Stereoselective syntheses of (+)-goniodiol, (-)-8-epigoniodiol, and (+)-9-deoxygoniopypyrone via alkoxyallylboration and ring-closing metathesis

Article abstract of DOI:10.1021/jo0259358

A convenient synthesis of (+)-goniodiol, (-)-8-epigoniodiol, and (+)-9-deoxygoniopypyrone has been developed via asymmetric alkoxyallylboration and ring-closing metathesis pathways.

Full text of DOI:10.1021/jo0259358

Ster eoselective Syn th eses of (+)-Gon iod iol,
(-)-8-Ep igon iod iol, a n d
(+)-9-Deoxygon iop yp yr on e via
Alk oxya llylbor a tion a n d Rin g-Closin g
Meta th esis
P. Veeraraghavan Ramachandran,*
J . Subash Chandra, and M. Venkat Ram Reddy
Herbert C. Brown Center for Borane Research,
Department of Chemistry, Purdue University,
West Lafayette, Indiana 47907-1393
chandran@purdue.edu
Received May 14, 2002
Abstr a ct: A convenient synthesis of (+)-goniodiol, (-)-8-
epigoniodiol, and (+)-9-deoxygoniopypyrone has been devel-
oped via asymmetric alkoxyallylboration and ring-closing
metathesis pathways.
F IGURE 1.
their use as painkillers9 and mosquito repellants.7b
Several of these styryllactones have also been found to
possess excellent antitumoral properties.7d-f,10
Due to the broad spectrum of pharmacological proper-
ties associated with these molecules, several syntheses
have been reported in the literature.11,12 For example, Ley
and co-workers have recently reported the synthesis of
(+)-goniodiol via a Lewis acid-mediated diastereoselective
oxygen-to-carbon rearrangement of an anomerically linked
silyl enol ether.12f Tsubuki et al. have described a
stereocontrolled synthesis of several styryllactones start-
5,6-Dihydro-2H-pyran-2-ones (R-pyrones) are present
in a large number of biologically active organic mol-
ecules.1 Examples of such molecules include fostreicin,2
pironetin,3 passifloricins,4 and cryptopyranmoscatones.5
R-Pyrones have been utilized as intermediates for syn-
thetic transformations.6 Once the asymmetric center is
introduced, it can be used to induce stereospecificity to
the neighboring carbons in a variety of optically active
molecules via substrate-controlled reactions.6
Goniopyrones, a series of styryllactones, isolated from
various species of the genus Goniothalamus (Figure 1),7
have been traditionally used for the treatment of edema
and rheumatism.8 Other general applications include
(9) Sam, T. W.; Yeu, C. S.; Matsieh, S.; Gan, E. K.; Razak, D.;
Mohamed, A. L. Tetrahedron Lett. 1987, 28, 2541.
(10) (a) Fang, X. P.; Anderson, J . E.; Chang, C.-J .; Fanwick, P. E.;
McLaughlin, J . L. J . Chem. Soc., Perkin Trans. 1 1990, 1655. (b) Fang,
X. P.; Anderson, J . E.; Chang, C.-J .; McLaughlin, J . L. Tetrahedron
1991, 47, 9751.
(1) (a) Davies-Coleman, M. T.; Rivett, D. E. A. Fortschr. Chem. Org.
Naturst. 1989, 55, 1. (b) Davies-Coelman, M. T.; Rivett, D. E. A. In
Progress in the Chemistry of Organic Natural Products; Zechmeister,
L., Ed.; Springer-Verlag: New York, 1989; Vol. 55, p 1.
(2) (a) Boger, D. L.; Ichikawa, S.; Zhong, W. J . Am. Chem. Soc. 2001,
123, 4161. (b) Chavez, D. E.; J acobsen, E. N. Angew. Chem., Int. Ed.
2001, 40, 3667.
(3) (a) Gurjar, M. K.; Henri, J . T.; Bose, D. S.; Rao, A. V. R.
Tetrahedron Lett. 1996, 37, 6615. (b) Keck, G. E.; Knutson, C. E.; Wiles,
S. A. Org. Lett. 2001, 3, 707.
(4) Echeverri, F.; Arango, V.; Quinones, W.; Torres, F.; Escobar, G.;
Rosero, Y.; Archbold R. Phytochemistry 2001, 56, 881.
(5) Cavalheiro, A. J .; Yoshida, M. Phytochemistry 2000, 53, 811.
(6) (a) Harris, J . M.; Keranen, M. D.; Nguyen, H.; Young, V. G.;
O’Doherty, G. A. Carbohydr. Res. 2000, 328, 17. (b) Nicolaou, K. C.;
Mitchell, H. J . Angew. Chem., Int. Ed. 2001, 40, 1576.
(11) (a) Shing, T. K. M.; Zhou, Z. H. Tetrahedron Lett. 1992, 33, 3333.
(b) Tsubuki, M.; Kanai, K.; Honda, T. J . Chem. Soc., Chem. Commun.
1992, 1640. (c) Shing, T. K. M.; Zhou, Z. H.; Mak, T. C. W. J . Chem.
Soc., Perkin Trans. 1 1992, 1907. (d) Shing, T. K. M.; Tsui, H. C.; Zhou,
Z. H. Tetrahedron Lett. 1993, 34, 691. (e) Zhou, W. S.; Yang, Z. C.
Tetrahedron Lett. 1993, 34, 7075 (f) Tsubuki, M.; Kanai, K.; Honda,
T. Synlett 1993, 653. (g) Freisen, R. W.; Bissada, S. Tetrahedron Lett.
1994, 35, 5615. (h) Fuganti, C.; Fantoni, G. P.; Sarra, A.; Servi, S.
Tetrahedron: Asymmetry 1994, 5, 1135. (i) Yang, Z. C.; Zhou, W. S. J .
Chem. Soc., Perkin Trans. 1 1994, 3231. (j) Yang, Z. C.; Zhou, W. S.
Tetrahedron 1995, 51, 1429. (k) Goh, S. H.; Ee, G. C. L.; Chuah, C. H.;
Wei, C. Aust. J . Chem. 1995, 48, 199. (l) Shing, T. K. M.; Tsui, H. C.;
Zhou, Z. H. J . Org. Chem. 1995, 60, 3121. (m) Surivet, J . P.; Gore, J .;
Vatele, J . M. Tetrahedron 1996, 52, 14877. (n) Surivet, J . P.; Gore, J .;
Vatele, J . M. Tetrahedron Lett. 1996, 37, 371. (o) Surivet, J . P.; Gore,
J .; Vatele, J . M. Tetrahedron: Asymmetry 1996, 7, 3305.
(7) (a) J ewers, K.; Daivs, J . B.; Dougan, J .; Manchanda, A. H.;
Blunden, G.; Kyi, A.; Wetchapinon, S. Phytochemistry 1972, 11, 2025.
(b) Talapatra, S. K.; Basu, D.; Deb, T.; Goswami, S.; Talapatra, B.
Indian J . Chem., Sect. B 1985, 24, 29. (c) El-Zayat, A. A. E.; Ferrighi,
N. R.; McKenzie, T. G.; Byrn, S. R.; Cassady, J . M.; Chang, C.-J .;
McLaughlin, J . L. Tetrahedron Lett. 1985, 26, 955. (d) Alkofahi, A.;
Ma, W.-W.; McKenzie, A. T.; Byrn, S. R.; McLaughlin, J . L. J . Nat.
Prod. 1989, 52, 1371. (e) Fang, X.-P.; Anderson, J . E.; Chang, C.-J .;
McLaughlin, J . L.; Fanwick, P. E. J . Nat. Prod. 1991, 54, 1034. (f)
Bermejo, A.; Leonce, S.; Cabedo, N.; Andreu, I.; Caignard, D. H.; Atassi,
G.; Cortes, D. J . Nat. Prod. 1999, 62, 110. (g) Blazquez, M. A.; Bermejo,
A.; Zafra-Polo, M. C.; Cortes, D. Phytochem. Anal. 1999, 10, 161. (h)
Wang, S.; Zhang, Y.-J .; Chen, R.-Y.; Yu, D.-Q. J . Nat. Prod. 2002, 65,
835.
(12) (a) Surivet, J . P.; Vatele, J . M. Tetrahedron Lett. 1997, 38, 819.
(b) Mukai, C.; Hirai, S.; Hanaoka, M. J . Org. Chem. 1997, 62, 6619.
(c) Freisen, R. W.; Bissada, S. Can. J . Chem. 1998, 76, 94. (d) Cao, S.
G.; Wu, X. H.; Sim, K. Y.; Tan, B. K. H.; Pereira, J . T.; Goh, S. H.
Tetrahedron 1998, 54, 2143. (e) Surivet, J . P.; Vatele, J . M. Tetrahedron
Lett. 1998, 39, 7299. (f) Dixon, D. J .; Ley, S. V.; Tate, E. W. J . Chem.
Soc., Perkin Trans. 1 1998, 3125. (g) Yi, X. H.; Meng, Y.; Hua, X. G.;
Li, C. J . J . Org. Chem. 1998, 63, 7472. (h) Mu, Q.; Tang, W. D.; Li, C.
M.; Lu, Y.; Sun, H. D.; Zheng, H. L.; Hao, X. J .; Zheng, Q. T.; Wu, N.;
Lou, L. G.; Xu, B. Heterocycles 1999, 51, 2969. (i) Tsubuki, M.; Kanai,
K.; Nagase, H.; Honda, T. Tetrahedron 1999, 55, 2493. (j) Surivet, J .
P.; Vatele, J . M. Tetrahedron 1999, 55, 13011. (k) Chen, W. P.; Roberts,
S. M. J . Chem. Soc., Perkin Trans. 1 1999, 103. (l) Mereyala, H. B.;
Gadikota, R. R.; J oe, M.; Arora, S. K.; Dastidar, S. G.; Agarwal, S.
Bioorg. Med. Chem. 1999, 7, 2095. (m) Bruns, R.; Wernicke, A.; Koll,
P. Tetrahedron 1999, 55, 9793. (n) Su, Y. L.; Yang, C. S.; Teng, S. J .;
Zhao, G.; Ding, Y. Tetrahedron 2001, 57, 2147.
(8) Wu, Y. C.; Duh, C. Y.; Chang, F. R.; Chang, G. Y.; Wang, S. K.;
Chang, J . J .; McPhail, D. R.; McPhail, A. T.; Lee, K. H. J . Nat. Prod.
1991, 54, 1077.
10.1021/jo0259358 CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/21/2002
J . Org. Chem. 2002, 67, 7547-7550
7547

SCHEME 1
F IGURE 2.
F IGURE 3.
We began with the synthesis of (+)-goniodiol (1) and
(-)-8-epigoniodiol (2). In addition to the R-pyrone unit,
1 possesses an anti diol and 2 possesses a syn diol unit
on the side chain. Our retrosynthetic analysis is shown
in Scheme 1.
ing from 2,3-O-isopropylidene-D-glyceraldehyde employ-
ing NBS-mediated lactol formation, followed by chemo-
selective phenyl addition using triisopropoxyphenylti-
tanium,12i and Vatele and Surivet have synthesized
enantiopure styryllactones starting from a common chiral
precursor ethyl-4-(tert-butyldimethylsilyloxy)-2,3-isopro-
pylidinedioxy-4-phenylbutanoate, prepared from (R)-
mandelic acid.12j
As part of our program on the synthesis of biologically
active natural products13 via pinane-based versatile
reagents,14 we undertook the synthesis of styryllactones.
Although asymmetric allyl- and crotylboration using
terpenes as chiral auxiliaries have been well exploited
for organic syntheses15 (Figure 2), the corresponding
alkoxyallylboration16 has received little attention.16b-f We
envisaged alkoxyallylboration and ring-closing meta-
thesis17 reactions using Grubbs’ catalysts (Figure 3) as
the most appropriate sequence for a short synthesis of
styryllactones. The alkoxy moiety in the alkoxyallyl-
boranes proved to be crucial for the achievement of the
synthesis. Herein we discuss our successful synthesis of
styryllactones.
As can be seen, we chose the syn homoallylic diol for
the synthesis of both 1 and 2. One of the chiral centers
was inverted for the synthesis of 1. We explored the
possibility of utilizing R-pinene-based asymmetric alkoxy-
allylboration due to the demonstrated capability of these
reagents in affording monoprotected syn diols with
excellent diastereo- and enantioselectivities. With this in
mind, we prepared the (Z)-γ-aryloxyallyldiisopinocam-
phenylborane from allyl p-methoxyphenyl ether 11. The
idea was to obtain R-aryloxy syn homoallylic alcohol,
which could be readily converted to the bis-arylated anti
diol, using a Mitsunobu inversion18 with p-methoxy
phenol as the nucleophile. Thus, the same R-phenoxy-
homoallylic alcohol would afford both syn and anti diols,
which could further be transformed to 2 and 1, respec-
tively, with a minimum number of protection/deprotec-
tion steps.
Aryloxyallylboration of benzaldehyde with B-γ-p-meth-
oxyphenoxyallyldiisopinocampheylborane (12), prepared
from (+)-B-methoxydiisopinocampheylborane and lithi-
ated allyl p-methoxyphenyl ether in THF at -78 °C,
followed by oxidation, provided a 76% yield of the
monoprotected hydroxy olefin 13a (Scheme 2).19 The
enantiopurity of this material was determined by HPLC
analysis using a CHIRALCEL OD-H column20 and found
to be 96%.
(13) (a) Reddy, M. V. R.; Yucel, A. J .; Ramachandran, P. V. J . Org.
Chem. 2001, 66, 2512. (b) Reddy, M. V. R.; Rearick, J . P.; Hoch, N.;
Ramachandran, P. V. Org. Lett. 2001, 3, 19. (c) Ramachandran, P. V.;
Reddy, M. V. R.; Brown, H. C. Tetrahedron Lett. 2001, 41, 583. (d)
Ramachandran, P. V.; Reddy, M. V. R.; Brown, H. C. J . Ind. Chem.
Soc. 1999, 76, 939. (e) Reddy, M. V. R.; Brown, H. C.; Ramachandran,
P. V. J . Organomet. Chem. 2001, 624, 239.
(14) Brown, H. C.; Ramachandran, P. V. J . Organomet. Chem. 1995,
500, 1.
(15) Ramachandran, P. V. Aldrichimica Acta 2002, 35, 23. (a)
Brown, H. C.; J adhav, P. K. J . Org. Chem. 1984, 49, 4089. (b) Brown,
H. C.; J adhav, P. K. J . Am. Chem. Soc. 1983, 105, 2095.
(16) (a) Brown, H. C.; J adhav, P. K.; Bhat, K. S. J . Am. Chem. Soc.
1988, 110, 1535. (b) Smith, A. L.; Pitsinos, E. N.; Hwang, C. K.; Mizuno,
Y.; Saimoto, H.; Scarlato, G. R.; Suzuki, T.; Nicolaou, K. C. J . Am.
Chem. Soc. 1993, 115, 7612. (c) Burgess, K.; Henderson, I. Tetrahedron
Lett. 1990, 31, 6949. (d) Nakata, M.; Osumi, T.; Ueno, A.; Kimura, T.;
Tamai, T.; Tatsuta, K. Tetrahedron Lett. 1991, 32, 6015. (e) Burgess,
K.; Chaplin, D. A.; Henderson, I. J . Org. Chem. 1992, 57, 1103. (f)
Anderson, O. P.; Barrett, A. G. M.; Edmunds, J . J .; Hachiya, S.-I.;
Hendrix, J . A.; Horita, K.; Malecha, J . W.; Parkinson, C. J .; VanSickle,
A. Can. J . Chem. 2001, 79, 1562.
(17) For recent reviews, see: (a) Grubbs, R. H.; Chang, S. Tetrahe-
dron 1998, 54, 4413. (b) Furstner, A. Angew. Chem., Int. Ed. 2000,
39, 3013. (c) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953. (d) Chatterjee, A. K.; Morgan, J . P.; Scholl, M.; Grubbs,
R. H. J . Am. Chem. Soc. 2000, 122, 3783. (e) Lee, C. W.; Grubbs, R. H.
Org. Lett. 2000, 2, 2145. (f) Biewalski, C. W.; Grubbs, R. H. Angew.
Chem., Int. Ed. 2002, 39, 2903.
The benzylic hydroxy group in 13a was inverted under
Mitsunobu conditions using p-methoxyphenol as the
(18) For recent reviews see: (a) Hughes, D. L. Organic Reactions;
Wiley & Sons: New York, 1992; Vol. 42, p 335. (b) Hughes, D. L. Org.
Prep. Proc. Int. 1996, 28, 127.
(19) (a) We believe that we have the (S,S) isomer of 13a on the basis
of analogy with similar alkoxyallylborations reported in the literature.16
To prove that the syn homoallylic alcohol was obtained in the reaction,
13a was inverted under Mitsunobu conditions using p-nitrobenzoic acid
as the nucleophile followed by ester hydrolysis to obtain the (R,S)-
isomer of 13a . The specific rotation of this isomer was found to be
consistent with the value reported in the literature: lit.21a [R]20D -20.6
(c 1.6, CHCl3); observed [R]20 -20.5 (c 0.9, CHCl3). (b) We also tested
D
the aryloxyallylboration of acetaldehyde with the reagent (+)-12 and
obtained an ee of 95% as determined by HPLC.
(20) Chiralcel OD-H is a trademark of Chiral Technologies, Inc.,
Exton, PA.
7548 J . Org. Chem., Vol. 67, No. 21, 2002

SCHEME 2a
product bis-aryloxy homoallylic alcohol 16 (Scheme 3).
The diastereomeric excess was again determined using
HPLC and was found to be 95%. Esterification with
acrylic acid yielded the corresponding acrylate 17, which
upon ring-closing metathesis reaction with Grubbs’ first
generation ruthenium catalyst 9 furnished the R-pyrone
18 in 85% yield. After achieving the penultimate molecule
in six steps, we proceeded to the final deprotection of the
p-methoxyphenyl groups. Unfortunately, the usual oxida-
tive cleavage with ceric ammonium nitrate21 in acetoni-
trile provided a complex mixture of products. Varying the
reaction parameters such as solvents, temperature, or
stoichiometry was also futile. We also attempted the use
of several other ether-cleaving agents such as dimethyl-
bromoborane,22 iodotrimethylsilane,23 and B-bromocat-
echolborane.24 However, we did not succeed in realizing
the expected product in optimal yields.
a
Reaction conditions: (a) sec-BuLi, THF, -78 °C, 0.5 h. (b) (+)-
Ipc2BOMe, -78 °C, 1 h. (c) BF3‚Et2O, -78 °C, 5 min. (d) RCHO,
-100 °C, 10 h. (e) NaOH/H2O2, rt, 6h.
SCHEME 3a
Since deprotection of the p-methoxyphenyl groups in
our protocol proved to be difficult, we turned to protecting
groups that can be cleaved under milder conditions. For
this purpose, we chose the methoxyethoxymethyl (MEM)
group,25 a protective group that can be cleaved under a
variety of mild Lewis and protic acid conditions. We
resumed our synthesis with alkoxyallylboration of ben-
zaldehyde with (+)-B-γ-methoxyethoxymethoxyallyldi-
isopinocampheylborane 19 (Scheme 4).16 As expected,
excellent diastereo- and enantioselectivities were achieved
and the product R-alkoxyhomoallylic alcohol 20 was
obtained in 71% yield and 98% ee as determined by
HPLC analysis. The stereochemistry of the benzylic
hydroxy group in 20 was inverted with p-nitrobenzoic
acid under Mitsunobu conditions, and the resulting
p-nitrobenzoate ester 21 was hydrolyzed under basic
medium to obtain the monoprotected anti diol 22. The
free hydroxy group in 22 was protected as its tert-
butyldimethylsilyl ether 23, and the oxidative cleavage
of the terminal double bond in 23, followed by allylbo-
ration with 8a , provided the corresponding homoallylic
alcohol 25. The diastereomeric excess was determined to
be 92% by derivatizing the alcohol as its cinnamate
ester26 (26) and analysis using HPLC. Ring-closing me-
tathesis of the cinnamate ester 26 with Grubbs’ second-
generation imidazolyl ruthenium-based catalyst 10 pro-
vided the R-pyrone 27.27 Both TBS and MEM groups were
a
Reaction conditions: (a) p-Methoxyphenol, PPh3, DIAD, THF,
70 °C, 8h, 78%. (b) (i) OsO4, NMO, acetone:water, 6 h; (ii) NaIO4,
acetone:water, 25 °C, 99%. (c) (i) (+)-8a , ether-pentane, -100 °C;
(ii) NaOH, H2O2, rt, 6 h, 75%. (d) Acrylic acid, DCC, DMAP,
CH2Cl2, 0 °C, 15 h, 70%. (e) 9, CH2Cl2, 60 °C, 6 h, 85%. (f) CAN,
Me2BBr, Me3SiI, etc.
nucleophile. The reaction proceeded smoothly in refluxing
THF, and we obtained a 78% yield of the inverted bis-
aryloxy olefin 14. The terminal double bond in 14 was
oxidatively cleaved using OsO4/NaIO4, and allylboration
of the resulting aldehyde 15 with B-allyldiiso-2-cara-
nylborane15 (8a ) in a Et2O-pentane mixture at -100 °C
for 3 h, followed by oxidation, afforded a 75% yield of the
SCHEME 4a
a
Reaction conditions: (a) (i) PhCHO, -100 °C; (ii) NaOH/H2O2, 25 °C, 71%. (b) p-Nitrobenzoic acid, PPh3, DEAD, toluene, -50 °C, 8
h, 76%. (c) NaOH, MeOH, rt, 1 h, 78%. (d) TBSCl, imidazole, DMF, 0 °C, 86%. (e) (i) OsO4, NMO, acetone:water, 0 °C, 6h; (ii) NaIO4,
acetone:water, rt, 50%. (f) (i) (+)-8a , ether-pentane, -100 °C; (ii) NaOH, H2O2, rt, 6 h, 76%. (g) (E)-Cinnamoyl chloride, Py, DMAP,
CH2Cl2, 0 °C, 15 h, 63%. (h) 9, toluene, 120 °C, 3 h, 76%. (i) HCl:THF:H2 (1:8:1) 65%.
J . Org. Chem, Vol. 67, No. 21, 2002 7549

SCHEME 5a
SCHEME 6 a
a
Reaction conditions: (a) TBSCl, imidazole, DMF, 0 °C, 89%.
a
(b) (i) OsO4, NMO, acetone:water, 0 °C, 6 h; (ii) NaIO4, acetone:
water, 20 min, 50%. (c) (i) (+)-8a , ether-pentane, -100 °C, 2h;
(ii) NaOH, H2O2, rt, 6 h, 73%. (d) (E)-Cinnamoyl chloride, Py,
DMAP, CH2Cl2, 0 °C, 15 h, 70%. (e) 10, toluene, 120 °C, 3 h, 77%.
(f) HCl:THF:H2O (1:8:1), 68%. (g) DBU, THF, 0 °C, 6 h, 86%.
Reaction conditions: (a) (i) p-Nitrobenzoic acid, PPh3, DEAD,
toluene, -50 °C; (ii) NaOH, MeOH, 25 °C. (b) Conc. HCl, MeOH,
25 °C. (c) DMP, PPTS, CH2Cl2. (d) (i) OsO4, NMO, 0 °C; (ii) NaIO4,
25 °C. (e) (i) (+)-7a , ether-pentane, -100 °C; (ii) NaOH/H2O2, rt.
(f) (E)-Cinnamic acid, DCC, DMAP, CH2Cl2, 0 °C. (g) 10, toluene,
120 °C. (h) HCl:THF:H2O, rt.
deprotected in a single step with HCl in THF to afford
goniodiol 1 in 65% yield. The overall yield of 1 starting
from benzaldehye was 7.2%.
required anti and syn diols 33 and 39 were prepared by
the acidic cleavage of the MEM groups from 22 and 20,
respectively. Both the diols were then protected as
acetonides, and the syntheses of 1 and 2 were completed
via the periodate cleavage, allylboration with (+)-7a ,
DCC condensation with cinnamic acid, ring-closing me-
tathesis, and deprotection (Scheme 6). Fortunately, the
MEM-cleavage, acetonide and aldehyde formation did not
require any purification, which increased the overall
yields of 1 and 2 by 70% starting from benzaldehyde.
In conclusion, we have developed a simple synthesis
of (+)-goniodiol, (-)-8-epigoniodiol, and (+)-9-deoxy-
goniopypyrone via alkoxyallylboration and ring-closing
metathesis reaction pathways. We have also developed
a new aryloxyallylborating agent, which furnishes PMP-
protected homoallylic alcohols in high de and ee. These
reaction sequences are shorter than several procedures
that are currently available in the literature. All of these
reactions can be carried out with ease and are amenable
to scale-up. The ready availability of both isomers of
inexpensive R-pinene makes these procedures especially
attractive.
Starting with homoallylic alcohol 20 and essentially
following the same steps mentioned above in Scheme 4,
except for the Mitsunobu inversion, the synthesis of (-)-
8-epigoniodiol 2 was also achieved without difficulty. The
overall yield of 2 starting from benzaldehyde was 8.5%.
Eventually, 2 was converted into (+)-9-deoxygoniopypy-
rone 3 via 1,7-diazabicyclo[5.4.0]undec-7-ene (DBU)-
catalyzed intramolecular Michael addition11d (Scheme 5).
The overall yield of 3 starting from benzaldehyde was
7.2%.
In an attempt to improve the overall yield, we intro-
duced the acetonide-protecting group in our schemes. The
(21) (a) Hafner, A.; Duthaler, R. O.; Marti, R.; Rihs, G.; Rothe-Streit,
P.; Schwarzanbach, F. J . Am. Chem. Soc. 1992, 114, 2321. (b) Enders,
D.; Geibel, G.; Osborne, S. Chem. Eur. J . 2000, 6, 1302. (c) Trost, B.
M.; Tsui, H.-C.; Toste, F. D. J . Am. Chem. Soc. 2000, 122, 3534.
(22) Guindon, Y.; Morton, H. E.; Yoakim, C. Tetrahedron Lett. 1983,
24, 3969.
(23) Olah, G. A.; Narang, S. C. Tetrahedron 1982, 38, 2225.
(24) Guindon, Y.; Yoakim, C.; Morton, H. E. J . Org. Chem. 1984,
49, 3912.
(25) Corey, E. J .; Gras, J . L.; Ulrich, P. Tetrahedron Lett. 1976, 11,
809.
(26) Esterification with acryloyl chloride provided poor yields of the
acrylate. Hence, we had to resort to the cinnamate ester.
(27) Utilization of catalyst 9 provided dismal yields of 27, and most
of the starting material was recovered.
Ack n ow led gm en t. Financial support from the Her-
bert C. Brown Center for Borane Research (Contribution
#19) and Aldrich Chemical Co. are gratefully ac-
knowledged.
J O0259358
7550 J . Org. Chem., Vol. 67, No. 21, 2002