Handbook of Functionalized Organometallics Applications in S

OTIPS
I
iPrMgCl
OTIPS
4.3 Further Applications of Functionalized Grignard Reagents
1)
MeO
OMe O
N
OTIPS
MeO
2) n-BuLi
MeO
O
N
MgCl
3) O
MeO
OH
309 310: 74%
Scheme 4.68 Formation of a functionalized arylmagnesium
in the course of an alkaloid synthesis.
Aromatic iodides and bromides bearing a good leaving group in the ortho-position
can generate 1,2-dehydrobenzene and related substrates (arynes) through an
elimination reaction [166]. This approach has been used successfully for a variety
of organometallic reagents, but the harsh reaction conditions or the high reactivity
of the organometallic reagent (especially the lithio-derivatives) made this method
incompatible with a variety of functional groups [167,168]. Performing the I/Mgexchange
on ortho-iodotosylates 311 leads to stable Grignard reagents of type 312
that react readily with various electrophiles at low temperatures, leading to products
of type 313 such as 313a in 95% yield (Scheme 4.69) [169].
OSO 2Ar
I
FG
– iPrI
FG
311 312
Ph
OH
iPrMgCl
-78 ºC
Ar = 4-Cl-C6H4 FG = CO2Me; NO2;CN; CF3;H;I;COPh OSO 2Ar
CN
OSO 2Ar
MgCl
PhOC
I
O
E +
-78 ºC
to rt
-78 ºC
O 2N
OSO 2Ar
E
FG
O
[4+2]
O
I
MeO 2C
313a: 95% 68% 75% 71%
Scheme 4.69 Preparation of functionalized arynes.
FG 313
314
up to 95%
FG
O
up to 91%
O
153