COMMUNICATIONS
[10]At temperatures above 55 8C, intramolecular alkylation of the C32
benzyl ether to form the corresponding tetrahydrofuran was observed.
For a similar side reaction, see: D. A. Evans, A. M. Ratz, B. E. Huff,
G. S. Sheppard, J. Am. Chem. Soc. 1995, 117, 3448 3467.
[11]D. A. Evans, D. W. C. MacMillan, K. R. Campos, J. Am. Chem. Soc.
1997, 119, 10859 10860.
(TBDPSCl, Im, DMAP, CH2Cl2, 90%), exchange of the C14
hydroxy protecting group (DDQ, CH2Cl2/pH 7 buffer, 90%;
TESCl, Im, CH2Cl2, 100%), and benzyl deprotection[16]
(LiDBB, THF, ꢀ788C) afforded 27, the fully elaborated
precursor needed for the diene formation step.
[12]T. Fukuyama, S.-L. Lin, L. Li, J. Am. Chem. Soc. 1990, 112, 7050
7051; see also: D. A. Evans, B. W. Trotter, P. J. Coleman, B. Cote, L.
Carlos Dias, H. A. Rajapakse, A. N. Tyler, Tetrahedron 1999, 55,
8671 8726.
[13]Conditions adapted from: M. Hartman, E. Zibral, Tetrahedron Lett.
1990, 31, 2875 2878. Both Wittig and Petersen conditions resulted in
aldehyde decomposition with no observed product.
[14]D. A. Evans, G. C. Fu, A. H. Hoveyda, J. Am. Chem. Soc. 1992, 114,
6671 6674.
[15]B. E. Rossiter, T. R. Verhoeven, K. B. Sharpless, Tetrahedron Lett.
1979, 20, 4733 4736.
[16]a) P. K. Freeman, L. L. Hutchinson, J. Org. Chem. 1980, 45, 1924
1930; b) R. E. Ireland, M. G. Smith, J. Am. Chem. Soc. 1988, 110, 854
860.
[17]No undesired tetrahydropyran byproducts were observed in this
reaction.
On the basis of convergency considerations the C1 C30
ABCDE fragment 27 was employed as the electrophilic
partner in the Julia olefination with the b-alkoxy sulfone 22.[21]
Oxidation[22] of alcohol 27 to aldehyde 28 (SO3¥Py, Et3N,
DMSO/CH2Cl2) was followed by the addition of LiHMDS to
a pre-mixed solution of 28 and sulfone 22 in THF at ꢀ788C to
provide the desired diene 29 as a 88:12 mixture of C32
epimers (72% over two steps, E:Z > 95:5).[23] Pursuant to
revealing the terminal carboxyl residue, N-phenylamide 29
was activated through its N-Boc imide, and hydrolysis to the
acid (LiOH, H2O2, THF/H2O) proceeded with with concom-
itant C33-OTMS deprotection to give pectenotoxin-4 seco
acid.[24] Macrocyclization under Yamagichi conditions[25]
(2,4,6-trichlorobenzoyl chloride, iPr2NEt, toluene, then
DMAP, toluene) at room temperature provided adduct 30.
Selective deprotection of the C14 and C36 OTES ethers with
PPTS in MeOH/CH2Cl2 (35% over three steps), oxidation to
the diketone[8] (Dess Martin periodinane, py, CH2Cl2, 72%)
and global deprotection[26] (TAS-F, H2O, DMF, 85%) afford-
ed pectenotoxin-4 in 36 steps (longest linear sequence) and
0.3% overall yield. The synthetic material was identical by
1H NMR spectroscopy and optical rotation to natural pecte-
notoxin-4.[27] Further proof of structure was obtained by
isomerizing synthetic pectenotoxin-4 to pectenotoxin-8[28]
(1% TFA in CH3CN/H2O, 40%), and this material was
[18]J. B. Baudin, G. Hareau, S. A. Julia, O. Ruel, Bull. Soc. Chim. Fr. 1993,
130, 856 878.
[19]PMB deprotection with DDQ was incompatible with the pectenotoxin
diene, as exclusive allylic oxidation was observed. For successful
deprotections of PMB ethers in the presence of allylic dienes see: a) N.
Murakami, W. Wang, M. Aoki, Y. Tsutsui, M. Sugimoto, M.
Kobayashi, Tetrahedron Lett. 1998, 39, 2349 2352; b) G. Pattenden,
A. T. Plowright, J. T. Tornos, T. Ye, Tetrahedron Lett. 1998, 39, 6099
6102.
[20]a) J. A. Marshall, R. C. Andrews, J. Org. Chem. 1985, 50, 1602 1606;
b) D. A. Evans, R. P. Polniaszek, K. M. DeVries, D. E. Guinn, D. J.
Mathre, J. Am. Chem. Soc. 1991, 113, 7613 7630.
[21]For examples of b-alkoxy sulfone couplings see: a) ref. [19b]; b) D. A.
Evans, D. M. Fitch, T. E. Smith, V. J. Cee, J. Am. Chem. Soc. 2000, 122,
10033 10046; c) A. B. Smith, B. M. Brandt, Org. Lett. 2001, 3, 1685
1688.
1
identical to natural pectenotoxin-8 as judged by H NMR,
HPLC, TLC Rf, and UV spectroscopy.
[22]J. R. Parikh, W. E. von Doering, J. Am. Chem. Soc. 1967, 89, 5505
5507.
[23]Initial feasibility studies on a model system revealed a dramatic
counterion effect for this Julia coupling reaction. The use of KHMDS
as the base resulted in a 29:71 ratio of C32 epimers favoring the
undesired product. We attribute this epimerization side reaction to be
due to ring-F cleavage through b-alkoxy elimination and readdition to
the intermediate unsaturated sulfone.
Received: September 18, 2002 [Z50191]
[1]D. A. Evans, H. A. Rajapakse, D. Stenkamp, Angew. Chem. 2002, 114,
4751; Angew. Chem. Int. Ed. 2002, 41, 4569.
[2]A full account of this work will be published in due course.
[3]P. A. Bartlett, S. D. Rychnovsky, J. Am. Chem. Soc. 1981, 103, 3964
3966.
[24]D. A. Evans, P. H. Carter, C. J. Dinsmore, J. C. Barrow, J. L. Katz,
D. W. Kung, Tetrahedron Lett. 1997, 38, 4535 4538.
[25]J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull.
Chem. Soc. Jpn. 1979, 52, 1989 1993.
[4]D. A. Evans, D. M. Fitch, J. Org. Chem. 1997, 62, 454 455.
[5]Abbreviations: TBS ¼ tert-butyldimethylsilyl; DCC ¼ dicyclohexyl
carbodiimide; DMAP ¼ 4-(N,N-dimethylamino)pyridine; Cp ¼ cyclo-
pentadienyl, d.r. ¼ diastereomeric ratio; NIS ¼ N-iodosuccinimide;
AIBN ¼ 2,2’-azobisisobutyronitrile; TBAF ¼ tetra-(n-butyl)ammoni-
um fluoride; THF ¼ tetrahydrofuran; py ¼ pyridine; Bn ¼ benzyl;
TBAI ¼ tetra-(n-butyl)ammonium iodide; DMF ¼ dimethylforma-
mide; DDQ ¼ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; TMS ¼ tri-
methylsilyl; DMS ¼ dimethyl sulfide; Im ¼ imidazole; TPS ¼ triphe-
nylsilyl; TIPS ¼ triisopropylsilyl; lut. ¼ 2,6-lutidine; DIBAL-H ¼ dii-
sobutylaluminum hydride; LiHMDS ¼ lithium hexamethyldisilazide;
[26]K. A. Scheidt, H. Chen, B. C. Follows, S. R. Chemler, D. S. Coffey,
W. R. Roush, J. Org. Chem. 1998, 63, 6436 6437.a) For previous uses
of TAS-F for silyl ether deprotection see: R. A. Holton, C. Somoza,
H.-B. Kim, F. Liang, R. J. Biediger, P. D. Boatman, M. Shindo, C. C.
Smith, S. Kim, H. Nadizadeh, Y. Suzuki, C. Tao, P. Vu, S. Tang, P.
Zhang, K. K. Murthi, L. N. Gentile, J. H. Liu, J. Am. Chem. Soc. 1994,
116, 1597 1598; b) P. A. Wender, N. F. Badham, S. P. Conway, P. E.
Floreancig, T. E. Glass, C. GrÂnicher, J. B. Houze, J. JÂnichen, D. Lee,
D. G. Marquess, P. L. McGrane, W. Meng, T. P. Mucciaro, M.
Muhnlebach, M. G. Natchus, H. Paulsen, D. B. Rawlings, J. Satkofsky,
A. J. Shuker, J. C. Sutton, R. E. Taylor, K. Tomooka, J. Am. Chem.
Soc. 1997, 119, 2755 2756.
m-CPBA ¼ meta-chloroperoxybenzoic
acid;
Bt ¼ benzthiazole;
TES ¼ triethylsilyl; PPTS ¼ pyridinium
para-toluenesulfonate;
TBDPS ¼ tert-butyldiphenylsilyl; LiDBB ¼ lithium di-tert-butylbiphe-
nylide; Boc2O ¼ di-tert-butyl dicarbonate; LDA ¼ lithium diisopropy-
lamide; HMPA ¼ hexamethylphosphoramide; TBODPS ¼ tert-butox-
ydiphenylsilyl; RT¼ room temperature; TAS-F ¼ tris(dimethyami-
no)sulfur(trimethylsilyl)difluoride.
[27]A natural sample of pectenotoxin-4 was unavailable for comparison.
Professor M. Satake of Tohoku University is thanked for kindly
1
providing copies of H NMR spectra of pectenotoxin-1, -4, and -8, as
well as samples of pectenotoxin-1 and -8.
[28]K. Sasaki, J. L. C. Wright, T. Yasumoto, J. Org. Chem. 1998, 63, 2475
2480. We observed a 11:10:79 ratio of pectenotoxins-1:-4:-8.
[6]A. Chen, A. Nelson, N. Tanikkul, E. J. Thomas, Tetrahedron Lett. 2001,
42, 1251 1254.
[7]S. H. Pine, R. Zahler, D. A. Evans, R. H. Grubbs, J. Am. Chem. Soc.
1980, 102, 3270.
[8]D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277 7287.
[9]M. T. Reetz, K. Kesseler, J. Org. Chem. 1985, 50, 5434 5436.
4576
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