N. D. D’Angelo et al. / Tetrahedron Letters 47 (2006) 5045–5048
5047
Table 2. Effect of microwave on Ullmann ether synthesis yields with different heterocycles
HO
copper powder (0.1 eq.), Cs2CO3 (3 eq.),
DMF, 100 oC, 60 Watts (microwave only)
O
Het
+
Het-X (1.0 eq.)
9-13
(R=H)
2
Entry
1
Het–X
Product
Conventional heating
yielda (%)
Microwave heating
yielda (%)
4-Chloroquinoline
72
80
O
N
(9)
N
O
2
3
2-Chloropyrimidine
85
76
97
87
N
(10)
S
N
O
2-Chlorobenzothiazole
(11)
4
5
6
7
8
9
4-Bromopyridine
4-Iodopyridine
3-Chloropyridine
2-Chloropyridine
2-Bromopyridine
2-Iodopyridine
4-Phenoxypyridine (3)
4-Phenoxypyridine (3)
3-Phenoxypyridine (12)
2-Phenoxypyridine (13)
2-Phenoxypyridine (13)
2-Phenoxypyridine (13)
32
82
Trace
11
64
83
75
4
49
83
86
91
a Isolated yield.
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Acknowledgements
We thank Professors Stephen Buchwald and Eric Jacob-
sen and Dr. Michael Martinelli for helpful discussion
and encouragement.
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14. Microwave irradiation of just the copper powder in DMF,
followed by coupling using conventional heating at 100 °C
for 18 h afforded only a modest increase in the yield of 3,
from 17% to 25%.
15. General microwave reaction procedure: 4-chloropyridine
hydrochloride (224 mg, 1.5 mmol) and phenol (221 mg,
2.24 mmol) were suspended in DMF (3.3 ml) in a micro-
wave vial and copper powder (9.5 mg, 0.15 mmol, Aldrich
99%, 1–5 lm), and cesium carbonate (1.45 g, 4.45 mmol)