Synthesis of ovalicin starting from D-mannose

Article abstract of DOI:10.1021/jo051686m

A new synthesis of epoxyketone 22 is described that is a key intermediate in Barton's synthesis of ovalicin (2), a powerful anti-angiogenetic inhibitor. The key process for the construction of 22 was ring-closing metathesis of olefins 11 and 12 obtained f

Full text of DOI:10.1021/jo051686m

Synthesis of Ovalicin Starting from
D-Mannose
Shunya Takahashi,* Nobuyuki Hishinuma,
Hiroyuki Koshino, and Tadashi Nakata
RIKEN (The Institute of Physical and Chemical Research),
Wako-shi, Saitama, 351-0198, Japan
shunyat@riken.go.jp
Received August 10, 2005
FIGURE 1. Structures of Anti-Angiogenesis Inhibitors.
al. modified the original total synthesis8a of racemic 2 to
develop an elegant asymmetric synthesis of 2,8b while
Bath, Barton, and co-workers reported the total synthesis
of 2 using L-quebrachitol as a chiral pool.9 In addition, a
formal total synthesis of 2 was also disclosed.10 However,
more efficient syntheses of 2 and its derivatives are still
required for further studies on detailed examination of
its biological activity with significant therapeutic poten-
tial.11 In connection with our synthetic studies12 on
heterocyclic natural products based on the “Chiron”
approach,13 we describe herein an efficient synthesis of
2 starting from D-mannose.
A new synthesis of epoxyketone 22 is described that is a key
intermediate in Barton’s synthesis of ovalicin (2), a powerful
anti-angiogenetic inhibitor. The key process for the construc-
tion of 22 was ring-closing metathesis of olefins 11 and 12
obtained from 2,3:5,6-di-O-isopropylidene-R-D-mannofura-
nose (4) and regioselective desilylation of tri-TES ether 19.
Furthermore, an alternative stereoselective route from 22
into 2 has also been developed, and the overall yield of 2
from 4 was 10.0%.
(4) For synthetic approaches to fumagillin, see the following: (a)
Corey, E. J.; Snider, B. B. J. Am. Chem. Soc. 1972, 94, 2549-2550. (b)
Kim, D.; Ahn, S. K.; Bae, H.; Choi, W. J.; Kim, H. S. Tetrahedron Lett.
1997, 38, 4437-4440. (c) Taber, D. F.; Christos, T. E.; Rheingold, A.
L.; Guzei, I. A. J. Am. Chem. Soc. 1999, 121, 5589-5590. (d) Vosburg,
D. A.; Weiler, S.; Sorensen, E. J. Angew. Chem., Int. Ed. 1999, 38,
971-974. (e) Boiteau, J.-G.; Van de Weghe, P.; Eustache, J. Org. Lett.
2001, 3, 2737-2740. (f) Hutchings, M.; Moffat, D.; Simpkins, N. S.
Synlett 2001, 661-663. (g) Vosburg, D. A.; Weiler, S.; Sorensen, E. J.
Chirality 2003, 15, 156-166. (h) Bedel, O.; Haudrechy, A.; Langlois,
Y. Eur. J. Org. Chem. 2004, 3813-3819. (i) Yamaguchi, J.; Sumiya,
T.; Hibino, K.; Shoji, M.; Kakeya, H.; Osada, H.; Hayashi, Y. In
Abstracts of Papers, 46th Tennen Yuki Kagobutu Toronkai, Hiroshima,
Japan, Oct. 7, 2004; pp 563-568. (j) For a synthesis of FR65814, see
the following: Amano, S.; Ogawa, N.; Ohtsuka, M.; Chida, N. Tetra-
hedron 1999, 55, 2205-2224.
Angiogenesis, the growth and development of new
capillary blood vessels, is a process that takes place
normally during wound healing. Abnormal angiogenesis
is now recognized as a feature of many proliferative
diseases.1 For example, the growth and metastatic spread
of solid tumors is known to be dependent on angiogenesis.
This suggests that inhibition of angiogenesis is a promis-
ing approach for the treatment of cancer.2 In 1990, an
antibiotic, fumagillin (1),3,4 was reported to have potent
anti-angiogenetic activity (Figure 1),5 but its high toxicity
and instability made the application of 1 to an anti-cancer
drug difficult. As a result of further extensive studies,
ovalicin (2), which was first isolated from cultures of
Pseudorotium ovalis Stolk,6 was found to be nontoxic,
noninflammatory, and more potent than 1; the potency
was the same as that of the most active analogue, AGM-
1470 (3),5 which is being evaluated in phase III clinical
trials as a potential cancer drug.7 These positive observa-
tions have stimulated synthetic chemists, and Corey et
(5) Ingber, D.; Fujita, T.; Kishimoto, S.; Sudo, K.; Kanamaru, T.;
Brem, H.; Folkman, J. Nature 1990, 348, 555-557.
(6) (a) Sigg, H. P.; Weber, H. P. Helv. Chim. Acta 1968, 51, 1395-
1408. (b) Sassa, T.; Kaise, H.; Munakata, K. Agric. Biol. Chem. 1970,
34, 649-651. (c) Bollinger, P.; Sigg, H. P.; Weber, H. P. Helv. Chim.
Acta 1973, 56, 78-79.
(7) (a) Marui, S.; Itoh, F.; Kozai, Y.; Sudo, K.; Kishimoto, S. Chem.
Pharm. Bull. 1992, 40, 96-101. (b) Dezube, B. J.; Von Roenn, J. H.;
Holden-Wiltse, J.; Cheung, T. W.; Remick, S. C.; Cooley, T. P.; Moore,
J.; Sommadossi, J. P.; Shriver, S. L.; Suckow, C. W.; Gill, P. S. J. Clin.
Oncol. 1998, 16, 1444-1449. (c) Stadler, W. M.; Kuzel, T.; Shapiro,
C.; Sosman, J.; Clark, J.; Vogelzang, N. J. J. Clin. Oncol. 1999, 17,
2541-2545. (d) Logothetis, C. J.; Wu, K. K.; Finn, L. D.; Daliani, D.;
Figg, W.; Ghaddar, H.; Gutterman, J. U. Clin. Cancer Res. 2001, 7,
1198-1203.
* Address correspondence to this author. Phone: +81-48-467-9223.
Fax: +81-48-462-4627.
(1) (a) Folkman, J.; Klagsbrun, M. Science 1987, 235, 442-447. (b)
Folkman, J. Nature Med. 1995, 1, 27-31. (c) Hanahan, D.; Folkman,
J. Cell 1996, 86, 353-364.
(2) (a) Folkman, J. N. Engl. J. Med. 1971, 285, 1182-1186. (b)
Auerbach, W.; Auerbach, R. Pharmacol. Ther. 1994, 63, 265-311. (c)
Giannis, A.; Rubsam, F. Angew. Chem., Int. Ed. 1997, 36, 588-590.
(d) Powell, D.; Skotnicki, J.; Upeslacis, J. Annu. Rep. Med. Chem. 1997,
32, 161-170.
(3) (a) Eble, T. E.; Hanson, F. R. Antibiot. Chemother. 1951, 1, 54-
58. (b) McCowen, M. C.; Callender, M. E.; Lawlis, J. F., Jr. Science
1951, 113, 202-203. (c) Katznelson, H.; Jamieson, C. A. Science 1952,
115, 70-71. (d) Killough, J. H.; Magill, G. B.; Smith, R. C. Science
1952, 115, 71-72.
(8) (a) Corey, E. J.; Dittami, J. P. J. Am. Chem. Soc. 1985, 107, 256-
257. (b) Corey, E. J.; Guzman-Perez, A.; Noe, M. C. J. Am. Chem. Soc.
1994, 116, 12109-12110.
(9) (a) Bath, S.; Billington, D. C.; Gero, S. D.; Quiclet-Sire, B.;
Samadi, M. J. Chem. Soc., Chem. Commun. 1994, 1495-1496. (b)
Barton, D. H. R.; Bath, S.; Billington, D. C.; Gero, S. D.; Quiclet-Sire,
B.; Samadi, M. J. Chem. Soc., Perkin Trans. 1 1995, 1551-1558.
(10) Barco, A.; Benetti, S.; De Risi, C.; Marchetti, P.; Pollini, G. P.;
Zanirato, V. Tetrahedron: Asymmetry 1998, 9, 2857-2864.
(11) Mazitschek, R.; Huwe, A.; Giannis, A. Org. Biomol. Chem. 2005,
3, 2150-2154 and references therein.
10.1021/jo051686m CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/20/2005
10162
J. Org. Chem. 2005, 70, 10162-10165

SCHEME 1. Synthesis of Cyclohexanol 17a
To construct the carbon backbone of 2, we adopted
Barton’s strategy9 that uses a stereoselective coupling
reaction between cyclohexane 22 and vinyllithium re-
agent 23 developed by Corey et al.8a Key features in our
synthesis of 22 involve an efficient preparation of cyclo-
hexanol 17 utilizing a ring-closing olefin metathesis
(RCM)14 of olefins 11 and 12 and multifunctionalization
on the cyclic ring system through a regioselective desi-
lylation of tri-TES ether 19. Furthermore, a new efficient
route from the coupling product 24 into 2 was also
developed.
Synthesis of 2 started with regioselective silylation of
acetal 515 obtained from 2,3:5,6-di-O-isopropylidene-R-D-
mannnofuranose (4) in 76% yield (Scheme 1). Wittig
reaction of the resulting silyl ether 6 under mild condi-
tions using a base such as n-BuLi and SHMDS in THF
at 0 °C to room temperature (rt) resulted in a low yield
of olefin 7. However, methylenation under the forcing
conditions16 gave the desired olefin 7 in 97% yield. After
O-methylation of 7, exposure of the resulting methyl
ether 8 to mildly acidic conditions led to selective deiso-
propylidenation to afford diol 9. For the construction of
another olefin unit in 9, selective oxidation17 of the
primary hydroxyl group was attempted but failed. DIBAL
reduction of the corresponding monobenzylidene deriva-
tive also gave unsatisfactory results. Consequently, al-
dehyde 10 was prepared by sodium periodate oxidation
of 9, and reaction of 10 with several vinylating reagents
was examined. The results are shown in Table 1. Under
all conditions tried, a low polar substance was obtained
as a major product. We estimated that the major isomer
was 3S-alcohol 11 because this reaction would occur
through an R-chelation-controlled mode. The estimation
was confirmed at the later stage (vide infra). RCM of 11
with Grubbs’s second generation catalyst proceeded
nicely to give the desired cyclohexene 13 in good yield.
Similarly, the epimer 12 afforded cyclohexenol 14; the
yield slightly decreased because of low recovery of the
reaction products. Both compounds 13 and 14 were
hydrogenated to afford cyclohexanes 15 and 17, respec-
1
tively. In the H NMR spectra of 15, H-2 was observed
at 3.56 ppm as doublets of a doublet (J1,2 ) 6.0 Hz and
J2,3 ) 4.4 Hz), while the coupling constant between H-1
and -2 of 17 was 3.8 Hz. The large coupling constant (6.0
Hz) of 15 shows the 1,2-trans relationship of two hydroxyl
groups, thus establishing the stereochemistry of alcohols
11 and 12. To invert the stereochemistry at the C-1
a Reagents and conditions: (a) ref 15; (b) TBDPSCl, DMAP,
Et3N, CH2Cl2, 0 °C to rt, 85%; (c) Ph3P+CH3Br-, KOt-Bu, toluene,
105 °C, 97%; (d) NaH, MeI, THF, 0 °C, 97%; (e) aq. AcOH, 50 °C,
72%; (f) NaIO4, THF/H2O, rt, and then (CH2OH)2, quant.; (g)
vinylmagnesium chloride, THF, -20 °C, 68% for 11, 28% for 12;
(h) Grubbs’s second generation catalyst, toluene, 80 °C, 94% for
13, 84% for 14; (i) 10% Pd/C, H2, EtOAc, rt, 99% for 15, 95% for
17; (j) DEAD, Ph3P, benzoic acid, THF, 0 °C to rt; (k) NaOMe,
MeOH, rt, 95% from 15 (two steps).
(12) (a) Takahashi, S.; Terayama, H.; Kuzuhara, H. Tetrahedron
Lett. 1991, 32, 5123-5126. (b) Takahashi, S.; Terayama, H.; Kuzuhara,
H. Tetrahedron Lett. 1992, 33, 7565-7568. (c) Takahashi, S.; Ter-
ayama, H.; Kuzuhara, H. Tetrahedron Lett. 1994, 35, 4149-4152. (d)
Takahashi, S.; Kuzuhara, H. J. Carbohydr. Chem. 1998, 17, 117-128.
(e) Takahashi, S.; Maeda, K.; Hirota, S.; Nakata, T. Org. Lett. 1999,
1, 2025-2028. (f) Takahashi, S.; Nakata, T. J. Org. Chem. 2002, 67,
5739-5752. (g) Takahashi, S.; Ogawa, N.; Sakairi, N.; Nakata, T.
Tetrahedron 2005, 61, 6540-6545.
position of 15, this was subjected to the Mitsunobu
reaction (diethyl azodicarboxylate, triphenylphosphine,
benzoic acid)18 to afford benzoate 16, whose benzoyl group
was removed by sodium methoxide in methanol to give
17 in 95% overall yield from 15.
After several attempts to prepare 20 from 17, a simple
method was developed as follows (Scheme 2). Initially,
all protecting groups in 17 were removed by the action
of hydrogen chloride in methanol, and the resulting
tetraol 18 was silylated to give tri-TES ether 19 quan-
titatively. When this was treated with TBAF (0.75 mol
(13) Hanessian, S. Total Synthesis of Natural Products, the “Chiron”
Approach; Pergamon Press: Oxford, 1983.
(14) Grubbs, R. H. Handbook of Metathesis, Vols. 1-3; Wiley-VCH:
Weinheim, Germany, 2003.
(15) Witczak, Z. J.; Whistler, R. L.; Daniel, J. R. Carbohydr. Res.
1984, 133, 235-245.
(16) (a) Conia, J. M.; Limasset, J. C. Bull. Soc. Chim. Fr. 1967,
1936-1938. (b) Fitjer, L.; Quabeck, U. Synth. Commun. 1985, 15, 855-
864.
(17) (a) Einhorn, J.; Einhorn C.; Ratajczak, F.; Pierre, J.-L. J. Org.
Chem. 1996, 61, 7452-7454. (b) Luca, L. D.; Giacomelli, G.; Porcheddu,
A. Org. Lett. 2001, 3, 3041-3043.
(18) Mitsunobu O. Synthesis 1981, 1-28.
J. Org. Chem, Vol. 70, No. 24, 2005 10163

TABLE 1. Vinylation of Aldehyde 10
SCHEME 3. Coupling Reaction of 22 with 23 and
Total Synthesisa
temp
ratiob
yield
(%)
entry
reagentsa
solvent
THF
(°C)
(11/12)
1
2
3
4
5
6
vinylMgBr
vinylMgBr
vinylMgCl
vinylMgCl
vinylLic
-20
-20
-20
-20
0
78:22
81:19
71:29
85:15
59:41
54:46
95
69
96
78
82
63
THF/HMPA
THF
THF/HMPA
ether
ether/HMPA
vinylLic
-20
a A quantity of 2.0-4.0 mol equiv of reagent was employed.
b Determined by 1H NMR analysis. c Prepared from MeLi and
(vinyl)4Sn at 0 °C.
SCHEME 2. Synthesis of Epoxyketone 22a
a Reagents and conditions: (a) THF, -78 °C, 85%; (b) TBAF,
THF, 0 °C, 90%; (c) TPAP, NMO, MS4A, CH2Cl2, 0 °C to rt; 79%;
(d) VO(acac)2, t-BuO2H, benzene/decane, 0 °C to rt, 64%.
reaction. Epoxidation of 24 under Sharpless’s condition20
resulted in a stereoisomeric mixture (ca. 2-3:1) of di-
epoxides as previously reported.9 We estimated that the
bulky silyl group may interfere with the stereoselective
epoxidation. Consequently, the silyl group was removed
with TBAF at 0 °C quickly, giving diol 25 in high yield.
The prolonged reaction time and higher reaction tem-
perature decreased the yield. Oxidation of the unstable
diol 25 was performed by the action of n-tetrapropyl-
ammonium perruthenate (TPAP)-N-methylmorpholine
oxide21 to produce ketone 26 in good yield. Finally,
epoxidation8 of 26 afforded ovalicin 2 stereoselectively.
The spectral and physical data of synthetic 2 were
identical to those of natural 2.
a Reagents and conditions: (a) HCl/MeOH, 0 °C to rt, 97%; (b)
TESCl, imidazole, DMF, 0 °C, 95%; (c) TBAF, THF, -78 °C, 87%;
(d) (i) p-TsCl, DMAP, Et3N, CH2Cl2, 0 °C to rt; (ii) K2CO3, MeOH,
0 °C, 93%; (e) Dess-Martin periodinane, NaHCO3, CH2Cl2, 0 °C,
98%.
This “Chiron” approach enabled us to synthesize 2 as
an optically pure form in 10.0% overall yield from a
commercially available 2,3:5,6-di-O-isopropylidene-R-D-
mannofuranose (4) (total 23 steps). The strategy de-
scribed herein should be applicable to the preparation of
pharmacologically important analogues of 2.
equiv) in tetrahydrofuran at -78 °C, regioselective desi-
lylation occurred to afford the desired mono-TES ether
20 in 87% yield. The use of 1.5-2.0 mol equiv of TBAF
decreased the yield of 20 due to the production of a
considerable amount of 18. In contrast, reaction with a
catalytic amount of TBAF (0.1 mol equiv) was sluggish.
This regioselecivity would be explained by silyl migration
derived from the neighboring group participation of the
tert-hydroxyl group. The triol 20 was transformed into
monoepoxide 21 via the corresponding tosylate.10 Upon
treatment with Dess-Martin periodinane19 in the pres-
ence of NaHCO3, 21 gave Barton’s key intermediate 22
(98%). The overall yield of 22 from 2,3:5,6-di-O-isopro-
pylidene mannofuranose (4) was 26.0% (total 18 steps).
Introduction of the side chain into 22 was performed
according to Barton’s procedure9 (Scheme 3). Thus,
ketone 22 was treated at -78 °C with vinyllithium
reagent 238 prepared from acetone 2,4,6-triisopropylben-
zenesulfonyl hydrazone to afford the coupling product 24
as a single stereoisomer in 85% yield. We found that the
use of a small excess (1.3-1.4 mol equiv) of base was
necessary for high yield and the reproducibility of the
Experimental Section
(1S,4S,5S,6R)-4-(tert-Butyldiphenylsilanyloxymethyl)-
4,5-O-isopropylidenedioxy-6-methoxy-2-cyclohexene-
1-ol (13). A mixture of 11 (5.46 g, 11.0 mmol) and Grubbs’ second
generation catalyst (110 mg, 0.13 mmol) in toluene (86 mL) was
heated at 80 °C for 1.5 h with stirring and then cooled. After
addition of florisil, the resulting mixture was stirred at room
temperature for 1 h, filtered through a pad of Celite, and then
concentrated. The residue was chromatographed on silica gel
(n-hexane/EtOAc ) 8:1) to give 13 (4.87 g, 94%) as a light yellow
oil: [R]28 +66.6 (c 1.04, CHCl3); IR (neat) 3480, 3073, 2986,
D
1
2828, 1589, 1473, 1429, 1412, 1381, 1375, 1250, 1120 cm-1; H
NMR (270 MHz, CDCl3): δ 7.74-7.69 (m, 4H), 7.42-7.38 (m,
6H), 5.91 (dd, J ) 10.4, 4.6 Hz, 1H), 5.56 (d, J ) 10.4 Hz, 1H),
(20) (a) Sharpless, K. B.; Michaelson, R. C. J. Am. Chem. Soc. 1973,
95, 6136-6137. (b) Hill, J. G.; Rossiter, B. E.; Sharpless, K. B. J. Org.
Chem. 1983, 48, 3607-3608.
(21) Griffith, W. P.; Ley, S. V.; Whitcombe, G. P.; White, A. D. J.
Chem. Soc., Chem. Commun. 1987, 1625-1627.
(19) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155-4156.
10164 J. Org. Chem., Vol. 70, No. 24, 2005

4.68 (d, J ) 4.9 Hz, 1H), 4.09 (m, 1H), 3.77 (t, J ) 4.6 Hz, 1H),
3.74, 3.58 (each d, J ) 10.6 Hz, 2H), 3.51 (s, 3H), 2.89 (d, J )
9.0 Hz, 1H), 1.49 (s, 3H), 1.46 (s, 3H), 1.08 (s, 9H); 13C NMR
(67.5 MHz, CDCl3): δ 135.6, 135.5, 132.9, 132.8, 129.6, 129.5,
128.6, 128.3, 127.5, 127.5, 109.8, 81.3, 80.2, 74.9, 66.0, 65.7, 58.7,
28.5, 27.7, 26.8, 19.3. Anal. Found: C, 69.26; H, 7.70. Calcd for
C27H36O5Si: C, 69.20; H, 7.74.
at -78 °C for 3 h and at 0 °C for 1 h. After addition of NaCl
brine, the resulting mixture was extracted with EtOAc. The
extracts were washed with brine, dried, and concentrated. The
residue was chromatographed on silica gel (n-hexane/EtOAc )
2:1) to give 20 (498 mg, 87%) as a colorless liquid: [R]28D -66.7
(c 1.18, CHCl3); IR (neat) 3460, 2953, 2878, 1458, 1414, 1238,
1
1120, 1078, 1037 cm-1; H NMR (270 MHz, CDCl3): δ 4.25 (m,
(1R,4S,5S,6R)-4-(tert-Butyldiphenylsilanyloxymethyl)-
4,5-O-isopropylidenedioxy-6-methoxy-2-cyclohexene-1-
ol (14). Treatment of 12 (1.28 g, 2.57 mmol) with Grubbs’ second
generation catalyst (39.0 mg, 0.05 mmol) in toluene (30 mL) as
1H), 3.91 (d, J ) 10.2 Hz, 1H), 3.77, 3.42 (each d, J ) 10.2 Hz,
2H), 3.40 (s, 3H), 3.22 (dd, J ) 9.3, 2.1 Hz, 1H), 3.10-2.70 (brs,
3H), 1.80-1.55 (m, 3H), 1.48-1.43 (m, 1H), 0.96 (t, J ) 7.9 Hz,
9H), 0.59 (q, J ) 7.9 Hz, 6H); 13C NMR (67.5 MHz, CDCl3): δ
82.7, 73.2, 72.6, 69.8, 65.6, 57.0, 27.0, 26.0, 6.8, 4.9; HRMS calcd
described above gave 14 (1.01 g, 84%) as a light yellow oil: [R]28
D
+11.7 (c 0.41, CHCl3); IR (neat) 3480, 3073, 2986, 2830, 1589,
C12H25O5Si (M - Et): 277.1552. Found: 277.1462. Anal.
1471, 1429, 1410, 1375, 1252, 1220, 1080 cm-1
;
1H NMR (270
Found: C, 54.42; H, 9.99. Calcd for C14H30O5Si‚0.2H2O: C, 54.23;
MHz, CDCl3): δ 7.77-7.71 (m, 4H), 7.43-7.36 (m, 6H), 5.68 (brd,
J ) 10.1 Hz, 1H), 5.44 (brd, J ) 10.1 Hz, 1H), 4.82 (d, J ) 4.0
Hz, 1H), 4.40 (m, 1H), 3.91 (t, J ) 4.1 Hz, 1H), 3.78, 3.53 (each
d, J ) 10.6 Hz, 2H), 3.49 (s, 3H), 2.57 (d, J ) 11.2 Hz, 1H), 1.50
(s, 3H), 1.40 (s, 3H), 1.10 (s, 9H); 13C NMR (67.5 MHz, CDCl3):
δ 135.6, 135.5, 133.0, 132.8, 130.0, 129.6, 129.5, 127.6, 127.5,
108.6, 80.2, 79.0, 71.3, 65.5, 65.2, 59.0, 28.0, 27.5, 26.9, 19.3 Anal.
Found: C, 69.29; H, 7.54. Calcd for C27H36O5Si: C, 69.20; H,
7.74.
H, 9.88.
Acknowledgment. We are grateful to Dr. T. Chi-
hara and his collaborators in RIKEN for the elemental
analyses. We also thank Drs. T. Nakamura and Y.
Hongo (RIKEN) for mass spectral measurements. This
work was supported by the Chemical Biology Project
(RIKEN).
(1S,2S,3R,4R)-1-Hydroxymethyl-4-triethylsilyloxy-3-meth-
oxycyclohexane-1,2-diol (20). To a stirred solution of 19 (1.00
g, 1.87 mmol) in tetrahydrofuran (17 mL) was added dropwise
a 1.0 M solution of n-tetrabutylammonium fluoride (1.4 mL, 1.4
mmol) in tetrahydrofuran at -78 °C, and the mixture was stirred
Supporting Information Available: Experimental pro-
cedures and NMR spectra of 24-26 and 2. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO051686M
J. Org. Chem, Vol. 70, No. 24, 2005 10165