Reactivities of mixed organozinc and mixed organocopper reagents. Part 13 Kinetic study for phosphine-catalyzed acylation of alkylarylzincs and effect of residual group on the transfer rate of alkyl group

Article abstract of DOI:10.1002/poc.3517

Kinetics of reactions of di-n-butylzinc, n-Bu₂Zn, and mixed n-butyl(substituted phenyl)zinc reagents and n-Bu(functional group (FG)-C₆H₄)Zn with benzoyl chloride in the presence of tri-n-butylphosphine have been investigated. Reaction rates of transferable n-butyl group have been determined in tetrahydrofuran at 0 °C to compare the transfer rate of n-butyl group in homo and mixed diorganozincs. Rate law is consistent with a third-order reaction, which is first order in diorganozinc, benzoyl chloride, and n-Bu₃P, and a mechanism was proposed. The lower reaction rate of n-BuPhZn than that of n-Bu₂Zn and negative reaction constant in Hammett plot are in accordance with the carbanionic charge of transferable n-butyl group in the acylation reaction. These findings support the hypothesis that the reaction rate of transferable group, R_T, changes depending upon the residual group, R_R, in R_RR_TZn reagents.

Full text of DOI:10.1002/poc.3517

Research article
Received: 24 June 2015,
Revised: 18 September 2015,
Accepted: 30 October 2015,
Published online in Wiley Online Library: 19 January 2016
(wileyonlinelibrary.com) DOI: 10.1002/poc.3517
Reactivities of mixed organozinc and mixed
†
organocopper reagents. Part 13 Kinetic study
for phosphine‐catalyzed acylation of
alkylarylzincs and effect of residual group on
‡
the transfer rate of alkyl group
Özgen Ömür Pekel *
a
Kinetics of reactions of di-n-butylzinc, n-Bu Zn, and mixed n-butyl(substituted phenyl)zinc reagents and n-Bu(functional
2
6 4
group (FG)–C H )Zn with benzoyl chloride in the presence of tri-n-butylphosphine have been investigated. Reaction rates
of transferable n-butyl group have been determined in tetrahydrofuran at 0 °C to compare the transfer rate of n-butyl group
in homo and mixed diorganozincs. Rate law is consistent with a third-order reaction, which is first order in diorganozinc,
benzoyl chloride, and n-Bu
and negative reaction constant in Hammett plot are in accordance with the carbanionic charge of transferable n-butyl group
in the acylation reaction. These findings support the hypothesis that the reaction rate of transferable group, R , changes
depending upon the residual group, R , in R Zn reagents. Copyright © 2016 John Wiley & Sons, Ltd.
3 2
P, and a mechanism was proposed. The lower reaction rate of n-BuPhZn than that of n-Bu Zn
T
R
R T
R
Keywords: acylation of diorganozincs; kinetics of diorganozincs; mixed diorganozincs; phosphine catalyst
[
51–54]
1 2
reactions
and group selectivity in reactions of R R Zn
INTRODUCTION
reagents is in the order of alkenyl ~ phenyl > Me > Et > t-Bu.
[
56–66]
Diorganozinc reagents, R
Na, MgX), which are most reactive than RZnCl, are one of the most
used organometallic reagents due to their functional group
2
Zn, and triorganozincates, R
3
ZnM (M¼Li,
In their systematic work,
Erdik and coworkers observed
1
2
that the group selectivities of mixed diorganocuprates, R R CuM
[
56–58]
[59]
1
2
[58,60–66]
(M¼MgBr),
catalyzed mixed triorganozincates, R (R ) ZnMgBr,
2
ZnI,
diorganozincs, R R Zn,
and Cu-
depend
[
1–3]
1
2
[58,63]
compatibility to many functional groups.
CuM (M¼Li, MgX, ZnX; X¼Br, Cl), are also commonly used in
organic synthesis due to their soft nucleophilicity toward carbon
Diorganocuprates,
R
2
on the reaction parameters, that is, the electrophilic substrate,
the solvent, and the temperature as well as the transition metal
catalyst and organocatalyst, and reported that the group selectivity of
mixed organocopper and organozinc reagents can be controlled by
changing the reaction parameters. They also developed new atom-
[4–6]
electrophiles.
However, in the reactions of R CuM, R Zn, and
2 2
R3ZnM reagents, a synthetic problem arises because only one of
the R groups can be transferred to the electrophile. This limitation
to the atom-economic use of R CuM, R Zn, and R ZnM reagents
[56–58,63,64,66]
[58–61]
economic synthetic procedures for C–C,
C-acyl,
and
2
2
3
[62]
has been solved by using either (i) mixed organocopper
C–N coupling employing mixed arylzinc reagents. However, probing
the origin of group selectivity in the mixed organocopper and
organozinc reagents still seems a problem.
The group selectivity of mixed cuprates, R R CuLi, is considered
to be a function of R E or R E formation in the reductive elimina-
1
2
[7–16]
1
2
[17–31]
and organozinc reagents of R R CuM,
R R Zn,
type, in which the R group has a lower transfer rate
than R group, or (ii) mixed organocopper and organozinc reagents
and
1
2
[32–37]
2
(
R ) R ZnM
2
1
1 2
[7,8,38–46]
[47–55]
[7,38,56–68]
1
2
of R R CuM,
R R Zn,
R
and (R ) R ZnM type,
R
T
T
R 2 T
1
2
in which R is residual (dummy) group and R is transferable group.
tion of Cu(III) intermediates, R R CuE, which is formed in the oxida-
tive addition step (Scheme 1). The long accepted hypothesis in
R
T
In the mixed diorganocuprates, R R CuM, both organyl
R
T
[
38–41]
groups
R2P,
and nonorganyl groups, such as RS, R N, and
2
[
42–45]
have been frequently used as residual groups, R . The
R
1
2
*
Correspondence to: Ö. Ömür Pekel, Science Faculty, Ankara University,
Beşevler, Ankara 06100, Turkey.
group selectivity in the reactions of R R CuLi reagents was found
to be in the order of n-Bu ~ s-Bu > t-Bu; Ph > alkenyl > Me>
alkynyl in their C–C coupling reactions,
E-mail: oomur@science.ankara.edu.tr
[
7,9,10]
however, in the
†
‡
reversed order of Me > alkynyl ≫ alkenyl in their 1,4-addition
The number of the serial work has been used with the permission of Ender
Erdik.
[11]
reactions.
Me CPhCH
place selectively.
Mixed diorganozinc reagents of both R R Zn and R
In the reactions of (FG–C
6 4
H )RCuLi, in which R is
2
2
or Me CCH , transfer of functionalized aryl group takes
3
8]
2
[
This paper is dedicated to my PhD Supervisor Prof. Dr Ender Erdik.
1
2
R
T
R Zn types
a Ö. Ömür Pekel
[
47–50]
have been greatly used in the 1,2-addition
and 1,4-addition
Ankara University, Science Faculty, Beşevler, Ankara 06100, Turkey
J. Phys. Org. Chem. 2016, 29 190–195
Copyright © 2016 John Wiley & Sons, Ltd.

KINETIC STUDY FOR PHOSPHINE‐CATALYZED ACYLATION OF ALKYLARYLZINCS
[
73]
by using standard syringe–septum cap techniques. Quantitative
gas–liquid chromatography analysis was performed on a Thermo
Finnigan (San Jose, CA, USA) gas chromatograph equipped with
a ZB-5 capillary column packed with phenylpolysiloxane using
internal standard technique. Tetrahydrofuran (THF) was
distilled from sodium benzophenone dianion. n-Butyl bromide,
bromobenzene, and 4-methyl-, 3-methyl-, 4-methoxy-, 3-methoxy-,
and 4-bromobenzenes were obtained commercially (Sigma-Aldrich,
St. Louis, MO, USA) and were used without further purification.
Mg turning for Grignard reagents was used without further
Scheme 1. Group selectivity in the reaction of mixed diorganocuprates
with an electrophile
substitution and 1,4-addition of mixed diorganocuprates is that
the group with a stronger Cu–C bond acts as the group of lower
[
7,38,67,68]
selectivity, that is, a better residual group.
Theoretical
purification. ZnCl
reduced pressure at 100 °C for 2 h and used as a THF solution.
Benzoyl chloride (Sigma-Aldrich) and n-Bu P (Sigma-Aldrich) were
obtained commercially and were used without further purifica-
tion. Grignard reagents n-BuMgBr and FG–C
2
(Merck, Kenilworth, NJ, USA) was dried under
studies of Nakamura established that the group selectivity is
controlled by thermodynamic stability and kinetic reactivity in
the reductive elimination of triorganocopper(III) intermediates
3
[
69,70]
formed in these reactions.
Bertz reported that R
6
H
4
MgBr (FG¼H b,
R
groups in R
R
T
R CuLi reagents impart
4-Me c, 3-Me d, 4-MeO e, 3-MeO f, 4-Br g) were prepared in
peculiar properties to π-complexes of the cuprates formed in
THF by standard methods and their concentration were
determined by titration prior to use.
[
71]
[74]
1,4-addition reactions.
Recently, Nakamura introduced the
intrinsic effects of organyl groups on the reactivity and selectivity
of gas phase alkylation reactions between mixed methyl cuprates,
For the preparation of n-butyl(aryl)zinc reagents n-Bu(FG–C
(1ab–1ag) (FG¼H b, 4-Me c, 3-Me d, 4-MeO e, 3-MeO f, 4-Br g),
arylzinc chlorides FG–C ZnCl were reacted with n-BuMgBr.
FG–C H ZnCl were prepared by addition of arylmagnesium bromide
6 4
H )Zn
[
59]
ϴ
[72]
[
RMeCu] (R= Alkyl, benzyl, phenyl), and methyl iodide.
6 4
H
2
Erdik has also hypothesized that the reaction rate of R group
6
4
1
2
in mixed diorganocuprates, R R CuM (M = Li, MgX, ZnX), and
diorganozincs, R R Zn, should depend on R group leading to a
rate different from those of homo diorganocuprates, (R ) CuM,
and homo diorganozincs, (R ) Zn, respectively. A series of kinetic
(10 mmol) to ZnCl (10 mmol) in THF (10 ml) at ꢀ20 °C with stirring
2
1
2
1
at that temperature for 15 min. To freshly prepare FG–C H ZnCl
6
4
2
reagent (10 mmol), n-BuMgBr (10 mmol) in THF was added dropwise
and the mixture was stirred at ꢀ20 °C for another 15 min.
Homo di-n-butylzinc n-Bu Zn (1a ) reagent was prepared by
2
2
2
studies on the reactions of mixed diorganocuprates and
diorganozincs supported this hypothesis. They observed that
the alkylation rate of transferable n-Bu group in n-BuPhCuMgBr
2
2
addition of 2 mol equivalent of n-BuMgBr reagent in THF to a
solution of 1 mol equivalent of ZnCl in THF at ꢀ20 °C, stirring
2
[
57]
is lower than that in n-Bu CuMgBr
and also acylation rate of
at that temperature for 20 min.
2
[
59]
n-Bu group in n-BuPhCuZnI is lower than that in n-Bu CuZnI.
A typical kinetic procedure for reaction of n-BuPhZn (1ab)
2
In addition, alkylation rate of n-Bu group in n-Bu(FG–C H )CuMgBr
with benzoyl chloride 2 catalyzed by n-Bu P in THF at 0 °C under
6
4
3
reagents and acylation rate of n-Bu group in n-Bu(FG–C H )CuZnI
reagents change depending on FG substituents. However,
alkylation rate of Ph group in catalytic n-BuPhCuMgBr, which is
pseudo-first-order conditions in the presence of excess 1ab is
given in the succeeding text: In a flame-dried, two-necked flask
with septum caps and a stirring bar, n-BuPhZn (1ab) (10 mmol)
6
4
derived from n-BuPh ZnMgBr and CuI catalyst, was found higher
was prepared using THF solution of ZnCl (10 mmol), PhMgBr
(10 mmol) in THF, n-BuMgBr (10 mmol) in THF as explained in
2
2
[
63]
than that of catalytic homocuprate Ph
2
CuMgBr.
They also
compared the reaction rate of transferable Ph group in allylation
the previous text. To the stirred mixture, internal standard
of (n-alkyl)PhZn reagents and found that it changes depending
3
nonane (1 mmol) and n-Bu P catalyst (0.1 mmol) and then
[
65]
on n-alkyl group, and all higher than that in Ph
2
Zn.
PhCOCl 2 (1 mmol) were added. While carrying out the pseudo-
first-order kinetic experiments, the volume of the reaction
mixture was kept constant in order to keep the concentration
of benzoyl chloride (2) constant. The mixture was quickly
thermostated by immersing the flask in cooling bath at constant
0 °C temperature on a magnetic stirrer. Aliquots (8–12) were
withdrawn from the mixture by syringe under nitrogen
atmosphere at 15 s–2 min intervals and were hydrolyzed in a
vial containing 1 N HCl solution. The aqueous phase was
extracted with ether, and the ethereal phase was analyzed
by gas chromatography (GC). The rate data were collected by
measuring the concentration of coupling product 4 in each
sample. Self consistent data could be obtained for two-four
half lives. The uncertainty of the rate constants was lower than
12%, which is in the error limit of GC analysis, that is,
generally ± 5–14%.
In connection with my recent studies on the control of group
[
60,61]
selectivity in acylation of n-alkylphenylzinc reagents
kinetics of acylation of iodozinc alkylarylcuprates,
and
I focused
[
64]
my interest on the acylation of n-alkylarylzinc reagents with the
objectives of kinetics and mechanism of phosphine-catalyzed
acylation of diorganozincs and providing another kinetic support
for Erdik’s hypothesis regarding the dependence of R
transfer ability on R group in reactions of R Zn reagents.
According to the best of my knowledge, there is a limited number
T
group
R
R T
R
[
60,61]
of reported work on the kinetics of reactions of uncatalyzed
and Cu(I)- and Ni(II)-catalyzed reactions
[
56,62]
of monoorganozincs
and diorganozincs. A theoretical study for transfer ability in mixed
[
71]
diorganozincs has been also published.
Herein, I report a
)Zn
detailed kinetic investigation of acylation of n-alkyl(FG–C
6 4
H
reagents with benzoyl chloride and discuss the effect of residual
FG–C H group on the transfer rate n-alkyl group in acylation.
6
4
RESULTS AND DISCUSSION
EXPERIMENTAL
Our recent work showed that tri-n-butylphosphine-catalyzed
acylation of n-BuPhZn (1ab) with benzoyl (2) chloride takes place
with selective n-Bu group transfer (Scheme 2).
All reactions were carried out under dry nitrogen atmosphere
using oven-dried glassware. Reagents and solvents were handled
J. Phys. Org. Chem. 2016, 29 190–195
Copyright © 2016 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/poc

Ö. ÖMÜR PEKEL
d½PhCOClꢁ
x
y
z
Rate ¼ ꢀ
¼ k½n-BuPhZnꢁ ½PhCOClꢁ ½n-Bu3Pꢁ
(1)
dt
Through a series rate data collected under pseudo-conditions,
Scheme 2. Phosphine-catalyzed acylation reactions of diorganozinc
n-BuRZn (1) with benzoyl chloride (2)
3
the reaction order in n-BuPhZn (1ab), PhCOCl (2), and n-Bu P (3)
was found.
Determination of the order x in n-BuPhZn (1ab) and y in
PhCOCl (2): at a constant and low catalyst n-Bu P 3 concentra-
3
tion, the concentration of n-BuPhZn (1ab) was used in excess
to find the order y in PhCOCl (2). Rate can be written as
y
Rate ¼ k1½PhCOClꢁ
(2)
whereas pseudo-rate constant k can be expressed using Eqn 3.
1
x
z
k1 ¼ k ½n-BuPhZnꢁ ½n-Bu3Pꢁ
(3)
Scheme 3. Phosphine-catalyzed acylation of n-butylphenylzinc (1ab),
di-n-butylzinc (1a ), and n-butyl(substituted phenyl)zinc (1ac–1ag)
2
reagents with benzoyl chloride (2) in tetrahydrofuran. These reactions
are n-Bu group-selective
As [n-Bu
P] is kept constant, Eqn 3 can be also expressed as
3
x
k1 ¼ k2½n-BuPhZnꢁ
(4)
So, in the kinetic and mechanistic study on the phosphine-
catalyzed acylation of alkyl(FG–C H )Zn reagents with benzoyl
6 4
Pseudo-rate constant k
2
shows dependence on catalyst loading:
chloride aiming a new kinetic support for the dependence of
reaction rate of transferable n-Bu group on the residual group,
I planned to determine
z
k2 ¼ k ½n-Bu3Pꢁ
(5)
The reaction order x in n-BuPhZn (1ab) was determined by
changing the concentration of n-BuPhZn at the constant
concentration of PhCOCl (2) and n-Bu P (3) in a series of reactions.
According to Eqn 4, the slope of the log k → log[n-BuPhZn] plot
gives the value of x. For this purpose, the concentration of
n-BuPhZn (1ab) was changed between 7 and 13 times than that
of PhCOCl (2) while the concentration of n-Bu P (3) is 10 mol% of
PhCOCl. The rate data were evaluated as pseudo-first order
because log c values versus time proved linear up to 50–80%
(i) the rate constant of acylation of n-BuPhZn reagent (1ab),
(
ii) the rate constant of acylation of n-Bu Zn reagent (1a ) to
2
2
3
compare the transfer ability of n-Bu group in mixed and
homo diorganozincs, and also
1
(
iii) the rate constant of acylation of n-Bu(FG–C H )Zn reagent
6 4
(
1ac–1ag) (FG¼4-Me c, 3-Me d, 4-MeO e, 3-MeO f, 4-Br g)
to evaluate the dependence of the transfer ability of n-Bu
group on the residual FG–C group (Scheme 3).
3
6 4
H
t
completion of the reaction. As an example for a pseudo-first-order
For the evaluation of the rate data, I used the method that we al-
plot, see Fig. S1a. Pseudo-first-order rate constants k
1
were
calculated by linear regression analysis (r > 0.98). For rate
constants, k , see Table S1, and for the linearity of k values with
excess concentration of n-BuPhZn (1ab), see Fig. S2. The plot of
ready successfully used in the kinetics work of stoichiometric mixed
2
1
2
[56]
1
2
[59]
1
cuprates,[ R R CuMgBr
and R R CuZnI,
catalytic mixed
59,63]
2
[65]
1
1
cuprates,
and also mixed diorganozincs, R R Zn. In applying
this method for concentration of electrophilic partner at time t, cal-
culated value was used rather than directly measured value and it
was calculated as c = [Electrophile] = [Electrophile] ꢀ ∑[Product] .
2
1
log k →log[n-BuPhZn] gave a slope of 1.08 (r = 0.97) indicating
the first-order reaction in n-BuPhZn. These results confirm the
pseudo-second-order acylation of n-BuPhZn in the presence of
t
0
t
It was found that using this method gave more accurate results in
the evaluation of the rate date of acylation reaction minimizing
the errors due to the hydrolysis of the acylating agent during the
work-up of aliquots.
phosphine catalysis. Pseudo-second-order rate constants k
as k =k /[n-BuPhZn] are also given in Table S1. Taking the average
led to a rate constant of k
2
calculated
2
1
ꢀ
1
ꢀ1
2
= 0.362 ± 0.013 M min within the
uncertainty of max 4%, which is in the error limit of GC analysis.
The phosphine-catalyzed acylation of n-BuPhZn (1ab) under
pseudo-conditions is quite fast and virtually complete within
As acylation of mixed diorganozincs n-Bu(FG–C H )Zn
6
4
(
1ab–1ag) give only 4 as product, c = [Benzoyl chloride] ; that
t
t
is, concentration of benzoyl chloride at time t was calculated as
c = [Benzoyl chloride] -[n-BuCOPh] . The rates of the reactions
8–12 min. So I carried out several trials to obtain reproducible
t
0
t
results. Order in n-BuPhZn (1ab) was also established directly by
determining the overall reaction order at equimolar concentration
(
i)–(iii) were studied by monitoring the formation of the
product, n-BuCOPh (4) in THF at 0 °C. The rate data were
collected by taking at least 8–12 samples at 15 s-2 min intervals
and doing the GC analysis of quenched aliquots to measure the
concentration of 4.
of 1ab and benzoyl chloride (2) in the presence of catalyst n-Bu
3
P
(
3). The plot of 1/c values versus time gave a straight line indicating
t
that the reaction is second order in the presence of catalyst and
therefore the reaction is first order in (1ab) and (2) (Fig. S1b). The rate
ꢀ
1
ꢀ1
constant was found to be k =0.34M min . As seen, rate constants
2
Kinetics of the acylation of n-BuPhZn and n-Bu
2
Zn with
k calculated by applying pseudo-first-order or pseudo-second-order
conditions resulted in the same values within the same error limit.
benzoyl chloride in the presence of n-Bu P catalysis
3
A reasonable empirical rate law for the reaction (i) in Scheme 2
can be expressed in terms of concentrations of three compo-
nents by Eqn 1.
Determination of the order z in catalyst n-Bu P (3): As
shown in Eqn 5, pseudo-second-order rate constant k2
depends on phosphine catalyst (3) concentration; the reaction
3
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Copyright © 2016 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2016, 29 190–195

KINETIC STUDY FOR PHOSPHINE‐CATALYZED ACYLATION OF ALKYLARYLZINCS
order in catalyst was established by determining the rate
of diorganozincs under phosphine catalysis, it also seemed quite
constant k at various catalyst concentrations. For this purpose,
interesting to test the dependence of transfer rate of n-Bu group
2
rate constants k
2
were determined at catalyst loadings of
to electronic effects of FG substituent on residual group in the
1
0–50 mol% under pseudo-first-order conditions, that is, using
phosphine-catalyzed acylation of n-Bu(FG–C
this purpose, Erdik et al. already reported the correlation of n-Bu
group transfer rate to electronic effects of residual FG–C
6 4
H )Zn reagents. For
excess n-BuPhZn (1ab) ([n-BuPhZn]:[PhCOCl] = 7:1). The results
of this set of experiments are given in Table S2 and linear plot of
6 4
H
[57]
k
2
values against concentration of n-Bu
Fig. S3. Subsequent plot of log k →log[n-Bu
order of 1.23 (r = 0.98). Using excess n-BuPhZn (1ab) in
n-BuPhZn]:[PhCOCl] = 8:1 ratio for rate determination in catalyst
3
P (3) catalyst are given in
group in the alkylation of n-Bu(FG–C
6 4
H )CuMgBr reagents
[59]
2
3
P] yielded catalyst
and acylation of n-Bu(FG–C )CuZnI reagents. Hammett plots
6 4
H
2
with positive slopes were in accordance with the proposed
mechanism for these reactions of mixed cuprate. However, the
reactivity of organozinc reagents is known to increase depending
on the negative charge on the Zn center. This is in good agree-
ment with the lower rate constant for n-Bu group transfer in
mixed diorganozinc reagent n-BuPhZn (1ab) than that in homo
[
loading gave a similar catalyst order of 1. As orders close to 1 are
most logically explained by unimolecular dependence, it is
reasonable to conclude that the acylation reaction proceeds through
a catalytic intermediate involving one molecule of n-Bu
The reaction rate constants k were calculated as k = k
using k values found applying pseudo-first-order benzoylation
of n-BuPhZn (1ab) in the presence of n-Bu P (3) and they are
also included in Table S2. Taking the average gave
3
P (3).
2
/[n-Bu
3
P]
2 2
diorganozinc reagent n-Bu Zn (1a ) to the acyl electrophile. The
2
possible explanation is simply that ꢀI effect of Ph group in
n-BuPhZn (1ab) decreases the carbanionic charge leading to a
less ionic n-Bu-Zn bond compared with that in n-Bu-Zn-n-Bu
3
ꢀ
2
ꢀ1
k = 193.2 ± 23.7 M min with the uncertainty of max, 12%,
which is in the error limit of GC analysis.
(1a
mixed diorganozincs
group R . I simply expected that in the acylation of n-Bu group
of n-Bu(FG–C H )Zn (1ab–1ag) reagents, n-Bu group transfer will
2
). As seen, the reaction rate of transferable R
T
group in
R T
R R Zn depends upon the residual
Thus, the rate data for phosphine-catalyzed acylation of n-BuPhZn
R
(1ab) can be described accurately by the rate law in Eqn 6.
6
4
be favored with +I,+M type (alkyl) and ꢀI> +M type (alkoxy)
substituents whereas it will be inhibited ꢀI≫+M type (halogen)
substituents resulting in a Hammett plot with a negative slope.
To test Hammett correlation, the rate constants were deter-
mined for the reaction of benzoyl chloride (2) with a small set
of n-Bu(FG–C H )Zn reagents (1ab–1ag) (FG¼H b, 4-Me c,
d½PhCOClꢁ
Rate ¼ ꢀ
¼ k½n-BuPhZnꢁ½PhCOClꢁ½n-Bu3Pꢁ (6)
dt
I carried out a second set of experiments to find the rate
constant of n-Bu P (3)-catalyzed acylation of n-Bu Zn (1a ) with
benzoyl chloride (3) in THF at 0 °C (Scheme 2(2)) to compare
the reaction rates of mixed n-BuPhZn (1ab) and homo n-Bu Zn
1a ) reagents. For this purpose, the rate constant k′ was mea-
sured in similar pseudo-first-order conditions used for the rate
data of 1ab. First, the pseudo-first-rate constant k ′ in the
presence of excess 1a and 10 mol% n-Bu P was determined.
6 4
3
2
2
3
-Me d, 4-MeO e, 3-MeO f, 4-Br g) under n-Bu P (3) catalysis
3
(
Scheme 2(3)). The second-order reaction rate constants k were
2
2
determined in pseudo-first-order conditions at constant n-Bu3P
(
2
concentration similar to that used for acylation of n-BuC H Zn
6
5
2
(
1ab) (Table 1), and the r value was found close to unity for
1
the slopes of each line in the kinetic experimental data of the
reagents 1ab–1ag.
It is pleasant that the resulting Hammett plot of rate constants
2
3
An example for a pseudo-first-order plot is given in Fig. S1c. k
values are listed in Table S3, and linearity of rate constants k
1
′
1
′
k of n-Bu(FG–C
ρ = ꢀ0.29, with a good correlation (r = 0.910) (Fig. 1).
result confirms Erdik’s hypothesis on the dependence of transfer
rate of R group to the electronic effect of residual R groups in
CuM and R Zn reagents. This small value of reaction
constant indicates a negligible effect of donation of electron
density on R = FG–C group to R = n-Bu group via C–Zn–C
bonds to react with C¼O electrophile.
6 4
H )Zn reagents (1ab–1ag) gave a negative slope,
against excess concentration of n-Bu
Fig. S4. The plot of log k ′ → log [n-Bu Zn] gave a slope of 1.01
r = 0.98) indicating the first-order reaction in 1a2. Following
confirmation the pseudo-second-order acylation of 1a in
the presence of n-Bu P (3) rate constants, k ′ were calculated
as k ′ = k ′/[n-Bu Zn] (Table S3) and taking the average gave
′ = 2.46 ± 0.05 M min
0 mol% n-Bu P. As n-Bu
2 2
Zn (1a ) is shown in
2
[75]
This
1
2
2
(
T
R
2
R
R
R T
R T
R
3
2
2
1
2
ꢀ
1
ꢀ1
H
4
T
k
1
(
2
with the uncertainty of 2% at
P-catalyzed benzoylation of n-BuPhZn
R
6
3
3
1ab) was found to be first order in n-Bu P, the determination of
3
the pseudo-second-order rate constants in the presence of varying
Reaction pathway for the phosphine-catalyzed acylation of
diorganozincs
concentrations of n-Bu P was not repeated. The reaction rate
3
constant was calculated as k′ = k ′/[n-Bu P] and found to be
2
3
ꢀ
2
ꢀ1
For the phosphine-catalyzed acylation of diorganozincs, a cata-
9
34.8 M min with the uncertainty of 2%.
[
61]
lytic cycle has been already given
depending on the forma-
The total rate law for the phosphine-catalyzed acylation of
⊕
ϴ
[76–78]
tion of acyl n-butylphosphonium ions, RCOP (n-Bu)
3
Cl A.
n-Bu Zn (1a ) can be written as
2
2
According to the kinetic data obtained in this study, a pathway
for the catalytic acylation is given in Eqn 8. Three molecular
d½PhCOClꢁ
′
[79,80]
Rate ¼ ꢀ
¼ k ½n-Bu2Znꢁ½PhCOClꢁ½n-Bu3Pꢁ
(7)
collisions are rather rare in organic reactions,
and in this
dt
case, the reaction does not take place in one step. The formation
1
of the acylation product R COR 4 in the reaction of diorganozinc
(
1), acyl halide (2), and phosphine (3) could involve first forma-
Effect of residual group FG–C
group in the acylation of n-Bu(FG–C
chloride in the presence of n-Bu P catalysis
6
H
4
on the transfer rate of n-Bu
tion of catalytic acylphosphonium complex A from 2 and 3 and
then reaction of A with 1. The mechanism consists of an
equilibrium as a first step and the rate-determining step is either
first step or second step depending on the observed third-order
reaction kinetics.
6 4
H
)Zn with benzoyl
3
Before providing an explanation for the rate laws expressed by
Eqns 6 and 7 and proposing a reaction pathway for the acylation
J. Phys. Org. Chem. 2016, 29 190–195
Copyright © 2016 John Wiley & Sons, Ltd.
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Ö. ÖMÜR PEKEL
Â
ÃÂ
Ã
Table 1. Rate constants k of acylation of n-butyl(substituted
1
Rate ¼ k2 PhCOPðn-BuÞ Cl R 2Zn
3
phenyl)zinc reagents (1ab–ag) with benzoyl chloride (2) in
a
Â
Ã
1
(11)
3
the presence of n-Bu P (3) in tetrahydrofuran at 0 °C
k1k2½PhCOClꢁ½n-Bu3Pꢁ R 2Zn
¼
Â
Ã
1
kꢀ1 þ k2 R 2Zn
If the first step is considered as a rapid pre-equilibrium and the
1
2
second step is a rate-determining step, that is, kꢀ1 ≫ k
following expression is obtained:
2
[R
Zn], the
ꢀ
1
ꢀ1
FG
k2, M min
b
k1k2
kꢀ1
Â
Ã
H, b
0.336
0.364
0.344
0.381
0.317
0.264
1
Rate ¼
½PhCOClꢁ½n-Bu3Pꢁ R 2Zn
(12)
4
3
4
3
4
-Me, c
-Me, d
-MeO, e
-MeO, f
-Br, g
As seen, the simplified rate law corresponds to the rate equa-
tion for the catalyzed acylation, which is first order in
diorganozinc (1), acyl halide (2), and phosphine catalyst (3) as
observed.
a
[
n-Bu(FG–C
n-Bu P] = 0.0026 M.
From Table S1.
6 4
H )Zn] = 0.236 M, [PhCOCl] = 0.026 M,
For acylation of diorganozincs (1) with catalytic acylphos-
phonium ion A, an addition–elimination mechanism is also given
in Scheme 4, with a transition state similar to that proposed for
[
3
b
[
81–83]
the addition of diorganozincs to aldehydes.
Scheme 4. Proposed mechanism for the phosphine-catalyzed acylation
of diorganozinc reagents
Figure 1. Hammett plot for the n-Bu
FG–C
furan at 0 °C
3
P (3)-catalyzed acylation of n-Bu
H )Zn reagents (1ab–1ag) with benzoyl chloride (2) in tetrahydro-
6 4
(
R12Zn
Proposed reaction mechanism for the phosphine-catalyzed
acylation is supported by the sign and magnitude of ρ in
the Hammett plot. Negative reaction constant ρ indicates that
the reaction of diorganozincs 1 with acylphosphonium ion A
corresponds to the rate-determining step, that is, the second step
in reaction pathway (Eqn 3). A small interaction of FG on the FG–
C H group with the reaction center n-Bu in n-Bu(FG–C H )Zn
6 4 6 4
reagent in the transition state is consistent with the low value
of ρ.
kꢀ1
Â
Ã
⊕
⊖
1
PhCOCl þ n-Bu3P ⇄ PhP ðn-BuÞ Cl
→k2 PhCOR
3
k1
(8)
1
þ R ZnCl þ n-Bu3P
According to the steady-state kinetics, an explanation is pro-
vided for the rate laws expressed by Eqns 1 and 2. In the first
step, catalytic intermediate A is formed and it is used up to form
PhCOCl (2) and n-Bu
3
P (3) again by the reverse reaction or to
1
2
form the product 4 by reacting with R
Zn (1) in the second step.
As A is a reactive unstable species, it is expected that A is con-
sumed at a rate at which it is formed:
CONCLUSION
⊕
⊖
k1½PhCOClꢁ½nꢀBu3Pꢁ ¼ kꢀ1½PhCOP ðnꢀBuÞ Cl ꢁ
3
⊕
⊖
1
A detailed kinetic study of the phosphine-catalyzed acylation
of mixed diorganozinc, n-BuPhZn, homo diorganozinc, n-Bu Zn,
þ k2½PhCOP ðnꢀBuÞ Cl ꢁ½R 2Znꢁ (9)
3
2
and rearrangement of Eqn 4 provides the expression in Eqn 10
and n-Bu(FG–C H )Zn reagents was reported with the aim of
6
4
⊕
ϴ
for [PhCOP (n-Bu) Cl ].
gaining support for the hypothesis that the rate of transferable
group R in R Zn reagents on the residual group R . The
3
Â
Ã
k ½PhCOClꢁ½n-Bu Pꢁ
T
R
R
T
R
⊕
⊖
1
3
PhP ðn-BuÞ Cl ¼ ꢀ
Â
Ã
(10)
3
1
kinetic law for the reaction in THF at 0 °C was found to be
kꢀ1 þ k2 R 2Zn
rate = k[R Zn][acyl halide][n-Bu P]. Hammett methodology was
2
3
⊕
ϴ
By using the value for [PhCOP (n-Bu) Cl ], the following rate
also used in the acylation of n-Bu(FG–C H )Zn reagents for
6 4
3
expression can be obtained for the second step:
the correlation of the reaction rate of transferable group
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Copyright © 2016 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2016, 29 190–195

KINETIC STUDY FOR PHOSPHINE‐CATALYZED ACYLATION OF ALKYLARYLZINCS
n-Bu to the electronic effects of residual FG–C H group. The
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version of this article at the publisher’s website.
§
Correction added on 2 February 2016, after first online publication: the first
author's name in reference 72 was corrected.
J. Phys. Org. Chem. 2016, 29 190–195
Copyright © 2016 John Wiley & Sons, Ltd.
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