3.4 Ullmann Coupling
Coupling between a phenoxide and a bromoaryl derivative catalysed by copper(I)
salts led efficiently to biarylethers. The intramolecular version of this process has
been used for the synthesis of bulbophylol-B 51, a dihydrodibenzo[b,f]oxepin with
significant cytotoxic properties (Scheme 21) [36].
Under basic conditions, a tandem Knoevenagel reaction/Ullmann coupling has
been devised to synthesise dibenzooxepin 53 from 2-hydroxybenzonitrile and
2-bromobenzaldehyde 52 in high yield (98 %) (Scheme 22) [37].
H
O
O
t-Bu-O
O
O
O
O
O
H
BF 3 .OEt 2
CH 2 Cl 2 , -40 °C
O
O
O
OH
H
H
H
45
O
O
H
H
3
44
12%
Scheme 18 Formation of four fused oxepanes by a cascade process
RuCl 3 (5 mol %)
NaIO 4 (7 equiv)
O Ru
O
O
O
O
Ru
O
O
O
OH
O
HO
47
CH 3 CN / AcOEt
(dr > 95:5)
0 °C
Low valent
Ru species
46
63%
Scheme 19 Formation of 2,7-disubstituted oxepane by oxidative cyclisation of 1,7-dienes
O O
H
O
Et 3 SiH, TMSOTf
CH 2 Cl 2 , 0 °C, 1h
48
84%
(+)-Isolaurepan, 49
Scheme 20 Direct synthesis of (+)-isolaurepan by reductive cyclisation of a hydroxyl ketone
Synthesis of Seven-Membered Ring Ethers and Lactones
293