PALLADIUM(II) CHLORIDE 1
Use as Source of Pd0 Catalyst. PdII salts are reduced to Pd0
Palladium(II) Chloride1
catalysts with various reducing agents. Although Pd(OAc)2 is
more convenient for this purpose than PdCl2 and its derivatives,
PdCl2
PdCl2 derivatives are used in many cases. Typically, Pd(Ph3P)2Cl2
is reduced to form a Pd0 phosphine complex.
[7647-10-1] Cl2Pd (MW 177.32)
Oxidations.
InChI = 1/2ClH.Pd/h2*1H;/q;;+2/p-2/f2Cl.Pd/h2*1h;/q2*-1;m
InChIKey = PIBWKRNGBLPSSY-LCTIVKCBCE
Oxidative Reactions of Alkenes.2 Oxidative reactions of
(used as an oxidizing agent and to a lesser extent as a source of alkenes can be classified into two types: oxidative substitution and
Pd0 complexes) oxidative addition, as shown in eq 1. Here X- and Y- represent
nucleophiles such as HO-, RO-, RCO2-, R2N- and CO, as well
ć%
Physical Data: mp 678 C (dec).
as soft carbon nucleophiles such as active methylene compounds.
Solubility: slightly sol H2O; sol H2O in the presence of chloride
ion; sol aqueous HCl; sol PhCN, forming Pd(PhCN)2Cl2; insol R
+ Pd0 + HCl
organic solvents.
R
X
X
Form Supplied in: commercially available as a rust-colored stable
R
+ PdCl2 (1)
powder or crystalline solid.
X PdCl R
HY
Handling, Storage, and Precautions: air stable; not hygroscopic.
+ Pd0 + HCl
X Y
X and Y = nucleophiles
Original Commentary
Reaction with Water.2a,b Oxidation of ethylene to acetalde-
hyde under oxygen atmosphere is an industrial process called the
Jiro Tsuji
Wacker process. PdCl2 and Copper(II) Chloride in aqueous HCl
Okayama University of Science, Okayama, Japan
are used as the catalysts. As shown by eq 2, the Wacker process
comprises three unit reactions; CuCl2 is a unique reoxidant of Pd0.
General Considerations. Many of the reactions described
below can be accomplished using derivatives of palladium
CH2=CH2 + H2O + PdCl2 MeCHO + 2 HCl + Pd0
chloride such as Potassium Tetrachloropalladate(II), Disodium
Pd0 + 2 CuCl2 PdCl2 + 2 CuCl
Tetrachloropalladate(II), Bis(benzonitrile)dichloropalladium(II),
(2)
dichlorobis(acetonitrile)palladium, and dichlorobis(tripheny-
2 CuCl + 2 HCl + 0.5 O2 2 CuCl2 + 2 H2O
lphosphine)palladium. The physical properties of these alterna-
tive reagents are described under their separate entries, but their
CH2=CH2 + 0.5 O2 MeCHO
chemistry is included in this article.
Synthetic applications of PdCl2 and its derivatives can be classi- Higher terminal alkenes are also oxidized in organic solvents
containing water; DMF is most widely used as the solvent.3 On
fied into three types: use as oxidizing agents, use as PdII catalysts,
a laboratory scale the oxidation can be carried out easily in a
and use as a source of Pd0 catalysts. Characteristic features of
way similar to the hydrogenation of alkenes under atmospheric
these applications are briefly summarized below.
pressure. Instead of Pd black and hydrogen, the oxidation is car-
ried out with PdCl2 and the copper salt under an oxygen atmo-
Use as Oxidizing Agents. PdCl2 and Palladium(II) Acetate
sphere at room temperature using a similar apparatus. Since the
are representative PdII salts used for various oxidation reactions,
reaction proceeds under mild neutral conditions, many functional
but their uses are different. For example, oxidative reactions of
groups such as esters, acetals, THP ethers, alcohols, halogens,
aromatic compounds are possible only with Pd(OAc)2; PdCl2 and
its derivatives cannot be used. Oxidation reactions of various sub- and amines are tolerated. The ketones obtained by the oxidation
are sometimes chlorinated with CuCl2 to give chloro ketones as
strates with PdCl2 are stoichiometric and Pd0 is formed after the
byproducts. For this reason, nonchlorinating Copper(I) Chloride
oxidation. Sometimes, but not always, Pd0 can be reoxidized in
is recommended as the reoxidizing agent. This is easily preoxi-
situ to PdII with proper reoxidizing agents. In such a case, the
dized to the CuII state with oxygen.4 In a laboratory synthesis, a
oxidation reaction can be carried out with a catalytic amount of
stoichiometric amount of 1,4-Benzoquinone is conveniently used
PdCl2. Examples of reoxidants include CuCl2, CuCl, Cu(OAc)2,
as the reoxidant.
MnO2, HNO3, benzoquinone, alkyl nitrites, H2O2, and organic
The reaction is a unique method for the one-step synthesis of
peroxides. Since solubility of PdCl2 in water and organic solvents
ketones from alkenes, and allows alkenes to be regarded as masked
is small, the more soluble Dilithium Tetrachloropalladate(II),
ketones which are stable to acids, bases, and nucleophiles. Partic-
Na2PdCl4, K2PdCl4, and Pd(PhCN)2Cl2 are sometimes used for
ularly useful is the oxidation of terminal alkenes, which provides
similar purposes.
methyl ketones (eq 3).5 As a typical application, the allylation
of a ketone, followed by the oxidation, affords a 1,4-diketone.
Use as PdII Catalyst. Pd(PhCN)2Cl2 is used as a homogeneous
PdII catalyst for some non-oxidative reactions such as rearrange- A cyclopentenone can then be prepared by an aldol condensa-
tion (eq 4).5 The annulation method has widespread uses in the
ment reactions.
Avoid Skin Contact with All Reagents
2 PALLADIUM(II) CHLORIDE
synthesis of natural products such as pentalenene,6 muscone,7 elegant application of the reaction was a brevicomin synthesis
and coriolin.8 1,5-Diketones are prepared by 3-butenylation of a (eq 10).13
ketone followed by the oxidation. This process has been used to
prepare cyclohexenones (eq 5).5
R
R
+ 2 MeOH + PdCl2 + Pd0 + 2 HCl
PdCl2, CuCl
MeO OMe
R
(9)
(3)
RCOMe
O2, DMF
OH
O O
O
PdCl2, CuCl2 O
O
PdCl2, CuCl (10)
DME
O2, DMF
OH 45%
O
68%
Alkenes with an electron-withdrawing group such as styrene,
O (4)
Acrylonitrile, and acrylate are converted to acetals of the aldehy-
des rather than the ketones. The reaction of styrene with ethylene
glycol affords the cyclic acetal (eq 11).12a 3,3-Dimethoxypropio-
O
nitrile is produced commercially using methyl nitrite as the reoxi-
O O
dant. The nitrite can be regenerated easily by the oxidation of NO
CO2Me
PdCl2, CuCl
CO2Me
with oxygen (eq 12).14
O2, DMF
58%
O
PdCl2
O
+ Ph (11)
Ph
(5) O
HO OH CuCl2
90%
Simple internal alkenes are difficult to oxidize. However, the
MeO
PdCl2
CN
+ 2 MeONO + NO
regioselective oxidation of internal alkenes takes place in the pres-
MeO CN
ence of suitably disposed oxygen functional groups by neigh-
(12)
boring group participation. For example, Ä…,²-unsaturated esters
2 NO + 2 MeOH + 0.5 O2 2 MeONO + H2O
are oxidized to ²-keto esters using Na2PdCl4 as catalyst and
tert-Butyl Hydroperoxide as the reoxidant (eq 6).9 Allylic ethers
The intramolecular reaction of phenols or enols affords furans
are oxidized to ²-alkoxy ketones which can be converted to
Ä…,²-unsaturated ketones for use in annulation reactions (eq 7).10 and pyrans (eq 13).15
Cyclohexene and cyclopentene can not be oxidized under the usual
conditions, but are oxidized to cyclohexanone and cyclopentanone O O O O
O O
PdCl2(PhCN)2
under different conditions. For example, chloride-free PdII salts,
(13)
+
prepared from Pd(OAc)2 and HClO4, H2SO4, or HBF4, are active
benzene
catalysts (eq 8).11 For additional examples of the Wacker pro- O O
NaO
cess, see Palladium(II) Chloride Copper(I) Chloride and Palla-
40 46% 42 50%
dium(II) Chloride Copper(II) Chloride.
O
Na2PdCl4
CO2Me
(6)
CO2Me
t-BuOOH
Reaction with Carboxylic Acids.2c The intramolecular reac-
83%
tion of carboxylic acids with alkenes affords unsaturated lactones
(eq 14).16
O
PdCl2, CuCl
O
OBn PdCl2(MeCN)2
DMF MeONa
OBn
(14)
67%
Na2CO3 O
CO2H
86%
O
(7)
O
Reaction with Amines and Amides.2c Reaction of amines with
O
Pd(OAc)2, HClO4
alkenes proceeds most smoothly as an intramolecular version.
(8)
benzoquinone
Amides can be used in the intramolecular reaction to afford var-
ious heterocyclic compounds. In the example shown in eq 15, it
should be noticed that the PdII species is regenerated by the ²-
Reaction with Alcohols and Phenols.2c The reaction of alco- elimination of OH, rather than the ²-hydrogen. For this reason the
hols with terminal alkenes affords acetals of ketones (eq 9).12 An reaction proceeds catalytically without a Pd0 reoxidant.17
A list of General Abbreviations appears on the front Endpapers
PALLADIUM(II) CHLORIDE 3
OH
R1 R2
R1 R2
CO2Me + PdCl2 + HCl (18)
Pd
MeCON
Cl
PdCl2(MeCN)2
MeCN
CO2Me
CO2Me
NaH
+ (19)
N
Pd DMSO
CO2Me
CO2Me
Cl
Ts
OH
Based on this reaction, allylic alkylation of alkenes is possi-
COMe COMe
CO2Me CO2Me
ble. Active methylene compounds, such as malonates and ²-keto
N N
esters, can be introduced to a steroid skeleton by the reaction of
Pd
+ PdCl2 (15)
the steroidal Ä„-allylpalladium complex in DMSO (eq 20).23 The
Cl 95%
reaction of carbon nucleophiles also proceeds in the presence of
N N
an excess of Triphenylphosphine (eq 21).24
Ts Ts
R
Reaction with Carbon Nucleophiles. The cyclooctadiene (cod)
THF
+ Na2PdCl4
complex of PdCl2, which is insoluble in organic solvents, reacts
in ether with malonate or acetoacetate under mild heterogeneous
O
conditions; facile carbon carbon bond formation takes place to
give a new complex in a quantitative yield. Further intramolecu-
lar reaction of the complex with a base affords the cyclopropane
CO2Me
derivative. Attack of a second malonate on the complex yields the
CO2Me
[3.3.0] system (eq 16).18 Carbopalladation of the double bond of
(20)
ć%
O DMSO, NaH O
N-vinylcarbamate with acetoacetate at -78 C, and subsequent
carbonylation of the Pd carbon bond, proceeds smoothly to yield Pd
MeO2C CO2Me
Cl
the carbocarbonylation product in 92% yield (eq 17).19
90%
CO2Me
Cl
CO2Me
CO2Me
Na2CO3 CO2Me
, NaH
Pd
+
CuCl2 SOPh
100%
+ PdCl2
CO2Me
Pd
AcONa, AcOH Ph3P, THF
Cl Cl
Pd
CO2Me
Cl
CO2Me
CO2Me
base (16)
CO2Me
SOPh
MeO2C
(21)
CO2Me
CO2Me
CO2Me
MeO2C
ortho-Palladation of Aromatic Compounds and Cyclopallada-
tion of Allyl and Homoallyl Compounds.25 Azobenzene,26 N,N-
OO
Pd(PhCN)2Cl2
dimethylbenzylamine,27 and related aromatic compounds react
+
CO2Bn
N OBn Et3N,  78 °C
with Na2PdCl4 in ethanol to form stable ortho-palladation com-
plexes. These carbon palladium Ã-bonded complexes are useful
for the preparation of ortho-substituted aromatic compounds by
O O
the facile insertion of alkenes, alkynes, and CO. For example,
CO2Bn CO CO2Bn
(17)
insertion of CO to the azobenzene complex affords 2-aryl-3-
MeOH
Pd MeO2C
indazolone (eq 22),28 and facile insertion of styrene to the benzy-
92%
Cl NHCO2Bn NHCO2Bn
lamine complex yields a stilbene derivative (eq 23).1a,29
Ä„-Allypalladium Complex Formation.20 Ä„-Allylpalladium
complexes are prepared by the reaction of alkenes with PdCl2 Cl
Pd
O
or its soluble forms under various conditions (eq 18).21 These
CO
N
HN
+ Na2PdCl4 N (22)
N
Ä„-allylpalladium chloride complexes react with carbon nucle-
N
N
MeOH
ophiles in DMSO as a coordinating solvent to form carbon carbon
bonds.22 Thus Ä„-allylpalladium complexes are clearly different
in chemical reactivity from other organometallic reagents, which
97%
normally react with electrophiles (eq 19).
Avoid Skin Contact with All Reagents
4 PALLADIUM(II) CHLORIDE
PdCl2, CuCl2
NMe2 R
NMe2 Ph NMe2
+ CO + MeOH
O2
+ Na2PdCl4 Ph
Pd-Cl
AcOH
(23)
R CO2Me
R
R
+ CO2Me + (27)
CO2Me
OMe CO2Me
The cyclopalladation of allylic or homoallylic amines and sul-
fides proceeds due to the chelating effect of N and S atoms,
and has been used for functionalization of alkenes. For exam-
Intramolecular oxycarbonylation and aminocarbonylation are
ple, i-propyl 3-butenyl sulfide is carbopalladated with methyl cy-
also known. As an example, frenolicin has been synthesized
clopentanecarboxylate and Li2PdCl4. Reduction of the chelated
using oxycarbonylation at 1.1 atm of CO as a key step (eq 28).35
complex with Sodium Cyanoborohydride affords the alkylated
The intramolecular aminopalladation of a carbamate group
keto ester in 96% yield (eq 24).30 Functionalization of 3-N,N-
and subsequent carbonylation of the substituted 3-hydroxy-4-
dimethylaminocyclopentene for the synthesis of a prostaglandin
pentenylamine proceeds smoothly in AcOH (eq 29).36
skeleton has been carried out via a N-chelated palladium com-
plex as an intermediate. In the first step, malonate was intro- MeO O Pr
duced regio- and stereoselectively by carbopalladation (eq 25).31
Pd(MeCN)2Cl2
OH
Elimination of a ²-hydrogen generated a new cyclopentene, and + CO + MeOH
CuCl2
its oxypalladation with 2-chloroethanol, followed by insertion of
70%
1-octen-3-one and ²-elimination, afforded the final product.
O
MeO O Pr
O
NaBH3CN
O
CO2Me
+ + Li2PdCl4 (28)
S CO2Me
96%
O
S
O
O
(24)
CO2Me
OH
O
PdCl2, CuCl2
+ CO (29)
AcOH, AcONa
NHCO2Me
95%
NCO2Me
Oxidative Carbonylation.32
Oxidative Carbonylation of Alkenes. Oxidative carbonylation
Oxidative Carbonylation of Alkynes. Terminal alkynes are car-
of alkenes with PdCl2 in benzene affords ²-chloroacyl chlorides
bonylated to give acetylenecarboxylates using PdCl2 and CuCl2
(eq 26).33 Oxidative carbonylation of alkenes in alcohol affords
as catalysts (eq 30).37 The acetylenecarboxylate in a ²-lactam has
Ä…,²-unsaturated esters and ²-alkoxy esters by monocarbonylation
been prepared by this procedure and then converted to a ²-keto
and succinate derivatives by dicarbonylation (eq 27).34
ester (eq 31).38
Me Me
Me Me
N PdCl2, CuCl
N
CO2Me
+ CO + MeOH (30)
RR CO2Me
PdCl
+ + Li2PdCl4 Et3N
CO2Me
CO2Me
CO2Me
R3SiO
Me Me
PdCl2
N
CO2Me
Li2PdCl4 O
+ CO + MeOH
CuCl2
OH N
CO2Me
Cl
86%
O Ar
92%
Me Me
R3SiO R3SiO
N
O
CO2Me
CO2Me (31)
CO2Me
86%
CO2Me
N N
(25)
O Ar O Ar
O
Cl
O
Oxidative dicarbonylation of acetylene with Pd(PhCN)2Cl2 in
benzene affords the chlorides of maleic, fumaric, and muconic
50%
acids (eq 32).39 Methyl muconate is obtained by passing acetylene
and oxygen through MeOH containing thiourea and a catalytic
amount of PdCl2.40 The oxidative dicarbonylation of alkynes pro-
R
R
+ CO + PdCl2 + Pd0 (26) duces maleate derivatives as a main product using PdCl2 and
Cl COCl
CuCl2 as catalysts under oxygen in alcohol.41
A list of General Abbreviations appears on the front Endpapers
PALLADIUM(II) CHLORIDE 5
100 °C MeOH
Ä…,²-Unsaturated esters are obtained by the carbonylation
H H + CO + Pd(PhCN)2Cl2
of alkenylboranes49 and alkenyl- or arylpentafluorosilicates
(eq 37).50 Conjugated dienes and diaryls are formed by the cou-
CO2Me CO2Me
pling of alkenyl- and arylstannanes. The homocoupling of the
MeO2C
++ (32)
CO2Me
vinylstannane of benzoquinone is catalyzed by PdCl2(PhCN)2
MeO2C CO2Me
with benzoquinone as the reoxidant (eq 38).51
PdCl2, LiCl
C6H13 C6H13
benzoquinone
Oxidative Carbonylation of Alcohols. Oxalates and carbonates
+ CO + MeOH (37)
AcONa
are formed by the oxidative carbonylation of alcohols. The reac- B(Sia)2 CO2Me
73%
tion can be made catalytic by using PdCl2 and CuCl2 under oxygen
in the alcohol.42 Either oxalate or carbonate is obtained chemose-
lectively under different conditions (eq 33). Alkyl oxalates are pro-
O
duced commercially using alkyl nitrites as reoxidants (eq 34).43
O
Pd(PhCN)2Cl2
benzoquinone
O
(38)
OMe
PdCl2
CO2Me
SnBu3 CuI
CO + MeOH O + (33)
80% O
CO2Me O
O
CuCl2
OMe
PdCl2
CO2Bu
Miscellaneous Oxidation Reactions. Some oxidative reac-
2 BuONO + 2 CO + 2 NO
CO2Bu
tions can be carried out only with Pd(OAc)2, but not with PdCl2.
(34)
However, Pd(OAc)2 can be generated in situ by the reaction of
2 NO + 2 BuOH + 0.5 O2 2 BuONO + H2O
PdCl2 with AcOK or AcONa. The oxidative coupling of aromatic
rings is a typical example of a Pd(OAc)2-promoted reaction. The
following coupling reaction proceeds by Pd(OAc)2 generated in
Reactions via Transmetallation of Organometallic Reagents.
situ from PdCl2 (eq 39).52
Transmetalation of organometallic compounds of Hg, B, Sn,
Si, Tl, etc., with PdCl2 produces the reactive organopalladium
MeO
species, which undergoes insertion and coupling reactions. Aryl-
Li2PdCl4
or alkenylpalladium complexes, generated in situ from aryl- or
MeO Bu
AcONa
alkenylmercury compounds, undergo insertion reactions with
O 87%
MeO
alkenes;44,45 an example is shown in eq 35.46 The arylmercury
O
compound with 1,3-cyclohexadiene and Li2PdCl4 generates a Ä„-
MeO
allylpalladium intermediate, which then attacks the amide group
intramolecularly to yield the cyclized product (eq 35).46 CO inser-
(39)
MeO Bu
tion produces ketones and esters.47 The ortho-thallation of ben-
O
zoic acid and subsequent transmetalation with PdII generates a MeO
reactive arylpalladium complex, which reacts with butadiene to O
give an isocoumarin (eq 36).48
The following oxidative rearrangement of a propargylic ester
NHCOMe
proceeds with a catalytic amount of PdBr2 under oxygen. Inter-
MeCN
+ + Li2PdCl4
estingly, the reoxidation of Pd0 takes place with oxygen without
HgCl
addition of other reoxidants (eq 40).53
COMe COMe
O
NH N
i-Pr O
(35)
PdCl
K2PdBr4
74%
O2
95%
O
CO2H
CO2H
Li2PdCl4
+ Tl(O2CCF3)3
O
Tl(O2CF3)2
O
O
i-Pr i-PrOCO
CHO
O
CO2H
base
O (36)
(40)
PdCl
95%
87% O O
Avoid Skin Contact with All Reagents
6 PALLADIUM(II) CHLORIDE
Catalytic Reactions with PdII. The Claisen rearrangement of 2-(allylthio)pyrimidin-4-(3H)-one
affords the N-1 allylation product as a main product rather than
Exchange Reactions of Vinyl Ethers and Esters.54 Vinyl the N-3 allylation product (eq 49).63
ethers are activated by PdII. Exchange with other alcohols to
O O
give mixtures of acetals and vinyl ethers is catalyzed by PdCl2
Pd(PhCN)2Cl2
H
(48)
(eq 41).55 This reaction was used as the key step in the total syn-
rt
thesis of rhizobitoxine (eq 42).56
95%
MeO MeO
Pd(PhCN)2Cl2
syn 98%
+ R2OH + R1OH (41)
OR1 OR2
O O
BnCO2NH MeO
CO2Bn
PdCl2(PhCN)2
O
BnO OH +
HN HN
Pd(PhCN)2Cl2
NHCO2Bn
+ N (49)
S N S N
rt
80% S N
NHCO2Bn
H
BnO O CO2Bn
76:24
(42)
NHCO2Bn
The rearrangement of allylic esters, a useful reaction, is
catalyzed efficiently by PdII.64 The allylic rearrangement shown
The exchange reaction of the acid component of vinyl esters
in eq 50, used in a prostaglandin synthesis, proceeds in one di-
with other acids is catalyzed by PdCl2 (eq 43).54 Thus various
rection irreversibly, yielding the thermodynamically more stable
vinyl esters are prepared from easily available Vinyl Acetate. Asan
product possibly due to steric reasons.65 The diacetate of a 1,5-
example, vinyl itaconate is prepared by the reaction of vinyl ac-
diene-3,4-diol is isomerized to the more stable conjugated diene
etate with itaconic monomethyl ester (eq 44).57 N-Vinyllactams
with complete transfer of chirality (eq 51).66 The PdII-catalyzed
and cyclic imides are prepared by the exchange reaction of lactams
allylic rearrangement has been explained by an oxypalladation or
and imides with vinyl acetate (eq 45).58
cyclization-induced rearrangement. It is mechanistically different
Pd(PhCN)2Cl2
from rearrangements catalyzed by Pd0 complexes, which proceed
+ R2CO2H + R1CO2H
OCOR1 OCOR2
by formation of Ä„-allylpalladium intermediates.
(43)
AcO AcO
CO2H CO2
Li2PdCl4
+ + AcOH (44)
C5H11
C5H11
OAc Pd(MeCN)2Cl2
68%
Br
CO2Me CO2Me Br
(50)
THF
O
O
O 93%
O
O
O
Na2PdCl4
N
NH
+ + AcOH (45)
OAc
OAc
Pd(MeCN)2Cl2
BnO
85%
OBn
THF
OAc
82%
PdII-catalyzed Rearrangement Reactions. Cope rearrange-
OAc
ments are accelerated by catalytic amounts of Pd(PhCN)2Cl2,
BnO
(51)
such that they proceed at room temperature in benzene or CH2Cl2 OBn
(eq 46).59 Successful PdII catalysis appears to require that atoms OAc
2 and 5 of the substituted 1,5-hexadienes have one H and one
Skeletal rearrangements of some strained compounds, such
 nonhydrogen substituent.60 Oxy Cope rearrangements proceed
as bulvalene to bicyclo[4.2.2]deca-2,4,7,9-tetraene,67 cubane to
at room temperature using Pd(PhCN)2Cl2 catalysis (eq 47).61
cuneane,68 hexamethyl Dewar benzene to hexamethylbenzene
Pd(PhCN)2Cl2 (eq 52),69 and quadricyclane to norbornadiene (eq 53),70 are cat-
Ph Ph
+ (46)
alyzed by derivatives of PdCl2.
87%
Ph
93:7
Pd(PhCN)2Cl2
(52)
Pd(PhCN)2Cl2
(47)
65%
O
OH
The Pd(PhCN)2Cl2 catalyzed Claisen rearrangement of allyl
Pd
vinyl ethers has been studied to a lesser extent. The Claisen rear-
Cl Cl
rangement shown in eq 48 proceeds smoothly even at room tem-
(53)
100%
perature to give the syn product with high diastereoselectivity.62
A list of General Abbreviations appears on the front Endpapers
PALLADIUM(II) CHLORIDE 7
C6H13
Pd(PhCN)2Cl2
Intramolecular Reactions of Alkynes with Carboxylic Acids,
+ H2O
Alcohols, and Amines. Addition of carboxylic acids, alco-
MeCN
HO
hols, and amines to alkynes via oxypalladation and aminopal- 95%
ladation proceeds with catalysis by PdII salts. Intramolecu-
O
O
lar additions are particularly facile.71 Unsaturated Å‚-lactones
are obtained by the treatment of 3-alkynoic acid and
(59)
C6H13
C6H13
4-alkynoic acid with Pd(PhCN)2Cl2 in THF in the presence
OH
O
of Et3N (eq 54), and ´-lactones are obtained from 5-alkynoic
acids.72 5-Hydroxyalkynes are converted to the cyclic enol ethers
(eq 55).71 The oxypalladation is a trans addition. Thus stere-
oselective enol ether formation by reaction of the alkynoic Cyclopentenone formation by the isomerization of 3-acetoxy-
alcohol with Pd(PhCN)2Cl2, followed by reduction with Am- 1,4-enynes is catalyzed by Pd(PhCN)2Cl2 (eq 60).76
monium Formate, has been applied to the synthesis of prosta-
cyclin (eq 56).73 Intramolecular addition of amines affords
cyclic imines. 3-Alkynylamines are cyclized to 1-pyrrolines while
O
5-alkynylamines are converted to 2,3,4,5-tetrahydropyridines
Pd(PhCN)2Cl2
AcO
(60)
(eq 57).74
68%
C6H13
Pd(PhCN)2Cl2
C6H13
(54)
O
CO2H
O
95%
OH O
Pd(PhCN)2Cl2
(55)
90%
Bu
Generation of Carbenes from Diazo Compounds. Both PdCl2
Bu
and Pd(OAc)2 are used for carbene generation from azo
HO
compounds.77 The cyclopentenone carboxylates have been
Pd(PhCN)2Cl2
CO2Me
prepared by intramolecular insertions of the carbenes generated
from Ä…-diazo-²-keto esters (eq 61).78
HCO2NH4
71%
R3SiO
R3SiO
CO2Me
O
O
CO2Me
Pd(PhCN)2Cl2
CO2Me
(61)
N2
55%
(56)
O
R3SiO
R3SiO
Generation of Pd0 catalysts. Pd0 catalysts can be generated
in situ from PdII in the presence or absence of phosphine lig-
NH2 Pd(MeCN)2Cl2
(57)
ands. Tetrakis(triphenylphosphine)palladium(0) is a commer-
70%
C8H17 C9H19 N
cially available Pd0 complex used frequently as a catalyst, but it is
air unstable. Therefore in situ generation of Pd0(Ph3P)n catalysts
Simple alkynes cannot be hydrated with a palladium catalyst,
by the reduction of PdII in the presence of Ph3P is convenient to
but triple bonds are hydrated regioselectively to yield ketones
use. In many cases the in situ reduction to Pd0 takes place without
with participation of suitably located carbonyl or hydroxy groups.
addition of reducing agents. Alkenes, alcohols, CO, and phos-
1,5-Diketones are prepared by the participation of a 5-keto group
phines, present in the reaction medium, behave as the reducing
(eq 58).75 4-Hydroxyalkynes are converted to 4-hydroxy ketones
agent and react with PdII to give Pd0. Generation of Pd0 by reduc-
and then oxidized to 1,4-diketones (eq 59).71
tion of Pd(OAc)2 with phosphines has been reported.79 Similarly,
PdCl2 and its derivatives have been converted to Pd0 species with
O
phosphines and bases.
Pd(MeCN)2Cl2
CO2Me
PdCl2 itself is used for the carbonylation of an aryl iodide in the
H2O, MeCN
presence of a base (eq 62).80 More frequently, Bis(benzonitrile)
HO
77%
dichloropalladium(II) is used for various Pd0-catalyzed reac-
OH
tions. The coupling reaction of an acyl chloride with a disi-
O
O
lane is catalyzed by Pd0, generated from Pd(PhCN)2Cl2 and
CO2Me
Ph3P (eq 63).81 The intermolecular coupling of a vinylenedis-
(58)
tannane with two alkenyl iodides has been carried out using
HO
Pd(PhCN)2Cl2 without addition of Ph3P in a total synthesis of
OH
rapamycin (eq 64).82
Avoid Skin Contact with All Reagents
8 PALLADIUM(II) CHLORIDE
OMe Br
I Br Br
OH
PdCl2, K2CO3 Pd(Ph3P)2Cl2 KF
O O
+ CO + + TMS
I
benzene CuI, Et3N
MeO Br Br
12 atm
PhS Br
70%
OMe O
O
(62)
(65)
O
MeO
I O
PhS
28%
O
MeMe
Pd(PhCN)2Cl2
Pd(Ph3P)2Cl2
Si
+
O Cl Si Cl
OAc + CO + Ac2O
Ph3P
Et3N
ClCO MeMe
O 76%
OAc
O
(66)
+ Cl2SiMe2 (63)
O
Me
Si
Cl
Me O
In some cases, Pd(Ph3P)2Cl2 is reduced to Pd0 in situ with
reducing agents such as metal hydrides, and used for Pd0 catalyzed
83%
reactions. For example, Pd(Ph3P)2Cl2 is reduced with Diisobutyl-
aluminum Hydride and used for coupling reactions (eq 67).85
O O
O
Bu
Pd(Ph3P)2Cl2
H OH
+ (67)
SnBu3 I OMe
i-Bu2AlH
Pd(PhCN)2Cl2, DMF Cp2ZrCl
Br Bu
+
I
i-Pr2NEt, 25 °C
Bu3Sn
28%
O OH
The carbonylation of alkenes in alcohols to give saturated es-
ters proceeds smoothly with PdCl2 or Pd(Ph3P)2Cl2 as a cata-
OMe lyst (eq 68).86 Alkynes are carbonylated efficiently to give Ä…,²-
unsaturated esters with the same catalyst in the presence of
Iodomethane (eq 69).87 In some reactions the Pd0 species gen-
OH
erated from PdCl2 Ph3P and Pd(OAc)2 Ph3P show different re-
O
activities. For example, in the carbonylation of 1,3-Butadiene, 3-
H
pentenoate is obtained with PdCl2 Ph3P, while 3,8-nonadienoate
is obtained with Pd(OAc)2 Ph3P. The presence of chloride anion
(64)
in the coordination sphere of palladium gives different catalytic
activity (eq 70).88
O OH
Pd(Ph3P)2Cl2
R
+ CO + MeOH
OMe
30% recovery of starting material
R
R
+ (68)
CO2Me
CO2Me
Dichlorobis(triphenylphosphine)palladium is used for Pd0-
catalyzed reactions without adding a reducing agent. For ex-
O
Pd(Ph3P)2Cl2
ample, the coupling of terminal alkynes with halides is carried
+ CO + Et2NH
MeI
O
out with Pd(Ph3P)2Cl2 and Copper(I) Iodide in the presence of
92%
Triethylamine without addition of a reducing agent. Hexaethynyl-
benzene is prepared by the coupling of hexabromobenzene with
trimethylsilylacetylene (eq 65).83 Similarly, the carbonylation of
O
CONEt2
(69)
cinnamyl acetate, to give naphthyl acetate, is carried out in the
O
presence of Et3N (eq 66).84
A list of General Abbreviations appears on the front Endpapers
PALLADIUM(II) CHLORIDE 9
PdCl2
+ CO + MeOH
Br(CH2)3COCl
+
Et3N
THF, rt
Pd(OAc)2, Ph3P
CO2Me
96%
Br R
(70)
PdCl2, Ph3P R Br
+
(72)
CO2Me
O O
R = Br(CH2)3
Yield (%)
endo:exo
91
1:1
40
First Update 1.7:1(without PdCl2)
V. Sridharan
University of Leeds, Leeds, UK
Five-membered Rings. [4 + 1] processes: Several examples of
Pd(PPh3)2Cl2-catalyzed [4 + 1] processes have been reported in
Cascade Reactions. Cascade reactions can be defined as multi
which carbon monoxide was used as a one-carbon component.
reaction  one pot sequences in which the first reaction creates
A typical example is shown in eq 73. The choice of catalyst and
the functionality to trigger the second reaction and so on. Cas-
additives are important to obtain either indanone or indenone in
cade reactions have also been termed tandem or domino processes
this particular cascade reaction.91,92
by some authors. This section is concerned with Pd(PPh3)2Cl2-
[to generate Pd(0)] or PdCl2-catalyzed processes in which two or
I
more carbon-carbon/carbon-heteroatom bonds are formed.
+ CO
Cycloaddition Cascades. These processes involve combina-
tions of a starter molecule, which comprises a vinyl, aryl,
allylic, or benzylic halide, triflate, etc., with one (or more)
n-Bu4NCl
Et3N
acceptor molecules (alkene, alkyne, 1,2-diene, 1,3-diene, etc.).
Pd(PPh3)2Cl2 Pd(OAc)2
C5H5N
MeCN/C6H6, 80 °C
Carbon monoxide is also a valuable one-carbon acceptor
DMF, 80 °C
molecule. Other cycloaddition processes include Diels Alder re-
actions, 1,3-dipolar cycloaddition reactions, etc., catalyzed by Pd
O O
(MeCN)2Cl2.
(73)
Three-membered Rings. [2 + 1] processes: Several examples of
PdCl2-catalyzed cascade cyclopropanation processes have been
reported in the literature.89 Thus, enyne ketone reacted with 50% 100%
styrene in the presence of PdCl2 to afford the cyclopropanated
Kundu et al.93 have reported a highly regio- and stereoselec-
product in excellent yield and in high diastereoselectivity (eq 71)
tive synthesis of (Z)-arylidene isoindolin-1-ones via a palladium-
via a palladium 2-furyl carbene complex.
catalyzed [4 + 1] cycloaddition process using alkynes as acceptor
molecules (eq 74).
Ph
Ph
I
O H Pd(PPh3)2Cl2
PdCl2
O
+ OMe
+ (71)
N
CuI, Et3N, DMF
Ph
Ph THF, rt
Ph
89%
80%
O
21:79 (cis:trans)
Ph
OMe
H
O
(74)
Pd
NPh
O
Four-membered Rings. [2 + 2] processes: PdCl2-catalyzed [3 + 2] processes: Most of the reported examples of
[Ä„2s + Ä„2a] cycloaddition reactions of Ä…-bromoalkyl ketenes and five-membered ring formation have involved a [3 + 2]
cyclopentadiene were found to occur in increased yield and exo- process. In this manner, Balme and co-workers94 have
selectivity compared with the uncatalyzed reaction (eq 72).90 developed a formal [3 + 2] cycloaddition process based
Avoid Skin Contact with All Reagents
10 PALLADIUM(II) CHLORIDE
H
EtO2C CO2Et CO2Et
Pd(PPh3)2Cl2/n-BuLi
CO2Et
+ +
I
THF/DMSO, rt
Ph
X
X
Ph
O
OH
X = H, 89%
(75)
X = m-CF3, 78%
X = p-OMe, 80%
H
I
CO2Et
CO2Et
Pd
_
CO2Et Pd
CO2Et
Ph
O
O
X
X
on a palladium-catalyzed three-component reaction. Thus adducts in 80% yield (9:1) (eq 80).102 An intramolecular PdCl2-
propargyl alcohol or amine (as Michael donor), aryli- catalyzed oxime to metallonitrone to isoxazoline cascade has also
dene or alkylidene malonate (as Michael acceptor), and been reported to occur in good yield.103
aryl/vinyl halide or triflate in the presence of Pd(PPh3)2Cl2 cata-
lyst afforded highly substituted 3-arylidene- (or 3-alkenylidene-)
tetrahydrofurans in excellent yield (eq 75).
HO
A closely related two-component process to synthesize pyrroles
Pd(PPh3)2Cl2
O
+
has also been reported to occur in good yield.95 Mono- and
K2CO3
di-substituted alkynes have been successfully employed as two-
NMP, 80 °C
Br
carbon components in the palladium-catalyzed [3 + 2] cycload- 52%
dition process. Thus Garibay and co-workers96 have described a
palladium-catalyzed [3 + 2] cycloaddition process to synthesize
O
O
aceanthrylenes in good yield using mono-substituted alkynes as
(77)
acceptor molecules (eq 76).
Br
Pd(PPh3)2Cl2, PPh3
+ H R
CuSO4, Al2O3, Et3N
I
C6H6, 80 °C
Pd(PPh3)2Cl2
.
+
n-BuEt3NCl
H
N
Na2CO3
R
OMe
CO2tBu MeCN, 90 °C
80%
(76)
R = CMe2OH, 91%
(78)
OMe
R = SiMe3, 93%
N
CO2tBu
Mono-substituted alkynes have also been used as two-carbon
components in the palladium-catalyzed [3 + 2] cycloaddition pro-
_
cess affording benzo[b]thiophenes in good yield.97 1,2-Dienes,
+
Me O
1,3-dienes, and hetero-cumulenes have been successfully em-
N
ployed as acceptor molecules in the palladium-catalyzed [3 + 2]
PdCl2(MeCN)2
cycloaddition process.98 Thus, Å‚-lactones (eq 77) and azaindoli- +
OEt
CHCl3, 70 °C
nones (eq 78) have been synthesized in good yield via a palladium-
60%
catalyzed [3 + 2] cycloaddition process using 1,3-dienes or 1,2-
dienes as acceptor molecules.99,100
Finally, in the [3 + 2] theme, 1,3-dipolar cycloadditions of
Ph Ph
nitrones and vinyl ethers were found to be catalyzed by PdCl2
(79)
+
affording the diastereomeric adducts as a 1:1 mixture in 60% yield
Me N Me N
O O
OEt OEt
(eq 79). No reaction occurred without the catalyst in chloroform
ć%
at 70 C.101 Oximes also underwent a PdCl2-catalyzed stereo-
1:1
specific and highly facially selective cascade to afford enantiopure
A list of General Abbreviations appears on the front Endpapers
PALLADIUM(II) CHLORIDE 11
O H
PdCl2(MeCN)2
N N OH + CMe2OMe
N
O
O
N Et3N, DCM
Cl
Ph O O Pd
Me
80%
PPh2 Cl
+
N
AgSbF6
O
DCM, - 78 °C
91%
Ph N Ph N
H H
N N
O O
(80)
+
H H
H H
O
O
O O
O O N
N
O
(82)
+
Me Me N
O
O N
O
9:1
9:1
91% ee
Six-membered Rings. [4 + 2] processes: Larock and co-workers
have utilized both alkynes104,105 and 1,2-dienes106 as accep-
XH
PdCl2, DPPF
tor molecules to prepare isoquinolines, pyridines, and ²- or
+ CO +
Å‚-carbolines via palladium-catalyzed [4 + 2] cycloaddition pro-
i
Pr2NEt, 400 psi
I
cess in good yield (eq 81). This process could also be adapted
C6H6, 50 °C
to synthesise analogous carbocycles via a [4 + 2] cycloaddition
77%
X = S, O, NTs
process.107 PdCl2 has also been found to catalyze intermolecular
and intramolecular Diels Alder reactions. Recently asymmetric
Diels Alder reactions mediated by palladium catalysts have O
been reported.108 111 A highly efficient catalytic asymmetric
(83)
Diels Alder reaction using PdCl2 with chiral 1,3-oxazoline lig-
ands is shown in eq 82.
X
I
Pd(PPh3)2Cl2
N t
Bu
+ Ph
Cyclization-anion-capture Process. Grigg et al.115 were in-
CuI, Et3N
N
terested in devising ring-forming processes with concomitant in-
DMF, 100 °C
Me
64%
troduction of functionality by replacing the ²-hydride elimination
step of the Heck reaction with a group or atom transfer. This led to
the development of cascade cyclization-anion-capture processes.
Ph
Carbonylation Cascades. The norbornene enamide shown un-
N
derwent a palladium-catalyzed 5-exo-trig cyclization followed by
carbonylation (1 atm) to give a spirocyclic product as a single di-
N
Me
astereoisomer (eq 84). In this case ring strain prevents the compet-
ing ²-hydride elimination pathway.116 Similar diastereoselective
t
three-component cascade processes proceed smoothly in excellent
Bu
N
Pd(PPh3)2Cl2
yield (eq 85).117
+ Ph
CuI, Et3N
Ph I
DMF, 55 °C
59%
Pd(PPh3)2Cl2
I
CO (1 atm), TlOAc
N
N Ph
(81)
MeCN, 65 °C
86%
Ph Ph
O
[3+2+1] processes: A three-component palladium-catalyzed
MeO2C
cascade cycloaddition process using carbon monoxide and allene
(84)
as relay species has been shown to occur in good yield (eq 83)112
with formation of thiochroman-4-one derivatives. Closely related
N Ph
processes using oxygen and nitrogen nucleophiles have also been
O
reported to occur efficiently.113,114
Avoid Skin Contact with All Reagents
12 PALLADIUM(II) CHLORIDE
process) and on the size of the incipient ring in the cyclization-
Pd(PPh3)2Cl2
carbopalladation.121 The effect of pressure is appropriately illus-
I
t
BuMe2SiO
CO (1 atm), Et3N
trated by the studies of Negishi and co-workers.122 For example,
H
DMF-MeCN-H2O, 85 °C
H
at a CO pressure of 40 atm, carbonylation is faster than 5-exo-trig
94%
cyclization and ²-hydride elimination as illustrated by the triple
carbonylation process (eq 89).
CO2Me
(85)
t
BuMe2SiO
H
Pd(PPh3)2Cl2
O
I
A novel, three-component, palladium-catalyzed, cascade cycli- EtO2C
N
TlOAc, CO (1 atm)
EtO2C
N
EtOH, 80 °C
zation-anion-capture process which involves in situ generation
(88)
50%
of a zipper molecule has been reported.118 Thus, 2-iodobenzoyl
chloride, an acetophenone imine, and carbon monoxide react in
CO2Et
the presence of Pd(PPh3)2Cl2 to give isoindolin-1-one in moderate
yield (eq 86).
Ph
CO2Me
I
Me
Pd(PPh3)2Cl2
(86)
+ + N
N
CO
Et3N
Cl
Ph (14 atm)
MeOH-MeCN, 100 °C
O
56%
O
O
Ph
Ph
PdI
I
N
N
O
O
O
H
Recently Aggarwal et al.119 reported a palladium-catalyzed I
Pd (PPh3)2Cl2
cyclization-carbonylation (2 atm) of bromodienes to give Å‚,´- un-
O
CO (40 atm)
saturated esters in good yield (eq 87). Carbonylation occurs at a
H
Et3N, MeOH
R
R
much faster rate than ²-hydride elimination under these reaction
MeCN/ C6H6, 95 °C
CO2Me
conditions.
(89)
This constitutes a pentamolecular queuing process and pro-
Pd(PPh3)2Cl2, PPh3
Br
duces mixtures of diastereomers (5:1). Finally, a series of penta-
TsN
(87)
CO (2 atm), Et3N TsN
CO2Me
molecular queuing cascades employing aryl (triflate, iodide) and
MeOH-DMF-H2O (1:2:0.1)
vinyl (bromide, triflate) as starter species and carbon monoxide, al-
85 °C, 69%
lenes as relay species have been achieved (eq 90).123 The strategy
x
employed in these cascades is analogous to that in eq 88 in which
the initial oxidative product undergoes CO insertion in preference
toa 4-exo-trig cyclization.
TsN
I
+ CO +
+
N
H
Double Carbon Monoxide Insertions. Cyclization forming a
four-membered ring was likely to be slower than carbonylation
under 1 atm. A series of substrates was designed to take advan-
O
tage of this rate differential and permit incorporation of two carbon
O
Pd(PPh3)2Cl2
monoxide molecules into the product (eq 88).120 In the above case
(90)
toluene, 110 °C
(eq 88), the first CO insertion occurs faster than slow 4-exo-trig
N
carbopalladation allowing a facile 5-exo-trig acylpalladation. The
relative rates of CO insertion and intramolecular carbopallada-
75%
tion are dependent on CO pressure (CO insertion is a reversible
A list of General Abbreviations appears on the front Endpapers
PALLADIUM(II) CHLORIDE 13
Novel Palladium Chloride-based Catalysts for Carbon dimethylglycine improves the regioselectivity of the reaction. Her-
Carbon/Carbon Heteroatom Bond Formations. The past rmann et al.154 pioneered the use of palladacycles and palladium
decade has witnessed the development of novel palladacycles as carbenes as catalysts in conjunction with n-Bu4NBr for Heck re-
a new class of catalysts for carbon-carbon/carbon-heteroatom action of activated aryl chlorides (Table 1, entry 3). These condi-
bond-forming reactions.124,125 Several types of palladacycles tions were not effective for electron-neutral or electron-rich aryl
(derived from PdCl2) have appeared in the literature. chlorides. Nitrogen and sulfur-containing palladacycles have also
These include PC type,126 PCP pincer type,127 phosphite been effective in catalyzing the Heck reaction of activated aryl
palladacycles,128 131 NC type,132 140 NCN pincer type,141 chlorides (Table 1). Li et al.148 have demonstrated that the com-
and sulfur containing palladacycles.142,143 Heterogeneous mercially available air stable Pd(II) complexes of phosphinous
palladacycles have also been reported in the literature.144 These acid ligands are useful for the Heck reaction of electron-poor aryl
palladacycles are obtained via direct metallation from appropriate chlorides (Table 1, entry 5). Finally, Dupont and co-workers have
ligands with either PdCl2 or Na2PdCl4. Typical examples are reported the use of PdCl2 (SEt)2/n-Bu4NBr in catalyzing the Heck
shown in Scheme 1. reaction of aryl chlorides.155.eps
t
Cl Cl
Bu
S
O
R2
PR2 N Pd N
O
P OAr
C6H13HN NH
P
Pd Cl
OAr
PR2 But
Pd
Pd Cl
2
O
Cl
N N
2
Pd
R = i-Pr, 4MeO-C6H4 Ar = 2,4,tBu2C6H3
R = naphthyl
Cl
Cl
OH
NMe2
But
Me
P Cl
But Cl tBu
Pd Cl
N
But Pd Pd Cl
t
Bu
HO P Pd P OH
Me
Pd
Pd Cl NMe2 Cl Cl
P
t
t t
Bu
N Bu Cl Bu
Cl 2
PR2
Me
OH
t
R1
But tBu
But Bu
SR1
O P P O
Cl
Pd Cl
SR2 R
H Pd Pd H
Pd
SR1 Cl
O P P O
Cl
2
But tBu But tBu
R1 = Me, R2 = tBu R = H, R1 = tBu
R = NHAc, R1 = tBu The most versatile method that has been reported to date
for the Heck reaction of unactivated aryl chlorides employs
Pd(0)/P (tBu)3 as the catalyst (Table 2, entry 1). Recently, In-
Other highly active palladium chloride-based catalysts include
dolese and co-workers156 have developed a palladacycle and sec-
di-2-pyridylmethylamine-based palladium,145 trans-bidentate
ondary phosphane catalyst for the Heck reaction of electron-rich
pyridine,146 and PdCl2/phosphinous acid complexes.147 150
aryl chlorides (Table 2.eps, entry 2).
Typical examples are shown in Scheme 2. This section is con-
cerned with the coupling reactions of aryl chlorides using the
Carbon Nitrogen Bond-forming Process. Palladium-cataly-
above PdCl2-based catalysts. Chloro arenes are cheap to man-
zed carbon-nitrogen bond formation has recently emerged as
ufacture and therefore play a vital role as intermediates in the
one of the most powerful method for the synthesis of ani-
chemical industry. The low reactivity of chlorides is usually at-
line derivatives. Buchwald157 and Hartwig158 have pioneered
tributed to the strength of the C-Cl bond. Remarkable progress has
the above process. This section is concerned with the use of
been achieved since 1998 in the development of palladium-based
PdCl2-based catalysts in the amination of chloro arenes. In 1997,
catalysts that can in fact accomplish cross-couplings and Heck
Tanaka and co-workers159 described the first example of palla-
reactions.151
dium chloride-catalyzed amination of unactivated aryl chlorides,
using PdCl2(PCy3)2 as the catalyst (Table 3, entry 1). Reactions of
Heck Reaction. The palladium-catalyzed coupling of aryl, het-
cyclic secondary amines furnish the highest yield, and secondary
eroaryl, vinyl halides, and triflates with olefins is referred to
anilines reacted smoothly. PCy3 appears to be effective at achiev-
as the Heck reaction (the reaction shown in Table 1),152 and
ing oxidative addition of the aryl chloride to palladium, but it is not
constitutes an important carbon-carbon bond-forming reaction in
always ideal for promoting reductive elimination over ²-hydride
organic synthesis. The Heck reactions of activated aryl chlorides
elimination. The amination reactions of aryl chlorides with sec-
involving PdCl2-based catalysts are summarized in Table 1. Reetz
ondary or primary aryl amines catalyzed by PdCl2-based catalysts
et al.153 have reported the use of simple Pd(II) complexes such
are summarized in Table 3. N-Heterocyclic carbine palladacycles
as PdCl2(MeCN)2 in conjunction with tetraphenylphosphonium
are also found to be active in aryl amination reactions (Table 3,
salts (Table 1, entry 1) in the Heck reaction of electron-poor and
entry 3).160.eps
electron-neutral aryl chlorides with styrene. The addition of N,N-
Avoid Skin Contact with All Reagents
14 PALLADIUM(II) CHLORIDE
Table 1 Heck reactions of activated aryl chlorides
R R R1
catalyst
+
Cl
base, solvent
R1
temp
Conditions
Entry RR1 Catalyst Yield (%)
Ph
1 4-CHO, H NaOAc, NMP, 150 °C 96 98
PdCl2(MeCN)2/PPh4Cl
2 4-NO2 51 71
Ph, CO2Et K2CO3, NMP, 150 °C
Cl
Pd
NMe2 2
N OH
3 4-CN, NO2 K2CO3, NMP, 150 °C 60 79
Ph, CO2Et
Pd
Cl
2
N
4 CO2Bu
4-CHO NaOAc, DMF, 120 °C 75
N
N
Pd
Me
Cl
Me
n-Bu4NBr
5 4-COMe CO2tBu PdCl2P(tBu)2(OH)2 NaOAc, DMF, 130 °C 66
O
PiPr2 CsOAc, dioxane, 120 °C 81 99
6 4-CHO, Me Ph
Pd
Cl
PiPr2
O
Ph
Cl
7 4-NO2 60
CO2Bu NaOAc, DMA
Pd Cl
Bu4NBr, 150 °C
N
Me2 2
Table 2 Heck reactions of unactivated aryl chlorides
R1
RR
catalyst
Cl +
R1 base, solvent
temp
Entry R Catalyst Conditions
R1 Yield (%)
CO2Bu
1 4-OMe, 2-Me,
Pd2(dba)3/P(tBu)3 Cy2NMe, dioxane, 120 °C 72 89
2,6-diMe
4-OMe, 4-Me 100
2 CO2Bu Me2N Pd PHR2 Na2CO3, DMA, 140 °C
Cl
R = norbornyl
A list of General Abbreviations appears on the front Endpapers
PALLADIUM(II) CHLORIDE 15
Table 3 Amination of aryl chlorides
R1
R R R1
catalyst
+ H N
Cl N
R2 base, solvent
R2
temp
Entry Catalyst Yield (%)
R Amine Conditions
secondary cyclic, PdCl2(PCy3)2
1 4-C, H, Me NaOMe, toluene, 120 °C 56 88
secondary aryl
primary aryl PdCl2P(tBu)2(OH)2
2 NaOMe, dioxane, 110 °C
4-Me 97
3 4-MeO secondary acyclic, NaOtBu, dioxane, 80 °C 92
N Pd Cl
primary aryl,
Me2
primary alkyl
N
N
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