Chapter 4. Equilibrium of the compositions of Grignard reagents.
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Transcript of Chapter 4. Equilibrium of the compositions of Grignard reagents.
Chapter 4
Equilibrium of the compositions of Grignard reagents
n-butyllithium and potassium t-butoxide(super base)
CH2C(CH3)3 CH2
Cn-BuLi
KOC(CH3)3
CH3
CH2Li
C C
CH2
CH3 CH2
CH3
C C
CH2
LiH2C CH2
CH2Lin-BuLi
KOC(CH3)3
Metal-halogen exchange
forming the morestable organolithium reagentRX R'Li RLi R'X+ +
C C
H
Ph Ph
H t-BuLi'
THF-Et2O
C C
H
Ph Li
H
pentane-
greater stability of sp2 carbanions
Retention of configuration
Metal-halogen exchange
Metal-halogen exchange
Reduction of sulfides
O
SPh
O
Li
LDMAN
PhSCSi(CH3)3
CH3
CH3
LDMANLiCSi(CH3)3
CH3
CH3
dimethylaminonaphthalene(LDMAN)
PhCH2CH2SPh PhCH2CH2LiLi or
Shapiro reaction
NHNTs
C2H5
CH3
Li
C2H5
CH3
2 n-BuLi
TMEDA
vinyllithium compounds
OTBS
NNHSO2ArOPN
OBnTPSO
OHCOBn
OPN
OBn
OBn
OTBS
OHH
TPSO
+
n-BuLiTHF,then
-78 C0 C¡£
¡£
I-Pr
I-Pr
I-Pr
Ar =15, 67 98:R = Piv
Nicolaou et al. J.Am.Chem.Soc.Vol.117,No.2,1995,634.
Reactions with Alkylating Agents Limited in scope Radicals involved
n-C4H9Br n-C4H9Li
CH(CH3)2
CH3(CH2)6CH3 CH3CH2CH=CH2CH3CH2CH2CH3+ + +
(43%) (3%) (19%)
disproportionation
+
C
CH3
CH3
C
CH3
CH3 (18%)
coupling of radicals
Hydrogen abstraction
CHCH2
CH2
ClLi
PhPhCH2CH=CH2
C14
**
~75%
Alkylation by allylic halides
Allyllithium and benzyllithium reagents
PhCH2LiC
CH2CH3
BrH
CH3
C
CH2CH3
H
CH3PhCH2(58% yield,100% inversion)
S 2N
C=CCH3
H
CH3
Br
C=CCH3
H
CH3
CH3(CH2)3
LiCH3(CH2)3I
1)2)
RI or RBr(77%)
Ring closureCH2I
CH2I
t-BuLi
(97%)
Grignard reagentsCH3
CH3 CH3
CH3 BrCH3
CH3 CH3
CH3 CH2CH=CH2Mg
CH2=CHCH2Br
MeX, X, ArCH2X
1)2)
(79%)
Reaction with Carbonyl Compoundds addition of Grignard reagents
MgR
X
OR'
R'Mg - R
XC O Mg R
R'
R'
R
CR'
R
O Mg
X
R
MgX2
termolecular complex
+
+H O2
nitriles
RMgX R'C N RCR' RCR'
NMgX O
+H O2
O
C N
CH3MgIHCl (52-59%)
CCH3
O
CH3(CH2)5MgBr CH3CH2CH2CCl CH3(CH2)5C(CH2)2CH3
O-30 CTHF
excess at low temperature
¡£
(92%)
+
good leaving group
NH
S
+
Competing reactionsMeerwein- Pondorff-Verley reduction
With hindered ketones
H
OMg
R
R
R
R
R'
R'
X
R
R
R
R
O
R'R'
H
Mg
X
+
cyclic T.S
Enolization of the ketone
ROMgX R'CCR''2 ROH
RMgX
RH
R'C=CR''2H
+
R'CCR''2
O
H
-
++
O O
HFacilitate by alkoxide
1 2 3 4 123 4123
4
homoallylic system
Lewis acid
directed ortho lithiation
CN(C2H5)2
CH3O
CH3O
CN(C2H5)2
CH3O
CH3O
Li
CH3
CH3O
O=CH
OMe
C=O
OH OMeOMe
CH3O
OMeCH3
(C2H5)2N
t-BuLi
(63%)
+(CH3)3COCHCH=CH2CH3(CH2)5I
C=CH
(CH3)3CO
H
(CH2)6CH3
(86%)allylic shiftLi
stable at low temperature
(DMF)
CH3(CH2)3CHCH=O BrCHCO2C2H5 CH3(CH2)3CHCHCHCO2C2H5
C2H5 CH3 CH3C2H5
OH
H+
1)2)
H O2+
(87%)
(97%)
Lewis acid Catalysis:O
Br
PhCH=OEt2AlCl
O
CHPh
OH-20 C
¡£
Zn+
+ +
mechanism
[R2Cu] R'CH=CHCR R2Cu R'CH=CHCR
O
RCu
O
R'CH=CHCR
O--£®
R
- +
fast electron transfer step no free radicals are generated
Heck reactions:
C=CC6H13
H
I
H
C=C
H
BrMg
H
H
C=CC6H13
H
CH=CH2
H
C=CC4H9
H
C4H9
H
C=CC4H9
H
Br
HC4H9Li
Pd(PPh3)4
Pd(PPh3)4
+
+
(75%)
(63%)
Kumada coupling
Organozinc compounds (Negishi coupling)
ZnCl
CH3
NO2Br
CH3CH3
NO2
Pd(PPh3)4+
(78%)
Pd(PPh3)4CH2=CHCH2CH2ZnCl C=C
H
I
(CH2)3CH3
CH3+ C=C
H
CH2=CHCH2CH2
(CH2)3CH3
CH3
(81%)
C=CC2H5
Ph
Ph
BrPd(PPh3)4+ ZnCl C=C
C2H5
Ph
Ph
OMe
(84%)
MeO
SYNTHESIS September 1992Palladium-Catalysed Reactions of Organotin CompoundsTetence N.MitchellFachbereich Chemli,Universitāt Dortmund,Posifach 500 500,D-4600 Dortmund 50. GermanyReceived 16 August 1991;revised 12 December 1991
Pd(PPh3)4
+O
SnMe3
t-BuPh2SiO
I
OSiPr-i3
OSiPr-i3Pd(PPh3)4 / THF
OSiPr-i3
OSiPr-i3
Ot-BuPh2SiO
NH
N
N
NH
Br
Br
CO2MeCO2Me
NH
N
N
NH
CO2MeCO2Me
Bu3Sn
85%
90%
C=C
R
H
Pd2+
X
HR'M C=C
R
H
Pd2+
R'
H
C=C
R
H H
R'
MX Pd(0)+ + +
coupling of terminal alkynes with vinyl ro aryl halides
copper acetylide
HC CR CuC CR
R'X Pd R'Pd X
R'Pd R'C Pd
Cu(I)
R3N
+
+0
110
CR
C CR
11
Sonogashira Coupling
synthesis of enynes
O
Br
BrEtO Et3N
(Ph3P)2PdCl2, CuI,
SiMe3 O
SiMe3
EtO
SiMe3(88%)
N
O
PhO
OH
O
Cl
SiMe3
Ph(OAc)2, PPh3
CuI, nBuNH2 (88%)
N
O
PhO
OH
O
SiMe3
Skeleton Reanangement
R3P NiCl
Ph
R3P
(CH3)2CHMgX R3P Ni
Ph
CH
CH3
CH3R3P
R3P
R3P
Ni
HPh
CH2
CH
CH3secondary
nickel - alkene complex
primary
PhCH2CH2CH3
+ R3P Ni
Ph
R3P
CH2CH2CH3
