, and then cooled to 0 °C. Methanol (2 mL) was added
dropwise. The mixture was concentrated to give a residue. THF (5
mL) was added. To the resulting solution was added a mixture of
NaOH (3 M, 2 mL, 6 mmol) and H2O2 (30%, 2 mL, 23 mmol) at room
temperature. The reaction mixture was stirred for 12 h and brine (10
mL) was added. The mixture was extracted with Et2O (3 × 15 mL).
The combined organic layer was dried (MgSO4). Concentration and
silica-gel chromatography (ethyl acetate-hexane, 1:1) gave 17 as a
white solid (29 mg, 60%). Recrystallization (CHCl3-MeOH) gave
colorless crystals, mp 155.5-156 °C: 1H NMR (400 MHz, CDCl3) δ
4.68 (dd, J ) 4.8, 2.8 Hz, 1 H), 4.47 (d, J ) 2.8 Hz, 1 H), 3.74 (A of
ABX, JAB ) 11.1, JAX ) 9.4 Hz, 1 H), 3.62 (B of ABX, JAB ) 11.1,
JBX ) 6.0 Hz, 1 H), 2.35 (t, J ) 4.6 Hz, 1 H), 2.31-2.07 (m, 4 H),
2.07-1.88 (m, 3 H), 1.88-1.77 (m, 1 H), 1.77-1.66 (m, 1 H), 1.43-
1.30 (m, 1 H), 1.27 (s, 3 H), 1.06 (d, J ) 6.4 Hz, 3 H), 0.91 (d, J )
6.4 Hz, 3 H); 13C NMR (100.6 MHz, CDCl3) δ 179.6, 81.4, 66.8, 64.2,
55.8, 51.1, 45.4, 44.8, 44.5, 30.5, 29.0, 28.7, 24.4, 21.24, 21.19; IR
(neat) 3417, 1761 cm-1; HRMS calcd for C15H24O4 268.1674, found
268.1680. Anal. Calcd for C15H24O4: C, 67.14; H, 9.01. Found: C,
67.04; H, 9.10. [R]17 +10.9 (c 1.32, CH3OH).
D
(1R,2S,5S,6R,7R,8R,11S)-5-(Azidomethyl)-7-hydroxy-11-isopro-
pyl-6-methyl-9-oxatricyclo[6.2.1.02,6]undecan-10-one (19). To a solu-
tion of 17 (35 mg, 0.13 mmol) in CH2Cl2 (2 mL) was added Et3N
(0.018 mL, 1.3 mmol) and methanesulfonyl chloride (0.011 mL, 0.14
mmol) at room temperature. The reaction mixture was stirred at room
temperature for 1.5 h and diluted with Et2O (20 mL). The mixture
was washed with a saturated NaHCO3 solution and brine. The organic
layer was separated and dried (Na2SO4). Filtration with Celite and
concentration gave crude product 18. The crude product 18, unstable
on exposure to silica-gel chromatography, was used for the next step
without purification. Data of crude 18: 1H NMR (400 MHz, CDCl3)
δ 4.69 (dd, J ) 4.4, 3.1 Hz, 1 H), 4.37 (dd, J ) 10.3, 8.0 Hz, 1 H),
4.27 (dd, J ) 5.7, 3.1 Hz, 1 H), 4.10 (dd, J ) 10.3, 7.0 Hz, 1 H), 3.00
(s, 3 H), 2.41 (d, J ) 5.7 Hz, 1 H), 2.36 (t, J ) 4.4 Hz, 1 H), 2.28-
2.19 (m, 1 H), 2.19-2.06 (m, 2 H), 2.06-1.93 (m, 2 H), 1.91-1.81
(m, 2 H), 1.57-1.45 (m, 1 H), 1.26 (s, 3 H), 1.05 (d, J ) 6.4 Hz, 3 H),
0.90 (d, J ) 6.8 Hz, 3 H); MS (EI) m/z 347 (M+, 1), 207 (60), 151
(21), 113 (32), 95 (100), 94 (30). To a solution of crude 18 in DMF
(10 mL) was added NaN3 (62 mg, 1.2 mmol) and 18-crown-6 (40 mg,
0.15 mmol). The reaction mixture was heated to 100 °C and stirred
for 1.5 h. After cooling to room temperature, water (10 mL) was added.
The mixture was extracted with Et2O (3 × 20 mL). The combined
organic layer was washed with brine (20 mL) and dried (MgSO4).
Concentration and silica-gel chromatography (ethyl acetate-hexane,
1:5) gave 19 (31 mg, 80%) as a colorless liquid: 1H NMR (300 MHz,
CDCl3) δ 4.68 (dd, J ) 3.8, 2.9 Hz, 1 H), 4.27 (d, J ) 2.9 Hz, 1 H),
3.38 (A of ABX, JAB ) 12.6, JAX ) 8.7 Hz, 1 H), 3.31 (B of ABX,
JAB ) 12.6, JBX ) 7.0 Hz, 1 H), 2.35 (t, J ) 4.5 Hz, 1 H), 2.19-2.05
(m, 2 H), 2.05-1.91 (m, 3 H), 1.91-1.76 (m, 2 H), 1.71 (br, 1 H),
1.54-1.39 (m, 1 H), 1.26 (s, 3 H), 1.06 (d, J ) 6.1 Hz, 3 H), 0.91 (d,
J ) 6.3 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 179.1, 80.8, 67.2,
53.4, 52.9, 50.9, 45.1, 45.0, 44.4 , 29.9, 29.8, 28.7, 24.4, 21.23, 21.17;
IR (neat) 3481, 2102, 1763 cm-1; MS (FAB) m/z 294 (M+ + H, 53),
266 (100), 251 (51), 222 (42), 154 (71), 137 (83), 95 (53), 81 (52);
(1S,2S,6R,8R,10R,11S)-10-(3-Chloroperoxybenzoyl)-11-isopropyl-
6-methyl-5-methylene-9-oxatricyclo[6.2.1.02,6]undecan-7-one (13). To
a solution of 12 (97 mg, 0.37 mmol) in CH2Cl2 (30 mL) was added
molecular sieve (3 Å, 1 g) and a solution of m-CPBA (80%, 100 mg,
0.56 mmol) and BF3‚OEt2 (0.047 mL, 0.37 mmol) in CH2Cl2 (30 mL).
The reaction mixture was stirred for 3.5 h. After filtration with Celite,
the solution was washed with a saturated Na2S2O3 solution (20 mL).
The aqueous layer was extracted with CH2Cl2 (2 × 15 mL). The
combined organic layer was washed with a saturated NaHCO3 solution,
brine, and dried (MgSO4). Concentration gave crude peroxy compound
13 as a brown solid: 1H NMR (300 MHz, CDCl3) δ 7.92 (br s, 1 H),
7.83 (d, J ) 7.9 Hz, 1 H), 7.56 (d, J ) 7.9 Hz, 1 H), 7.38 (t, J ) 7.9
Hz, 1 H), 5.72 (s, 1 H), 4.85 (br s, 1 H), 4.74 (br s, 1 H), 4.36 (d, J )
5.9 Hz, 1 H), 2.84-2.51 (m, 4 H), 2.46-2.37 (m, 1 H), 2.37-2.20
(m, 1 H), 1.83-1.79 (m, 1 H), 1.44-1.30 (m, 1 H), 1.25 (s, 3 H), 1.02
(d, J ) 6.0 Hz, 3 H), 0.94 (d, J ) 6.0 Hz, 3 H); IR (neat) 1765, 1718
cm-1; MS (EI) m/z 404 (M+, <1), 248 (18), 156 (30), 139 (36), 94
(100), 79 (54); HRMS calcd for C22H2535ClO5 and C22H2537ClO5
404.1390 and 406.1379, found 404.1388 and 406.1397.
(1R,2S,6R,8R,11S)-11-Isopropyl-6-methyl-5-methylene-9-oxatri-
cyclo[6.2.1.02,6] undecane-7,10-dione (14). To a solution of crude
peroxy compound 13 from the previous stage in CH2Cl2 (5 mL) was
added DBU (0.17 mL, 1.1 mmol). The reaction mixture was stirred at
room temperature for 1 h. A saturated NaHCO3 solution (10 mL) was
added. The reaction mixture was extracted with Et2O (2 × 10 mL).
The combined organic layer was washed with brine and dried (Na2-
SO4). Concentration and silica-gel chromatography (ethyl acetate-
hexane, 1:15) gave 14 (57 mg, 62% from 12). Recrystallization
(CH2Cl2) gave colorless crystals, mp 161.5-162 °C: 1H NMR (300
MHz, CDCl3) δ 4.91 (t, J ) 2.2 Hz, 1 H), 4.74 (t, J ) 2.6 Hz, 1 H),
4.56 (d, J ) 5.6 Hz, 1 H), 2.76-2.49 (m, 3 H), 2.47-2.37 (m, 2 H),
2.25-2.00 (m, 2 H), 1.55-1.38 (m, 1 H), 1.28 (s, 3 H), 0.97 (d, J )
6.5 Hz, 3 H), 0.93 (d, J ) 6.4 Hz, 3 H); 13C NMR (75 MHz, CDCl3)
δ 204.7, 177.5, 152.8, 108.3, 83.9, 58.1, 54.4, 46.4, 44.8, 30.6, 26.6,
25.7, 24.7, 20.6, 19.5; IR (neat) 1785, 1714 cm-1; HRMS calcd for
[R]29 -49.9 (c 1.31, CHCl3).
D
(1R,2S,5S,6R,8R,11S)-5-(Azidomethyl)-11-isopropyl-6-methyl-9-
oxatricyclo[6.2.1.02,6]undecane-7,10-dione (20). To a solution of 19
(42 mg, 0.14 mmol) in acetone was added Jones reagent (0.5 mL),
prepared from CrO3 (13.36 g), concentrated H2SO4 (11.5 mL) and water
(25 mL), dropwise at room temperature. The reaction mixture was
stirred for 1.5 h. Isopropyl alcohol (1 mL) and water (20 mL) was
added to quench the reaction. The mixture was extracted with Et2O
(3 × 20 mL). The combined organic layer was washed with saturated
NaHCO3 solution brine and dried (MgSO4). Concentration and silica

Synthesis of (-)-Dendrobine
J. Am. Chem. Soc., Vol. 119, No. 18, 1997 4135
gel chromatography (ethyl acetate-hexane, 1:5) gave 20 (30 mg, 94%)
as a white solid. Recrystallization (CH2Cl2) gave colorless crystals,
mp 108-108.5 °C: 1H NMR (300 MHz, CDCl3) δ 4.46 (d, J ) 5.6
Hz, 1 H), 3.32 (A of ABX, JAB ) 12.0, JAX ) 4.7 Hz, 1 H), 3.01 (B
of ABX, JAB ) 12.0, JBX ) 10.3 Hz, 1 H), 2.62 (t, J ) 4.8 Hz, 1 H),
2.44-2.30 (m, 2 H), 2.12-1.98 (m, 4 H), 1.72-1.50 (m, 2 H), 1.37
(s, 3 H), 0.98 (d, J ) 6.5 Hz, 3 H), 0.91 (d, J ) 6.5 Hz, 3 H); 13C
NMR (100.6 MHz, CDCl3) δ 207.7, 177.3, 83.3, 55.6, 53.9, 53.3, 53.1,
45.8, 44.8, 30.9, 29.6, 28.7, 24.5, 20.9, 19.5; IR (neat) 2097, 1790,
1714 cm-1; MS (FAB) m/z 292 (M+ + H, 6), 264 (100), 249 (16), 171
6.0 mmol). The reaction mixture was stirred and heated at 120 °C for
12 h. After cooling to room temperature, the reaction mixture was
basified on adding a NaOH solution (3 M, 30 mL) and extracted with
CH2Cl2 (4 × 30 mL). The combined organic layer was dried (MgSO4).
Concentration and silica-gel chromatography (ethyl acetate-hexane-
methanol, 25:25:1) gave 1 (24 mg, 42% from 20) as a white solid.
Recrystallization (hexane-Et2O, 2:1) gave colorless crystals, mp
133.0-133.5 °C, lit.13 mp 134.6-136 °C: 1H NMR (400 MHz, CDCl3)
δ 4.82 (dd, J ) 5.6, 3.2 Hz, 1 H), 3.13 (t, J ) 8.6 Hz, 1 H), 2.67 (dd,
J ) 8.4, 7.6 Hz, 1 H), 2.64 (d, J ) 2.8 Hz, 1 H), 2.48 (s, 3 H), 2.43
(t, J ) 5.0 Hz, 1 H), 2.34 (m, 1 H), 2.15-1.96 (m, 4 H), 1.88-1.73
(m, 2 H), 1.59-1.47 (m, 1 H), 1.36 (s, 3 H), 0.95 (d, J ) 6.4 Hz, 3 H),
0.94(d, J ) 6.0 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 179.0, 79.1,
66.9, 62.0, 53.7, 52.5, 51.5, 43.9, 43.1, 36.5, 32.8, 32.7, 30.8, 24.5,
21.1, 20.4; IR (neat) 1767 cm-1; MS (EI) m/z 263 (M+, 38), 220 (100),
206 (14), 178 (10), 96 (17); HRMS calcd for C16H25NO2 263.1885,
found 263.1880; [R]21 -46.7 (c 1.38, CH3OH), lit.13 [R]4 -48.4 (c
(69), 137 (20), 91 (46); [R]25 +18.9 (c 1.62, CHCl3).
D
(1S,4S,7S,8R,11R 12R,13S)-13-Isopropyl-12-methyl-10-oxa-2-
azatetracyclo[5.4.1.18,11.04,12]tridecan-9-one (21). To a solution of
20 (64 mg, 0.22 mmol) in THF (5 mL) was added Ph3P (69 mg, 0.26
mmol). The reaction mixture was stirred at room temperature for 12
h. To this mixture was added CH3OH (4 mL), HOAc (0.14 mL, 2.45
mmol), and NaBH3CN (70 mg, 1.1 mmol). The resulting mixture was
stirred for 12 h. Dilute HCl (1 M, 10 mL) was added. After stirring
for 1 h, the mixture was washed with Et2O (10 mL). The aqueous
layer was basified on adding NaOH solution (3 M, 10 mL) and extracted
with CH2Cl2 (4 × 20 mL). The combined CH2Cl2 layer was dried
(MgSO4). Concentration gave crude product 21 (42 mg). The crude
product was used for the next step without purification. Data of crude
21: 1H NMR (300 MHz, CDCl3) δ 4.61 (dd, J ) 5.3, 3.5 Hz, 1 H),
3.18 (dd, J ) 11.4, 8.5 Hz, 1 H), 2.86 (d, J ) 3.5 Hz, 1 H), 2.83 (dd,
J ) 11.4, 6.9 Hz, 1 H), 2.47-2.43 (m, 1 H), 2.35-2.20 (m, 1 H),
2.20-2.00 (m, 5 H), 1.89-1.71 (m, 2 H), 1.55-1.39 (m, 1 H), 1.34
(s, 3 H), 0.96 (d, J ) 6.4 Hz, 3 H), 0.95 (d, J ) 6.4 Hz, 3 H); MS (EI)
m/z 249 (M+, 38), 206 (100), 193 (31), 163 (27), 150 (44), 95 (29), 82
(58).
D
D
1.98, CH3OH).
Acknowledgment. This work is supported by a grant (NSC-
85-2113-M-007-016) from the National Science Council of the
Republic of China. We thank Professor T. Livinghouse for
1
providing us the H NMR, 13C NMR, and MS spectra of their
synthetic dendrobine for comparison.
Supporting Information Available: X-ray crystallographic
1
data and molecular drawing of 11, H NMR spectra of 1-4,
7-14, and 17-21, and 13C NMR spectra of 1-4, 7-9, 11, 12,
14, 17, 19, and 20 (38 pages). See any current masthead page
for ordering and Internet access instructions.
(-)-Dendrobine (1). To crude product 21 (42 mg) was added water
(5 mL), HCOOH (3.3 g, 72 mmol), and paraformaldehyde (180 mg,
JA9643432