138 JOURNAL OF CHEMICAL RESEARCH 2009
R~C02Et
----R]
B,
Pd(PPh3)4/CuI_
_
+
DMF, r.t., 24 h
H
~
2
3
]
R
Scheme 2
Table
1
Synthesis of (Z)-2-ethoxyca rbonyl-substituted
of using 1 in cross-coupling
reactions with alkynyl bromides
1,3-e nynes 3a-h
2. Gratifyingly, when the cross-coupling
reactions of 1 with
a variety of alkynyl bromides 2 were conducted in DMF at
room temperature using Pd(PPh3)4 and CuI as co-catalyst
Entry
R
R1
Product
Yield/Yo"
1
2
3
4
5
6
7
8
n-C4H
g
n-C4H
Ph
Ph
n-C6H13
g
3a
3b
3c
3d
3e
3f
86
81
73
78
75
79
80
82
(Scheme 2), fairly rapid reactions occurred affording stereo-
selectively the desired coupling products 3 in good yields. The
experimental results are summarised in Table I. However, we
found that when the cross-coupling reactions of (E)-a-stannyl-
a,13-unsaturated esters 1 with alkynyl iodides were performed
under the same conditions, only trace coupling products were
obtained.
n-C4H
g
Ph
Ph
Ph
Ph
CH30CH2
n-C4H
g
n-C6
H13
Ph
3g
3h
n-C4H
g
n-C
6
H13
In summary,
a
convenient
synthetic method for (Z)-2-
"Isolated
yield based on the (E)-a-stannyl-a,l3-unsaturated
esters 1 used.
ethoxycarbonyl-substituted
the palladium-catalysed
I ,3-enynes has been developed by
hydrostannylation
of alkynyl esters,
Ie: Oil. IR (film):
1183,1034,788,695;
V
(cm-') 3059,2958,2923,
'H NMR (400 MHz, CDCI3): 1) 7.32-7.29 (m,
1700, 1596, 1463,
followed by a cross-coupling
in the presence of Pd(PPh3)4 and CuI. The present method
reaction with alkynyl bromides
5H), 6.70 (s, 3JSn_H= 64 Hz, 1H), 4.17 (q, J = 7.2 Hz, 2H), 1.58-
1.52 (m, 6H), 1.37-1.32 (m, 6H), 1.22 (t, J = 7.2 Hz, 3H), 1.07
(t, J = 8.0 Hz, 6H), 0.91 (t, J = 7.2 Hz, 9H); l3C NMR (100 MHz,
CDCI3): 1) 173.2, 142.1, 139.8, 137.0, 128.3, 128.1, 128.0,60.3,28.9,
27.3, 14.2, 13.7, 10.6; MS (E1): m/z 466 (W , 1.5),409 (100), 407
(87), 179 (54), 177 (46); Anal. Calcd for C23H3802Sn: C, 59.37; H,
8.23. Found: C, 59.57; H, 8.35%.
has the advantages
of readily available starting materials,
straightforward
and simple procedures, mild reaction
conditions and good yields.
Experimental
'H NMR spectra were recorded on a Bruker AC-P400 (400 MHz)
spectrometer with TMS as an internal standard using CDCI3 as the
solvent. l3C NMR (100 MHz) spectra were recorded on a Broker AC-
P400 (400 MHz) spectrometer using CDCI3 as the solvent. IR spectra
were determined on an FTS-185 instrument as neat films. Mass spectra
were obtained on a Finnigan 8239 mass spectrometer. Microanalyses
were measured using a Yanaco MT-3 CHN microelemental analyser.
All reactions were carried out in pre-dried glassware (150°C, 4 h) and
cooled under a stream of dry Ar. Benzene was distilled from sodium
prior to use. DMF was dried by distillation over calcium hydride.
General procedure for the synthesis of (Z)-2-ethoxycarbonyl-
substituted 1.3-enynes 3a-h
(E)-a-Stannyl-a,13-unsaturated
ester I (1.0 mmol) and alkynyl
bromide 2 (1.1 mmol) were dissolved in DMF (10 mL) under Ar at
room temperature. Pd(PPh3)4 (0.05 mmol) and CuI (0.75 mmol) were
then added. The mixture was stirred for 20-24 h at room temperature
and monitored by TLC (Si02) for the disappearance of the starting
(E)-a-stannyl-a,13-unsaturated ester 1. The reaction mixture was
diluted with diethyl ether (30 mL), filtered and then treated with 20%
aqueous KF (10 mL) for 30 min before being dried and concentrated.
The residue was purified by column chromatography on silica gel
(eluent: light petroleum ether/EtOAc, 19:I).
General procedure for the synthesis of (E)-a-stannyl-a.13-unsaturated
esters la-e
3a: Oil. IR (film):
V
(cm-') 2958, 2931, 2872, 2220,1728,1447,
CAUTION: Appropriate care was taken in handling benzene due
to its carcinogenicity
1374, 1211, 1174, 1024; 'H NMR (400 MHz, CDCI3): 1) 6.48 (t,
J = 7.6 Hz, 1H), 4.23 (q, J = 7.2 Hz, 2H), 2.59-2.53 (m, 2H), 2.33
(t, J = 6.8 Hz, 2H), 1.55-1.28 (m, 11H), 0.96-0.85 (m, 6H); l3C
NMR (100 MHz, CDCI3): 1) 165.2, 152.8, 116.6, 89.8, 77.8, 60.9,
31.1,30.7,29.6,22.4,21.9,19.0,14.1,13.9,13.6;
(M+, 15),207 (41),167 (50),115 (100); Anal. Calcd forC,sH2402: C,
76.23; H, 10.24. Found: C, 76.05; H, 10.32%.
A 25 mL, two-necked, round-bottom flask equipped with a magnetic
stir bar and argon was charged sequentially with alkynyl ester
(I mmol), benzene (4 mL), Pd(PPh3)4 (0.02 mmol) and BU3SnH
(1.05 mmol). If toluene in used instead of benzene the reactions
occurred with low regioselectivity and low yields. The mixture was
stirred at room temperature for 4 h. After removal of the solvent
under reduced pressure, the residue was diluted with light petroleum
ether (20 mL) and filtered to remove the palladium catalyst.
The resulting solution was concentrated under reduced pressure
and the residue was purified by flash chromatography on silica gel
(eluent: light petroleum ether/EtOAc, 19:I).
MS (E1): m/z 236
3h: Oil. IR (film):
V
(cm-') 2958, 2928, 2856, 2216, 1722, 1597,
1490, 1443, 1371, 1210, 1138, 756, 690; 'H NMR (400 MHz,
CDCI3): 1) 7.47-7.44 (m, 2H), 7.33-7.30 (m, 3H), 6.68 (t,J= 7.6 Hz,
1H), 4.27 (q, J = 7.2 Hz, 2H), 2.68-2.63 (m, 2H), 1.49-1.34 (m,
7H), 0.93 (t, J = 7.2 Hz, 3H); l3C NMR (100 MHz, CDCI3): 1) 164.8,
154.6,131.6,128.4,128.3,123.2,116.4,88.8,86.8,61.1,31.1,29.8,
22.5,14.2,13.9; MS (E1): m/z 256 (W , 5.1),129 (30), 115 (41),105
(100); Anal. Calcd for C17H2002: C, 79.65; H, 7.86. Found: C, 79.38;
H,7.64%.
la: Oil. IR (film):
V
(cm-') 2958,2929, 1709, 16m, 1464, 1182,
1038; 'HNMR(400MHz, CDCI3): 1) 6.04 (t,J= 6.8 Hz, 3JSn_H=64Hz,
1H), 4.14 (q, J = 7.2 Hz, 2H), 2.44-2.40 (m, 2H), 1.58-1.26 (m,
19H), 0.95-0.84 (m, 18H); l3C NMR (100 MHz, CDCI3): 1) 171.3,
3e: Oil. IR (film):
1215,1094,755,690;
V
(cm-') 3062,2957,2226,
1726, 1595, 1490,
'H NMR (400 MHz, CDCI3): 1) 7.52-7.49 (m,
153.6,135.6,59.9,31.8,31.4,29.9,27.3,22.3,14.4,
13.9, 13.7, 10.3;
2H), 7.39-7.33 (m, 8H), 7.27 (s, 1H), 4.27 (q, J= 7.2 Hz, 2H), 1.25
(t, J = 7.2 Hz, 3H); l3C NMR (100 MHz, CDCI3): 1) 165.8, 143.2,
134.7, 131.7, 129.2, 128.8, 128.6, 128.4, 128.3, 122.8, 116.9, 91.7,
87.0,61.7, 13.9; MS (E1): m/z 276 (W , 89), 231 (54),203 (100), 105
(90); Anal. Calcd for C'9H'602: C, 82.58; H, 5.84. Found: C, 82.32;
H,5.61%.
MS (E1): m/z 446 (W , 2.3), 389 (69), 387 (48), 205 (50),105 (100),
73 (75); Anal. Calcd for C2,H4202Sn: C, 56.64; H, 9.50. Found: C,
56.34; H, 9.25%.
Ih: Oil. IR (film):
V
(cm-') 2957, 2927, 1709, 1603, 1464, 1377,
1180; 'H NMR (400 MHz, CDCI3): 1) 6.04 (t, J= 7.2 Hz, 3JSn_H= 64
Hz, 1H), 4.14 (q, J= 7.2 Hz, 2H), 2.45-2.39 (m, 2H), 1.53-1.26 (m,
23H), 0.96-0.84 (m, 18H); l3C NMR (100 MHz, CDCI3): 1) 171.3,
153.7, 135.5, 59.9, 32.1, 31.7, 29.2, 29.0, 28.9, 27.3, 22.6, 14.4,
14.1,13.7,10.3; MS (E1): m/z 417 (W-Bu, 100),371 (21),291 (19),
235 (28), 179 (38); Anal. Calcd for C23H4602Sn: C, 58.36; H, 9.79.
Found: C, 58.08; H, 9.62%.
3d: Oil. IR (film):
1447,1373,1211,1174,1024,753,694;
V
(cm-') 3025, 2930, 2218, 1728, 1598, 1493,
'HNMR(400MHz,CDCl3):
1) 7.31-7.29 (m, 5H), 7.10 (s, 1H), 4.21 (q, J= 7.2 Hz, 2H), 2.39 (t,
J = 7.2 Hz, 2H), 1.45-1.25 (m, 8H), 1.20 (t, J = 7.2 Hz, 3H), 0.92
(t, J = 7.2 Hz, 3H); l3C NMR (100 MHz, CDCI3): 1) 166.3, 141.8,