BF3·Et2O-mediated cascade cyclizations: Synthesis of schweinfurthins F and G

Article abstract of DOI:10.1021/jo800951q

(Chemical Equation Presented) The total synthesis of the natural stilbene (+)-schweinfurthin G (8) has been accomplished through a sequence based on an efficient cationic cascade cyclization. This cascade process is initiated by Lewis acid promoted ring opening of an epoxide and terminated through a novel reaction with a phenolic oxygen "protected" as its MOM ether. Several Lewis acids have been examined for their ability to induce this new reaction, and BF₃·Et₂O was found to be the most effective. The only major byproduct under these conditions was one where the expected secondary alcohol was found as its MOM ether derivative (e.g., 30). While this byproduct could be converted to the original target compound through hydrolysis, it also could be employed as a protected alcohol to allow preparation of a benzylic phosphonate (43) without dehydration of the secondary alcohol. The resulting phosphonate was employed in a Horner-Wadsworth-Emmons condensation with an aldehyde representing the right half of the target compounds, an approach complementary to previous studies based on condensation of a right-half phosphonate and a left-half aldehyde.

Full text of DOI:10.1021/jo800951q

BF3 · Et2O-Mediated Cascade Cyclizations: Synthesis of
Schweinfurthins F and G
Nolan R. Mente, Jeffrey D. Neighbors, and David F. Wiemer*
Department of Chemistry, UniVersity of Iowa, Iowa City, Iowa 52242-1294
daVid-wiemer@uiowa.edu
ReceiVed May 2, 2008
The total synthesis of the natural stilbene (+)-schweinfurthin G (8) has been accomplished through a
sequence based on an efficient cationic cascade cyclization. This cascade process is initiated by Lewis
acid promoted ring opening of an epoxide and terminated through a novel reaction with a phenolic oxygen
“protected” as its MOM ether. Several Lewis acids have been examined for their ability to induce this
new reaction, and BF3 · Et2O was found to be the most effective. The only major byproduct under these
conditions was one where the expected secondary alcohol was found as its MOM ether derivative (e.g.,
30). While this byproduct could be converted to the original target compound through hydrolysis, it also
could be employed as a protected alcohol to allow preparation of a benzylic phosphonate (43) without
dehydrationofthesecondaryalcohol.TheresultingphosphonatewasemployedinaHorner-Wadsworth-Emmons
condensation with an aldehyde representing the right half of the target compounds, an approach
complementary to previous studies based on condensation of a right-half phosphonate and a left-half
aldehyde.
Introduction
philes. Previous work in this particular arena utilized harsh
conditions to achieve cyclization and often suffered from low
yields.3
Carbon-carbon bond formation is the central operation of
organic synthesis, and reactions that accomplish this objective
while bringing added complexity to the reaction product are
particularly valuable. Consideration of the range of natural
products generated in plants, animals, and fungi through cationic
cascade cyclizations makes clear that this process has abundant
potential.1 However, to date, synthetic chemistry based on
cationic cascades has been able to recapture only a fraction of
the varied structures produced through biosynthesis and even
the “successful” reactions often afford complex mixtures and
modest yields. The history of cationic cascade cyclizations is
extensive with much attention directed toward transformations
of epoxy-enes.2 There is considerably less precedence for
cationic cascade cyclizations terminated by phenolic nucleo-
Our interest in cationic cascade cyclizations originated in an
effort to prepare some natural hexahydroxanthenes. The tetra-
cyclic schweinfurthins A (1) and B (2), along with a simpler
stilbene named schweinfurthin C (3), were isolated from the
plant Macaranga schweinfurthii and were reported to have an
interesting profile of anticancer activity (Figure 1).4 A short time
later, a fourth member of this family with a hydrated terminal
olefin in the geranyl chain was isolated from the same plant
and named schweinfurthin D (4).5 The tetracyclic schwein-
furthins are closely related to the natural product vedelianin (5),
which bears a prenyl group on the D-ring instead of the geranyl
group of the first schweinfurthins and was isolated from M.
(3) (a) Barua, A. K.; Banerjee, S. K.; Basak, A.; Bose, P. K. J. Ind. Chem.
Soc. 1976, 53, 638–639. (b) Mechoulam, R.; Yagen, B. Tetrahedron Lett. 1969,
5349–5352. (c) Stevens, K. L.; Jurd, L. Tetrahedron 1976, 32, 665–668. (d) de
Alleluia, I. B.; Braz Fo, R.; Gottlieb, O. R.; Magalhaes, E. G.; Marques, R.
Phytochemistry 1978, 17, 517–521. (e) Manners, G.; Jurd, L.; Stevens, K.
Tetrahedron 1972, 28, 2949–2959.
* To whom correspondence should be addressed. Tel: 319-335-1365. Fax:
319-335-1270.
(1) For some recent reviews, see: (a) Tang, Y.; Oppenheimer, J.; Song, Z. L.;
You, L. F.; Zhang, X. J.; Hsung, R. P. Tetrahedron 2006, 62, 10785–10813. (b)
de la Torre, M. C.; Sierra, M. A. Angew. Chem., Int. Ed. 2004, 43, 160–181.
(2) Taylor, S. K. Org. Prep. Proced. Int. 1992, 24, 245–284.
(4) Beutler, J. A.; Shoemaker, R. H.; Johnson, T.; Boyd, M. R. J. Nat. Prod.
1998, 61, 1509–1512.
(5) Beutler, J. A.; Jato, J.; Cragg, G. M.; Boyd, M. R. Nat. Prod. Lett. 2000,
14, 399–404.
10.1021/jo800951q CCC: $40.75
Published on Web 09/17/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 7963–7970 7963

Mente et al.
FIGURE 1. Structures of the natural schweinfurthins and vedelianin.
Vedeliana.6 Very recently, several new hexahydroxanthene
natural products that bear D-ring prenyl groups were isolated
from M. alnifolia and named as schweinfurthins E-H (6-9).7
While the biosynthesis of the tetracyclic schweinfurthins has
not been studied, both the structure of the hexahydroxanthene
system and the co-occurrence of schweinfurthin A and B with
schweinfurthin C strongly suggest a sequence that includes a
cationic cascade cyclization. A process initiated through opening
of an epoxide and terminated by reaction with a phenol would
easily explain the A/B/C-ring system of schweinfurthin F and
G, while a more oxidized precursor could lead to the A-ring
diol schweinfurthins through a parallel process. From the
standpoint of chemical synthesis, a biomimetic route to the
schweinfurthins would be attractive, but past examples of
cascade cyclizations have emphasized use of olefins, arenes,
and hydroxyl groups for termination of the cascades.2 Phenols
or protected forms of them have been less studied3,8 but may
still offer great opportunity because they may be reasonably
stable to the reaction conditions and yet serve as potent
nucleophiles. The available precedents for cascade cyclizations
of MOM-protected phenols were not encouraging. A paper from
Kitahara and co-workers9a reported treatment of an epoxide
bearing a remote MOM ether with picric acid and then with
methanolic HCl. The desired cyclization product was obtained,
but this compound was isolated in just 2% yield, and the loss
of a second MOM ether under the reaction conditions makes it
FIGURE 2. Structures of schweinfurthin analogues.
unclear if MOM cleavage occurred prior to or during the
cyclization. A more recent study of the same substrate was
unable to effect cyclization with either protic or Lewis acids
and found instead only inseparable mixtures.9b There is a
precedent for chromane formation through a cyclization of an
epoxide with a MOM-protected phenol,10 but whether this
process could be extended to formation of a hexahydroxanthene
was not known. In this paper, we describe the synthesis of two
schweinfurthins, F (7) and G (8), and two schweinfurthin
analogues, 3-deoxyschweinfurthin A (3dSA, 10, Figure 2) and
3-deoxyschweinfurthin B (3dSB, 11), via efficient cascade
cyclizations mediated by BF3 ·Et2O.
Results and Discussion
Our general, convergent approach to the schweinfurthins (12)
takes advantage of a Horner-Wadsworth-Emmons (HWE)
condensation to provide the central stilbene as the penultimate
step (Scheme 1). The utility of this strategy was demonstrated
first in the synthesis of schweinfurthin C (3).11 The parallel
coupling of a “left-half” aldehyde (13) and a “right-half”
(6) Thoison, O.; Hnawia, E.; Guieritte-Voegelein, F.; Sevenet, T. Phytochem-
istry 1992, 31, 1439–1442.
(7) Yoder, B. J.; Cao, S.; Norris, A.; Miller, J. S.; Ratovoson, F.; Razafit-
salama, J.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. J. Nat.
Prod. 2007, 70, 342–346.
(8) For a cyclization catalyzed by a nonracemic Lewis acid, see: Ishihara,
K.; Ishibashi, H.; Yamamoto, H. J. Am. Chem. Soc. 2002, 124, 3647–3655.
(9) (a) Kumanireng, A. S.; Kato, T.; Kitahara, Y. Chem. Lett. 1973, 1045–
1047. (b) Begley, M. J.; Fish, P. V.; Pattenden, G. J. Chem. Soc., Perkin Trans.
1 1990, 2263–2271.
(10) Sato, K.; Nishimoto, T.; Tamoto, K.; Omote, M.; Ando, A.; Kumadaki,
I. Heterocycles 2002, 56, 403–412.
(11) Treadwell, E. M.; Cermak, S. C.; Wiemer, D. F. J. Org. Chem. 1999,
64, 8718–8723.
7964 J. Org. Chem. Vol. 73, No. 20, 2008

BF3 ·Et2O-Mediated Cascade Cyclizations
SCHEME 1. Retrosynthetic Analysis of Schweinfurthins
TABLE 1. Attempted Cyclizations of Epoxide 19
distribution (by GC vs
internal standard)
19 20 21
SCHEME 2. Synthesis of an Epoxide for Preparation of
Schweinfurthin F
trial #
acid
time (min) T (°C)
1
2
3
4
5
6
7
8
Ti(OiPr)4
Ti(OiPr)4
Ti(OiPr)4
TiCl4
5
5
1.5
5
5
30
1
5
5
8
0.5
1
2
4
-78
rt
rt
-78
-78
-78
rt
100
100
100
0
0
0
0
55
0
14
0
0
0
0
0
0
0
0
0
0
SnCl4
0
0
CH3AlCl2
In(OTf)3
In(OTf)3
In(OTf)3
In(OTf)3
BF3 ·Et2O
BF3 ·Et2O
BF3 ·Et2O
BF3 ·Et2O
BF3 ·Et2O
17a
65
29
60
36
44
64
68a
49a
51
8a
0
phosphonate (14) at this stage offers the opportunity to use
common precursors in the synthesis of several schweinfurthins.11
The left-half aldehydes were envisioned to arise from phenol-
terminated cationic cascade cyclizations of enantiopure epoxides
15. The intermediate epoxides were expected to be available
through Shi epoxidation12 of a geranyl derivative (16) of
commercially available vanillin (17) or through Shi epoxidation
of a geranyl ester and alkylation of a vanillin derivative (18).13
Several right-half phosphonates appropriate for this strategy are
known from our previous work.11,14,15
-78
0
0
2
3
6
11
7a
11a
15
9
10
11
12
13
14
15
-35
-78
-78
-78
-78
-78
0
0
0
8
a Isolated yields following column chromatography.
The current studies began with the known compound
bromovanillin (18), available through direct bromination of
commercially available vanillin (17), and readily converted to
the geranylated epoxide 19 (Scheme 2).13 Vanillin is an
especially attractive starting material for schweinfurthins with
a C-ring methoxy group (e.g., schweinfurthin F), and conversion
of epoxide 19 to an intermediate hexahydroxanthene has been
reported using a Brønsted acid to induce cyclization.16 While
that approach allowed preparation of some key targets, in the
best cases, the acid-catalyzed cyclization proceeds in just
30-40% yield. A Lewis acid mediated cascade cyclization
would be attractive if it allowed use of milder reaction conditions
and proceeded in better yield.
Studies on the use of Lewis acids to induce a cascade reaction
were performed with epoxide 19 (Figure 3) to determine the
conditions necessary to enact cyclization and formation of the
desired tricycle (Table 1). Several Lewis acids were examined
with varying conditions of reaction times and temperatures.
Upon treatment with Ti(OiPr)4, no reaction was detected (trials
1-3), and the starting epoxide could be recovered unchanged,
suggesting that this Lewis acid was unable to enact cyclization
in this system. In contrast, upon treatment with TiCl4 (trial 4)
or SnCl4 (trial 5), no isolable compounds were obtained and no
starting materials could be recovered.17 A reaction with
MeAlCl2, which has been used in a number of other cationic
cascades,18 gave the desired products in modest yield (trial 6).
The use of In(OTf)3 gave more promising results (trials 7-10),
including formation of significant amounts of the desired tricycle
and merits further evaluation as a reagent to promote these
cascade cyclizations.19 However, reactions with BF3 ·Et2O were
inexpensive, convenient, and easily amenable to larger scales.
They appeared to have great promise in providing tricycle 20,
and thus this Lewis acid became our immediate focus.20 Even
very brief exposure to this Lewis acid at low temperature (trial
FIGURE 3. Lewis acid mediated cyclization of epoxide 19.
(12) (a) Shi, Y. Acc. Chem. Res. 2004, 37, 488–496. (b) Shu, L.; Shi, Y.
Tetrahedron Lett. 1999, 40, 8721–8724.
(13) Neighbors, J. D.; Mente, N. R.; Boss, K. D.; Zehnder, D. W., II; Wiemer,
D. F. Tetrahedron Lett. 2008, 49, 516–519.
(14) Mente, N. R.; Wiemer, A. J.; Neighbors, J. D.; Beutler, J. A.; Hohl,
R. J.; Wiemer, D. F. Bioorg. Med. Chem. Lett. 2007, 17, 911–915.
(15) Neighbors, J. D.; Salnikova, M. S.; Wiemer, D. F. Tetrahedron Lett.
2005, 46, 1321–1324.
(16) Neighbors, J. D.; Beutler, J. A.; Wiemer, D. F. J. Org. Chem. 2005, 70,
925–931.
(17) (a) Yee, N. K. N.; Coates, R. M. J. Org. Chem. 1992, 57, 4598–4608.
(b) Corey, E. J.; Liu, K. J. Am. Chem. Soc. 1997, 119, 9929–9930.
(18) (a) Corey, E. J.; Sodeoka, M. Tetrahedron Lett. 1991, 32, 7005–7008.
(b) Zhang, J. H.; Corey, E. J. Org. Lett. 2001, 3, 3215–3216. (c) Taylor, S. K.;
Ivanovic, M.; Simons, L. J.; Davis, M. M. Tetrahedron: Asymmetry 2003, 14,
743–747.
(19) (a) Lacey, J. R.; Anzalone, P. W.; Duncan, C. M.; Hackert, M. J.; Mohan,
R. S. Tetrahedron Lett. 2005, 46, 8507–8511. (b) Bogenstatter, M.; Limberg,
A.; Overman, L. E.; Tomasi, A. L. J. Am. Chem. Soc. 1999, 121, 12206–12207.
J. Org. Chem. Vol. 73, No. 20, 2008 7965

Mente et al.
SCHEME 3. Synthesis of a C-5 MOM Ether and its BF3 ·Et2O-Mediated Cyclization
SCHEME 4. Synthesis of Schweinfurthin G and 3dSA
11) gave a yield comparable to the best obtained from reactions
with protic acids. At slightly longer times (trials 12 and 13),
the yield of the tricyclic alcohol 20 improved to 64-68% and
the major byproduct was the tricyclic compound with an A-ring
methoxymethyl (MOM) ether 21. Thus the total yield of
hexahydroxanthene was ∼75% under these conditions, or nearly
double the best reported from the protic acid catalyzed reactions
in similar systems.16 Further increases in reaction time did not
lead to improved yields (trials 14 and 15).
To determine if these conditions could be applied to other
substrates, and to gain access to intermediates for more facile
synthesis of hexahydroxanthenes with a C-ring phenol, aromatic
compounds with two MOM groups were sought. Our synthesis
of schweinfurthin G (8) and its analogue 3dSA (10) proceeded
from bromovanillin (18) through treatment with aluminum(III)
chloride as a standard demethylation21 to provide catechol 22
(Scheme 3). Protection of compound 22 as its MOM ether (23)
followed by reduction of the aldehyde afforded the known
benzylic alcohol 24.11 The resultant alcohol was masked as the
silyl ether to give differentially protected bromide 25. Treatment
of bromide 25 with n-BuLi enacted halogen metal exchange,
and subsequent reaction with geranyl bromide installed the
geranyl chain to provide compound 26 in 86% yield. A Shi
epoxidation12 of geranylated arene 26 was observed upon
treatment with hydrogen peroxide in the presence of sugar
catalyst 27 and acetonitrile in buffered solution to afford epoxide
28 in a modest yield but excellent enantioselectivity (vide infra).
In addition, this application of the Shi epoxidation generally
results in recovery of 33-54% of the starting olefin, so yields
based on recovered starting material are very attractive. With
epoxide 28 in hand, the stage was set for Lewis acid mediated
cascade cyclizations. Brief treatment with BF3 ·Et2O afforded
tricycle 29 in a 52% yield along with tricycle 30 in 30% yield,
representing very efficient formation of the tricyclic system.
Removal of the silyl protecting group of tricycle 29 was
successful using standard conditions, and oxidation gave the
new left-half aldehyde 32.
(20) (a) Aggarwal, V. K.; Bethel, P. A.; Giles, R. J. Chem. Soc., Perkin
Trans. 1 1999, 3315. (b) Nagamitsu, T.; Sunazuka, T.; Obata, R.; Tomoda, H.;
Tanaka, H.; Harigaya, Y.; Omura, S.; Smith, A. B., III J. Org. Chem. 1995, 60,
8126–8127. (c) Smith, A. B., III; Kinsho, T.; Sunazuka, T.; Omura, S.
Tetrahedron Lett. 1996, 37, 6461–6464. (d) Sen, S. E.; Roach, S. L.; Smith,
S. M.; Zhang, Y. Z. Tetrahedron Lett. 1998, 39, 3969–3972.
Formation of the A-ring MOM ethers as byproduct of the
cyclization of both epoxides 19 and 28 was not expected. These
(21) Lange, R. G. J. Org. Chem. 1962, 27, 2037–2039.
7966 J. Org. Chem. Vol. 73, No. 20, 2008

BF3 ·Et2O-Mediated Cascade Cyclizations
SCHEME 5. Synthesis of Hexahydroxanthene Phosphonates en route to Stilbenes
products can be readily explained by formation of a formal
CH3OCH2+ cation during the course of cyclization and ultimate
reaction of this cation with the nucleophilic oxygen of the C-2
hydroxyl group. However, the corresponding byproduct from
the reaction of such a cation at the benzylic oxygen was not
observed, so a more complex mechanism may be at play and
further studies will be necessary to clarify this process.
Completion of the target compounds proceeded in a straight-
forward manner. Aldehyde 32 was employed for the synthesis
of schweinfurthin G (8) and 3dSA (10). In the first case, an
HWE condensation of aldehyde 32 and known phosphonate 3314
provided the penultimate compound as stilbene 34. Acidic
hydrolysis of the three MOM ethers yielded schweinfurthin G
(8) in 57% yield (Scheme 4). This route represents the first total
synthesis of schweinfurthin G, and spectral data matched that
of the isolated natural product. Analysis of the product by HPLC
indicated an ee of ∼94%, originating in the Shi epoxidation. A
similar strategy was used for the synthesis of 3-deoxyschwein-
furthin A (10). For this target aldehyde, 32 underwent a smooth
HWE condensation with known phosphonate 3511 to afford
stilbene 36. Treatment of compound 36 with TsOH resulted in
cleavage of the three MOM groups and provided the new
schweinfurthin analogue 10 in a modest yield. Finally, standard
cleavage of the silyl protecting group of tricycle 20 followed
by MnO2 oxidation to the corresponding aldehyde represents a
formal synthesis of both schweinfurthin F (7)12 and 3dSB (11).16
Synthesis of 3dSB through this BF3 ·Et2O-mediated cyclization
shows consistent transmission of stereochemical integrity from
the epoxide through the cyclization, in parallel with our work
using protic acids.16
phosphite. In contrast, if the A-ring alcohol is left unprotected,
attempted reactions with triethyl phosphite resulted in dehydra-
tion. An HWE condensation of phosphonate 38 with aldehyde
3922 (Scheme 5), readily available by MnO2 oxidation of the
corresponding benzylic alcohol,11 gave the desired stilbene 40
in a modest yield (Scheme 5). Final hydrolysis of the three
MOM groups by treatment with TsOH in methanol gave the
desired 3dSB (11). Through a parallel sequence, compound 30
was converted to the benzylic alcohol 41 and then to phospho-
nate 42. In this case, the HWE condensation with aldehyde 39
gave stilbene 43 in a good yield, and final deprotection of the
four MOM groups gave 3dSA (10) in 52% yield, along with a
partial hydrolysis product (44) that retained the A-ring MOM
group (33%). These experiments show that the adventitious
formation of the A-ring MOM compound allows preparation
of the benzylic phosphonate, and that condensation of this
phosphonate left-half with an aldehyde right-half is a viable
alternative to the reverse strategy (i.e., a phosphonate right half
with an aldehyde left-half) that has been employed in all
previous studies. Although the yields have not been optimized
and currently are somewhat lower for this approach than for
the original strategy, this allows attractive flexibility in distribu-
tion of the number of steps between the two branches of the
convergent synthesis.
In conclusion, the scope of Lewis acid mediated cascade
cyclizations has been expanded to include two examples of
efficient epoxy-ene cyclizations mediated by brief treatment with
BF3 ·Et2O and terminated by reaction with a MOM-protected
phenol. These cyclizations were used to provide the hexahy-
droxanthenecorenecessaryforthesynthesisoftwoschweinfurthin
natural products (schweinfurthins F and G) and two parallel
schweinfurthin analogues (3dSA and 3dSB). Further application
of the use of Lewis acid mediated cascade cyclizations,
particularly those terminated by oxygen nucleophiles, will be
reported in due course.
In principle, the A-ring MOM compounds 21 and 30 could
be hydrolyzed to the corresponding alcohols 20 and 29 and thus
recycled into the desired stilbenes. Instead we chose to take
advantage of these compounds as protected A-ring alcohols and
use them in a different manner. Accordingly, compound 21 was
treated with TBAF to afford the benzylic alcohol 37, and this
alcohol was converted to the corresponding phosphonate through
sequential treatment with mesyl chloride, NaI, and triethyl
(22) Wang, B.; Zhang, Y.; Chen, J.; Zhang, W.; Song, J.; Del, B. U.; Brown,
L.; Miller, G. PCT Int. Appl., 2003, CODEN: PIXXD2 WO 2003009807 A2
20030206 CAN 138:153318 AN 2003:97274.
J. Org. Chem. Vol. 73, No. 20, 2008 7967

Mente et al.
(s, 3H), 0.09 (s, 6H); 13C NMR δ 145.9, 143.1, 132.6, 123.0, 121.4,
114.3, 96.3, 96.1, 84.2, 76.6, 64.9, 56.2, 55.7, 47.2, 38.4, 37.8, 27.5,
26.1(3C), 25.4, 23.4, 19.9, 18.6, 15.2, -5.1 (2C); HRMS (EI+)
m/z calcd for C27H46O6Si (M+) 494.3064, found 494.3057.
Tricyclic Alcohol 31. To a solution of tricycle 29 (112 mg, 0.25
mmol) in THF at 0 °C was added TBAF (0.3 mL, 0.3 mmol, 1 M
in THF). The reaction was stirred for 2 h and quenched with NH4Cl
(sat.), extracted with EtOAc, and washed with H2O and brine. The
combined organics were dried (MgSO4) and concentrated in vacuo
to afford alcohol 31 (83 mg, 99%) as a white solid: [R]26.4D ) +43.5
(c 1.0, CHCl3); 1H NMR δ 6.96 (d, J ) 1.8 Hz, 1H), 6.81 (d, J )
1.8 Hz, 1H), 5.19 (d, J ) 6.3 Hz, 1H), 5.15 (d, J ) 6.6 Hz, 1H),
4.56 (s, 2H), 3.51 (s, 3H), 3.40 (dd, J ) 11.7, 3.0 Hz, 1H), 2.72 (s,
1H), 2.70 (d, J ) 3.0 Hz, 1H), 2.15-2.05 (m, 1H), 1.86-1.81 (m,
2H), 1.69-1.63 (m, 4H), 1.26 (s, 3H), 1.09 (s, 3H), 0.87 (s, 3H);
13C NMR δ 146.1, 143.7, 132.2, 123.4, 122.6, 115.1, 96.0, 78.1,
76.9, 65.4, 56.3, 46.8, 38.5, 37.9, 28.4, 27.4, 23.3, 20.0, 14.4; HRMS
(EI+) m/z calcd for C19H28O5 (M+) 336.1937, found 336.1932.
Tricyclic Aldehyde 32. To a solution of alcohol 31 (19 mg,
0.06 mmol) in CH2Cl2 was added manganese dioxide (120 mg,
1.2 mmol). The resulting solution was stirred for 16.5 h and
quenched by filtration through a Celite pad. After the pad was rinsed
with CH2Cl2 and EtOAc, the combined organic extracts were dried
(MgSO4) and concentrated to afford aldehyde 32 (19 mg, 100%)
as a white solid: [R]26.4D ) +74.8 (c 2.0, CHCl3); 1H NMR δ 9.79
(s, 1H), 7.45 (d, J ) 1.8 Hz, 1H), 7.35 (d, J ) 1.8 Hz, 1H), 5.23
(d, J ) 6.6 Hz, 1H), 5.19 (d, J ) 6.6 Hz, 1H), 3.51 (s, 3H), 3.42
(dd, J ) 11.7, 4.5 Hz, 1H), 2.79 (s, 1H), 2.77 (d, J ) 4.5 Hz, 1H),
2.16-2.10 (m, 1H), 1.91-1.84 (m, 2H), 1.74-1.60 (m, 4H), 1.26
(s, 3H), 1.11 (s, 3H), 0.89 (s, 3H); 13C NMR δ 191.0, 150.1, 146.7,
128.9, 127.3, 123.5, 115.4, 95.8, 78.5, 77.9, 56.4, 46.6, 38.6, 37.7,
28.3, 27.4, 23.2, 20.2, 14.4. Anal. Calcd for C19H26O5: C, 68.24;
H, 7.84. Found: C, 67.94; H, 8.07.
Experimental Section
Benzylic Silyl Ethers 20 and 21. To a solution of epoxide 19
(320 mg, 0.66 mmol) in CH2Cl2 was added BF3 ·Et2O (0.35 mL,
2.8 mmol) at -78 °C. The resulting solution was allowed to stir
16 min, and triethylamine (0.5 mL, 4 mmol) was added. After an
additional 10 min, water (75 mL) was added, the phases were
separated, and the aqueous phase was extracted with CH2Cl2. The
combined organic phase was washed with water and brine, then
dried (MgSO4), and concentrated. Final purification by flash
chromatography (15:1 to 3:1 hexanes:EtOAc) afforded the tricyclic
alcohol 20 (132 mg, 48%) as a clear oil with spectral data matching
previously reported data.13,16 Also isolated as a clear oil (69 mg,
22%) was the A-ring methoxymethylether 21: [R]26.4 ) +8.9 (c
D
1
3.0, CHCl3); H NMR δ 6.70 (s, 1H), 6.64 (s, 1H), 4.77 (d, J )
6.6 Hz, 1H), 4.64 (d, J ) 6.6 Hz, 1H), 4.64 (s, 2H), 3.83 (s, 3H),
3.41 (s, 3H), 3.27 (dd, J ) 11.3, 4.0 Hz, 1H), 2.70-2.67 (m, 2H),
2.13 (dt, J ) 12.7, 3.2 Hz, 1H), 1.97 (dq, J ) 13.0, 3.7 Hz, 1H),
1.85-1.52 (m, 3H), 1.24 (s, 3H), 1.08 (s, 3H), 0.95 (s, 9H), 0.90
(s, 3H), 0.11 (s, 6H); 13C NMR δ 148.6, 141.4, 132.3, 122.2, 119.0,
107.4, 96.1, 84.0, 76.4, 64.9, 55.8, 55.8, 47.0, 38.3, 37.5, 27.4, 26.0
(3C), 25.2, 23.1, 19.4, 18.4, 15.1, -5.2(2C); HRMS (EI+) m/z calcd
for C26H44O5Si (M+) 464.2958, found 464.2944.
5-((2E)-3,7-Dimethyl-6-epoxyocta-2-enyl)-3,4-bis(O-methoxy-
methyl)benzyloxy-tert-butyldimethylsilane (28). To a solution of
olefin 26 (689 mg, 1.4 mmol) in acetonitrile (0.4 mL), n-butanol
(10 mL), and a buffer solution (5 mL, 2 M K2CO3, 0.4 mM EDTA)
at 0 °C was added the sugar catalyst 27 (95 mg, 0.4 mmol).
Hydrogen peroxide (0.85 mL, 30% solution, 8.3 mmol) was added
dropwise to the cooled mixture, and the reaction was stirred for
22 h. The reaction was quenched by addition of Na2SO3 and
extracted with EtOAc. The combined organic extracts were washed
with H2O and brine, dried (MgSO4), and concentrated in vacuo to
afford a pale liquid. Final purification by flash column chromatog-
(2R,4aR,9aR)-Tri(O-methoxymethyl)schweinfurthin G (34).
To a suspension of NaH (42 mg, 1.04 mmol, 60% oil dispersion)
and 15-crown-5 (0.01 mL, 0.05 mmol) in THF at 0 °C was added
a solution of phosphonate 33 (33 mg, 0.08 mmol) and aldehyde 32
(20 mg, 0.06 mmol) in THF. After the reaction was allowed to
warm to room temperature and stirred for 18 h, it was quenched
by addition of H2O and extracted with EtOAc. The combined
organic extracts were washed with H2O and brine, dried (MgSO4),
concentrated in vacuo to a yellow liquid, and purified by flash
column chromatography (2:1 hexanes/EtOAc) to afford stilbene 34
raphy (8% EtOAc in hexanes) provided epoxide 28 (277 mg, 39%)
as a colorless liquid: [R]26.4 ) +1.5 (c 2.7, CHCl3); H NMR δ
1
D
6.98 (d, J ) 1.8 Hz, 1H), 6.78 (d, J ) 1.5 Hz, 1H), 5.36 (t, J ) 7.2
Hz, 1H), 5.17 (s, 2H), 5.08 (s, 2H), 4.64 (s, 2H), 3.59 (s, 3H), 3.49
(s, 3H), 3.41 (d, J ) 6.9 Hz, 2H), 2.71 (t, J ) 6.3 Hz, 1H),
2.20-2.05 (m, 2H), 1.73 (s, 3H), 1.70-1.60 (m, 2H), 1.27 (s, 3H),
1.25 (s, 3H), 0.92 (s, 9H), 0.09 (s, 6H); 13C NMR δ 149.7, 143.6,
137.6, 135.5, 135.4, 123.3, 120.5, 112.2, 99.2, 95.3, 64.8, 64.3,
58.4, 57.6, 56.2, 36.5, 28.6, 27.6, 26.0 (3C), 25.0, 18.9, 18.5, 16.3,
-5.1 (2C). Anal. Calcd for C27H46O6Si·1/2H2O: C, 64.38; H, 9.40.
Found: C, 64.48; H, 9.35.
1
(18 mg, 50%) as a colorless oil: H NMR δ 7.12 (d, J ) 2.1 Hz,
1H), 6.95-6.93 (m, 2H), 6.90 (s, 2H), 6.89 (s, 1H), 5.25-5.18
(m, 7H), 3.55 (s, 3H), 3.51 (s, 6H), 3.47-3.44 (m, 1H), 3.38 (d, J
) 7.2 Hz, 2H), 2.74 (s, 1H), 2.71 (d, J ) 3.0 Hz, 1H), 2.15-2.05
(m, 1H), 1.90-1.80 (m, 2H), 1.79 (s, 3H), 1.75-1.70 (m, 3H),
1.66 (s, 3H), 1.24 (s, 3H), 1.11 (s, 3H), 0.89 (s, 3H); 13C NMR δ
156.6 (2C), 146.9, 144.6, 137.4, 131.8, 129.8, 128.8, 127.4, 123.9,
123.5, 122.8, 120.1, 114.7, 106.7 (2C), 96.6, 95.2 (2C), 78.7, 77.8,
57.0, 56.8 (2C), 47.5, 39.1, 36.5, 30.0, 29.0, 26.6, 23.9, 23.5, 20.7,
18.6, 15.0; HRMS (EI+) m/z calcd for C35H48O8 (M+) 596.3351,
found 596.3349.
Tricycles 29 and 30. To a solution of epoxide 28 (355 mg, 0.7
mmol) in CH2Cl2 (60 mL) at -78 °C was added BF3 ·Et2O (0.36
mL, 2.8 mmol) dropwise. The reaction was stirred for 3.5 min and
quenched by addition of triethylamine, treated with NH4Cl (sat.),
and extracted with CH2Cl2. The combined organics were washed
with H2O and brine, dried (MgSO4), and concentrated in vacuo to
give a yellow liquid. Final purification by flash column chroma-
tography (15% EtOAc in hexanes) provided tricycles 29 (163 mg,
52%) and 30 (108 mg, 30%) as colorless oils. For compound 29:
[R]26.4D ) +38.7 (c 2.0, CHCl3); 1H NMR δ 6.91 (s, 1H), 6.75 (s,
1H), 5.17 (d, J ) 6.6 Hz, 1H), 5.13 (d, J ) 6.3 Hz, 1H), 4.61 (s,
2H), 3.50 (s, 3H), 3.39 (dd, J ) 11.7, 3.1 Hz, 1H), 2.71 (s, 1H),
2.70-2.66 (m, 1H), 2.10-2.00 (m, 1H), 1.80-1.65 (m, 5H), 1.22
(s, 3H), 1.09 (s, 3H), 0.94 (s, 9H), 0.87 (s, 3H), 0.10 (s, 6H); 13C
NMR δ 145.9, 143.1, 134.7, 123.1, 121.5, 114.4, 96.2, 78.3, 76.7,
65.0, 56.3, 47.0, 38.6, 38.0, 28.5, 27.6, 26.3 (3C), 23.5, 20.1, 18.7,
14.5, -4.9 (2C); HRMS (EI+) m/z calcd for C25H42O5Si (M+)
(2R,4aR,9aR)-Schweinfurthin G (8). To a solution of stilbene
34 (24 mg, 0.04 mmol) in MeOH was added TsOH (31 mg, 0.18
mmol) at room temperature, and the solution was stirred for 19 h.
The reaction was quenched by addition of NaHCO3 (sat.) and
extracted with EtOAc. The combined extracts were washed with
H2O and brine, dried (MgSO4), and concentrated in vacuo to afford
a yellow oil. Final purification by flash column chromatography
(3:2 hexanes/EtOAc) afforded stilbene 8 (11 mg, 57%) as a colorless
oil: [R]26.4 ) +58.4 (c 0.7, CH3OH); literature7 [R]22 ) +32.4
450.2802, found 450.2809. For compound 30: [R]26.4 ) +18 (c
D
D
D
1.7, CHCl3); 1H NMR δ 6.91 (d, J ) 1.8 Hz, 1H), 6.74 (d, J ) 1.8
Hz, 1H), 5.17 (d, J ) 6.6 Hz, 1H), 5.13 (d, J ) 6.3 Hz, 1H), 4.77
(d, J ) 6.9 Hz, 1H), 4.64 (d, J ) 6.9 Hz, 1H), 4.62 (s, 2H), 3.50
(s, 3H), 3.41 (s, 3H), 3.25 (dd, J ) 11.7, 4.2 Hz, 1H), 2.71 (s, 1H),
2.69-2.66 (m, 1H), 2.12-2.04 (m, 1H), 2.02-1.94 (m, 1H),
1.80-1.65 (m, 3H), 1.23 (s, 3H), 1.08 (s, 3H), 0.94 (s, 9H), 0.89
(c 0.04, CH3OH); both H and 13C NMR spectra matched that of
the natural product;7 HRMS (EI+) m/z calcd for C29H36O5 (M+)
464.2563, found 464.2565. The HPLC analyses were performed
on a Shimadzu LC-20AT instrument with a Chiralcel OD-H
column. The enantiomeric excess for compound 8 was determined
by elution with a 4:1 mixture of hexanes and 2-propanol. Retention
1
7968 J. Org. Chem. Vol. 73, No. 20, 2008

BF3 ·Et2O-Mediated Cascade Cyclizations
times for the enantiomers of schweinfurthin G (8) were 15.2 min
(3.1%) and 17.9 min (96.9%), respectively.
1.8 Hz, 1H), 6.81-6.80 (m, 1H), 5.19 (d, J ) 6.9 Hz, 1H), 5.15
(d, J ) 6.3 Hz, 1H), 4.77 (d, J ) 7.2 Hz, 1H), 4.64 (d, J ) 6.6 Hz,
1H), 4.55 (s, 2H), 3.51 (s, 3H), 3.41 (s, 3H), 3.27 (dd, J ) 11.4,
4.2 Hz, 1H), 2.71 (s, 1H), 2.68 (d, J ) 4.2 Hz, 1H), 2.15-2.05 (m,
1H), 2.02-1.95 (m, 1H), 1.90-1.80 (br s, 1H), 1.75-1.65 (m, 3H),
1.23 (s, 3H), 1.08 (s, 3H), 0.89 (s, 3H); 13C NMR (CDCl3) δ 146.0,
143.8, 132.2, 123.4, 122.6, 114.9, 96.2, 95.9, 84.1, 76.8, 65.3, 56.3,
55.8, 47.1, 38.3, 37.7, 27.5, 25.3, 23.3, 19.9, 15.2; HRMS (EI+)
m/z calcd for C21H32O6 (M+) 380.2199, found 380.2201.
(2R,4aR,9aR)-Tri(O-methoxymethyl)-3-deoxyschwein-
furthin A (36). To a suspension of NaH (50 mg, 1.24 mmol, 60%
oil dispersion) and 15-crown-5 (0.01 mL, 0.05 mmol) in THF at 0
°C was added a solution of phosphonate 35 (37 mg, 0.08 mmol)
and aldehyde 32 (25 mg, 0.08 mmol) in THF. After the reaction
was allowed to warm to room temperature and stirred for 20 h, it
was quenched by addition of H2O and extracted with EtOAc. The
combined organic extracts were washed with H2O and brine, dried
(MgSO4), concentrated in vacuo to a yellow liquid, and purified
by flash column chromatography (2:1 hexanes/EtOAc) to afford
Phosphonate 42. To a solution of alcohol 41 (38 mg, 0.10 mmol)
in CH2Cl2 at 0 °C was added triethylamine (0.08 mL, 0.58 mmol).
Methanesulfonyl chloride (0.05 mL, 0.64 mmol) was added
dropwise, and the solution was stirred for 5.5 h. The reaction was
quenched by addition of H2O and extracted with CH2Cl2. The
combined organic layers were washed with NH4Cl (sat.) and brine,
dried (MgSO4), and concentrated in vacuo to a yellow oil, which
was then dissolved in acetone and treated with sodium iodide (79
mg, 0.53 mmol) for 15 h. After the solvent was removed in vacuo,
the red oily residue was extracted with EtOAc. The organic layers
were washed with H2O, NaHCO3 (sat.), and then Na2S2O3 until
the reddish color dissipated. The combined aqueous layers were
extracted with EtOAc. The combined organic extracts were washed
with brine, dried (MgSO4), and concentrated to a yellow oil which
was subsequently dissolved in P(OEt)3 (0.08 mL, 0.47 mmol). This
solution was heated for 7 h at 80 °C and then quenched by addition
of H2O and extracted with EtOAc. The organic extracts were
washed with H2O and brine, dried (MgSO4), and concentrated in
vacuo to a yellow liquid. Final purification by flash column
chromatography (20-100% EtOAc in hexanes) yielded phospho-
stilbene 36 (33 mg, 66%) as a colorless oil: [R]26.4 ) +39.0 (c
D
2.0, CHCl3); 1H NMR δ 7.11 (d, J ) 2.1 Hz, 1H), 6.96-6.94 (m,
2H), 6.90 (s, 2H), 6.87-6.86 (s, 1H), 5.23-5.19 (m, 7H),
5.07-5.04 (m, 1H), 3.54 (s, 3H), 3.51-3.49 (m, 7H), 3.39 (d, J )
6.9 Hz, 2H), 2.73 (s, 1H), 2.71 (d, J ) 3.2 Hz, 1H), 2.15-2.05 (m,
3H), 2.00-1.80 (m, 5H), 1.79 (s, 3H), 1.75-1.70 (m, 2H), 1.64
(s, 3H), 1.57 (s, 3H), 1.25 (s, 3H), 1.11 (s, 3H), 0.89 (s, 3H); 13C
NMR δ 156.0 (2C), 146.3, 144.0, 136.8, 134.8, 131.4, 129.2, 128.2,
126.8, 124.5, 123.3, 122.8, 122.2, 119.7, 113.7, 106.2 (2C), 96.1,
94.6 (2C), 78.1, 77.1, 56.4, 56.1 (2C), 46.9, 40.0, 38.5, 37.9, 28.4,
27.4, 26.9, 25.7, 23.4, 23.1, 20.1, 17.8, 16.2, 14.4; HRMS (EI+)
m/z calcd for C40H56O8 (M+) 664.3975, found 664.3989.
(2R,4aR,9aR)-3-Deoxyschweinfurthin A (10). To a solution of
stilbene 36 (4.9 mg, 0.01 mmol) in MeOH was added TsOH (7.3
mg, 0.04 mmol) at room temperature, and the solution was stirred
for 24 h. The reaction was quenched by addition of NaHCO3 (sat.)
and extracted with EtOAc. The combined extracts were washed
with H2O and brine, dried (MgSO4), and concentrated in vacuo to
afford a yellow oil. After final purification by flash column
chromatography (3:2 hexanes/EtOAc), stilbene 10 (2.7 mg, 69%)
was obtained as a colorless oil: 1H NMR (CD3OD) δ 6.83 (d, J )
16.5 Hz, 1H), 6.81-6.80 (m, 1H), 6.73-6.72 (m, 1H), 6.71 (d, J
) 16.2 Hz, 1H), 6.43 (s, 2H), 5.23 (t, J ) 6.6 Hz, 1H), 5.06 (t, J
) 6.9 Hz, 1H), 3.34-3.28 (m, 3H), 2.74-2.69 (m, 2H), 2.05-2.00
(m, 4H), 1.95-1.90 (m, 2H), 1.75 (s, 3H), 1.70-1.65 (m, 3H),
1.61 (s, 3H), 1.55 (s, 3H), 1.21 (s, 3H), 1.08 (s, 3H), 0.86 (s, 3H);
13C NMR (CD3OD) δ 157.3 (2C), 147.0, 142.2, 137.5, 134.8, 132.0,
131.0, 128.6, 127.5, 125.5, 124.6, 124.0, 120.4, 115.9, 111.1, 105.7
(2C), 78.7, 78.2, 48.6, 41.0, 39.5, 38.9, 29.0, 27.9, 27.8, 25.9, 24.0,
23.2, 20.2, 17.7, 16.3, 14.8; HRMS (EI+) m/z calcd for C34H44O5
(M+) 532.3189, found 532.3193.
Alcohol 37. To a solution of silyl ether 21 (39 mg, 0.08 mmol)
in THF at 0 °C was added a solution of TBAF (0.10 mL, 0.10
mmol, 1 M in THF). The resulting solution was stirred for 4 h,
quenched by addition of NH4Cl (sat.), and extracted with EtOAc.
The organic extracts were washed with H2O and brine, dried
(MgSO4), and concentrated in vacuo to give a yellow liquid. Final
purification by flash column chromatography (40% EtOAc in
hexanes) afforded alcohol 37 (20 mg, 68%) as a colorless oil:
[R]26.4D ) +31 (c 0.42, CHCl3); 1H NMR (CDCl3) δ 6.73 (d, J )
1.8 Hz, 1H), 6.70 (s, 1H), 4.77 (d, J ) 6.6 Hz, 1H), 4.64 (d, J )
7.2 Hz, 1H), 4.57 (s, 2H), 3.84 (s, 3H), 3.41 (s, 3H), 3.26 (dd, J )
11.4, 4.2 Hz, 1H), 2.71-2.68 (m, 2H), 2.13 (dt, J ) 12.0, 3.3 Hz,
1H), 2.02-1.94 (m, 2H), 1.85-1.75 (m, 2H), 1.24 (s, 3H), 1.07
(s, 3H), 0.89 (s, 3H); 13C NMR (CDCl3) δ 148.9, 142.2, 132.1,
122.7, 120.5, 108.5, 96.2, 84.1, 76.8, 65.5, 56.1, 55.7, 47.1, 38.3,
37.7, 27.5, 25.4, 23.2, 19.8, 15.2; HRMS (EI+) m/z calcd for
C20H30O5 (M+) 350.2093, found 350.2095.
nate 42 (31 mg, 62%) as a colorless oil: [R]26.4 ) +20.0 (c 2.0,
D
CHCl3); 1H NMR (CDCl3) δ 6.86 (s, 1H), 6.74 (s, 1H), 5.17 (d, J
) 6.3 Hz, 1H), 5.13 (d, J ) 6.6 Hz, 1H), 4.77 (d, J ) 6.9 Hz, 1H),
4.64 (d, J ) 6.9 Hz, 1H), 4.07-3.99 (m, 4H), 3.49 (s, 3H), 3.41
(s, 3H), 3.27 (dd, J ) 11.4, 4.2 Hz, 1H), 3.03 (d, JPH ) 21.3 Hz,
2H), 2.69 (s, 1H), 2.66 (d, J ) 4.2 Hz, 1H), 2.10-2.05 (m, 1H),
2.02-1.95 (m, 1H), 1.75-1.65 (m, 3H), 1.27 (t, J ) 6.9 Hz, 6H),
1.22 (s, 3H), 1.07 (s, 3H), 0.88 (s, 3H); 13C NMR (CDCl3) δ 145.9
(d, JCP ) 3.2 Hz), 143.1, 124.9 (d, JCP ) 7.6 Hz), 123.4 (d, JCP
)
2.7 Hz), 122.2 (d, JCP ) 9.2 Hz), 117.3 (d, JCP ) 6.4 Hz), 96.2,
96.0, 84.1, 77.4, 62.2 (d, JCP ) 6.9 Hz), 62.2 (d, JCP ) 6.9 Hz),
56.2, 55.8, 47.0, 38.3, 37.8, 33.0 (d, JCP ) 138.1 Hz), 27.5, 25.4,
23.2, 19.9, 16.5 (d, JCP ) 6.2 Hz), 16.5 (d, JCP ) 6.2 Hz), 15.2;
31P NMR δ 28.1; HRMS (EI+) m/z calcd for C25H41O8P (M+)
500.2541, found 500.2539.
(2R,4aR,9aR)-Tetra(O-methoxymethyl)-3-deoxyschwein-
furthin A (43). To a suspension of NaH (56 mg, 1.40 mmol, 60%
oil dispersion) and 15-crown-5 (0.01 mL, 0.05 mmol) in THF at 0
°C was added a solution of phosphonate 42 (31 mg, 0.06 mmol)
and aldehyde 39 (39 mg, 0.11 mmol) in THF. After the reaction
was allowed to warm to room temperature and stirred for 16 h, it
was quenched by addition of H2O and extracted with EtOAc. The
organic extracts were washed with H2O and brine, dried (MgSO4),
concentrated in vacuo to a yellow liquid, and purified by flash
column chromatography (10-25% EtOAc in hexanes) to afford
stilbene 43 (30 mg, 67%) as a colorless oil: [R]26.4 ) +42.2 (c
D
1
2.0, CHCl3); H NMR (CDCl3) δ 7.12 (d, J ) 1.8 Hz, 1H), 6.95
(d, J ) 1.5 Hz, 1H), 6.94-6.90 (m, 3H), 6.86 (d, J ) 16.2 Hz,
1H), 5.25-5.18 (m, 7H), 5.07 (t, J ) 6.9 Hz, 1H), 4.78 (d, J ) 6.9
Hz, 1H), 4.65 (d, J ) 6.6 Hz, 1H), 3.54 (s, 3H), 3.50 (s, 6H), 3.41
(s, 3H), 3.41-3.37 (m, 2H), 3.28 (dd, J ) 11.4, 4.2 Hz, 1H), 2.73
(s, 1H), 2.70 (d, J ) 4.2 Hz, 1H), 2.15-1.95 (m, 7H), 1.78 (s,
3H), 1.75-1.70 (m, 2H), 1.65 (s, 3H), 1.57 (s, 3H), 1.25 (s, 3H),
1.09 (s, 3H), 0.91 (s, 3H); 13C NMR (CDCl3) δ 156.1 (2C), 146.3,
144.0, 136.8, 134.8, 131.4, 129.2, 128.2, 126.7, 124.5, 123.3, 122.7,
122.2, 119.6, 113.6, 106.1 (2C), 96.3, 96.0, 94.6 (2C), 84.2, 77.1,
56.4, 56.1 (2C), 55.8, 47.2, 40.0, 38.4, 37.8, 27.7, 26.9, 25.8, 25.4,
23.3, 22.8, 20.0, 17.8, 16.2, 15.3; HRMS (EI+) m/z calcd for
C42H60O9 (M+) 708.4237, found 708.4231.
Alcohol 41. To a solution of silyl ether 30 (76 mg, 0.15 mmol)
in THF at 0 °C was added a solution of TBAF (0.18 mL, 0.18
mmol, 1 M in THF). The resulting solution was stirred for 16 h,
quenched by addition of NH4Cl (sat.), and extracted with EtOAc.
The organic extracts were washed with H2O and brine, dried
(MgSO4), and concentrated in vacuo to give a yellow liquid. Final
purification by flash column chromatography (30% EtOAc in
hexanes) afforded alcohol 41 (35 mg, 59%) as a colorless oil:
[R]26.4D ) +26.2 (c 3.0, CHCl3); 1H NMR (CDCl3) δ 6.95 (d, J )
J. Org. Chem. Vol. 73, No. 20, 2008 7969

Mente et al.
(2R,4aR,9aR)-3-Deoxyschweinfurthin A (10). To a solution of
stilbene 43 (28 mg, 0.04 mmol) in MeOH was added TsOH (43
mg, 0.25 mmol) at room temperature, and the solution was stirred
for 136 h. The reaction was quenched by addition of NaHCO3 (sat.)
and extracted with EtOAc. The organic extracts were washed with
H2O and brine, dried (MgSO4), and concentrated in vacuo to afford
a yellow oil. Final purification by flash column chromatography
(60:40 hexanes/EtOAc) afforded the desired target 3dSA (10, 11
mg, 52%) as a yellow oil: [R]26.4D ) +48.5 (c 0.6, CD3OD); with
spectral data matching that reported above. Also isolated was a
partially hydrolyzed analogue bearing an A-ring MOM ether (44,
122.2, 121.7, 119.7, 113.0, 109.6, 106.2 (2C), 105.8, 96.3, 84.0,
78.0, 63.9, 55.8, 47.6, 39.9, 38.4, 37.7, 27.5, 26.5, 25.8, 25.3, 22.8,
20.3, 17.9, 16.3, 15.2; HRMS (EI+) m/z calcd for C20H30O5 (M+)
350.2093, found 350.2095.
Acknowledgment. Financial support from the Roy J. Carver
Charitable Trust, the Children’s Tumor Foundation, the
Predoctoral Training Program in the Pharmacological Sci-
ences (2 T32 GM067795), and the UI Graduate College in
the form of a Presidential Fellowship to N.R.M. is gratefully
acknowledged.
1
7 mg, 33%) as a yellow oil: H NMR (CDCl3) δ 6.92 (d, J ) 2.1
Hz, 1H), 6.87 (d, J ) 16.8 Hz, 1H), 6.75 (d, J ) 16.2 Hz, 1H),
6.75-6.74 (m, 1H), 6.56 (s, 2H), 5.68 (br s, 2H), 5.49 (br s, 1H),
5.28 (t, J ) 6.6 Hz, 1H), 5.06 (t, J ) 5.4 Hz, 1H), 4.78 (d, J ) 6.6
Hz, 1H), 4.65 (d, J ) 7.2 Hz, 1H), 3.45-3.42 (m, 2H), 3.42 (s,
3H), 3.29 (dd, J ) 11.4, 3.6 Hz, 1H), 2.73-2.66 (m, 2H), 2.13-1.96
(m, 5H), 1.82 (s, 3H), 1.78-1.70 (m, 4H), 1.68 (s, 3H), 1.59 (s,
3H), 1.24 (s, 3H), 1.10 (s, 3H), 0.90 (s, 3H); 13C NMR (CDCl3) δ
155.5 (2C), 145.3, 139.1, 137.2, 132.2, 129.8, 128.5, 126.3, 123.9,
Supporting Information Available: Experimental para-
graphs for compounds 25, 26, 38, 39, 40, and 11, along with
1
complete H and 13C NMR spectra for compounds 8, 10, 21,
25, 26, 28-32, 34, and 36-44 can be found here. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO800951Q
7970 J. Org. Chem. Vol. 73, No. 20, 2008