354
L. R. Cox et al. / Tetrahedron: Asymmetry 16 (2005) 347–359
4.4.2. (E)-2-[4-(N,N-Diethylcarbamoyloxy)-5,5-difluoro-
penta-2,4-dienyloxy]-tetrahydropyran 18. Pyran 18
was preparedas for 17 using palladium(II) acetate
(12.8mg, 57.0lmol), triphenylarsine (68mg, 0.22mmol),
CuI (22.3mg, 0.12mmol), iodoalkene 10 (340mg,
1.11mmol) and( E)-2-[3-(tributylstannyl)-prop-2-enyl-
oxy]-tetrahydropyran 1419 (460mg, 1.07mmol) in
DMF (10mL). After 6.5h, the usual work-up afforded
a yellow oil. Purification over silica gel (20% diethyl
ether in light petroleum) afforded 1,3-diene 18 as a pale
yellow oil (90mg, 31%); Rf (20% diethyl ether in light
petroleum) 0.05; dH (300MHz, CDCl3) 6.31–6.22 (1H,
m), 5.74 (1H, dt, 3J 15.4, 5.9), 4.62 (1H, t, 3J 3.3),
4.34–4.26 (1H, m), 4.08–4.00 (1H, m), 3.87–3.80 (1H,
m), 3.52–3.45 (1H, m), 3.40–3.29 (4H, m), 1.87–1.45
(6H, envelope), 1.21–1.13 (6H, envelope); dC (75MHz,
edan orange oil. Purification by column chromatogra-
phy over silica gel (10% diethyl ether in light
petroleum) afforded 1,4-diene 20 as a pale yellow oil
(213mg, 87%); Rf (10% diethyl ether in light petroleum)
0.32; m (film/cmꢀ1) 3085 w, 1782 s (C@CF2), 1730 s
(C@O), 1643 m (C@C), 1476 m, 1460 m, 1426 s, 1383
m, 1288 s, 1246 s, 1211 s, 1157 s, 1074 s, 1036 m, 992
m, 958 m, 924 m, 785 m, 757 m; dH (300MHz, CDCl3)
5.79–5.66 (1H, m), 5.14–5.04 (2H, m), 3.30–3.20
(4H, m), 3.00–2.95 (2H, m), 1.10 (6H, t, 3J 7.0); dC
1
(75MHz, CDCl3) 154.2 (t, JCF 288.0), 152.7, 132.0
4
(t, JCF 3.0), 117.6, 110.6–109.8 (m), [42.2, 41.7],
3
31.2 (d, JCF 2.3), [13.7, 13.0]; dF (282MHz, CDCl3)
4
ꢀ99.32 (1F, dt, 2J 63.6, JHF 2.5), ꢀ111.49 (1F, dt,
4
2J 63.6, JHF 3.8); [HRMS (EI, M+H) Found:
220.1159; Calcdfor C 10H16NO2F2: 220.1149]; m/z (EI)
237 (35%, M+NH4), 220 (100%, M+H), 170 (24%),
100 (66%, ODEC), 74 (69%, NH2Et2), 58 (23%), 44
(12%).
1
CDCl3) 154.2 (dd, JCF 293.9, 291.6), 152.3, 125.6 (dd,
4
2
3JCF 11.9, 4.3), 119.0 (d, JCF 5.1), 111.7 (dd, JCF
40.7, 18.6), 97.9, 66.7, 62.1, [42.5, 41.9], 30.5, 25.3,
19.3, [14.0, 13.2]; dF (282MHz, CDCl3) ꢀ95.66 (1F, d,
2
4
2J 41.9), ꢀ105.72 (1F, dd, J 41.9, JHF 3.2); [HRMS
(ES-TOF, M+Na) Found: 342.1490; Calcd for
C15H23NO4F2Na: 342.1493]; m/z (Cl) 337.7 (49%,
M+NH4), 319.0 (3%, M), 253.5 (100%, M+NH4ꢀTHP),
218.4 (32%, MꢀOTHP), 102.3 (13%, OTHP+H).
4.4.5. (E)-5,5-difluoro-1-(40-methoxybenzoyl)-4-([meth-
oxyethoxy]methoxy)-penta-2,4-diene 21. A flask con-
taining palladium(II) acetate (28mg, 0.13mmol),
copper(I) iodide (199mg, 1.04mmol) and triphenylphos-
phine (136mg, 0.52mmol) was evacuatedandthe vac-
uum releasedto a nitrogen inlet. The procedure was
repeated twice. Dry, degassed DMF (5mL) was added
4.4.3. (E)-4-(N,N-Diethylcarbamoyloxy)-5,5-difluoro-1-
(40-methoxybenzoyl)-penta-2,4-diene 19. Ester 19 was
andthe resulting adrk solution warmedto 30
ꢁC.
prepared
from
tris(dibenzylideneacetone)dipalla-
Iodoalkene 16 (1.59g, 5.0mmol) was added as a solution
in DMF (1mL). The reaction mixture was warmedto
50ꢁC. Stannane 13 (2.76g, 6.0mmol) was added at
40ꢁC as a solution in DMF (1mL). The resulting solu-
tion was heatedfor 3h at 50 ꢁC andmonitoredby
TLC. Upon consumption of the starting material, the
solution was diluted with diethyl ether (20mL), then
transferredto a conical flask. An aqueous solution of
KF (20mL of a 0.97M solution) was added and the
resulting mixture stirredrapidly for 1h. The precipitated
dium(0)-chloroform adduct (23mg, 22lmol), triphenyl-
phosphine (58mg, 0.22mmol), CuI (26mg, 0.14mmol),
iodoalkene 16 (359mg, 1.1mmol) andstannane 11
(520mg, 1.11mmol). Following the usual work-up, a
crude brown oil was isolated. Purification by column
chromatography over silica gel (15% diethyl ether in
light petroleum ) 20% ethyl acetate in light petroleum)
afforded pentadienyl ester 19 as a pale orange oil
(355mg, 83%); Rf (20% ethyl acetate in light petroleum)
0.35; m (film/cmꢀ1) 1734 bds, 1606 m, 1511 m, 1421 m,
1381 w, 1251 s, 1168 m, 1097 m, 1031 m, 955 w, 847 w,
770 w; dH (300MHz, CDCl3) 8.03–7.98 (2H, m), 6.94–
solid(Bu SnF) was filteredunder vacuum andwashed
3
with ethyl acetate (20mL). The organic layer was sepa-
ratedandthe aqueous phase extractedwith ethyl acetate
(3 · 20mL). The combinedorganic extracts were dried
and concentrated under reduced pressure to afford an
orange oil, containing a redsediment ([(PPh 3)2PdI2]).
Purification by column chromatography over alumina
(Brockmann 1, pH9–11, 10% ethyl acetate in hexanes)
afforded pentadienyl ester 21 as a pale yellow oil
(730mg, 41%); Rf (20% ethyl acetate in hexanes) 0.32;
m (film/cmꢀ1) 1716 s, 1697 s, 1606 s, 1511 s, 1257 bds,
3
4
4
6.89 (2H, m), 6.38 (1H, ddt, J 15.5, J 1.5, JHF 2.4),
3
3
5.84 (1H, dt, J 15.5, 6.1), 4.86 (2H, dd, J 6.1, J 1.5),
4
3
3.86 (3H, s), 3.42–3.32 (4H, two overlapping q, J 7.0),
3
1.23–1.15 (6H, two overlapping t, J 7.0); dC (75MHz,
CDCl3) 165.7, 163.3, 154.2 (dd, JCF 294.4, 292.2),
1
4
152.1 (t, JCF 2.2), 131.5, 123.0 (dd, JCF 11.9, 4.5),
3
4
2
122.1, 120.1 (d, JCF 4.5), 113.5, 111.6 (dd, JCF 40.1,
18.7), 63.9, 55.2, [42.4, 41.8], [13.9, 13.0]; dF (282MHz,
2
2
3
CDCl3) ꢀ94.32 (1F, d, J 39.4), ꢀ104.59 (1F, dd, J
1168, 910, 848; dH (300MHz, CDCl3) 7.97 (2H, d, J
8.8), 6.91 (2H, d, J 8.8), 6.24 (1H, br d, J 15.6), 6.03
3
39.4, JHF 2.5); [HRMS (ES-TOF, M+Na) Found:
3
3
3
3
392.1289; Calcdfor C 18H21NO5F2Na: 392.1285]; m/z
(EI) 369 (27%, M), 269 (11%, MꢀODEC), 218 (8%,
MꢀOCOC6H4OMe), 152 (5%), 135 (58%, MeOC6H4-
CO), 100 (100%, CONEt2), 72 (68%, H2NEt2).
(1H, dt, J 15.6, 6.0), 4.91 (2H, s), 4.84 (2H, br d, J
6.3), 3.82 (3H, s), 3.84–3.81 (2H, m), 3.55–3.51 (2H,
m), 3.35 (3H, s); dC (75MHz, CDCl3) 165.9, 163.5,
1
3
155.3 (dd, JCF 295.0, 293.9), 131.7, 123.8 (dd, JCF
4
2
11.9, 4.5), 122.4, 121.3 (d, JCF 5.1), 115.2 (dd, JCF
4
35.6, 17.5), 113.6, 96.4 (t, JHF 2.8), 71.6, 68.7, 64.2,
4.4.4.
2-(N,N-Diethylcarbamoyloxy)-1,1-difluoro-1,4-
pentadiene 20. 1,4-Diene 20 was preparedfrom
tris(dibenzylideneacetone)-dipalladium(0)-chloroform
adduct (26mg, 50lmol Pd), CuI (29mg, 0.15mmol), tri-
phenylphosphine (60mg, 0.23mmol), freshly distilled
allyl bromide (100lL, 1.16mmol) andstannane 11
(519mg, 1.11mmol). After 18h, the usual work-up afford-
59.0, 55.4; dF (282MHz, CDCl3) ꢀ97.03 (1F, d, 2J
45.8), ꢀ105.68 (1F, dd, 2J 45.8, JHF 4.0); [HRMS
3
(ES-TOF, M+Na) Found: 381.1134; Calcd for
C17H20O6F2Na: 381.1126]; m/z (ES-TOF) 381.0 (100%,
M+Na). This material is unstable (neat), has a lifetime
of ca. 24h even in a refrigerated( ꢀ5ꢁC) environment