homogene katalyse 2011 - bcp.fu-berlin.de · c.c. tzschucke 32 heck reaction: stereochemistry...
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28C.C. Tzschucke
Heck Reaction
General reaction scheme
Initial publications
R1
XR2+ R1
R2
R1
X R2+ R1
R2
Pd-cat.base
Pd-cat.base
Mizoroki Bull Chem Soc Jpn 1971 44 581
Heck JOC 1972 37 2320
Heck JACS 1974 96 1133
29C.C. Tzschucke
Heck reaction: Mechanism
oxidative addition
ligand exchange
migratory insertionβ-hydride elimination
ligand exchange
reductive elimination
30C.C. Tzschucke
H2C CH2
CH3 H3C
O
OMe
N2 I OTf Br Cl OTsX = F OMe
Heck Reaction: Reactivity
Olefin:
Ar-X:
> > > >
> >> ~ >> >> >
14000 970 220 42 1
relative rates from competition
experiments
31C.C. Tzschucke
Heck Reaction: Stereochemistry
R
PdAr
XL
R
X
L
PdAr
HH H
R
X
L
PdH
ArH H
R
X
L
PdH
HAr H
RPd
H
XL
RArAr
PdH
XL
RRArAr
syn-addition
E-product Z-product
32C.C. Tzschucke
Heck Reaction: Stereochemistry
syn-addition
R2
PdAr
XL
R2
X
L
PdAr
R1H H
R2
X
L
PdH
ArR1
HR2
ArR1
R1
syn-elimination
MeO2C
Br CO2Me CO2Me
MeO2C
+
[Pd]
make trisubstituted olefins stereoselectivelybut: beware of base-induced isomerization
33C.C. Tzschucke
Heck Reaction: Regiochemistry
R RPh
R
Ph
Ph Br[Pd]
+ +
CO2Me CN
CH3
OMe
OMe
OMe
CH3
CO2MeH3C H3C
CH3
100% 100% 100% 100% 80%
100%99% 79% 90%
21%1% 7% 10%93%
20%
Heck Pure Appl Chem 1978 50 691
34C.C. Tzschucke
Heck Reaction: Conditions
bases: Et3N, Cy2NEt, NaOAc, Na2CO3, NaHCO3,...
solvents: DMF, NMP, DMA, dioxane, toluene, xylene, CH3CN,...
temperature: usually > 100 °C
palladium sources: Pd(OAc)2, Pd2(dba)3
ligands: PPh3, o-Tol3P, tBu3P, NHC...
CH2
PdP
Ar ArO
CH3H2C
PdP
ArArO
O
O
CH3Ar = o-tolyl
PdN
H3C OH
PdN
CH3HO
X
X
...
Herrmann-Beller-catalyst
catalyst loading: 0.1 - 5 mol%, but examples with TON ~ 1000000
35C.C. Tzschucke
Reduction of Palladium
Amine
Phosphine
Olefin
Alcohol
L
Pd XX
L
L
Pd XX
NEt
EtCH3
Et3N L
Pd XL
HEt
NEt
CH3
X
Pd(0)
Et3N
Et3NH X
PR3
Pd OAcAcO
PR3
PR3
Pd OAc
AcO
PR3
Pd(0)
AcO PR3
L
Pd XX
L
L
Pd XX
L
Pd X
X
L
Pd XH
X
Pd(0)
X HX
L
Pd XX
L
L
Pd OXMeOH L
PdX
H
Pd(0)CH3
O CH2 HX
cf. Wacker oxidation
36C.C. Tzschucke
Heck Reaction: Aryl Chlorides
Fu JOC 1999 64 10JACS 2001 123 6989
aryl chlorides usually not reactive enough
MeO
Cl
+
1.5 mol% Pd2(dba)36 mol% tBu3P
Cs2CO3, dioxane, 120 °CMeO
84%
MeO
Cl
CO2Me+
1.5 mol% Pd2(dba)36 mol% tBu3P
Cy2NMe, dioxane, 120 °CMeO
CO2MeCH3
CH3
72%
Br
CO2Me+
0.5 mol% Pd2(dba)31 mol% tBu3P
Cy2NMe, dioxane, r.t.
CO2Me
CH3
CH3
H3C
CH3
CH3 CH3
83%
37C.C. Tzschucke
Heck Reaction: Jefferey Conditions
MeO
I
+2 mol% Pd(OAc)2
1 equiv Bu4NCl2.5 equiv. K2CO3
DMF, r.t.
O
HMeO
O
H
+2 mol% Pd(OAc)2
1 equiv Bu4NCl2.5 equiv. K2CO3
DMF, r.t.
O
CH3I
O
CH3
I
+2 mol% Pd(OAc)2
1 equiv Bu4NCl2.5 equiv. K2CO3
DMF, r.t.
O
CH3 O
CH3
I
+
5 mol% Pd(OAc)210 mol% PPh31 equiv Bu4NClO
OMe
O
OMe
Na2CO3, H2Oor
NaHCO3, MS 4Å, DMF
Beletskaya J Organomet Chem 1983 250 551Jeffery JCS Chem Comm 1984 1287
THL 1985 26 2667
Jeffery THL 1994 35 3051, 4103TH 1996 52 10113
91%
91%
93%
>95%
Bu4NCl:
•increase reactivity
•lower temperature
•use sensitive alkenes
38C.C. Tzschucke
Heck Reaction: Silver Effect
Hallberg JOC 1985 50 3896JOC 1986 51 5286
Overman JOC 1987 52 4130
I
SiMe3+
3 mol% Pd(OAc)26 mol% PPh3
SiMe3
AgNO3Et3N, DMSO
R
R
R
3 mol% Pd2(dba)31 equiv Bu4NCl
KF, toluene, r.t.
O
NCH3
I
NOCH3
NOCH3
+
1 mol% Pd(OAc)2, 2 mol% PPh3Et3N, CH3CN
1 mol% Pd(OAc)2, 3 mol% PPh3AgNO3, Et3N, CH3CN
1:1
26:1
Silver salts:• prevent double bond
isomerization• increase rate of reaction
H
Pd XAg
− AgXPd(0)
Ar
Pd XAg
− AgX
Ar
Pd
40C.C. Tzschucke
Heck Reaction: Triflates
OTf
OBn+R R
2.5 mol% Pd(OAc)2
2.75 mol% dppp
Et3N, DMF, 100 °C
OBn
comparison of regiochemistryfor reaction of aryltriflates and aryl halides:
EWGOH
PhOH
100%100%
0%100%
5%90%
60%100%
20%80%
0%0%
100%0%
95%10%
40%0%
80%20%
• inversed regiochemistry• cationic mechanism• chelating ligands effective• similiar to use of Ag salts
Cabri Acc Chem Res 1995 28 2Hallberg TH 1994 50 285
JOC 2000 65 7235
42C.C. Tzschucke
Heck Reaction: Diazonium Salts
• fast reactions• high catalyst loadings• no base neccessary• no phosphine ligands
Genet THL 1999 40 4815Sengupta THL 1998 39 715Matsuda JOC 1981 46 4885
N2
Ph+2 mol% Pd(OAc)2
EtOH, 80 °C
BF4Ph
I I
2 mol% Pd(OAc)2
NaHCO3, Bu4NClDMF, 100 °C
PhCO2Et
EtO2C
N2
CO2Me+R R2 mol% Pd/CaCO3
MeOH, 30-50 °C15 min - 2 h
BF4CO2Me
N2
R R
AcONH2
+R5 mol% Pd(dba)3
tBuONO, HOAcClCH2CO2H, 50 °C
43C.C. Tzschucke
Heck Reaction: Acid Chlorides
OBn+X
X
OBn
2 mol% Pd(OAc)2
Et3N, 50 °C
O
Cl
1mol% Pd(OAc)2
xylene, 140 °C
O N Et
X
O
OBn
Blaser JOMC 1982 233 267Hallberg JOC 1988 53 235
JOC 1988 53 4257
O
ClMeO
OMe
OAc
+1mol% Pd(OAc)2
Et3N, xylene, 130 °C
MeO
OMe
OAc
• electron withdrawing substituents favor decarbonylation
• phosphines inhibit reaction
44C.C. Tzschucke
Decarbonylative Heck Reaction
R
O
OH
CH3
Ru-catR
O
O3 mol% PdBr2
NMP, 160 °C, 12 h
N OH
Br
R +O
+ CO
de Vries ACIE 1998 37 662Goossen Synlett 2002 1721
Angew Chem 2004 116 1115
similar: activated esters, anhydrides
R
O
XPd(0)
R
O
Pd X PdR
CO
X
R1
CO
PdR
X
R1
mechanism:
no salt waste
46C.C. Tzschucke
Decarboxylative Heck Reaction
Myers JACS 2002 124 11250
JACS 2005 127 10323
O
OH +
20 mol% Pd(O2CCF3)23 equiv Ag2CO3
5% DMSO, DMF, 120 °C
CH3
H3C CH3
O
H3C CH3
CH3
O
MeO
MeO OMe
O
O
Pd(O2CCF3)2MeO
MeO OMe
O
O
Pd
dmso
dmso
O2CCF3
CO2
dmso
dmso
O2CCF3
MeO
MeO
OMe
Pd
R
DMSO
dmso
O2CCF3
MeO
MeO
OMe
Pd
R• electron-rich arenes react faster
• ortho-substituent neccessary
• electron deficient Pd(II)
• electron-rich olefins react faster
rds
61%
47C.C. Tzschucke
Heck Reaction: Intramolecular
N
OBn
MeO I
DBSH
NDBS
OBn
OMe
10 mol% (Ph3P)2Pd(tfa)2
toluene, 120 °C
NCH3
N
O
O
O
Br
MeO
TBSO
H
N
O
O
O
MeO
TBSO
H
Pd(PPh3)4
proton spongetoluene rfx
PdX
XPd
PdX
exo-cyclization preferred
Hudlicky OL 1999 1 2085
Overman JACS 1993 115 11028
48C.C. Tzschucke
Heck Reaction: Zipper
I
O
O E E
[Pd]
O
O E E
O
O
EE
[Pd]
O
O
EE
[Pd]
O
O
EE
[Pd]
O
O
EE
10 mol% Pd(OAc)220 mol% PPh3
4 equiv Et3NCH3CN, 70 °C
Overman JACS 1988 110 2328