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A mechanistic study of Suzuki reaction

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Title:
A mechanistic study of Suzuki reaction
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Qian, Minfei
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English
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v, 51 leaves : illustrations ; 29 cm

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Degree Divisions:
Department of Chemistry, CU Denver
Degree Disciplines:
Chemistry

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Subjects / Keywords:
Chemistry, Organic ( lcsh )
Organometallic compounds ( lcsh )
Organotransition metal compounds ( lcsh )
Chemistry, Organic ( fast )
Organometallic compounds ( fast )
Organotransition metal compounds ( fast )
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bibliography ( marcgt )
theses ( marcgt )
non-fiction ( marcgt )

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Includes bibliographical references (leaves 49-51).
General Note:
Submitted in partial fulfillment of the requirements for the degree, Master of Science, Department of Chemistry
Statement of Responsibility:
by Minfei Qian.

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University of Colorado Denver
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Auraria Library
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37364299 ( OCLC )
ocm37364299
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LD1190.L46 1996m .Q53 ( lcc )

Full Text
A MECHANISTIC STUDY OF SUZUKI REACTION
by
Minfei Qian
M.S., East China University of Chemical Technology, 1987
B.S., East China University of Chemical Technology, 1984
A thesis submitted to the
University of Colorado at Denver
in partial fulfillment
of the requirements for the degree of
Master of Science
Chemistry
1995


This thesis for the Master of Science
degree by
Minfei Qian
has been approved
by
Professor Robert Damrauer
Professor Doris Kimbrough
Date


I
Qian, Minfei (M.S., Chemistry)
A Mechanistic Study of Suzuki Reaction
Thesis directed by Professor Robert Damrauer
ABSTRACT
This thesis described the general mechanism of the Suzuki Reaction the
stereo-specific cross-couplings in palladium-catalyzed reactions of organoborane
reagents with organic halides. It talked about the properties of the Pd catalyst
and intermediates.
The thesis also described the Kinetic method and competition method
used for mechanistic for studying of the Suzuki reaction. By the Kinetic study,
the order and the rough rate constant of the Suzuki reaction were determined
and measured. By the competition study, the relative rate constant Kx with
seven different substituents on the benzene ring were measured. By the
Hammett plot, p value is 1.83. R^ is pretty good at 0.972. The positive
value points out that: the electron-withdrawing groups on the benzene ring will
accelerate the reaction rate and the electron-donating groups on the benzene ring
in
will decrease the reaction rate.


The center Pd of the transition state of the Suzuki reaction must be a
little bit electron rich (electron negative). So, the electron withdrawing groups
would stabilize the transition state through the n system on the benzene ring.
This abstract
recommend its
accurately represents the content of the candidate's thesis,
publication.
Signed
I
IV


CONTENTS
CHAPTER
1. INTRODUCTION ..................................... 1
2. GENERAL SUZUKI REACTION MECHANISM
2.1 Mechanism of the Suzuki Reaction 7
2.2 Property of the Catalyst Pd(PPh3)4 ...................... 9
3. DISCUSSION AND RESULTS
3.1 Kinetic Study ................................. 12
3.2 Hammett Study 17
3.2.1 Competition Reaction Study 17
3.2.2 Hammett Equation 21
3.3 Conclusion 25
4. EXPERIMENT
4.1 Purification and Preparation of the Starting Materials 26
4.2 The Percentage Yields of the Reactions ( Transition Metal
Catalyzed Cross-coupling Reaction ) 29
4.3 Determining of the Rate and Order of the Suzuki Reaction 34
4.4 Competition Reactions .................................. 44
REFERENCES ....................................... 49
v


ACKNOWLEDGMENTS
I want to express profound thanks to my advisor, professor Robert
Damrauer for his guidance, his help, his concern and his support during the last
two years. His lecture and class were extremely interesting to me.
Additionally special thanks must go to-----
Dr. Dyckes and Dr. Kimbrough, who read and reviewed my master thesis very
carefully and gave me a number of excellent suggestions.
Dr. Kwochka and Mr. Dave Crocker, who helped me in my research
and experiments.
My sincere thanks go to all those mentioned.
Thank you.


1. Introduction
Inorganic complexes are finding increasing use in organic chemistry, both
as reagents and as catalysts for a variety of syntheses[l]. In many cases, metal
catalysis is uniquely suited for affecting reactions which are not otherwise
possible.
Metal catalysis is very important in industrial chemistry[2] since it allows
for high selectivity and economic efficiency in some processes such as :
hydrogenation[3], polymerization[4], oxychlorination[5], hydroformylation[6],
oxidation[7], oligomerization[8], epoxidation[9], and hydrocyanation[10].
Despite the large number and variety of important catalytic processes
extant, many of these major processes are understood only in general outline, and
others are hardly understood at all. This situation is a natural consequence of the
difficulty of studying catalytic reactions in which the steady state concentrations
of the reactive intermediates are very low. To promote further developments in
this field, a mechanistic understanding of the chemical interactions between the
metal complex and the organic substrate is desirable and important. This thesis is
directed toward obtaining just such a mechanistic understanding of the cross-
coupling reaction of organic halides with organoborane reagents catalyzed by
palladium.
Organometals, in which there is bonding between metal and a ligand, play
key roles as reactive intermediates in a number of these systems. However, there
is surprisingly little known about how these organometallic intermediates are
1


formed and how they undergo further reaction. There are two principal driving
forces to consider in the reactions of inorganic complexes: ligand coordination
and oxidation-reduction of the metal center. Collman[l 1] has pointed out that a
vacant coordination site is a very important property of a catalyst, for it allows the
substrate to be brought close to the metal. The optimal coordination number for
transition metal complex with dn configuration is ( 18 n ) / 2. For example, in
those metal centers with d6, d8, and dlO spin-paired configurations, full saturation
(normally total 18 or 16 electrons) in a metal complex is characterized by 6-, 5-,
and 4- coordination, respectively. Coordinate unsaturation is most commonly
effected in a metal complex by either loss of one ligand [12], dissociation of a
bridged dinuclear species[13], or ti-ct rearrangement of polyhapto ligands[14].
Alternatively, oxidative addition can also lead to coordinate unsaturation.( 16 or
14 electrons) Addition of electrophiles in this manner is tantamount to an overall
two equivalent oxidation, since the metal changes formal oxidation state from
M(n) to M(n+2)[15]. .A one-equivalent oxidation may also be effected by
electrophiles, in which the metal changes formal oxidation state from M(n) to
M(n+l)[16].
A number of examples of metal catalyzed cross-coupling reactions have
been reported. Corriu[17] published in 1972 that olefinic or aromatic halides and
aromatic Grignard reagents could be cross-coupled by the nickel catalysts [ NiCl2,
Ni(acac)2, Ni(pph3)2Cl2, and C0CI2]. Kumada[18] also reported in 1972 that the
selective carbon-carbon bond formation by cross-coupling of Grignard reagents
with organic halides was catalyzed by nickel-phosphine complexes.
2


Since those reports, a wide variety of such cross-coupling reactions have
been developed and some of them have achieved great success in synthetic
organic chemistry.
R-m + R-X ----------------------> R-R + mX
M = Ni, Pd
m = Mg, Zn, Al, Zr, Sn, Li, B
R- aryl, alkenyl
X = Cl, Br, I, OR, SR, SeR, OP(0)(OR)2
The cross-coupling reaction has been extended to aryl and alkenyl ethers,
sulfides, selenides, and phosphates. For example, Wenkert[19] reported that the
reactions changed enol ethers to olefins and ethers to biaryls by nickel-induced
conversion of carbon-oxygen into carbon-carbon bonds. Trost[20] also reported
that the regioselectivity of arylation of enol thioethers catalyzed by palladium can
provide new avenues for applications of these intermediates for structural
elaboration. Okamura[21] has found that the cross-coupling of alkenyl, aryl or
allylic selenides and Grignard reagents were catalyzed by nickel-phosphine
complexes. The reactivity order of coupling reaction with BuMgBr catalyzed by
NiCl[Ph2PCH2CH2] was found to be PhSeMe PhCl > PhSMe. In 1980,
Takai[22] published the cross-coupling of enol phosphates with organoaluminium
compounds catalyzed by palladium (0) complexes.
Recent studies by Negishi have demonstrated the synthetic utility of the cross-
coupling reaction by showing that organometallics containing zinc, aluminum,
and zirconium can enter into the cross-coupling reactions by the use of a
3


palladium catalyst. In 1978, Negishi[23] publishedthat metal catalysis in the
cross-coupling reaction and its application to the stereo- and regioselective
synthesis of trisubstituted olefins. In 1983, Russell[24] reported palladium
catalyzed acylation of unsaturated halides by anions of enol ethers. There were
seven schemes that they used for the cross-coupling reactions.
Later, organolithium, tin, and borane reagents had also been used in cross-
coupling reactions. In 1977, Millard[25] found a nickel catalyst for the arylation
and vinylation of lithium ester enolates. In 1979, Milstein[26] reported that
palladium catalyzed coupling of tetraorganotin compounds with aryl and benzyl
halides occurred and various functional groups were tolerated by this reaction and
generally high yields of the cross-coupled products were obtained.
From 1979 to 1981, Suzuki[27] published several papers that reported new
stereospecific cross-couplings in palladium-catalyzed reactions of alkenyl and aryl
boranes with aryl, alkenyl or alkynyl halides. Those reactions using
organoborane reagents reacting with organic halides catalyzed by palladium
complexes have become known as the Suzuki reaction.
RC = CH + HBX2
Br R4 R3 R'L H VR4
H BX2 PdL4, Base H R*~ "r3
X= L = PPh3.
In recent years, Suzuki[28] and coworkers have mainly focused to the cross-
coupling reactions of B-alkyl-9- borabicyclo[ 3,3,1 ] nonane ( AlkyI-9-BBN )
derivatives with aryl, alkenyl or alkynyl halides that were catalyzed by Palladium
complexes with base. In 1993, Martin[29] reported the palladium-catalyzed
4


cross-coupling reactions of organoboronic acids with organic electrophiles. This
is a modification of the Suzuki reaction and even can be carried out in aqueous
solution.
KH)2
'll +
Pd(PPh3)4
'Z ........................>
benzene, Na2C03 / H20
5-z
Z = Me, MeO, Cl, NO2, F, CHO
Today synthetic chemists have many options which are available for
consideration. Among the possibilities that were mentioned above, many
organometallic reagents will not tolerate sensitive functionalities, which may be
imperative for the total synthetic sequences. For instance, lithium, Grignard and
copper reagents will not tolerate various sensitive functional groups on either
coupling partner[30]. In addition, most of the organometallic reagents are air or
moisture sensitive, highly toxic or arduous to prepare, and few can be purified
and stored. Now organic chemists have realized that the organoborane reagents
maybe were the best choice to be handled easily and to be used in cross-coupling
reactions.
Our research group is working on the synthesis of organosilicon cage
compounds [ 31 a][31 b][31 c]. This project is carried out using the Suzuki
reaction form carbon-carbon bonds to make final cage compounds. Dr. Robert
Damrauer and Dr. William Kwochka have already gained great success in a part
of the work. [31c]
We thought that a mechanistic study of the Suzuki reaction would bring an
understanding of the details that affected the synthetic reaction procedure and
5


percentage yield. Another reason that we did the mechanistic study was that there
were a lot of papers published using the Suzuki reaction to synthesis different
types of new organic compounds, but just a few papers proposed a possible
mechanism [26] [28c][30]. Others didn't talk about the mechanism at all.
Compared to other cross-coupling reactions, the Suzuki reaction is a more
versatile process which tolerates a wide variety of functional groups.[29] Our
research focuses on the mechanism and details of the Suzuki reaction. We
determined the percentage yields, the reaction orders, rough reaction rate
constant, and also did a competition study on various aryl bromides reacting with
methyl-9BBN catalyzed by Pd(PPh3)4 at basic condition in THF. This work will
be detailed in several chapters.
The first thing that we considered was the nature of the reaction and the
choice of reactants for the mechanism study. We were mostly concerned with
how different substituted groups on the benzene rings of aromatic halides affected
the reactions. One reactant was arylbromides. The organoborane chosen by us
was Me-9BBN. It would give products that were simply identified because they
could be purchased. We could identify the products on the gas chromatography (
GC ) and the gas chromatography / mass spectroscopy ( GC/MS ) by using
external standards and comparing them. Also we could isolate the products by
using the column chromatography and analyze them. Me-9BBN was used as a
reactant because the percentage yields of the products were very high. Finally, no
elimination reactions can occur using Me-9BBN.
Now, let's take a look at the general mechanism of the Suzuki reaction.
6


2. General Suzuki Reaction Mechanism
2.1 Mechanism of the Suzuki Reaction
The principal features of this cross-coupling reaction, which are important
for delineating the mechanism, are as follows[28b][28c][32]:
a) Only catalytic amounts of palladium complexes (1-3 mole %) are
required to obtain the cross-coupling products.
b) The coupling reactions are highly regio- and stereo-specific and take
place while
retaining the original configurations of both the starting alkylboranes and
arylhalides.
c) A base is required to carry out a successful coupling.
d) THF is used as the solvent for the reactions. The solvent reflux
temperature of 60C is suitable for reaction.
As some papers proposed[28b][29], the general Suzuki reaction
mechanism given here is similar but some different due to the different base by
us.
Overall reaction:
Pd(PPh3)4 + K2C03
Ar-X + CH3-9BBN --------------------------> Ar-CH3 + KX + (9BBN)2C03
THF ( solvent)
7


Like other related reactions which are catalyzed by transition metals,
especially by nickel, palladium, or rhodium, this coupling reaction also should
involve an oxidative addition of organic halides to the palladium(O) complex (step
a ). This step is followed by the metathetical displacement of halide ion from
ArPdXL2 (A) to give an alkoxopalladium(2) or hydroxopalladium(2) complex(B)
(step b). Such a palladium complex then reacts with an alkylborane to provide the
diorganopalladium complex(C) (step c). Finally, reductive elimination of the
intermediate (C) yields the corresponding cross-coupling product and regenerates
the catalyst (step d).
As it has been confirmed that in a number of related coupling reactions the
steps a and d proceed through retention of configuration, the transmetalation
between alkylboranes and alkoxopalladium(2) complexes(B) (step c) in the
present reaction is also considered to take place via retention of configuration.
8


2.2 Property of the Catalyst Pd(PPh3)4
Palladium metal in the form of large particles is usually unreactive
toward organic reagents. The finely divided metal, especially when it is on a
support such as carbon, is more reactive and is commonly used as a catalyst for
hydrogenation and for a few other reactions. More often, soluble zero-valent
complexes are employed. The most common catalysts of this class are tetrakis
(triphenylphosphine) palladium(0)( Pd(PPh3)4) and bis (dibenzylideneacetone)
Palladium(0).[33]
Pd(PPh3)4 was used as the catalyst for the Suzuki reactions. It is
commercially available, or it may be prepared easily from dichlorobis
(triphenylphosphine) palladium, triphenylphosphine, and hydrazine as the
reducing agent[34],
2 Pd(PPh3)2Cl2 + 4 PPh3 + 5 N2H4 > 2 Pd(PPh3)4 + 4
N2H5+C1- + N2
The complex is slowly oxidized by air in the solid state ( stored in the
refrigerator) and rapidly in solution. It can be handled quickly in air but is best
used under nitrogen or argon[33]. The compound is quite reactive with
halogens, acids, and organic halides and undergoes oxidative addition reactions
with these materials: for example
Step a of the reactions.
Pd(PPh3)4 + ArBr -------------> ArPdBr(PPh3)2 + 2 PPh3
The color change from green (the color of the catalyst) to light brown
could be observed soon after the addition of catalyst. The high reactivity of the
complex is due to its ease of dissociation in solution to tris- and bis
9


(triphenylphosphine ) palladium(O). These 16- and 14-electron compounds,
respectively, are electron deficient (coordinatively unsaturated) and therefore
very reactive.
- PPh3 - PPh3
Pd(PPh3)4^ Pd(PPh3)3 , Pd(PPh3)2
The atomic number of palladium is 46. It has the outer electronic
configuration 4s2, 4p6,4d10.
Pd (46) Is2, 2s2, 2p6, 3s2, 3p6, 4s2, 3d10, 4p6, 5s, 4d10.
The ligand PPh3 has a tetrahedral geometry. The phosphine atom is sp3
hybridized.
P
( PPh3 )
The electron lone pair of phosphine can coordinate to the empty orbitals of
palladium. The sum of d electrons of palladium and coordinate-bond electrons
of PPh3 is 18[35]. It cannot exceed 18 ( not without involving higher-energy
anti-bonding levels, which usually results in unpaired electrons ). The
palladium atom is sp3 hybridized too. The tetrahedral geometry is found for
coordinatively saturated (18-electron ), diamagnetic, d10 complexes of
palladium.
10


z
L = PPh3.
From the proposed mechanism of the reactions, three intermediates
ArPdXL2, (ArPdL2)2C03, and ArPd(CH3)L2 in step a, step b, and step c are
all catalyst-oxidized state. The sum of d electrons of palladium and coordinate-
bond and bond electrons is 16 and the palladium atom is a dsp2 hybridization.
Planar geometry is encountered among the coordinatively unsaturated,
diamagnetic, d8 complexes of palladium(2).[36]
z
The final step d of the reaction is a reduction and return of the catalyst to
Pd(PPh3)4 (18-electrons ).
11


3. Discussion and results
3.1 Kinetic study
The first step in a kinetics study is to acquire experimental information
on the reaction speed or rate under a variety of conditions. The following
conditions affect the reaction rate: [37]
a) Temperature:
Collision theory tells us that reaction rate constants (and therefore
reaction rates) depend on the energy and number of collisions between reacting
molecules, on whether the collisions have the correct geometry, and on the
temperature. These requirements are summarized by the Arrhenius equation.
_ JiL
k = A e RT
The factor e_E*/RT is always less than 1, the higher the temperature, the
faster the reaction.
b) Catalysts:
From the Arrhenius equation, a fraction of molecules is the minimum
energy required for reaction. A catalyst accelerates a reaction by altering the
mechanism so that the activation energy E* is lowered. With a smaller barrier
to overcome, there are more reacting molecules with sufficient energy to
surmount the barrier, and the reaction occurs more readily.
12


c) Surface area of reactants:
When reactants are placed in solution, all molecules are fully exposed
to interactions with each other and the reaction proceeds more quickly.
The above conditions will affect the reaction rate constant k. In our
experimental procedures, we could keep them unchanged at every time. It is
very important for the determining of reactant concentration changes during
reactions and for the kinetic study.
d) Concentrations of reactants:
We know the rate expression of the following reaction.
a A + b B ----------> x X
Reaction rate = k [A]m[B]n
If that reaction is a total of the second order, then the rate can be.
d[A]
dt
d[B ] dx
dt dt
k[A][B]
a is the initial concentration of reactant. A.
k(a-x)(b-x)
13


b is the initial concentration of reactant B.
x is the concentration of product X. So,
dx
~r-----ZZ-----^ = kdt
(a x)(b x)
Integrating this equation, then
rx r-t
dx
Q (a x)(b x)

k dt
0
(a-b)
In
Let
1
y =
In
b ( a x )
a (b x )
b ( a x )
a (b x )
= kt
= kt
(a-b)
If we plot for the equation y = kt + 0, it is a straight line, the slope = k
and intercept = 0. At the different reaction time t, we can determine the
concentration x of the product X. All the t and x data should be identical to the
above equation.
We assumed that the Suzuki reaction was a second-order reaction and
both reactants are first-order. To determine the validity of this, we ran several
reactions at different initial reactant concentrations, recorded the data and
calculated them.
14


No. Reactant A a (mmole" Reactant B b (mmole) y = kt + 0(xl0's) R2
1 Br 13.55 Me-9BBN 5.95 y = 42.7t 290 0.994
2 19.29 Me-9BBN 6.60 y = 33.31-651 0.997
3 Br 6.39 Me-9BBN 11.46 y = 33.81 + 1378 0.987
4 Bf^^-OCH3 5.55 Me-9BBN 6.04 y = 34.2t 147 0.999
5 Br@-OCH3 10.88 Me-9BBN 6.88 y = 28.91 393 0.996
6 Bf^-OCH3 5.38 Me-9BBN 11.20 y = 16.6t + 1566 0.998
7 Br@-OCH3 10.72 Me-9BBN 6.16 y = 25.41 + 105 1.000
8 Br^-CH3 5.85 Me-9BBN 10.10 y = 39.31 78 0.997
9 Br^-CH3 11.74 Me-9BBN 7.06 y = 39.41 142 0.996
From these, we obtained several results.
The first result: Overall, the Suzuki reaction is a second-order
reactionn. Both reactants are first-order because the eight reactions fit to the
second-order reaction rate equation very well and all R2 of the calculation are
very close to 1.000.
The second result: We can obtain the rough reaction rate constant k
from the equation y = kt + 0. But it has been impossible for us through this
method to obtain the correct rate constant k of the Suzuki reaction and then to do
the hammett study because the S.D.( standard deriviation ) of k is so big and
same kind reactions didn't have exact same rate constant values sometime.
15


No. Reaction k + S.D. (x 10'3 Mimin'1)
1 Br-@ + Me-9BBN 7.32 + 1.06 ( n = 3 )
2 Br^-OCH3 + Me-9BBN 5.26 + 1.10 ( n = 4)
3 Bi-^-CH3 + Me-9BBN 7.88 0.02 ( n = 2 )
Besides the reaction conditions that we talked above will affect the
determining of reaction rate constant values, ( Arrhenius equation ) also we
find that the determining is affected by other conditions and factors as the
following:
1) Exact amounts of the reactants, solid base, catalyst, and solvent.
2) Heating speed to reflux the reaction solutions and temperature of
refluxing.
3) Stirring speed (caused by different size stirring bars and flask sizes
and shapes).
It is difficult to measure the reaction rate constants (k) exactly every time
as the reaction conditions are required same rather than strict. Otherwise, the
rate constant (k) of this kind reactions are not big but some are very close to one
another( that can be told from the relative rate constant ratios of the competition
study). Those bring in difficulties to determine them correctly. We couldn't use
those rate constants to compare the reaction rates and so, we had to adopt and
the competition reaction to obtain the reaction rate constant ratios and then to do
the Hammett study.
16


3.2 Hammett Study
3.2.1 Competition reaction study
Some attempts have been made to compare the reactivities of different
substituted arylbromides reacting with methyl-9BBN with the catalyst
Pd(pph3)4 and the base K2CO3 in the solvent THF.
We already know that those kind reactions are second-order and both
reactants, substituted arylbromide and methyl-9BBN, are first-order from the
result of the kinetic study. So, we have the following equation
A +
B
A
B
C
+ D
-x^Br
-- CH3-9BBN
-5fi9-CH3
d [ A ] d [ B ] d [ C ]
--------- = --------- = -------- = k[A][B]
d t d t d t
If two substituted arylbromides compete in the same flask for methyl-
9BBN, we will have equations as the following:
Ai + B > Ci + Di
A2 + B > c2 + d2
d[Ct] - = k, [ A] ] [ B ]
d t
17


d[C2]
--------- = k2[A2][B] (2)
dt
When the equation (1) is divided by equation ( 2), then
d [Cl ]
v d t ki [ Ai ]
d[C2]
dt
Simplifying the above equation, then
d [Ci ] _ k,[Ai]
d[C2] k2[A2]
If large amounts of the two substituted arylbromides are set to a reaction
compared to the amount of methyl-9BBN, it means that [ Ai ]Q and [ A2 ]0
[B]0
When the methyl-9BBN is reacted gone, the amounts of the two
substituted arylbromides look no changes and close to constants. [ Ai ] = [ Ai
]oand [ A2 ] = [ A2 ]o- If equal moles of the two substituted
arylbromides are put into a reaction, it means that [ Ai ]o= [ A2 ]o and so [ Ai ]
= [A2].
d [ Ci ] ki
d [ C2 ] k2 T'AS'U
Integrating the above equation, then
Ci
d[CI]
kl
C2
o
d[C2]
k2
ki
k2
18


so,
Cl C2
ki k2
Ci ki
C2 k2
It means that the amount of product C is proportional to the reaction
rate constant ( k ). The bigger the reaction rate constant ( k ), the higher the
amount of the product C.
Through determining the two product yields Ci and C2 of the cross-
coupling reactions and comparing them, we can obtain the ratios of the two
reaction rate constants (ki) and ( k2).
kn kH kp-F kp-ci kp-CH3 kp-cF3
n, kp-CH3 km-CH3 kH kp-F kp-OCH3 kp-ci
Average 1.486 1.005 1.057 3.340 1.656 3.559
S. D. 0.011 0.001 0.005 0.012 0.035 0.093
At the beginning of the experiment, we didn't know the order of relative
rate constants of arylbromide reactivity for the Suzuki reaction. We had to set
up the competion reactions to compare among them and finally the order of
relative rate constants was obtained. Then we repeated the reactions to compare
the reactivity of every two close arylbromides and to obtain the exact relative
rate constant ratios. This way will cause the smallest errors for the relative rate
19


constant ratios. From the above table, we found out that all the S. D. were very
small.
From the reaction rate constant ratios on the above table, the relative
reactivity of this series of compounds can be set and the kx/kH values can be
calculated.
20


3.2.2 Hammett Equation
Hammett first designated the ionization, in water at 25 C, of meta- and
para- substituted benzoic acids as his standard reference reaction.
So,
log k-x = p log K_x + C ( 1 )
Where p is the slope of this straight line, C is the intercept. When
-X = -H, it is also possible to write an exactly analogous equation.
logk-H = p logK_h + C (2)
Subtracting (2) from ( 1), we obtain,
k-x K-X
log--------- = p log-------------- ( 3 )
k-H K_h
The p value was set at 1.00 for the benzoic acid.
Knowing equilibrium constant K-H and K-X for a variety of differently
X-substituted benzoic acids, it is then possible to define a quantity, S_x, as
k-x
G-X = log------------ ( 4 )
k-H
21


So,
k-x K_x
log---------- = p log------------= p CJ_X (5 )
k-H K_h
Where O.x is a substituent constant, whose value will remain constant
for a specific substituent in a specific position (meta- or para-), irrespective of
the nature of the particular reaction in which a benzene derivative, carrying this
substituent, is involved.
It is possible to calculate a_x as required, and a selection of values
obtained in this way in shown below:
Substituent, X Om-X Op-X
CH3 -0.07 -0.17
H 0.00 0.00
OCH3 + 0.12 -0.27
F + 0.34 + 0.06
Cl + 0.37 + 0.23
CF3 + 0.46 + 0.54
The table of the selected Ox values and kx / kn that we measured is
shown below:
22


X P-CF3 p-Cl p-F p-H m-CH3 p-CH3 P-OCH3
Ox + 0.54 + 0.23 + 0.06 0.00 -0.07 -0.17 -0.27
kx 12.566 3.531 1.057 1.000 0.995 0.673 0.406
kH
1.099 0.548 0.024 0.000 - 0.002 -0.172 -0.391
The plot of log (k_x / k_H) to ax is below,
y = 7.4362e-2 + 1.8296X RA2 = 0.972
23


Discussion:
1. From the above diagram, we observed that the experimental points fit to
a straight line but not perfectly. When taking a look back at the determination of
the relative rate constant ratio values we measured, all the S. D. of the ratio
values are very small and the repeatability is very good. The experimental data
are reasonable.
2. The slope, p, = 1.83, is steep. It means this: strong electron-
withdrawing groups on the benzene ring affect and speed up the Suzuki reaction
a lot and electron-donating groups on the benzene ring slow down the reaction
rate very much. The value, kp-CF3 / kp-ocH3 = 30.95. When we look at the
proposal mechanism, we guess that several steps are affected by the functional
groups on the benzene ring. We are sure that the limited-step of the Suzuki
reaction is affected by those functional groups on the benzene ring strongly to
make the value, kp-CF3 / kp-0CH3 very big.
24


3.3 Conclusion
(A) The Suzuki reaction is a second-order reaction and both reactants are first-
order.
(B ) The rough rate constant kH of the Suzuki reaction is about 7.32
+ 1.06 x 10"^ M"lmin'l. Normally the reaction will finish in about fifteen
hours and isn't a fast reaction though with the catalyst Pd(PPh3)4.
(C) From the competition reaction study, we can tell that the electron-
donating and electron-withdrawing groups on the benzene ring affect the
reaction rate constant differently. The electron-donating groups slow down the
Suzuki reaction and the strong electron-withdrawing groups accelerate the
reaction a lot.
(D) The Hammett plot line for the Suzuki reaction fits to
y = 1.83 x + 0.07436 R2 = 0.972 .
not perfectly. The slope, p, = 1.83, is steep. It means this: the limiting-step of
the Suzuki reaction is affected by the functional groups on the Benzene ring
very strongly.
25


4. Experiment
4.1 Purification and Preparation of the Starting Materials[39]
A. Bromobezene ( b.p. 155.9C )
50ml bromobenzene is washed vigorous by with concentrated H2SO4,
the 10% NaOH solution and water. Then is dried with CaCl2, refluxing with
and distilling from sodium, using a glass helix-packed column. The pure
percentage is 99.61%. The rentention time of bromobezene on GC is about 7.2
minutes.
B. B-Methyl-9BBN
The procedure of reactions is
BOCH3
LiCH3
Pentane
------
-78 25 C
BCH3
+ LiOCH3
Because B-Methoxy-9-BBN can be pruchased from Aldrich company,
all we need to do is this step.
An oven-dried 300ml flask fitted with a septum inlet and a magnetic
stirring bar is flushed with nilrogen and maintained under a positive pressure of
the gas throughout the preparations.
22.8g of B-methoxy-9-BBN ( 0.15mole) and 100ml of dry, olefin-free
pentane is put in. Stirring is begun, and the flask is cooled in a dry, ice-acetone
26


bath. Standardized methyl lithium ether (75ml of 2.00M, 0.15 mole) is added
slowly through a long double-ended needle to the flask. After stirring about 10
minutes at -780C, allow the reaction mixture to warm to room temperature and
stir for 3 hours or more. The solid lithium methoxide is allowed to settle, and
the supernatant liquid is decanted via a double-ended needle, into a dried flasks.
The solid is washed with 2 x 75ml of pentane and allowed to settle, and the
supernatant liquid is decanted into the flask. Then, the flask is put on an
evacuated distillation apparatus where the solvent is flashed off. The residual
oil is vacuum distilled (kugelrohe apparatus) to give 13.5g ( about 66% yield )
of B-methyl-9-BBN ( b.p. 64 65C at 15 mm Hg ). The product is about
90% pure and the retention time on GC is about 8.7 minutes.
C. Pentane, (b.p. 36.10C)
1000ml pentane is stirred with successive portions of concentrated
H2SO4 until there was no further coloration during 12 hours, then washed with
water and aquous NaHC03. Dried with MgS04, then P2O5 and fractionally
distilled through a column packed with glass helices. The pure percentage and
retention time on GC are 99.88% and 2.4 minutes.
D. THF ( Tetrahydrofuran, b.p. 65.4C )
A lot THF is dried with Na2SC>4 for several hours. Then dried and
fractionally distilled from sodium when the solution colour is green or blue with
the benzophenone. The retention time of THF on GC is about 3.3 minutes.
E. TOLUENE ( B.P. 110.36C )
100ml toluene is shaked or stirred twice with cold concentracted
27


H2SO4, once with water, once with agueous 5% NaHCC>3, again with water,
then drying successively with CaS04 and P2O5, with final distillation from
P2O5.
The pure pencentage and retention time of toluene on GC are 99.98%
abd 4.800 minutes.
F. Mesitylene (b.p. 99.0 99.8C/100mm, 166.5-167/760 mm)
50ml mesitylene is dried with CaC12 and distilled from sodium in a
glass helices-packed column. Treated with silica gel and redistilled.The pure
percentage and retention time of mestylene on GC are 98.5% and 7.8 minutes.
All other chemicals that were used to be starting materials were purified
before using them and the purities were veryb high.
28


4.2 The Percentage Yield of the Reactions ( Transition metal catalyzed cross-
coupling reactions)
Reaction A:
Bromobenzene ( BrC6Hs ) reacts with methyl-9BBN under the catalyst
Pd(pph3)4 and the base K2CO3 in the solvent THF.
BCH3
K2CO3 + Pd(pph3)4
THF
MW: 157.02 136.05 138.21 1155.58 92.13
Equiv.: 1.0 1.0 2.5 0.05 1.0
l.OOOOg 0.8665g 2.2005g 0.3680g 0.5867g
Mmoles: 6.369 6.369 15.921 0.3185 6.369
A dried 50ml flask is added 1.000g ( 6.37 Mmoles ) bromobenzene and 5
mole % of Pd(pph3)4 and K2CO3 ( 2.5 equiv.) and flushed by N2 gas. Then 20 ml
THF and a little bit more than o.8665g ( about 6.37 Mmoles ) methyl-9BBN are
added by using a 2 ml syringe. The reaction solution is refluxed more than 15
hours. Then the solution is checked on GC to see whether or not the peak of
reactant bromobenzene ( the limiting reagent) disappears. If so, the reaction is
stopped and added internal standard mesitylene.
The theoretical yield of the product toluene is 0.5867g. The response factor
of toluene to mesitylene on GC is
Rf = 0.9752 (g/g)
29


The GC yield average of toluene is approximately 91.38 %.
Reaction B ~ reaction G have same experimental procedures as reaction A
and mesitylene is used as the internal standard for all reactions to determine the GC
yields. Mesitylene has a different retention time on GC to other reactants and
products. The program used on GC is 40 C to 280 C and 12 C per minute.
Reaction B:
4-Bromotoluene (BrC6H4CH3 ) reacts with methyl-9BBN under the
catalyst Pd(pph3)4 and the base K2CO3 in the solvent THF.
BCH3
!v
+ K2CO3 + Pd(pph3)4
THF
CH3
?*(^2C03
CH3
MW: 171.04 136.05 138.21 1155.58 106.17
Equiv.: 1.0 1.0 2.5 0.05 1.0
Amount: l.OOOOg 0.7954g 2.0160g 0.3350g 0.6207g
Mmoles: 5.847 5.847 14.616 0.2923 5.847
The average percentage yield of the product para-xylene is 97.45 %.
Reaction C:
3-Bromotoluene ( BrC6H4CH3 ) reacts with methyl-9BBN under the
catalyst Pd(pph3)4 and the base K2CO3 in the solvent THF.
30


BCH3
!v
+ K2CO3 + Pd(pph3)4
THF
CH3
2CO3
MW: 171.04 136.05 138.21 1155.58 106.17
Equiv.: 1.0 1.0 2.5 0.05 1.0
Amount: l.OOOOg 0.7954g 2.0160g 0.3350g 0.6207g
Mmoles: 5.847 5.847 14.616 0.2923 5.847
The average percentage yield of this reaction is 98.19 %.
Reaction D:
4-Bromoanisole ( BrC6H40CH3 ) reacts with methyl-9BBN under the
catalyst Pd(pph3)4 and the base K2CO3 in the solvent THF.
BCH3
!v
^ + K2CO3 + Pd(pph3)4
6 W-
OCH3
MW: 187.04 136.05 138.21 1155.58 122.17
Equiv.: 1.0 1.0 2.5 0.05 1.0
Amount: l.OOOOg 0.7274g 1.8470g 0.3090g 0.6532g
Mmoles: 5.346 5.346 13.365 0.2673 5.346
The average percentage yield of reaction D is 91.40 %.
Reaction E:
l-Bromo-4-fluorobenzene (BrC6H4F) reacts with methyl-9BBN under the
catalyst Pd(pph3)4 and the base K2CO3 in the solvent THF.
31


BCH3
!v
CH3
+ K2CO3 + Pd(pph3)4
THF
2CO3
MW: 175.01 136.05 138.21 1155.58 110.13
Equiv.: 1.0 1.0 2.5 0.05 1.0
Amount: l.OOOOg 0.7774g 1.9743g 0.3302g 0.6293g
Mmoles: 5.714 5.714 14.285 0.2857 5.714
Reaction E has a 91.82 % GC yield.
Reaction F:
4-Bromochlorobenzene ( BrC6H4Cl) reacts with methyl-9BBN under the
catalyst Pd(pph3)4 and the base K2CO3 in the solvent THF.
Jr ____ CH3
BCH3
!v
+ K2CO3 + Pd(pph3)4
THF
$+ (f^J2C03
Cl
MW: 191.46 136.05 138.21 1155.58 126.58
Equiv.: 1.0 1.0 2.5 0.05 1.0
Amount: l.OOOOg 0.7106g 1.8047g 0.3018g 0.661 lg
Mmoles: 5.223 5.223 13.058 0.2612 5.223
This reaction F can obtain 99.48 % GC yield.
Reaction G:
4-Bromo-N,N-dimethylaniline ( BrC6H4N(CH3)2 ) reacts with methyl-
9BBN under the catalyst Pd(pph3)4 and the base K2CO3 in the solvent THF.
32


F BCH3 9 +C^V + N(CH3)2 K2CO3 + Pd(pph3)4 - F^ A3. (I ^C3
y \p -i N(CH3)2
MW: 200.09 136.05 138.21 1155.58 135.21
Equiv.: 1.0 1.0 2.5 0.05 1.0
Amount: l.OOOOg 0.6799g 1.7269g 0.2889g 0.6757g
Mmoles: 4.998 4.998 12.495 0.2499 4.998
This reaction is very special. Two major products are obtained. The
percentage yield of the product 4-methyl-N,N-dimethylaniline (CH3C6H4N(CH3)2
) is 50.05 % and another product toluene ( CH3C6H5 ) is 38.04 % GC yield. The
Question that why the functional group left cannot be answered right now.
All percentage yields except reaction G are over 90 %.
33


4.3 Determining of the Rate and Order of the Suzuki Reaction
Reaction 1:
To determine the reaction rate order, we add 13.55 Mmole
bromobenzene K2CO3 and Pd(Pph3)4 and internal standard mesitylene to a
50ml flask, and flush them with N2 gas, Then add 5.95 m mole methyl-9BBN.
Heat the reaction solution fast to reflux and intermediately inject the solution
sample on GC and record time. Calculate the product concentration x and then
set up the table. Assumption of our reactions is the second order. Using that
equation
y =
1
-----------In
(a-b)
b ( a x )
a ( b x )
kt
If we plot for the equation y = kt + 0, the slope = k and intercept = 0.
£^) + BCH3 + K2CO3 + Pd(pph3)4 CH3 .
MW: 157.02 136.05 138.21 1155.58 92.13
Amount: 2.1280 0.8088 2.2005 0.3680
Mmoles: 13.55 5.95
So, it will have above equation of the concentrations with time relation,
a = [ bromobenzene ], b = [ methyl-9BBN ]
= 13.55 Mmol/20 ml = 5.95 Mmol / 20 ml
34


t (min) x (mmol / 20 ml) y (xlO'3)
0.00 0.058 0.72
36.00 0.764 10.46
69.00 1.673 26.13
94.00 2.172 36.80
127.00 2.629 48.40
176.00 3.336 71.11
217.00 3.846 92.98
Draw the diagram
Then get the equation: y = 42.682 t 289.69; R2 = 0.994
We repeat this reaction at several different concentration ratios. So, as
to get those following equations.
35


Reaction 2:
MW:
BCH3
0 + p+ K2CO3 + Pd(pph3)4
157.02 136.05 138.21 1155.58
3.0072 0.8876 2.1475 0.3235
19.29 6.60
THF
a = 19.291 Mmole / 20ml, b = 6.60 Mmole / 20ml
y = 651.39 + 33.271 x RA2 = 0.997
y = 33.27 t 651.39; R2 = 0.997
Reaction 3:
BCH3
+ + K2CO3 + Pd(pph3)4
THF
CH3
6
(?<>
MW: 157.02 136.05 138.21 1155.58 92.13
Amount: 1.0030 1.5586 2.4100 0.3170
Mmoles: 6.390 11.460
36


a = 6.390 Mmole / 20ml, b= 11.460 Mmole /20ml
y = 33.781 t+ 1378.2; R2 = 0.987
Also, we do other reactions and test the reaction rate equation.
Reaction 4:
MW:
Amount:
Mmoles:
BCH3
OCH3
187.04 136.05
1.0310 0.8212
5.551 6.036
a = 5.551
K2CO3 + Pd(pph3)4
138.21 1155.58
2.1115 0.3365
THF
CH3
2CO3
mmole/20ml, b = 6.036 mmole/ml
37


y = 34.179 t 147.11; R2= 0.999
Reaction 5:
^ BCH3 THF JL f B-\-
J + + K2C03 + Pd(pph3)4-------- Q U* hCOJ
0CH3
MW: 187.04 136.05 138.21 1155.58
Amount: 2.0345 0.9364 2.0395 0.3232
Mmole: 10.877 6.882
a = 10.877 mmole/ml, b = 6.882 mmole/ml
OCH3
122.17
38


y = 28.859 t 393.28; R2= 0.996
Reaction 6:
BCH3
!v
^ + K2CO3 + Pd(pph3)4
OCH3
MW: 187.04 136.05 138.21 1155.58
Amount: 1.0071 1.5244 2.5264 0.3400
Mmole: 5.384 11.204
a = 5.384 mmole/ml, b = 11.2

OCH3
122.17
39


y = 16.581 1+ 1566.0 R2= 0.998
Reaction 7:
CH3
+
BCH3 THF
+ K2CO3 + Pd(pph3)4 ----
0CH3 OCH3
+ (p^2C03
MW: 187.04 136.05 138.21 1155.58 122.17
Amount: 2.0050 0.8383 2.1325 0.3344
Mmoles: 10.720 6.161
a = 10.720 mmole/ml, b = 6.161 mmole/ml
40


y = 25.383 t + 105.35 R2 = 1.000
Reaction 8:
^ + BCH3 ^ + K2CO3 + THF Pd(pph3)4
CH3 CH3
MW: 171.04 136.05 138.21 1155.58 106.17
Amount: 1.0010 1.3920 2.0505 0.3705
Mmoles: 5.852 10.104
a = 5.852 mmole/ml, b = 10.104 mmole/ml
41


y = 78.480 + 39.276X RA2 = 0.997
y = 39.276 t 78.48 ; R2 = 0.997
Reaction 9:
111 + BCH3 + K2CO3 + Pd(pph3)4 CH3 E- irS (
CH3 y \ CH3
MW: 171.04 136.05 138.21 1155.58 106.17
Amount: 2.0084 0.9603 2.3940 0.3175
Mmoles: 11.742 7.058
a = 11.742 mmole/ml, b = 7.058 mmole/ml
2C03
42


y = 142.18 + 39.433X RA2 = 0.996
y= 39.433 t- 142.18; R2 = 0.996
All those experiments prove that this kind reactions are second-order.
43


4.4 Competition Reactions
(A) Determination of the ratio of k_H / kp-CH3
tr Br BCH3 lAy CH3 CH3
+ O + CH3 K2CO3 + Pd(pph3)4 THF (10ml) - (j£) + (£) CH3
MW: 157.02 171.04 136.05 92.13 106.17
Equiv.: 10 10 1
Amount: 2.295lg 2.5000g 0.2487g
Mmoles: 14.617 14.617 1.4617
Into a dry 25ml 3-necked flask with a magnetic stirring bar and reflux
condenser with a nitrogen inlet system is charged 2.295lg ( 14.617 Mmoles )
of bromobenzene, 2.5005g ( 14.615 Mmoles ) of 4-bromotoluene, 1.008g ( 3
equiv. to methyl-9BBN ) K2CO3, and 0.1675g ( 3 mole % ) Pd (Ppti3)4, and
flushed for about 5 minutes. Then 10ml dry THF is added and then 0.2489g (
1.4617 Mmoles, 79.87% pure ) of methyl-9BBN. The reactant concentration
ratio [ A ] / [ B ] is about 10 : 1. The mixture is stirred and heated to reflux at
about 60 C for a day.
After the reactant methyl-9BBN is gone ( Checked on GC ), two
attempts can be used to measure the ratio of the product amounts of the toluene (
the product of bromobenzene ) and the para-xylene ( the product of 4-
bromotoluene).
1) To add internal standard mesiylene to determine the amounts of the
toluene and para-xylene and then calculate the ratio of products.
44


2) To directly determine the ratio of the toluene and para-xylene through
making the standard solution of toluene and para-xylene. The response factor of
toluene to para-xylene on GC is
Rf-H/p-CH3 = 1.044 ( g/g )
Finally, the ratio of the reaction rate constants can be calculated
k-H C.h
---------------=----------------= 1) 1.489 : 1
kp-CH3 Cp-CH3
This reaction is repeated for three more times and several values are
obtained.
k_H 2) 1.490 : 1
kp-CH3 3) 1.471 : 1
4) 1.496 : 1
The average
k-H
---------- = 1.486 : 1
kp-CH3
Other competion reactions have similar procedures to the above reaction.
(B ) Determination of the ratio of k_n / km_cH3
*3r Br
+ ^J*CH3 K2CO3 + Pd(pph3)4
THF (10ml)
MW: 157.02 171.04 136.05 92.13 106.17
2.2950g 2.4999g 0.2490g
Mmoles: 14.616 14.616 1.4616
45


k_H C_h 1) 1.006 : 1
km-CH3 Cm-CH3 2) 1.005 : 1
The response factor of toluene to meta-xylene is
Rf-H/m-CH3 = 1-021 (g/g)
The average
k-H
--------- = 1.006 : 1
km-CH3
(C) Determination of the ratio kp-p / k-H
Br
6
BCH3
+ A
K2CO3 + Pd(pph3)4
THF ( 10ml)
MW: 157.02 175.01 136.05
2.3705g 2.642lg 0.2572g (79.87% pure )
Mmole: 15.097 15.097 1.5097
The response factor of 4-fluorotoluene to toluene is
Rf p-F / -H = 0.840 ( g/g )
kp-F Cp-F 1) 1.051 1
k-H C-H 2) 1.055 1
3) 1.059 1
4) 1.063 1
92.13
kp-F
------- = 1.057 : 1
k-H
110.13
46


(D) Determination of the ratio of kp_ci / kp_F
MW: 175.01
2.5580g
191.46
2.7984
K2CO3 + Pd(pph3)4
THF (10ml)
136.05
0.2490g (79.87% pure )
110.13 126.58
Mmoles: 14.616 14.616 1.4616
The result of this kind reactions:
The response factor of 4-chlorotoluene to 4-fluorotoluene is
Rfp-Cl / p-F = 0.819 (g/g)
kp-CI Cp-ci 1) 3.333 : 1
kp-F Cp-F 2) 3.324 : 1
3) 3.351 : 1
4) 3.352 : 1
F 0 j ~ = 3.340 : 1
% &
(E) Determination of the ratio of kp_cH3 / kp-ocH3
K2CO3 + Pd(pph3)4
THF ( 10ml)
MW:171.04 187.04 136.05
2.5000g 2.7339g 0.2490g ( 79.87% pure )
Mmoles: 14.616 14.616 1.4616
106.17 122.17
47


The result of this kind reactions:
The response factor of 4-bromotoluene to 4-bromoanisole is
Rfp-CH3/p-OCH3 = 1 -236 ( g/g )
kp-CH3 Cp-CH3 1) 1.713 : 1
kp-OCH3 Cp-ocH3 2) 1.653 : 1
3) 1.662 : 1
4) 1.628 : 1
5) 1.627 : 1
kp-CH3
--------- = 1.656
kp-OCH3
(F) Determination of the ratio of kp_cF3 / kp-ci
K2CO3 + Pd(pph3)4
THF (10ml)
MW: 191.46 225.01 136.05
2.8345g 3.3313g 0.2522g ( 79.87% pure )
Mmoles: 14.805 14.805 1.4805
The result of this kind reactions:
126.58 160.14
Rfp-CF3/p-Cl = 0-934 ( g/g )
kp-CF3 Cp-CF3 1)
kp-ci Cp-Cl 2)
kp-CF3 - 3 559 1
kp-ci
3.493 : 1
3.625 : 1
48


References
[ 1 ] a) A. P. Kozikowki and H. F. Wetter, Synthesis p.561 (1976). b) J.
Weill- Raynal, Sythesis, p.633 (1976). c) P. J. Smith, Chem. Ind.
(London) p. 1025 (1976).
[ 2 ] G. W. Parshall, J. Mol.cata. 4, 243 (1978).
[ 3 ] B: R. James, Homogeneous Hydrogenation." New York, (1973).
[ 4 ] P.J. T. Tait, Chemtech 5, 688 (1975).
[ 5 ] L. Friend, L. Wender, and J. C. Yarze, Adv. Chem. Ser. 70, 168
(1968).
[ 6 ] D. Evans, G. Yagupsky, and G. Wilkinson, J. Chem. Soc. A p 2660
(1968).
[ 7 ] R. Jira, W. Blau, and D. Grimm, Hydrocarbon Process. 55, 97 (1975).
[ 8 ] G. Wilke, Angew. Chem.,Int. Ed. Engl. 2, 105 (1963).
[ 9 ] N. Indictor and W. F. Brill, J. Org. Chem. 30, 2074 (1965).
[ 10 ] E. S. Brown, Aspects Homogeneous Catal. 2, 57 (1974).
[ 11 ] J. P. Collman, Acc. Chem. Res. 1, 136 (19680.
[ 12 ] P. M. Henry, J. Am. Chem. Soc. 86, 3246 (1964).
[ 13 ] R. Cramer, J. Am. Chem. Soc. 89, 1633 (1967).
[ 14 ] M. Tsutsui and A. Courtney, Adv. Organomet. Chem. 16, 241 (1977).
[ 15 ] L. P. Seiwell, Inorg. Chem. 15, 2560 (1976).
[ 16 ] N. G. Connelly and M. D. Kitchen, J. Chem. Soc. Dalton Trans, p.931
(1977).
(
49


[ 17 ] R.J.P. Corriu and J.P. Masse, J. Chem.Soc., Chem. Commun.,
p.144 (1972).
[ 18 ] K. Tamao, J. Am. Chem. Soc. 94, 4374 (1972).
[ 19 ] E. wenkert and E.L. Swindell, C. S. J. Am. Chem. Soc. 101, 2246
(1979) .
[ 20 ] B.M. Trost and Y. Tanigawa, J. Am. Chem. Soc. 101, 4743 (1979).
[ 21 ] H.. Okamura-and H.Takei, Tetrahedron Lett. 21, 87 (1980).
[ 22 ] K. Takai, K. Oshima and H. Nozaki, Tetrahedron Lett. 21,2531 '
(1980) .
[ 23 ] E. Negishi, J. Am. Chem. Soc. 100, 2254 (1978).
[ 24 ] C.E. Russell and L.S. Hegedus, J. Am. Chem. Soc. 105, 943 (1983).
[ 25 ] A.A. Millard and M.W. Rathke, J. Am. Chem. Soc. 99,4833 (1977).
[ 26 ] D. Milstein and J.K. Stille, J. Am. Chem. Soc. 101,4992 (1979).
[ 27 ] N. Miyaura and A. Suzuki, a) Tetrahedron Lett., p.3437 (1979). b) J.
Chem. Soc., Chem. Commun., p.867 (1979). c) Tetrahedron Lett.
22, 127 (1981).
[ 28 ] A. Suzuki, a) Pure & Appl. Chem. 63, 419 (1991). b) J. Am. Chem.
Soc. Ill, 314 (1989). c) J. Am. Chem. Soc. 107, 972 (1985). d)
Letters, April, p.221 (1990). e). Tetrahedron 32, 6923 (1991). f)
Chemtracts, Organic Chem., p.376 (1992). g) Chem. Lett., p.691
(1992).
[ 29 ] A.R. Martin amd Youhua Yang, Acta Chem. Scand. 47, 221 (1993).
[ 30 ] T. Hayashi, J. Am. Chem. Soc. 106, 158 (1984).
50


'V
[ 31 ] a) R. Damrauer and J.A. Hankin, Organometallics 1991, 10, 3962. b)
J.A. Hankin, R.W. Howe, N.H. Damrauer, K.A. Peterson, SJ.
Bruner and R. Damrauer, Main Group Metal Chemistry 1994, 17, 391.
c) W.R. Kwochka, R. Damrauer, M.W. Schmidt, and M.S. Gordon,
Organometallics 1994,13,3728.
[ 32 ] G.W. Parshall, J. Am. Chem. Soc. 96, 2360 (1974).
[ 33 ] S. Baba and E. Negishi, J. Am.Chem.Soc.98,6729(1976).
[ 34 ] R.F. Heck, Palladium Reagents in Organic Syntheses; Academic: New
York (1985).
[ 35 ] L. Maletesta and M. Angoletta, J. Chem. Soc., 1186 (1957).
[ 36 ] C.A. Tolman, Chem. Soc. Rev. 1, 337 (1972).
[ 37 ] J.P. Coliman, Principles and Applications of Organotransition Metal
Chemistry; University Science Books: Mill Valley, CA (1980).
[ 38 ] P. Sykes, A Guidebook to Mechanism in Organci Chemistry; Longman:
London and New York (1981).
[ 39 ] D.D. Perrin & W.L.F. Armarego, Purification of Laboratory
Chemicals; Pergamon Press: New York (1988).
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