Handbook of Functionalized Organometallics Applications in S

I
128
O
CO 2Et
I
N
Ts
4 Polyfunctional Magnesium Organometallics for Organic Synthesis
Similarly, reaction of Grignard reagent 112 with 2-methoxyallyl bromide [75]
leads to compound 113 that leads after acidic deprotection of the formamidine
moiety and the enol ether to the indole cyclization product 114 in 90% yield
(Scheme 4.25).
Cyclizations can be achieved with functionalized arylmagnesium reagents bearing
a remote leaving group like a tosylate 115 or an allylic acetate 116 as well. In
both cases, a stereoselective substitution reaction is observed (Scheme 4.26) [76].
The S N2 ring closure of 115 is catalyzed by CuCN´2LiCl [49] and proceeds with
complete inversion of configuration leading to 117 without eroding the original
enantiomeric excess of 60%ee.
Me
OTs
OAc
iPrMgCl
THF, -20 ºC,
1h
iPrMgBr
ClMg
O
MgBr
N
Ts
CO 2Et
Me
OTs
OAc
CuCN·2LiCl
(10 mol%)
-20 ºC to25ºC
O
CO 2Et
60 % ee 115 117: 83%;60%ee
118
THF, -10 ºC,
3.5 h
antisubstitution
H
Me
N H
Ts
116 119: 95%
Scheme 4.26 Stereoselective ring closure of arylmagnesium intermediates 115 and 116.
An anti-S N2' substitution is observed with Grignard reagent 116, readily available
from aryl iodide 118, providing the cis-tetrahydrocarbazole 119 in almost
quantitative yield. In this case, the Grignard reagent undergoes the ring closure in
the absence of a catalyst [76].
4.2.3.3 Halogen±Magnesium Exchange Using Lithium Trialkylmagnesiates
Oshima have shown that besides alkylmagnesium halides, lithium trialkylmagnesiates
(R 3MgLi) readily undergo iodine- or bromine±magnesium exchange reactions
at low temperatures [77,78]. Lithium trialkylmagnesiates are prepared by the
reaction of an organolithium reagent (RLi; 2 equiv) with an alkylmagnesium
halide (RMgX; 1 equiv) in THF at 0 C (30 min). Either 1 equiv or 0.5 equiv of the
lithium dibutylmagnesiate (Bu 3MgLi), relative to the aromatic halide, can be used,
showing that two of the three butyl groups undergo the exchange reaction. Compared
to the halogen±magnesium exchange performed with iPrMgBr, lithium
trialkylmagnesiates undergo the exchange reaction more readily and are less sensitive
to the electronic density of the aromatic ring. Importantly, trialkylmagnesiates
react more rapidly with aryl bromides than does iPrMgCl. Thus, the reaction