Handbook of Functionalized Organometallics Applications in S

120
N
CO 2Et
4 Polyfunctional Magnesium Organometallics for Organic Synthesis
I
iPrMgBr
THF, -20 ºC, 1 h
N
CO 2Et
MgBr
1) CuCN·2LiCl
2) CO2Et Br
N
CO 2Et
49 50 51: 81%
NMe 2
N
I I
CO 2Et
iPrMgBr
THF, -20 ºC, 5 min
52 53
NMe 2
N
I MgBr
CO 2Et
1) CuCN·2LiCl
2) O
Me
54
I
THF, P(OMe) 3, rt, 3 h
I
N
NMe 2
CO 2Et
55: 87%
Scheme 4.15 Arylmagnesium compounds containing nitrogen functional groups.
Me
CO 2Et
The more labile amidine [52] protecting group is also compatible with a magnesium±halogen
exchange and is a convenient mean for introducing primary
amines in a molecule. The diiodo-amidine 52 is converted within 5 min at ±20 C
into the arylmagnesium species 53. Remarkably, only one exchange reaction takes
place. After the first I/Mg-exchange the electron density of the aromatic ring
increases and thus hampers a second exchange. Transmetallation of 53 with
CuCN´2LiCl [49] provides the corresponding arylcopper derivative, which readily
undergoes an addition-elimination reaction with a,b-unsaturated carbonyl compound
54, leading to product 55 in 87% yield (Scheme 4.15) [53].
Likewise, an imine is a suitable way to protect both, anilines and aromatic aldehydes
(Scheme 4.16). Thus, 2-iodophenylenediamine 56 undergoes an iodine±
magnesium exchange with iPrMgBr (2 equiv.) at ±10 C in 3 h leading to Grignard
reagent 57. Transmetallation to the copper derivative by treatment with CuCN´
2LiCl [49] and subsequent allylation with allyl bromide gives the diimine 58 in
83% yield [54].
Whereas aryl iodides bearing an aldehyde group preferentially react with the
aldehyde function during attempted iodine±magnesium exchange, the corresponding
imine (59) undergoes a smooth exchange reaction leading to the
Grignard reagent 60. The addition of BiCl 3 followed by a silica gel column chromatographical
purification, provides the resulting functionalized triarylbismuthane
61 (Scheme 4.16) [55]. The tedious introduction and removal of a protecting
group can in principle be avoided for proton-donating groups through additional
equivalents of base. Although halogen±metal exchange reactions on aryl
halides bearing acidic protons have been successfully conducted with alkyllithium
reagents, the low temperatures (±78 C) and the considerable amounts of sideproducts
make this methodology less attractive. The formation of unprotected
O