Chemistry Reference
In-Depth Information
Table 5.10
Halogen-zinc exchange reaction in the presence of P4
1) ZnEt
2
, base, rt
solvent, time
I
H
2) H
3
O
+
CO
2
Et
CO
2
Et
Run
Base (mol%)
Solvent
ZnEt
2
(mol%)
Time (h)
Yield (%)
t
Bu-P4 (30)
1
THF
240
11
quant.
3
a
2
—
THF
240
21
3
P2 (30)
THF
240
12
33
4
P1 (30)
THF
240
12
0
5
DBU (30)
THF
240
11
0
t
Bu-P4 (10)
6
THF
200
11
56
t
Bu-P4 (10)
7
DMF
200
11
quant.
t
Bu-P4 (10)
8
NMP
200
11
quant.
t
Bu-P4 (1)
9
DMF
200
11
91
a
The reaction was carried out at 60
C.
the solvent was switched from THF to DMF. In DMF, 5mol% of
t
Bu-P4 base was
sufficient for activation of the exchange reaction. In the absence of
t
Bu-P4 base, the
exchange reaction in DMF was quite slow and it was found that
t
Bu-P4 base apparently
functions as an activator.
Using this exchange reaction, some functionalizations of aryl halides were examined. As
an example of 1,2-addition to a carbonyl group, the arylzinc prepared from 4-iodobenzoate
and diethylzinc in the presence of
t
Bu-P4 base in THF was reacted with benzaldehyde to
give the benzhydrol derivative in 78% yield. As for the 1,4-addition reaction, the arylzinc
prepared similarly in THF was reacted with chalcone and the 1,4-adduct was obtained in
71% yield under copper-free reaction conditions. Allylation was also carried out in the
absence of copper additive, and allylbenzoate was obtained in 98% yield. It has been
reported that arylzinc compounds are inert to 1,4-addition and allylation reaction in the
absence of additives and conventionally the employment of copper species has been widely
used. However, in this case the
t
Bu-P4 base is considered to promote the reactivity of
arylzinc compounds toward electrophiles [59] (Scheme 5.38).
The arylzinc compounds prepared in DMF can also be used in the palladium catalysed
Negishi coupling reaction and the reaction of the arylzinc with iodobenzene in the presence
of palladium catalyst gave the corresponding biarylcarboxylated in 53% yield [59]
(Scheme 5.39).
5.3.2.6 S
N
Ar Reaction of C-Nucleophile
Introduction of O-nucleophiles to aromatics has been well investigated for S
N
Ar reactions,
but there are limited successful examples for the arylation of carbanions by S
N
Ar reaction.
Highly activated aryl fluorides have been the only successful substrates for the S
N
Ar
reactions using malonates as nucleophiles. Diethyl methylmalonate was reacted with
