Notes
J . Org. Chem., Vol. 62, No. 11, 1997 3785
Ta ble 5. Cop p er (0)-P r om oted Cr oss-Cou p lin g Rea ction
mmol), copper(I) chloride (10 mg, 0.10 mmol), and terpyridine
(24 mg, 0.10 mmol) in NMP (1 mL) was added organotin (0.15
mmol) at room temperature. After being stirred for 2-3.5 h,
the reaction mixture was poured into ice-cold 5% HCl aqueous
and extracted with ethyl acetate. The combined extracts were
3
of 3-(Ch lor om eth yl)-∆ -cep h em 1 w ith Allyl a n d Ben zyl
a
Br om id es
washed with water and brine, dried over Na
trated under reduced pressure. The residue was purified by
column chromatography (SiO , benzene/ethyl acetate ) 8/1) to
afford the 3-alkenyl-∆ -cephems 2a -d .
2 4
SO , and concen-
2
3
3
p-Meth oxyben zyl 3-Allyl-7-(ph en ylacetam ido)-∆ -ceph em -
-ca r boxyla te (En tr y 1, 2a ). According to the general proce-
4
dure, the reaction of 1 with tributylvinyltin (48 mg, 0.15 mmol)
3
was carried out for 3.5 h to give the 3-allyl-∆ -cephem 2a (33
mg, 68%) and the dimer 4 (10 mg, 21%).
2
a : IR (KBr) 3412, 1783, 1721, 1682 cm 1; 1H NMR (200 MHz,
-
CDCl
3
) δ 2.88 (dd, J ) 7.7, 14.3 Hz, 1H), 3.25 (d, J ) 18.3 Hz,
H), 3.36 (d, J ) 18.3 Hz, 1H), 3.36 (dd, J ) 7.7, 14.3 Hz, 1H),
.61 (d, J ) 16.2 Hz, 1H), 3.64 (d, J ) 16.2 Hz, 1H), 3.79 (s,
H), 4.90 (d, J ) 4.8 Hz, 1H), 5.08, (d, J ) 16.0 Hz, 1H) 5.09 (d,
1
3
3
,
a
All reactions were carried out with allyl or benzyl halides (5.0
J ) 10.7 Hz, 1H), 5.17 (s, 2H), 5.75 (m, 1H), 5.76 (dd, J ) 4.8,
mol amt) and terpyridine (1.0 mol amt) in NMP at room temper-
ature.
9
7
5
1
.0 Hz, 1H), 6.16 (d, J ) 9.0 Hz, 1H), 6.87 (d, J ) 8.7 Hz, 2H),
13
3
.21-7.42 (m, 7H); C NMR (50 MHz, CDCl ) δ 27.9, 37.6, 43.3,
5.2, 57.3, 59.0, 67.6, 113.9, 117.9, 123.3, 127.1, 127.7, 129.1,
29.4, 130.5, 131.3, 133.7, 133.9, 159.8, 161.7, 164.5, 171.1.
Sch em e 7
Anal. Calcd for C26
Found: C, 64.95; H, 5.44; N, 5.66.
: IR (KBr) 3265, 1779, 1717, 1662 cm 1; 1H NMR (200 MHz,
CDCl ) δ 2.44 (t, J ) 8.3 Hz, 2H), 2.91 (t, J ) 8.3 Hz, 2H), 3.22
26 2 5
H N O S: C, 65.25; H, 5.48; N, 5.85.
-
4
3
(
d, J ) 18.3 Hz, 2H), 3.28 (d, J ) 18.3 Hz, 2H), 3.63 (s, 4H),
3
4
4
4
1
.79 (s, 6H), 4.88 (d, J ) 4.7 Hz, 2H), 5.16 (s, 4H), 5.75 (dd, J )
.7, 9.2 Hz, 2H), 6.46 (d, J ) 9.2 Hz, 2H), 6.87 (d, J ) 8.7 Hz,
H), 7.19-7.41 (m, 14H); 13C NMR (50 MHz, CDCl
) δ 28.6, 32.5,
3
3.1, 55.2, 57.8, 58.9, 67.5, 113.9, 123.0, 126.8, 127.3, 128.7,
28.8, 129.0, 129.2, 130.5, 134.1, 135.7, 159.8, 161.7, 165.5, 171.4.
Anal. Calcd for C48
46 4 10 2
H N O S : C, 63.84; H, 5.13; N, 6.20.
Found: C, 63.75; H, 5.21; N, 6.21.
p-Meth oxyben zyl 3-(2,3-Bu tadien yl)-7-(ph en ylacetam ido)-
-cep h em -4-ca r boxyla te (En tr y 2, 2b). According to the
general procedure, the reaction of 1 with allenyltributyltin (49
∆3
this concern, it should be remembered that in the reaction
of 1 with 5 mol amounts of allyl bromide and 1 mol
amount of copper powder, most of 1 was consumed. The
result suggests that the cross-coupling reaction of 1 with
allyl and benzyl bromides mainly proceeds through path
a rather than path b. In fact, the reaction of benzyl
bromide with copper powder (4 mol amounts) and bipyr-
idine (1 mol amount) in NMP afforded no appreciable
amount of the homo-coupling product (bibenzyl), result-
ing in the recovery of most of the benzyl bromide (57%).
mg, 0.15 mmol) was carried out for 2 h to give the 3-(2,3-
3
butadienyl)-∆ -cephem 2b (42 mg, 84%): IR (KBr) 3299, 1953,
-1
1
1
3
775, 1719, 1671 cm ; H NMR (200 MHz, CDCl ) δ 2.87 (dd,
J ) 8.0, 13.8 Hz, 1H), 3.26 (m, 1H), 3.30 (d, J ) 18.4 Hz, 1H),
3.41 (d, J ) 18.4 Hz, 1H), 3.62 (d, J ) 16.2 Hz, 1H), 3.63 (d, J
)
(
16.2 Hz, 1H), 3.80 (s, 3H), 4.73 (dt, J ) 2.8, 6.2 Hz, 2H), 4.90
d, J ) 4.7 Hz, 1H), 5.11 (m, 1H), 5.18 (s, 2H), 5.78 (dd, J ) 4.7,
9
7
5
.1 Hz, 1H), 6.02 (d, J ) 9.1 Hz, 1H), 6.86 (d, J ) 8.8 Hz, 2H),
.19-7.40 (m, 7H); 13C NMR (50 MHz, CDCl
) δ 28.1, 32.7, 43.2,
5.2, 57.2, 58.9, 67.6, 75.9, 86.7, 113.9, 123.0, 126.9, 127.6, 129.1,
3
129.4, 130.5, 131.5, 133.7, 159.7, 161.6, 164.5, 171.1, 209.3.
Anal. Calcd for C27 S: C, 66.10; H, 5.34; N, 5.71.
26 2 5
H N O
Found: C, 66.32; H, 5.45; N, 5.55.
Exp er im en ta l Section
p-Meth oxyben zyl 3-(3-Bu ten yl)-7-(p h en yla ceta m id o)-∆3-
cep h em -4-ca r boxyla te (En tr y 3, 2c). According to the general
procedure, the reaction of 1 with allyltributyltin (50 mg, 0.15
IR spectra were obtained on a J apan Spectroscopic Co. Ltd.
J ASCO FT/IR-5000 spectrometer. 1H and C NMR spectra were
13
1
3
recorded with a Varian Gemini 200 (200 MHz for H and 50 MHz
mmol) was carried out for 3 h to give the 3-(3-butenyl)-∆ -cephem
1
3
for C) spectrometer. Elemental analyses were performed on
a Perkin-Elmer 2400 Series II CHNS/O analyzer. The 3-(chlo-
2c (31 mg, 61%) and the dimer 4 (6 mg, 14%): IR (KBr) 3306,
-
1 1
1771, 1723, 1661 cm ; H NMR (200 MHz, CDCl ) δ 2.01-2.68
3
3
25
26
romethyl)-∆ -cephem 1 and organotins were prepared ac-
cording to the reported procedures in the literature. Copper
powder (200 mesh) was activated according to the literature
(m, 4H), 3.21 (d, J ) 18.1 Hz, 1H), 3.39 (d, J ) 18.1 Hz, 1H),
3.62 (s, 2H), 3.79 (s, 3H), 4.89 (d, J ) 4.7 Hz, 1H), 4.96 (d, J )
9.8 Hz, 1H), 4.98 (d, J ) 17.7 Hz, 1H), 5.17 (s, 2H), 5.73 (dd, J
) 4.7, 8.9 Hz, 1H), 5.61-5.82 (m, 1H), 6.25 (d, J ) 8.9 Hz, 1H),
2
7
before use.
NMP was distilled from calcium hydride under
1
3
reduced pressure and stored over 4A molecular sieves. All other
reagents were available from commercial sources and used
without further purification.
6.87 (d, J ) 7.4 Hz, 2H), 7.20-7.41 (m, 7H); C NMR (50 MHz,
CDCl ) δ 28.5, 32.3, 32.5, 42.8, 55.0, 57.5, 58.9, 67.2, 113.6, 115.5,
122.7, 126.8, 127.1, 128.1, 128.6, 129.1, 130.2, 133.9, 135.0, 136.6,
159.5, 161.6, 164.5, 171.3. Anal. Calcd for C27 S: C,
65.83; H, 5.73; N, 5.69. Found: C, 65.69; H, 5.95; N, 5.41.
3
Gen er a l P r oced u r e for Cop p er (I)-P r om oted Rea ction of
28 2 5
H N O
3
3
-(Ch lor om eth yl)-∆ -cep h em w ith Or ga n otin s (Ta ble 2).
3
3
To a mixture of the 3-(chloromethyl)-∆ -cephem 1 (50 mg, 0.10
p-Meth oxyben zyl 3-Cin n a m yl-7-(p h en yla ceta m id o)-∆ -
cep h em -4-ca r boxyla te (En tr y 4, 2d ). According to the gen-
eral procedure, the reaction of 1 with styryltributyltin (59 mg,
(
25) (a) Torii, S.; Tanaka, H.; Saitoh, N.; Siroi, T.; Sasaoka, M.;
3
Nokami, J . Tetrahedron Lett. 1982, 23, 2187. (b) Tanaka, H.; Taniguchi,
M.; Kameyama, Y.; Monnin, M.; Sasaoka, M.; Shiroi, T.; Nagao, S.;
Torii, S. Chem. Lett. 1990, 1867. (c) Tanaka, H.; Taniguchi, M.;
Kameyama, Y.; Monnin, M.; Torii, S; Sasaoka, M.; Shiroi, T.; Nagao,
S.; Yamada, T.; Tokumaru, Y. Bull. Chem. Soc. J pn. 1995, 68, 1385.
0.15 mmol) was carried out for 3.5 h to give the 3-cinnamyl-∆ -
cephem 2d (28 mg, 50%) and the dimer 4 (10 mg, 21%): IR (KBr)
-1
1
3
(
)
308, 1779, 1723, 1680 cm ; H NMR (200 MHz, CDCl
dd, J ) 8.2, 14.4 Hz, 1H), 3.29 (d, J ) 18.1 Hz, 1H), 3.40 (d, J
18.1 Hz, 1H), 3.50 (dd, J ) 5.1, 14.4 Hz, 1H), 3.61 (d, J ) 16.2
3
) δ 2.97
(
26) Tanaka, H.; Hai, A. K. M. A.; Ogawa, H.; Torii, S. Synlett 1993,
Hz, 1H), 3.63 (d, J ) 16.2 Hz, 1H), 3.78 (s, 3H), 4.91 (d, J ) 4.8
Hz, 1H), 5.20 (s, 2H), 5.77 (dd, J ) 4.8, 9.0 Hz, 1H), 6.16 (d, J )
9.0 Hz, 1H), 6.01-6.32 (m, 1H), 6.40 (d, J ) 15.8 Hz, 1H), 6.86
8
35.
(
27) Fusion, R. C.; Cleveland, E. A. Organic Synthesis; J ohn Wiley
Sons: New York, 1955; Vol. 3, p 339.
&