SCHEME 1. Retr osyn th etic Ap p r oa ch for th e
Syn th esis of Sola m in 1
types of annonaceous acetogenins possessing tetrahydro-
pyran (THP)20 and nonadjacent bis-THF21 have been
reported recently.
Very few syntheses of annonaceous acetogenins22 have
used a ring-closing metathesis reaction (RCM)23 to form
the THF central core, despite the proven usefulness of
RCM for generation of such cyclic ether moieties.24 To
the best of our knowledge, a ruthenium-based RCM
strategy has not been reported for the construction of the
central THF core of type A acetogenin. Only the synthesis
of Muconin, a THF-THP acetogenin prepared by RCM
with molybdenum catalyst is known.22a
In this note, we report the first application of RCM
using ruthenium catalyst for the total synthesis of
Solamin 125 demonstrating the efficiency of this reaction
for constructing type A acetogenins.
Our synthetic plans are centered on the assembly of
the THF core via a RCM reaction of the corresponding
suitably elaborated open diene 2. The RCM substrate 2
was obtained by assembly of two simple building blocks,
SCHEME 2. Syn th esis of Allyl Alcoh ol 3a
(16) (a) Hoye, T. R.; Hanson, P. R.; Kovelesky, A. C.; Ocain, T. D.;
Zhuang, Z. J . Am. Chem. Soc. 1991, 113, 9369-9371. (b) Hoye, T. R.;
Ye, Z. J . Am. Chem. Soc. 1996, 118, 1801-1802. (c) Naito, H.;
Kawahara, E.; Maruta, K.; Maeda, M.; Sasaki, S. J . Org. Chem. 1995,
60, 4419-4427.
(17) (a) Yazbak, A.; Sinha, S. C.; Keinan, E. J . Org. Chem. 1998,
63, 5863-5868. (b) Emde, U.; Koert, U. Tetrahedron Lett. 1999, 40,
5979-5982. (c) Trost, B. M.; Calkins, T. L.; Bochet, C. G. Angew. Chem.,
Int. Ed. 1997, 36, 2632-2635. (d) Marshall, J . A.; Hinkle, K. W. J .
Org. Chem. 1996, 61, 4247-4251. (e) Marshall, J . A.; Hinkle, K. W. J .
Org. Chem. 1997, 62, 5989-5995. (f) Marshall, J . A.; Piettre, A.; Paige,
M. A.; Valeriote, F. J . Org. Chem. 2003, 68, 1771-1779.
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6022-6028. (b) Sinha, S. C.; Keinan, E.; Sinha, S. C. J . Am. Chem.
Soc. 1998, 120, 9076-9077.
a
Reaction conditions: (a) (i) SO3-pyridine, NEt3, DMSO/CH2Cl2;
(ii) Ph3PCH3Br, NaHMDS, THF, 0 °C, 77% (two steps). (b)
BF3‚Et2O, DMPMOH, CH2Cl2, 75%. (c) NaH, BnBr, DMF, 95%.
(d) DDQ, CH2Cl2/H2O, 95%.
an allyl alcohol 3 and a vinyl-substituted epoxide 4, using
our regio- and stereospecific ring-opening methodology.26
This synthesis is therefore convergent and only required
the preparation of chiral building blocks, both of which
were obtained from propargyl alcohol (Scheme 1).
As both allyl alcohol 3 and vinyl-substituted epoxide
4 were synthesized via alkyne reduction yielding (E)- or
(Z)-allylic alcohol followed by Sharpless asymmetric
epoxidation using (+)- or (-)-DET, this synthesis is quite
flexible and all stereoisomers of the central THF core of
Solamin should be easily obtained.
The synthesis of substrate 3 is outlined in Scheme 2.
The precursor (2S,3R)-2,3-epoxypentadecanol 5 was syn-
thesized from propargyl alcohol in three steps following
a known procedure.27 Parikh-Doering oxidation28 of 5
with sulfur trioxide pyridine complex, followed by Wittig
olefination, gave vinyl-substituted epoxide 6 in 77% yield
(two steps). Ring opening of 6 with 3,4-dimethoxybenzyl
alcohol (DMPMOH) and BF3‚Et2O catalysis yielded al-
cohol 7 (75% yield).26 Standard benzylation conditions of
7 gave benzyl ether 8 (95% yield). Removal of the 3,4-
dimethoxybenzyl protecting group using DDQ afforded
the allyl alcohol 3 in 95% yield.29
(19) (a) Figade`re B.; Peyrat, J .-F.; Cave´, A. J . Org. Chem. 1997, 62,
3428-3429. (b) Zanardi, F.; Battistini, L.; Rassu, G.; Pinna, L.; Mor,
M.; Culeddu, N.; Casiraghi, G. J . Org. Chem. 1998, 63, 1368-1369.
(c) Zanardi, F.; Battistini, L.; Rassu, G.; Auzzas, L.; Pinna, L.;
Marzocchi L.; Acquotti D.; Casiraghi, G. J . Org. Chem. 2000, 65, 2048-
2064.
(20) (a) Takahashi, S.; Maeda, K.; Hirota, S.; Nakata, T. Org. Lett.
1999, 1, 2025-2028. (b) Yang, W.-Q.; Kitahara, T. Tetrahedron Lett.
1999, 40, 7827-7830. (c) Ba¨urle, S.; Hoppen, S.; Koert, U. Angew.
Chem., Int. Ed. 1999, 38, 1263-1266. (d) Takahashi, S.; Kubota, A.;
Nakata, T. Org. Lett. 2003, 5, 1353-1356. (e) Takahashi, S.; Kubota,
A.; Nakata, T. Tetrahedron 2003, 59, 1627-1638.
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6329-6340. (b) Marshall, J . A.; J iang, H. J . Org. Chem. 1998, 63,
7066-7071.
(22) (a) Schaus, S. E.; Branalt, J .; J acobsen, E. N. J . Org. Chem.
1998, 63, 4876-4877. (b) Zhu, L.; Mootoo, D. R. Org. Lett. 2003, 5,
3475-3478. (c) Evans, P. A.; Cui, J .; Gharpure, S. J .; Polosukhin, A.;
Zhang, H.-R. J . Am. Chem. Soc. 2003, 125, 14702-14703.
(23) For recent reviews, see: (a) Grubbs, R. H.; Chang, S. Tetra-
hedron 1998, 54, 4413-4450. (b) Armstrong, S. K. J . Chem. Soc., Perkin
Trans. 1 1998, 371-388. (c) Blechert, S.; Schuster, M. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2036-2056. (d) Fu¨rstner, A. Angew. Chem.,
Int. Ed. 2000, 39, 3012-3043.
(24) (a) Fu, G. C.; Grubbs, R. H. J . Am. Chem. Soc. 1992, 114, 5426-
5427, 7324-7325. (b) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H. J . Am.
Chem. Soc. 1993, 115, 9856-9857. (c) Fujimura, O.; Fu, G. C.; Grubbs,
R. H. J . Org. Chem. 1994, 59, 4029-4031. (d) Baylon, C.; Heck, M.-P.;
Mioskowski, C. J . Org. Chem. 1999, 64, 3354-3360. (e) Heck, M.-P.;
Baylon, C.; Nolan, S. P.; Mioskowski, C. Org. Lett. 2001, 3, 1989-
1991.
(25) Isolation: (a) Mynt, S. H.; Cortes, D.; Laurens, A.; Hocquemiller,
R.; Lebœuf, M.; Cave´, A.; Cotte, J .; Que´ro, M. Phytochemistry 1991,
30, 3335-3338. (b) Hisham, A.; Sreekala, U.; Pieters, L.; De Bruyne,
T.; Van Den Heuvel, H.; Claeys, M. Tetrahedron 1993, 49, 6913-6920.
Syntheses of Solamin: (c) Shina, S. C.; Keinan, E. J . Am. Chem. Soc.
1993, 115, 4891-4892. (d) Trost, B. M.; Shi, Z. J . Am. Chem. Soc. 1994,
116, 7459-7460. (e) Makabe, H.; Tanaka, A.; Oritani, T. J . Chem. Soc.,
Perkin Trans. 1 1994, 1975-1981. (f) Kuriyama, W.; Ishigami, K.;
Kitahara, T. Heterocycles 1999, 50, 981-988. Syntheses of cis-Sola-
min: (g) Makabe, H.; Hattori, Y.; Tanaka, A.; Oritani, T. Org. Lett.
2002, 4, 1083-1085. (h) See ref 10.
(26) (a) Prestat, G.; Baylon, C.; Heck, M.-P.; Mioskowski C. Tetra-
hedron Lett. 2000, 41, 3829-3831. (b) Baylon, C.; Prestat, G.; Heck,
M.-P.; Mioskowski C. Tetrahedron Lett. 2000, 41, 3833-3835.
(27) Makabe, H.; Tanaka, A.; Oritani, T. Biosci. Biotech. Biochem.
1993, 57, 1028-1029. (2S,3R)-2,3-epoxypentadecanol 5 was recrystal-
lized from hexane/CH2Cl2 (4/1). 19F NMR of Mosher’s esters of 5 showed
ee’s > 98%, mp ) 69-71 °C, [R]21 ) -3.5 (c ) 1.1, CHCl3).
D
(28) Parikh, J . R.; Doering, W. v. E. J . Am. Chem. Soc. 1967, 89,
5505-5507.
(29) We note that isomers of 3 can easily be obtained from precursors
of epoxides 5 or 6 using other reducing and/or asymmetric epoxidation
reagents.
J . Org. Chem, Vol. 69, No. 17, 2004 5771