Chapter 4
The Catalytic Chemistry of Palladium (II)
G. Poli
Main “Non-organometallic” Pd (II) Sources
Cl
[PdCl2]n
Pd
Pd
=
Cl
Cl
Cl
Cl
Pd
insoluble
n
Cl
2 LiCl
2 MeCN
2 PPh3
PdCl2(MeCN)2
2 AgCl
PdCl2(PPh3)2
Li2PdCl4
2 AgBF4
2 MeCN
O
Pd(OAc)2
Pd(MeCN)4(BF4)2
soluble
= Me
O
Me
Pd
O
O
G. Poli
Oxidative Palladations
[Pd(II)X2]
____→
[Pd(0)]
[Ox]
____→
[Pd(II)X2]
G. Poli
Reactivity of a Pd(II)-coordinated Alkene
Nu
anti palladation
PdX2
H .
R
H
X[Pd]X
Nu
X[Pd]
HX
Nu: H2O, X-, carbanions…
R
σ-alkyl-Pd
syn palladation
H .
H
R'[Pd]X
R'[Pd]X
R
H
H
R'
H
R
[Pd]X
σ-alkyl-Pd
as in Mizoroki-Heck chemistry
Addition of Nucleophiles to Alkenes: General Reactivity
stoichiometric reactions
NuA
R
PdCl2
R
Cl
Pd
Cl Pd Cl
Cl
add. to the most
substituted C atom
R
NuA
Cl[Pd]
(in solution)
R
[Pd(0)] + HCl
A
H
Cl[Pd]
R NuA
R
NuA
dehydropalladation
[Pd(0)] + Cl
B
Cl[Pd]
R
R
NuB
NuA
displacement
NuB
[Pd(0)] + HCl
C
NuA = H2O
Cl[Pd]
H
hydride shift
NuA
O
R
O H
Typical nucleophiles known to
react with the coordinated
alkenes:
water,
alcohols,
carboxylic acids, ammonia,
amines, enamines and active
methylene compounds.
H3C
R
See later the detailed
mechanism
Tsuji, J. Acc. Chem. Res. 1969, 2, 144
G. Poli
Hydroxypalladation
stoichiometric reactions
depending on the reaction conditions the intermediate β-hydroxypalladium complex may suffer
either hydride shift or displacement
+
PdCl2
H2O
Cl[Pd]
hydroxypalladation
H
O
H
[Pd(0)] + HCl
CH3CHO
hydride shift
[Pd(0)] + Cl
+
PdCl2, LiCl
H2O
hydroxypalladation
Cl[Pd]
Cl
OH
Cl
OH
displacement
Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, J.; Sabel, J. Angew. Chem. Int. Ed. Engl. 1962, 1, 80
G. Poli
Catalytic Hydroxypalladation: the Wacker Process
This is the industrial process for acetaldehyde production from ethylene, developed
simultaneously by Wacker-Chemie and by the group of Moiseev (1959).
PdCl2 cat, CuCl2 cat
CH3CHO
H2O, HCl, O2
50-130 °C, 3-10 atm
95%
C2H4 + PdCl42- + 3H2O -----> H3CCHO + Pd(0) + 2H3O+ + 4ClPd(0) + 2CuCl2 + 2Cl- ------> PdCl42-+ 2CuCl
4CuCl + 4H3O+ + 4Cl- + O2 -----> 4CuCl2 + 6H2O
C2H4 + 1/2 O2 ------> H3CCHO
Oxidation of Pd(0), a noble metal, with CuCl2, a base metal salt, is expected to be very difficult !
The CuCl is easily reoxidized to CuCl2 with oxygen.
Smidt, J.; Hafner, W.; Jira, R.; Sedlmeier, J.; Sieber, R.; Rüttinger R.; Kojer, H. Angew. Chem., 1959, 71, 176.
Feringa, B. L. in Wacker Oxidation, Transition Metals for Organic Synthesis, Beller, M. and Bolm, C. Ed., WileyVCH, 1998, chapter 2.8, pp 307-315.
G. Poli
The Mechanism of the Wacker Process
HCl, H2O, PdCl2 cat, CuCl2 cat, O2
CH3CHO
HCl
Pd(0)
PdCl2
Cl
Pd
2CuCl
Cl
Cl-
H2O
1/2 O2 + 2HCl
H
Cl
H2O
O
Cl
Cl-
Cl
H
Pd
Cl
O H
Cl
H2O
H+
Pd
Cl
H
OH
chloride mediated
reductive elimination
2 CuCl2
H2O
Pd
H
CH2
insertion
H2O
ClCl
H2O
H
Pd
H
H
Cl
OHdehydro- H2O
palladation
Pd
OH
The anti hydroxypalladation is likely due to the presence of chloride anion
Bäckvall, J. E.; Åkermark, B.; Ljunggren, S. O.; J. Am. Chem. Soc. 1979, 101, 2411
Keith, J. A.; Oxgaard, J.; Goddard, W. A. J. Am. Chem. Soc. 2006, 128, 3132-3
G. Poli
The Mechanism of the Wacker Process
The detailed mechanism of the hydride shift
Cl
H2O
Pd
Cl
H
hydride shift
O
Cl
OH
Pd
H2O
H
Cl-
dissociation
(rate det. step)
Cl
H2O
H
Pd
H
HCl H2O
H
CH3CHO + [Pd(0)]
CH2
insertion
dehydropalladation
OH
H
Cl
Pd
H2O
OH
HCl H2O
D2O
CH2DCHO + [Pd(0)]
no enol
decoordination
The reaction is formally a dehydrogenative coupling
H
+
H
O
+
H
1/2O2
H
cat.
OH
+
O
H
G. Poli
The Tsuji Variation of the Wacker Reaction
Higher alkenes can be oxidized to ketones in solvents that dissolve both the alkene and water (DMF).
Stoichiometric oxidants (benzoquinone, O2/CuCl2, S2O8, MeONO… ) can be used to re-oxidize Pd(0) to Pd(II).
The attack obeys the Markovnikov rule. Thus, terminal alkenes can be viewed as masked methyl ketones.
PdCl2 cat. CuCl cat
O2, H2O, DMF (68%)
O
O
good method to obtain 1,4-diketones
O
PdCl2 cat. CuCl cat
O2, H2O, DMF (~80%)
O
OAc
OAc
BnO
O
O
O
BnO
PdCl2 cat. H2O, DMF
45°C, (60%)
O
O
terminal alkenes are more
reactive than internal ones.
BnO
O
O
O
taxol derivative
O
OBn
OEDMS
O
OBn
OEDMS
CO2Me
Na2PdCl4 cat.
t-BuOOH, i-PrOH
(64%)
OBn
OEDMS
CO2Me
O
regioselective reaction with Michael
acceptors. In this case the peroxide,
and not H2O, is the nucleophile.
Tsuji, J. Comprehensive Organic Synthesis 1991, vol 7, 449
Iwadare, H.; Satoh, H.; Arai, H.; Shiina, I.; Mukaiyama, T. Chem. Lett. 1999, 817
G. Poli
Alkoxypalladation
stoichiometric reaction
hydride shift and dehydropalladation may be competitive paths
base HCl
+
MeOH
PdCl2, base
[Pd(0)] + HCl
[Pd(0)] Cl
Cl[Pd]
methoxypalladation
OMe
H
Cl[Pd]
H
OMe
OMe
H3C
H3C
hydride shift
MeOH
OMe
major
[Pd(0)] + HCl
OMe dehydropalladation
OMe
minor
G. Poli
Alkoxypalladation
Efficient reoxidation of Pd(0) to Pd(II) is sometimes possible (without copper) in the presence of special
ligands such as DMSO or pyridine. In this latter case the oxidation is expected to pass through a
peroxopalladium(II) complex
O2
O
Py2Pd
Py2Pd(0)
2 HCl
H2O2 + Py2PdCl2
O
peroxopalladium(II)
complex
Stahl, S. S.; Thorman, J. L.; Nelson, R.C.; Kozee, M. A. J. Am. Chem. Soc. 2001, 123, 7188
Pd(OAc)2 5 mol%
DMSO, O2 (95%)
H
H
+
OH
O
O
H
H
95
:
5
Rönn, M.; Bäckvall, J. E.; Andersson, P.G. Tetrahedron Lett. 1995, 36, 7749
G. Poli
Alkoxypalladation
Carbonylative oxidation
OMe
H
OH
PdCl2 (5mol%)
CuCl2 (2equiv.)
CO, MeOH
OMe
H
O
CO2Me
O
O
Propose a plausible mechanism for this transformation
Phenolic oxygen atoms participate easily in oxypalladations:
Review: Hosokawa, T.; Murahashi, S. Heterocycles, 1992, 33, 1079
O
Pd(MeCN)4(BF4)2
L*, benzoquinone
OH
MeOH, 25°C (90%)
N
O
97% ee
N
O
L* = (S,S)-ip-boxax
Uozumi, I.; Kato, K. Hayashi, T.J. Org. Chem. 1988, 63, 5071
G. Poli
Alkoxypalladation
The stereochemistry of the alkoxypalladation may be syn or anti depending on the reaction
conditions. The origin of this delicate balance has not been completely elucidated. The presence of
chloride anions has been evoked as a possible reason for anti addition.
D
bis[acetoxy(3,2,10-η3-pinene)Pd(II) (10%)
Cu(OAc)2 10%
O2, MeOH reflux (82%)
Pd
H
Ac
O
2
O
OH
mainly this isomer
via syn oxypalladation
PdCl2(MeCN)2 (10%)
D benzoquinone (1.0 equiv;)
Na2CO3 (2.0 equiv.) LiCl (2.0 equiv;)
THF, reflux (59%)
OH
bis[acetoxy(3,2,10-η3-pinene)Pd(II)
D
O
mainly this isomer and mainly
via anti oxypalladation followed
by dehydroPd, hydropd...
Hayashi, T., Yamasaki, K.; Mimura, M. M.; Uozumi, Y J. Am. Chem. Soc.. 2004, 126, 3036-7
Trend, R. M.; Ramtohul, Y. K.; Stolz, B. M. J. Am. Chem. Soc. 2005, 127, 17778-88
G. Poli
Alkoxypalladation
Syn alkoxypalladation
HX
HO
X[Pd]
X[Pd] O
HX
O
O
PdX2
Anti alkoxypalladation
HO
HX
HX
HX
HO
O
O
X[Pd]
PdX2
G. Poli
Acetoxypalladation
stoichiometric reaction
[Pd(0)] + AcOH
Industrial production of vinyl acetate (Kuraray). Pd supported on silica or alumina is used as
AcO[Pd]
H
Pd(OAc)2
a catalyst. Pd oxidation is
expected to take place on the surface of the support.
OAc
dehydropalladation
OAc
acetoxypalladation
(AcO is EWG: no H-shift)
catalytic reaction
H2O
1/2 O2
Pd(AcO)2/SiO2 Pd(0)/SiO2 + 2AcOH
+
AcOH
gas phase
OAc
Nakamura, S.; Yasui, T.J. Catal. 1976, 17, 366
G. Poli
Allylic Acetoxylation of Cyclohexene
The acetoxylation of cyclohexene does not proceed via acetoxypalladation as for ethylene and affords allylic
oxidation. Labeling experiments unveiled that a η3-allyllpalladium complex is involved.
Pd(OAc)2 cat.
AcOH
benzoquinone
OAc
OAc
OH
O
HO
2 AcOH
Pd(OAc)2
[Pd(0)]
O
O
O
OAc BQ
[Pd(0)]
Pd
O
H
H O
Pd
AcOH
O
O
OAc
O
O
Grennberg, H. and Bäckvall, J.E. Chem. Eur. J. 1998, 4, 1084
G. Poli
Intramolecular Carboxylation of Alkenes
Pd(TFA)2 (10 mol %), pyridine (40 mol%)
Na2CO3 (2.0 equiv.), MS3Å, 1 atm O2,
tol 80°C (86%)
O
O
CO2H
O
CO2H
Experiments
with
deuterated
substrates showed the operation of an
anti carbopalladation mechanism
D
CO2Et
CO2Et
CO2H
D
CO2Et
CO2Et
O
Pd(TFA)2 (10 mol %)
pyridine (20 mol%)
Na2CO3 (2.0 equiv.),
MS3Å, 1 atm O2,
tol 80°C (86%)
CO2Et
CO2Et
H
O
O
D
CO2Et
CO2Et
Trend, R. M.; Ramtohul, Y. K.; Stolz, B. M. J. Am. Chem. Soc. 2005, 127, 17778-88
G. Poli
Aminopalladation
PdCl2(MeCN)2
Cl
Pd
N
H2
stable
NH2
Cl
Aliphatic amines coordinate Pd(II) too strongly to
promote aminopalladation. On the other hand,
nitrogen-based nucleophiles with reduced availability
of the N lone pair (acetamides, tosylamides, anilines)
do undergo catalytic aminopalladation.
Cl
Cl Pd
PdCl2(MeCN)2
HN
O
N
Pd Cl
HN
O
O
stable
PdCl2(MeCN)2 (1 mol%)
benzoquinone (1.0 equiv.)
LiCl, THF (60-90%)
NH
Ts
N
Ts
PdCl2(MeCN)2 (2 mol%)
NRH
R = H, Ac, Ts
benzoquinone (2.0 equiv.)
LiCl, THF (60-86%)
N
R
Hegedus, L. S.; Comprehensive Organic Synthesis, 1991, 4, 551, 571
G. Poli
Aminopalladation
py2Pd(OAc)2 cat
O2 (1atm), xylene
80°C, (87%)
NH
Ts
N
Ts
Fix, S. R.; Brice, J. L.; Stahl, S. S. Angew. Chem. Int. Ed. 2002, 41, 164
G. Poli
1,4-Chloroacetoxylation and Diacetoxylation of 1,3-Dienes
OAc
Pd(OAc)2 cat.
LiOAc
benzoquinone
AcOH, LiCl
Pd(OAc)2 cat.
LiOAc
benzoquinone
AcOH
AcO
OAc
Cl
Pd(OAc)2 cat.
LiOAc
benzoquinone
AcOH, LiCl cat.
OAc
AcO
Bäckvall, J.-E. in Metal-Catalyzed Cross Coupling Reactions, Stang, P. J.; Diederich, F. Eds., Wiley - VCH,
Weinheim, 1998, p. 339.
G. Poli
1,4-Chloroacetoxylation and Diacetoxylation of 1,3-Dienes
OH
Pd(OAc)2
OH
2H
O
X
Pd(0)
Pd
AcO
OAc
O
O
X
Y
X
O
AcO
X
Y
Pd
AcO
O
AcO
O
G. Poli
1,4-Chloroacetoxylation and Diacetoxylation of 1,3-Dienes
Pd(OAc)2 cat., LiOAc, benzoquinone, LiCl, AcOHCl
OAc
Cl
AcO
-
Cl
Pd
L
-
-
Pd
OAc
Pd
Cl
L
L
L
Cl
Cl
BQ
Pd(OAc)2 cat., LiOAc, benzoquinone, LiCl cat. AcOH
-
OAc
OAc
Cl
AcO
-
Cl
Pd
L L
OAc
-
Pd
Pd
Cl
L
L
OAc
BQ
Pd(OAc)2 cat., LiOAc, benzoquinone, AcOH
OAc
AcO
OAc
O
Pd
L
-
AcO
Pd
L
Me
O
BQ
Bäckvall, J.-E. in Metal-Catalyzed Cross Coupling Reactions, Stang, P. J.; Diederich, F. Eds., Wiley - VCH,
Weinheim, 1998, p. 339.
G. Poli
Oxidative Carbocyclization of Allene-Substituted Olefins
MeO2C
CO2Me
Pd(O2CCF3)2 (10%),
BQ (20%),
FePc (10%),
O2, Tol 95°C
MeO2C
CO2Me
.
MeO2C
CO2Me
OH
Pd(II)
FePc(ox)
H2O
CO2Me
FePc =
FePc(red)
½ O2
O
Piera, J.; Närhi, K.; Bäckvall, J.-E. Angew. Chem. Int. 2006, 45, 6914-6917
N
Fe
N
N
N
O
Pd(0)
N
N
OH
MeO2C
N
N
Oxidative Carbocyclization of Allene-Substituted Olefins
MeO2C
CO2Me
MeO2C
CO2Me
Pd(II) coord
H
(D)H
H
(D)H
.
Pd
CO2Me
MeO2C
olefin
insertion
H
(D)H
.
F3CCO2
MeO2C
allene-attack
on Pd(II)
Pd
CF3CO2H
O2CCF3
O2CCF3
CO2Me
H
(D)H
F3CCO2[Pd]
dehydropd
[Ox]
CF3CO2Pd(D)H
Pd(0)
Pd(II)
CF3CO2(D)H
MeO2C
H
(D)H
F3CCO2
MeO2C
CO2Me
syn C-H clevage
by Pd(II)
.
(D)H
CO2Me
MeO2C
CO2Me
[Pd]O2CCF3 (D)H
Pd
O2CCF3
F3CCO2
MeO2C
CO2Me
.
reaction OK
MeO2C
CO2Me
allene
insertion
.
(D)H
Pd
CO2Me
MeO2C
no reaction
A mechanism involving π-allyl intermediates (see low path) is ruled
out by the results obtained using the substrates showed at the left.
Oxidative Carbocyclization of 1,3-Dienyl Allenes
MeO2C
Pd(OAc)2 (10 mol%)
Li2CO3 (5 equiv.)
BQ (2 equiv)
AcOH (20 equiv)
acetone, rt, 20 h, (79%)
CO2Me
.
MeO2C
AcO
CO2Me
H
[Pd(II)]
BQ
allene add
to [Pd(II)]
AcOH
[Pd(II)]
AcOH
[Pd(0)]
red elim
HQ
anti acetate
add
H[Pd]OAc
BQ
MeO2C CO2Me
MeO2C CO2Me
BQ
[Pd]OAc
syn vinyl-Pd
alkene carbopd
AcO
Pd
BQ
Löfstedt, J.; Franzén, J.; Bäckvall, J. E. J. Org. Chem. 2001, 66, 8015
Löfstedt, J.; Närhi, K.; Dorange, I.; Bäckvall, J.-E. J. Org. Chem. 2003, 68, 7243-7248.
Oxidative Carbocyclization of Indoles
Me
PdCl2(MeCN)2 cat, BQ, THF-DMF 80°C, (98%)
N
N
H
N Me
Me
N
H
O
HQ BQ
O
HX
H[Pd]X
[Pd(0)]
[Pd(II)]
st
1 hypothesis
[Pd]X
PdX2
H
N
N
O
H
2
nd
X
HX
N Me
carbopd
Me
H[Pd]X
O
N
H
dehydropd
N Me
N
H
O
dehydropd
hypothesis
X2Pd
HX
O
N
H
N
X
[Pd]
X[Pd]
N Me
N
Me
orthopd
N
H
O
Me
carbopd
O
N
H
Cyclization via the indol nitrogen can be
obtain by Pd(0) catalysis (see chapter 3)
Abbiati,G.; Beccalli, E.M.; Broggini, G.; Zoni, C. J. Org. Chem. 2003, 68, 7625-7628
G. Poli
Oxidative Mizoroki-Heck Coupling
Coupling of organometallic compounds of B, Sn and Si with alkenes as a halogen-free oxidative
Mizoroki-Heck type reaction takes place with catalytic amounts of Pd(II) in the presence of oxidants. In
this particular case the catalytic cycle starts with a transmetallation rather than an oxidative addition.
Pd(OAc)2, O2, Na2CO3
DMF, 50°C, 87%
OH
Ph B
OH
Ph
CO2Me
CO2Me
1/2 Na2CO3
AcONa 1/2 H2O + 1/2 CO2
transmetallation
HO
[Pd(II)]
B OAc
HO
Ph [Pd] OAc
[Pd(0)]
oxidation
CO2Me
insertion
H[Pd]OAc
dehydropalladation
H
[Pd]OAc
Ph
CO2Me conformational
change
Ph
[Pd]OAc
CO2Me
Jung, J.C.; Mishra, R. K.; Yoon, C. H.; Jung, K. W. Org. Lett. 2003, 5, 2231
Cho, C. S.; Uemura, S. J. Organometal. Chem. 1994, 465, 85
Hirabayashi, K.; Ando, J.; Nishihara, Y.; Mori, A.; Hiyama, T. Synlett,. 1999, 99
G. Poli
Non-oxidative Palladations
[Pd(II)] ____→ [Pd(II)]
G. Poli
Palladations followed by deoxypalladations
G. Poli
Acetoxypalladation / Carbopalladation
Me
Ligands
Me
OAc
Pd(OAc) cat.
AcOH, L
O
O
4-acetoxy-2-butenyl-2-alkynoate
AcO
O
trans acetoxypalladation
N
O
deacetoxypalladation
O
O
N
Me
Me
[Pd]OAc
OAc carbopalladation
AcO
N
N
[Pd]OAc
OAc
AcO
(92% ee)
O
O
O
O
In the presence of halide ligands, chloropalladation (instead of acetoxypalladation) takes
place. Excess of halide inhibits dehydropalladation
Lu, X.; Zhang, Q. J. Am. Chem. Soc., 2000, 122, 7604
G. Poli
Aminopalladation
OBn
MOMO
OBn
N
Boc
PdCl2(MeCN)2
(15 mol%)
OH
OBn
MOMO
diastereoselective
OBn
HO
OH
N
H
N
Boc
1-deoxymannojirimycin
OH
Pd(II)
OBn
MOMO
OBn
OBn
MOMO
OBn
PdCl2
N
Boc
OH
N
Boc
[Pd]Cl
OH
Yokoyama, H.; Otaya, K.; Kobayashi, H.; Miyazawa, M.; Yamagichi, S.; Hirai, Y. Org. Lett. 2000, 2, 2427
G. Poli
Aminopalladation
LiBr is essential to promote the desired deacetoxypalladation
O
O
O
O
NH
Ts
O
O
Pd(OAc)2, LiBr
diastereoselective
X
HO
OH
O
O
N
N
Ts
H
OH
X = OAc, OCONHTs
Lei, A.; Liu, G.; Lu, X. J. Org. Chem. 2002, 67, 974
G. Poli
Cycloisomerisations
Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215
Trost, B. M.; Krische, M. J. Synlett 1998, 1.
Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. Rev. 1996, 96, 635.
Trost, B. M. Janssen Chimica Acta, 1991, 9, 3.
G. Poli
Cycloisomerization of 1,6-enynes
R
R
H
intramolecular Alder-ene
thermal (very high temperatures)
Other transition metals such as Rh, Ru, Pt
are capable of effecting cycloisomerisation
H
with or without skeletal rearrangements of
1,6-enynes. 1,6-dienes can also undergo
similar cycloisomerizations
R
C C R
Pd(II) cat. intramolecular Alder-ene
R'
C CH
H
(via Pd hydride or oxidative
cyclization mechanism)
Pd(II) cat. skeletal rearrangement
(Ring Closing Metathesis)
R
C
H
C
H
and/or
R'
CH2 and
R'
C
H
C
CH2
(via oxidative cyclization)
CH2
regular bond
connectivity
anomalous bond
connectivity
Typical catalytic systems:
1. Pd(OAc)2 / PAr3;
2. Pd2(dba)3 / AcOH;
3. [Pd(MeCN)4]2+;
4. TCPC / P(OAr)3
MeO2C
MeO2C
CO2Me
Pd
(TCPC)
CO2Me
The mechanism of these completely atom economical
cyclizations is still matter of speculation. Catalytic systems
1-3 are expected to follow the Pd hydride mechanism,
whereas catalytic system 4 is supposed to trigger
oxidative cyclization.
G. Poli
The Hydridopalladium Mechanism
No redox in the catalytic cycle !
H
[Pd(II) or Pd(0)] cat.
and/or
H
1,4-diene
1,3-diene
dehydropalladation
H[Pd]OAc
H
H
H hydropalladation
OAc
carbopalladation
H
H
[Pd]OAc
H Pd
H
[Pd]OAc
H
H
The RCO2[Pd]H species is expected to be generated in situ via:
a) oxidative addition of [Pd(0)] on a carboxylic acid (i.e. AcOH or HCO2H)
b) interaction between the Pd(O2CR)2 and adventitious H2O)
a) [Pd(0)] + AcOH
b) Pd(O2CCF3) + H2O
AcO[Pd]H
CF3CO2[Pd]H + CF3CO2H
G. Poli
The Oxidative Cyclization Mechanism
H
[Pd(0 or II)] cat
H
and/or
reductive
elimination
[Pd(0 or II)]
H
oxidative
cyclization
H [Pd(0 or II)]
H
H
[Pd(II or IV)]
dehydroPd
H
H
and/or
[Pd(II or IV)]
H
[Pd(II or IV)]
G. Poli
1,3 Versus 1,4-Dienes as Products
Hydridopalladium Mechanism
H
H
R'
Oxidative Cyclization Mechanism
In the oxidative cyclization mechanism, exchange
between R-Pd-H and AcOH after beta-elimination,
but prior to reductive elimination cannot be ruled out.
R
H
H
R'
R
R'
AcO[Pd]H
R'
Hb
1,4-diene
Hb
[Pd]OAc
[Pd(II)]
H
Ha
R
Ha
R'
H
R'
Hb
Ha
[Pd(IV)]
R'
Ha
Hb
R
H
1,3-diene R
[Pd(II)]
R'
Ha
Hb
R
[Pd(II)]
R
Independently of the operating mechanism, dehydropalladation normally takes place on Ha thereby
affording a 1,4-diene. However, such a preference can be switched to favor the 1,3-diene if: a) steric
congestion is increased around Ha, b) CHa is bound to an EWG group, c) a juxtaposed unsaturation
on R blocks the conformational freedom via coordination to Pd. All these factors inhibiting
dehydropalladation via Ha.
G. Poli
Cycloisomerizations Leading to 1,4-Dienes
(Ph3P)2Pd(OAc)2 cat.
PhH, 70°C (77%)
OMe
OMe
PMBO
PMBO
Pd(OAc)2 5%
DCE, 60°C, (39%)
MeO2C
MeO2C
MeO2C
MeO2C
only
CO2Me
CO2Me
CO2Me
(Ph3P)2Pd(OAc)2 cat.
THF, 66°C, (85%)
the thermal cyclization
failed
CO2Me
CO2Me
CO2Me
G. Poli
Cycloisomerizations Leading to 1,3-Dienes
MeO2C
MeO2C
Steric congestion at
the allylic substituent
MeO2C
PMBO
Remote binding
MeO2C
Ha
MeO2C
MeO2C
(oTol3P)2Pd(OAc)2
Tol, 80°C, (80%)
Allylic carbon
bound to a
heteroatom
MeO2C
(Ph3P)2Pd(OAc)2 5%
THF, 66°C, (64%)
Ha
Hb
Hb
PMBO
OTBDMS
OTBDMS
Pd(OAc)2 5%
PhH, 60°C, (82%)
MeO2C
[Pd]OAc
or
No external allylic
hydrogen: no choice
MeO2C
MeO2C
1,3 : 1,4 = 15 : 1
[Pd(IV)]
Pd(OAc)2
C6D6, 60°C (96%)
PMBO
OMe
N
N
Ph (BBEDA) Ph
PMBO
OMe
1,3-diene
G. Poli
Asymmetric Cycloisomerization of 1,6-enynes
CO2Me
[(MeCN)4Pd](BF4)2 (5 mol %)
(S)-Xyl-SEGPHOS (10 mol%)
DMSO, 80°C (> 99% y, 96% ee)
CO2Me
R
O
O
O
O
[(MeCN)4]Pd](BF4)2
O
O
traces of H2O
H[Pd]+[BF4]-
(S)-Xyl-SEGPHOS
dehydropalladation
CO2Me
H
hydropalladation
+
[Pd] [BF4]O
[Pd]+[BF4]H
P
P
H
[Pd]+[BF4]-
carbopalladation
CO2Me
CO2Me
O
O
Hatano, M.; Terada, M.; Mikami, K. Angew. Chem. Int. 2001, 40, 249
G. Poli
Pd(0)-Catalyzed Cycloisomerization of 1,6-Alkenyl Allenes
MeO2C
MeO2C
CO2Me
CO2Me
Pd(dba)2 (5 mol%)
CO2Me
+
οC
.
MeO2C
AcOH, 120
8 minutes (83%)
88
:
MeO2C
CO2Me
12
[Pd(0)] + (D)HOAc
MeO2C
()
oxidative
addition
CO2Me
n
MeO2C
()
hydroPd
n
()
(D)HPdOAc
n
.
CO2Me
.
[Pd]
Pd
n = 0, 1
AcO
MeO2C
CO2Me
()
n
(D)
(D)
OAc
olefin
insertion
H(D)
MeO2C
CO2Me
()
dehydropd.
n
-HPdOAc
(D)
AcO
[Pd]
Närhi, K.; Franzén, J.; Bäckvall, J. E. Chem. Eur. J. 2005, 11, 6937-6943
Palladium (II) as Lewis Acid
(no organopalladium species involved)
G. Poli
Palladium Enolates
Preparation of the aqua and the hydroxy Pd complexes
PPh2
P
C C
P
PPh2
P
O
2AgCl
enantioselective aldol condensation
Ph
Ph
C
O
Pd
P
P
Pd
O
C
C
P
H
aqua Pd complex A
O
C
O
H H
HH
(R)-BINAP
OSiMe3
2TfO
NaOH
Pd 2+
1. PhCHO
cat A (1 mol%)
tetramethylurea
0°C
2. H3O+
2TfO
H
PdCl2 2AgOTf
wet DMF
mol. sieves
dinuclear Pd(µ-OH) complex B
mechanism
OH
Ph
H 2TfO
H O
2+ P
Pd
Me3Si
O
P
H
H
H2O
Ph
92%, 89%ee
TfOH, Me3SiOH
O
O
2TfO
2+
P
Pd
P
Ph
Pd enolate
Yamashima, Y.; Sodeoka, M. The Chemical Record, 2004, 4, 231-242
G. Poli