M. Johansson et al. / Tetrahedron 58 62002) 2523±2528
2527
order CuI (25 mg, 0.13 mmol), AsPh3 (80 mg, 0.26 mmol)
and Pd2(dba)3´CHCl3 (13.6 mg, 0.01 mmol). The dark
colour of the catalyst disappeared upon stirring giving a
yellow solution. After stirring for 10 min at room tempera-
ture a degassed solution of 1-tributylstannanyl-propenyl
(520 mg, 1.57 mmol) in NMP (5.3 ml) was added dropwise.
The solution was heated to 658C and stirred for 8 h. NH4Cl
(sat.) was added and stirring continued for 10 min. The
solution was extracted with diethyl ether, the organic
phase was washed with water, dried (MgSO4) and the
concentrated. Flash chromatography (hexane/ether 10:1)
afforded 190 mg (80%) of coupled cis and trans product.
This was isomerised (vide supra) to yield 190 mg (80%) 1,
as a colourless oil.
The saline was ®ltrated and extracted twice with ethyl
acetate. The organic phase was dried (Na2SO4), and after
evaporation of the solvent 3 was isolated from the extract by
preparative HPLC (Merck LiChrosorb Diolw, 7 mm, column
250±25 mm) using a linear cyclohexane/tert-butyl methyl
ether gradient. 186 mg (90%) 3 was obtained as white
20
crystals, mp 53±568C. [a]D 252.88 (c0.46, CHCl3);
nmax (®lm): 2960, 2925, 1755, 1215, 1190, 1020, 970, 900
and 755 cm±1. 1H NMR (CDCl3) d 1.06 (1H, ddd,
J14.6 Hz, J28.0 Hz, J313.9 Hz, ±CH(CH3)CH2±),
1.16 (1H, m, ±CH(O)CH2CH2±), 1.18 (3H, d, J7.3 Hz,
±CH3), 1.73 (1H, dddd, J12Hz, J23 Hz, J37.0 Hz,
J414.7 Hz, ±CH(O)CH2CH2±), 1.85 (1H, dddd, J1
13.4 Hz,
J27.2Hz,
J37.2Hz,
J43.0 Hz,
±CH(O)CH2CH2±), 2.07 (1H, dddd, J17.2Hz, J2
Negishi coupling of 7 and 1-tributylstannanyl-propenyl. To
a
7.5 Hz, J311.0 Hz, J414.7 Hz, ±CH(O)CH2CH2±), 2.24
solution of 1-tributylstannanyl-propenyl (616 mg,
(1H,
dt,
J17.4 Hz,
J27.4 Hz,
J313.9 Hz,
1.86 mmol) in THF (2.0 ml) was added n-BuLi (2.5 M in
hexane) (0.82ml, 2.04 mmol) at 2788C. The solution was
stirred for 15 min whereafter ZnCl2 (278 mg, 2.04 mmol) in
THF (2.0 ml) was added dropwise. The yellow colour dis-
appeared. The resulting solution was warmed to 2208C and
then stirred at that temperature for 10 min. During this time
Pd(Ph3P)4 (92mg, 0.08 mmol) in THF (2.0 ml) was added
to the iodo-butenolide 8 (342mg, 1.30 mmol) at room
temperature and then cooled to 08C. The resulting orange
solution was then added to the organozinc solution, and the
mixture was stirred at 08C for 20 min. The reaction mixture
was allowed to reach room temperature, quenched with
NH4Cl (sat.) and extracted with diethyl ether. The organic
phase was dried (MgSO4) and the solvent was evaporated.
The crude product was triturated with 1 ml of diethyl ether
and then ®ltered through SiO2 which was washed with 10 ml
of petroleum ether/diethyl ether 10:1. The ®ltrate was
concentrated and then puri®ed with ¯ash chromatography
(petroleum ether/diethyl ether 6:1) affording 169 mg (73%)
of cis/trans mixture, as a colourless oil, which was
±CH(CH3)CH2±), 2.43 (1H, dddd, J14.6 Hz, J27 Hz,
J37.4 Hz, J410.6 Hz, ±CH2CHCH2±), 2.63 (1H, dqdd,
J13.1 Hz, J27.3 Hz, J37.4 Hz, J48.0 Hz, ±CHCH3),
3.43 (1H, s, OH), 4.77 (1H, dd, J12.0 Hz, J27.5 Hz,
±CH(O)CH2CH2±),
7.01
(1H,
d,
J3.1 Hz,
±CH(CH3)CH±); 13C NMR (CDCl3) d 20.9, 29.0, 31.4,
33.0, 43.1, 81.8, 89.8, 130.7, 150.1, 169.7; HRMS (EI)
calcd for C11H14O3 194.0943, found 194.0945.
Acknowledgements
The Swedish National Research Council for Natural
Sciences is gratefully acknowledged for ®nancial support.
References
È
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20
isomerised (vide supra) to 169 mg pure 1. [a]D 236.5
(c1.4, CHCl3); nmax (®lm): 3020, 2920, 1755, 1450,
2. Weidler, M.; Rether, J.; Anke, T.; Erkel, G. FEBSLett. 2000,
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1215, 1115, 970, 920 and 760 cm21. H NMR (CDCl3) d
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-8H), 6.10 (1H, dd, J115.8 Hz, J20.8 Hz, -50H), 6.79
(1H, dq, J16.8 Hz, J215.8 Hz, -60H), 7.02(1H, d,
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È
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