222
G. Bluet, J.-M. Campagne
LETTER
Na2B2O4∑10H2O in EDTA 4.10-4 M), DMM 10 mL, CH3CN 5
mL, diene 7 (270mg, 1 mmol), tetrabutylammonium hydrogen
sulfate (15 mg, 0,04 mmol) and ketone 84 (77mg, 0.3 mmol)
is stirred at O °C. A solution of oxone (0.69g, 1,13 mmol) in
6 mL of EDTA 4.10-4 M, and a solution of potassium
carbonate (0,69 g, 5 mmol) in 6 mL of H2O are added,
separately and simultaneously, via 2 syringe pumps over 6
hours. The reaction is then immadiately quenched by the
addition of hexane and the aqueous layer further extracted
three times with hexane. The organic layers are washed with
brine, dried over MgSO4 and concentrated in vacuo. After
purification by flash chromatography (pentane/ EtOAc, 30/ 1)
on silicagel (buffered with NEt3 1%), compound 9 is obtained
as a clear yellow oil in 40-45% yield and 91% ee (determined
by HPLC: Chiracel OD 99/1 hexane / iPrOH, 240nm).
1H NMR : d (200 MHz,CDCl3): 0.06 (s, 6H), 0.9 (s, 9H), 1.81
(m, 4H), 3.04 (td, J = 6.4, 1.9 Hz, 1H), 3.30 (dd, J = 1.8, 7 Hz,
1H), 3.77 (s, 3H), 6.14 (d, J = 15.6 Hz, 1H), 6.71 (dd, J = 6.8,
15.6 Hz, 1H). 13C NMR d (75 MHz, CDCl3) -4.3, 18.0, 25.7,
35.0, 51.5, 56.2, 59.0, 59.3, 123.0, 144.9, 165.9. Elem. Anal.
Calc. for C14H24O4Si: C 58.7%, H 9.15%; found C 58.93%, H
9.16%. [a]D25 = +23° (c = 2, AcOEt).
O
HO
CHO
OEt
a
EtO
13
OTMS
b,c,d
12
O
OTBDMS
O
OTBDMS
e
O
N
15
14
Reagents: a) CuF((S)-tol-Binap) 10%, THF 0 °C, 24 h, 90%, (80%
ee) b) TBS-Cl/imidazole, r.t., 24 h, 81%; c) KOH, MeOH, reflux,
overnight; d) PyBOP11, Hunig's base, NH(OMe)Me, DCM, r.t., 8 h,
62% (2 steps); e) EtMgBr, 61%
Scheme 3
(7) Miyashita, M.; Hoshino, M.; Yoshikoshi, A. J. Org. Chem.
1991, 56, 6483.
(8) McRae, K. J.; Rizzacasa, M. A. J. Org. Chem. 1997, 62, 1196.
(9) Bluet, G.; Campagne, J. M. Tetrahedron Lett. 1999, 40, 5507.
(10) Experimental procedure for the synthesis of (S) ethyl 2-
methyl-5-hydroxy-5-isopropyl-2-pentenoate (13):
CuF((S)-tol-Binap) led to the formation of the vinylogous
Mukaiyama adduct 13 in 90% yield and 80% ee. 10 After
protection of the alcohol as the TBDMS ether, the ethyl
ester was transformed11 in 2 steps (62% yield) to the cor-
responding Weinreb amide 14. Reaction of 14 with ethyl-
magnesium bromide led in 61% yield to the (C8-C15)
fragment 15.
Under an argon atmosphere, a mixture of copper(II)
trifluoromethanesulfonate (19 mg, 0.052 mmol, 10%) and (S)-
Tol-BINAP (39.4 mg, 0.057 mmol, 11%) in 10 ml of freshly
distilled THF is stirred for 15 minutes (a clear yellow solution
is obtained). A solution of TBAT12 (56 mg, 0.103 mmol, 20%)
in 0.5 ml of THF is added dropwise and after 15 min a bright
yellow solution is obtained. After cooling to 0 °C, 1-ethoxy-1-
(trimethylsiloxy)-2-methyl-1,3 butadiene (12,13 208 mg,
0.778 mmol, 1.5 equiv) is added dropwise (the resulting
solution turns a red-brown color). Then a solution of
isobutyraldehyde (48 ml, 0.518 mmol, 1 equiv) in 0.5 ml of
THF, is slowly added and the reaction mixture is stirred for 24
hours at 0 °C. After quenching (MeOH/ HCl 9:1 20 min), the
reaction mixture is diluted with a satured aqueous solution of
NH4Cl and extracted with ether. The organic layers are
washed with brine, dried over MgSO4 and concentrated in
vacuo. After purification by flash chromatography on silicagel
(pentane/ EtOAc, 80/ 20), compound 13 is obtained as a clear
yellow oil in 90% yield (92 mg) and 80% ee (determined by
HPLC: chiracel OD, 98/02 hexane/ isopropanol).
In conclusion, the (C1-C7) and (C8-C15) sub-units of oc-
talactin A have been efficiently synthesized, using an
asymmetric Shi epoxidation and an asymmetric vinylo-
gous Mukaiyama-aldol reaction respectively.
Construction of the seco-acid 2 is currently in progress
and will be published in due course.
Acknowledgement
We are grateful to Prof. Pierre Potier for his kind interest and con-
stant encouragements, and to Melissa Laws for the revision of the
manuscript.
References and Notes
1H NMR : d (200 MHz,CDCl3) 0.92 (~d, J = 6.8 Hz, 6H), 1.26
(t, J = 7 Hz, 3H), 1.68 (m, 1H), 1.82 (s, 3H), 1.98 (s, OH), 2.31
(m, 2H), 3.53 (m, 1H), 4.16 (q, J = 7 Hz, 2H), 6.82 (m, 1H).
13C NMR : d (75 MHz, CDCl3) 12.5, 14.1, 17.1, 18.6, 33.2,
33.5, 60.4, 71.1, 129.2, 138.4, 168.1. IR (KCl) n 3451, 1709,
1648, 1279. Elem. Anal. Calc. for C11H20O3: C 65.97, H 10.07,
O 23.97; found C 65.71 H 10.19 O 23.74. [a]D25 = -16.1°
(c = 0.68, CHCl3).
(1) Tapiolas, D. M.; Roman, M.; Fenical, W.; Stout, T. J.; Clardy,
J. J. Am. Chem. Soc. 1991, 113, 4682.
(2) a) Buszek, K. R.; Sato, N.; Jeong, Y. J. Am. Chem. Soc. 1994,
116, 5511. b) McWilliams, J. C.; Clardy, J. J. Am. Chem. Soc.
1994, 116, 8378.
(3) a) Hulme, A. N.; Howells, G. E. Tetrahedron Lett. 1997, 38,
8245. b) Buszek, K. R.; Jeong, Y. Tetrahedron Lett. 1995, 36,
7189. c) Komada, M.; Matsushita, M.; Terada, Y.; Takeuchi,
A.; Yoshio, S.; Fukuyama, Y. Chem. Lett 1997, 117. d)
Andrus, M. B.; Argade, A. B. Tetrahedron Lett. 1996, 37,
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Tetrahedron Lett. 1995, 36, 3425.
(4) a) Wang, Z.-X.; Tu, Y.; Fronh, M.; Zhang, J.-R.; Shi, Y. J. Am.
Chem. Soc. 1997, 118, 11224. b) Fronh, M.; Dalkiewicz, M.;
Tu, Y.; Wang, Z.-X.; Shi, Y. J. Org. Chem. 1998, 63, 2948.
(5) Trost, B. M.; Kazmaier, U. J. Am. Chem. Soc. 1992, 114, 7933
(6) Experimental procedure for the synthesis of (R,R) ethyl 3[3-(2
t-butyldimethylsilyloxy-ethyl)-oxiranyl]-acrylate 9:
According to ref 4b, a mixture of 10 mL of buffer (0.05M
(11) a) Coste J.; Le-Nguyen, D.; Castro B. Tetrahedron Lett. 1990,
31, 205. b) Coste, J.; Frérot, E.; Castro, B. J. Org. Chem. 1994,
59, 2437.
(12) Pilcher, A.S.; Ammon, H.L.; Deshong P. J. Am. Chem. Soc.
1995, 117, 5166.
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1198.
Article Identifier:
1437-2096,E;2000,0,02,0221,0222,ftx,en;G29599ST.pdf
Synlett 2000, No. 1, 221–222 ISSN 0936-5214 © Thieme Stuttgart · New York