Handbook of Functionalized Organometallics Applications in S

Cl
MgBr
4.2Methods of Preparation of Grignard Reagents and their Uncatalyzed Reactions
CO2Me CO2Me CO2Me I
Cl iPrMgBr
THF, -30 ºC, 1 h
Cl
MgBr
Ph-N=C=O
-10 ºC tort
N
O
Ph
103 104 105: 75%
CO2Et Br
CuCN·2LiCl
106 107: 83%
Cl
CO 2Et
BnNH 2
K 2CO 3,THF
reflux, 24 h
Scheme 4.24 Reaction of chloromethyl substituted arylmagnesium species.
Bn
N
CO2Et 108: 75%
The reaction of the related arylmagnesium species 106 with ethyl (2-bromomethyl)acrylate
[73] furnishes the polyfunctionalized product 107 in 83% yield.
Subsequent treatment of 107 with benzylamine in the presence of K 2CO 3 in
refluxing THF provides the benzoazepine 108 in 75% yield [72]. In strong contrast
to the corresponding lithium reagent, which is stable only at ±100 C, [74] the
magnesium species 106 is stable for several hours at ±30 C. Recently, the reagent
106 has also been used for the preparation of an oxaphenanthrene [74].
Under slightly acidic conditions a formamidine used as protecting group reacts
in an intramolecular addition as an electrophilic function leading to different heterocycles.
Hence, the use of iPrMgBr allows the selective mono-exchange on protected
diiodoaniline derivatives of type 109 and the corresponding Grignard
reagents can react with a variety of isocyanates leading to amides such as 110.
Addition of HCl and treatment with silica gel furnishes the desired quinazolinones
111 in good yields (Scheme 4.25) [54].
NC
I
I
N NMe2 1) iPrMgBr
THF, -20 ºC,
30 min
I
N NMe2 HCl,
silica gel
I
N
I
2) R-N=C=O
0 ºC, 6 h
then MeOH
NC
O
H
N
R
THF, rt, 16 h
FG
N
R
O
109 R: m-CF3C6H4 110 111: 92%
N
NMe 2
I
1) iPrMgBr
I
N
NMe 2
HCl (conc.)
EtO 2C
CO2Et THF, -20 ºC,
30 min
2) CuCN·2LiCl
3)
CO2Et OMe THF/H2O, rt,
30 min
I
112 Br
OMe
113: 75% 114: 90%
Scheme 4.25 Synthesis of quinazolinones and indoles.
127
N
H
Me