Handbook of Functionalized Organometallics Applications in S

126
4 Polyfunctional Magnesium Organometallics for Organic Synthesis
O B
O
PinB
I
95
I
iPrMgBr·LiCl
MgCl·LiCl
E +
THF, -78 ºC, 2 h
OH
BPin
Ph
PinB
97a: 83% 97b: 70%
98
EtO 2C
PinB
O
I
Bu
1) iPrMgCl·LiCl
THF, -78 ºC, 2 h
2) PhCHO
-78 ºC, 2 h
3) H2O, DME
PdCl2(dppf), K2CO3 60 ºC, 8 h
EtO 2C
Scheme 4.22 Boron-functionalized arylmagnesium reagents.
I
-78 ºC tort
CO2Et BPin
PinB
96 97: upto96%
99: 73%
OH
Ph
E
97c: 96%
tion conditions, the preparation of ketone-containing arylmagnesium species
group can be achieved. To avoid side reactions a sterically hindered but reactive
Grignard reagent was chosen: neopentylmagnesium bromide (NpMgBr) [70] in
conjunction with N-methylpyrrolidinone (NMP) as a polar cosolvent to increase
the rate of the iodine±magnesium exchange.
I O
Me Me
Me
MgBr BrMg O
SPh O
(1.1 equiv)
-30 ºC, 1 h
THF/NMP (4:1)
PhSSPh
100 101 102: 72%
Scheme 4.23 Preparation of an arylmagnesium compound bearing a keto group.
Using these modifications, 2-iodophenyl cyclohexyl ketone (100) reacts with
NpMgBr (1.1 equiv) at ±30 C within 1 h in a 4:1 mixture of THF and NMP affording
the arylmagnesium reagent 101. The ortho-keto function facilitates formation
of the Grignard reagent by precoordination of NpMgBr and stabilizes the resulting
arylmagnesium species by chelation. Reaction with diphenyl disulfide furnishes
the thioether 102 in 72% yield (Scheme 4.23) [71].
Incorporating electrophilic functional groups in the ortho-position to the carbon±magnesium
bond allows two sequential alkylations leading to ring closure
(Scheme 4.24). Reacting benzylic chloride 103 with iPrMgBr in THF (±30 C, 1 h)
furnishes the corresponding Grignard reagent 104 that reacts at ±10 C with phenyl
isocyanate leading to the functionalized N-arylphthalimide derivative 105 in
75% yield [72].