Handbook of Functionalized Organometallics Applications in S

148
4 Polyfunctional Magnesium Organometallics for Organic Synthesis
Br
N
Br
CO 2Et
I
iPrMgCl·LiCl
THF, -50 ºC,
2h
iPrMgCl
THF, -20 ºC,
10 min
Br
N
MgCl·LiCl
CO 2Et
MgCl
Scheme 4.60 Synthesis of functionalized boronic esters.
Me
Me
Me
Me
O
B OMe
O
287
MOBPin
287
Br
N
288: 89%
BPin
CO 2Et
BPin
289: 91 %
A similar reaction was applied to the total synthesis of the antibiotic vancomycin
by Nicolaou. The selective conversion of aryl iodide 290 (X=I) to the corresponding
phenol 291 (X=OH) was needed in the final steps of the synthesis
(Scheme 4.61) [142]. Aryl iodide 290 was converted to the corresponding Grignard
reagent 292 by first deprotonating all acidic hydrogens with an excess of MeMgBr
and subsequent addition of iPrMgBr at ±40 C. Reaction of reagent 292 with
B(OMe) 3 leads to the boronic ester 293 that is readily oxidized to the corresponding
phenol 291 with an alkaline solution of H 2O 2 in ca. 50% overall yield.
HO
O
X
HO OTBS
Cl
O
MeO
HN
N
H
1) MeMgBr
2) iPrMgBr
O
H 2O 2 /NaOH
H
H
N
OMe
OMe
O
N
H
O
290: X=I
O
O
292: X=MgBr
Cl
H
N
O
NHDdm
293: X=B(OMe) 2
N
H
O
B(OMe) 3
291: X = OH (overall yield > 50 %)
Scheme 4.61 Formation of a functionalized arylmagnesium
during the synthesis of vancomycin.
Boc
N
Me
This two-step oxidation of a Grignard reagent to the corresponding phenol is a
very important reaction. Ricci developed a methodology that allows the direct con-