Reactivity of mixed organozinc and mixed organocopper reagents: 10 Comparison of the transferability of the same group in acylation of mixed and homo halozinc diorganocuprates with benzoyl chloride. A kinetic study

Article abstract of DOI:10.1016/j.jorganchem.2013.10.030

A detailed kinetic study has been carried out for the acylation of iodozinc n-butyl (substituted phenyl) cuprates, n-Bu(FG-C₆H₄)CuZnI and iodozinc din-butylcuprate, n-Bu₂CuZnI with benzoyl chloride in THF at 15-(-15)°C. Third order reaction was found which is first order in benzoyl chloride and second order in cuprate. We offered a reaction mechanism for the acylation of halozinc diorganocuprates depending on the kinetic data and activation parameters. Lower reaction rate of transferable group, n-Bu in mixed cuprate, n-Bu(PhCuZnI than that of homocuprate, n-Bu₂CuZnI and Hammett correlation of the reaction rate of transferable group, n-Bu in n-Bu(FG-C₆H₄)CuZnI reagents with the substituent constants of residual group, FG-C₆H₄ with a positive reaction constant (relative reactivity of FG: 4-Br >3-MeO > H > 3-Me > 4-Me > 4-MeO) are in accordance with the proposed mechanism. These findings support our hypothesis that the reaction rate of transferable group, R _T changes depending on the residual group, R_R in mixed cuprates. R_RR_TCuM (M = Li, MgX, ZnX) and also provide a kinetic explanation for the commonly accepted hypothesis regarding the dependence of the RT group transfer ability on the strength of the R _ReCu bond in mixed cuprates, R_RR_TCuLi.

Full text of DOI:10.1016/j.jorganchem.2013.10.030

Journal of Organometallic Chemistry 751 (2014) 644e653
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Journal of Organometallic Chemistry
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Reactivity of mixed organozinc and mixed organocopper reagents: 10
Comparison of the transferability of the same group in acylation of
mixed and homo halozinc diorganocuprates with benzoyl chloride.
A kinetic study
*
Özgen Ömür Pekel, Ender Erdik
Ankara University, Science Faculty, Bes¸evler, Ankara 06100, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
A detailed kinetic study has been carried out for the acylation of iodozinc n-butyl (substituted phenyl)
cuprates, n-Bu(FG-C6H4)CuZnI and iodozinc din-butylcuprate, n-Bu2CuZnI with benzoyl chloride in THF
at 15e(ꢀ15)ꢁC. Third order reaction was found which is first order in benzoyl chloride and second order
in cuprate. We offered a reaction mechanism for the acylation of halozinc diorganocuprates depending
on the kinetic data and activation parameters. Lower reaction rate of transferable group, n-Bu in mixed
cuprate, n-Bu(PhCuZnI than that of homocuprate, n-Bu2CuZnI and Hammett correlation of the reaction
rate of transferable group, n-Bu in n-Bu(FG-C6H4)CuZnI reagents with the substituent constants of
Received 29 June 2013
Received in revised form
13 October 2013
Accepted 15 October 2013
Keywords:
Mixed diorganocuprates
Acylation kinetics of iodozinc
diorganocuprates
Residual group effect
Third order reactions
residual group, FG-C6H4 with
a positive reaction constant (relative reactivity of FG: 4-Br >
3-MeO > H > 3-Me > 4-Me > 4-MeO) are in accordance with the proposed mechanism. These findings
support our hypothesis that the reaction rate of transferable group, RT changes depending on the residual
group, RR in mixed cuprates. RRRTCuM (M ¼ Li, MgX, ZnX) and also provide a kinetic explanation for the
commonly accepted hypothesis regarding the dependence of the RT group transfer ability on the strength
of the RReCu bond in mixed cuprates, RRRTCuLi.
Ó 2013 Elsevier B.V. All rights reserved.
1. Introduction
Whitesides [5], House [14], Posner [15] and Lipshutz [16]
investigated the group selectivity in the reactions of mixed
Diorganocuprates R2CuM (M ¼ Li, MgX, ZnX; X ¼ Br, Cl) are one
of the most useful organometallic reagents [1,2,3]. Mixed cuprates,
RRRTCuM (M ¼ Li, MgX) composed of one transferable group RT
together with a residual (dummy) group RR have been developed to
solve the problem of using two organyl groups to transfer only one
of them in homocuprates, R2CuM. As residual groups RR, both
organyl groups, such as cyano [4], 2-thienyl [5,6], 1-alkynyl [6],
trimethylsilylmethyl [7] and nonorganyl groups, such as RS [8], R2N
[9,10] and R3P [9,10,11] have been frequently used. In the mixed
cuprates of R1R2CuM type, one of the R1 and R2 groups has a higher
transfer rate than the other.
Mixed lithium cuprates, both RRRTCuLi type [4,5,6,8,9,10,11,12,13]
and R1R2CuLi type [5,7,14,15,16,17,18] have found application in
organic synthesis. The successful use of mixed bromomagnesium
cuprates, both RRRTCuMgBr type [19,20] and R1R2CuMgBr type
[19,21,22] have been also reported.
lithium cuprates, R1R2CuLi in detail and found the group selectivity
in the order of n-Bu w s-Bu > t-Bu >> Ph > alkynyl and
alkenyl
> Me in their substitution reactions [5,14,15], but
Me > alkenyl >> alkynyl in their 1,4-addition reactions [16].
The group selectivity in the reaction of mixed diorganocuprates,
R1R2CuM in the reaction with an electrophile E4 arises in the
process of reductive elimination of a Cu(III) intermediate R1R2CuM,
which is formed in the oxidative addition (Scheme 1) [2,3,23].
The long accepted hypothesis in the group selectivity of R(X)
CuLi reagents (X ¼ alkynyl, CN, RS, R2N, R3P) in their substitution
and 1,4-addition reactions has been that the group forming a
stronger CueC bond acts as the group of lower selectivity or as a
better residual group, RR. However, theoretical studies of Nakamura
on the allylic substitution [24] and 1,4-addition reactions [25] of
R(X)CuLi reagents (X ¼ t-Bu, alkynyl, CN, RS) indicated that the
group of lower selectivity is determined by thermodynamic sta-
bility and kinetic reactivity of Cu(III) intermediates and the group
which simultaneously binds to Cu and Li atoms acts as an effective
residual group, RR. Recently, Bertz observed peculiar properties of
* Corresponding author. Tel.: þ90 312 212 67 20/1039; fax: þ90 312 223 23 95.
E-mail address: erdik@science.ankara.edu.tr (E. Erdik).
0022-328X/$ e see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2013.10.030

Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
645
as model reaction. To the best of our knowledge, mechanistic
studies on the reaction of Grignard, organolithium organocopper
and organozinc reagents are very scarce in the literature. A study
on acylation of Grignard reagents under CuCl catalysis using
competitive kinetics was reported by Dubois et al. [37]. Recently,
Nakamura, et al. reported an experimental and computational
study on the mechanism of acyl electrophiles with lithium dio-
rganocuprates [38].
In this work, we describe the kinetics of acylation of mixed and
homo halozinc diorganocuprates, RRRTCuZnX and (RT)2ZnX, to
obtain additional proof for our hypothesis regarding the depen-
dence of the RT group transfer rate on the RR group.
Scheme 1. Group selectivity in the reaction of mixed diorganocuprates with an
electrophile.
RR groups in
p-complexes of RRRTCuLi reagents formed in their
1,4-addition reactions [26].
Our interest in the reactivity of mixed diorganocuprates,
diorganozincs and triorganozincates prompted us to carry out
systematic studies with the aim of (i) to find the dependence of the
group selectivity on the reaction parameters, both continuous and
discrete [27], (ii) to develop new atom-economic synthetic pro-
cedures by controlling the group selectivity, and (iii) to probe the
origin of group selectivity. In our continuing studies on the re-
actions of mixed bromomagnesium cuprates, R1R2CuMgBr [28,29],
diorganozincs, R1R2Zn [30,31,32,33,34] and Cu(I) catalyzed tri-
organozincates, R1R22ZnMgBr [35], we observed that the group
selectivity depends on the reaction parameters, such as solvent [30]
and temperature [35] and we developed new procedures for C-acyl
[31], C-alkyl [33] CeN coupling [32] using mixed arylzinc reagents.
We also think that in the reactions of mixed diorganocuprates,
R1R2CuM, not only group transfer ability, but also transfer rate of R1
group to an electrophile, E4 should depend on the strength of
R2-Cu bond. So, we hypothesized that residual R2 group can
change the transfer rate of transferable R1 group leading to
different reaction rate of mixed cuprates, R1R2CuM from that of
homocuprates, R12CuM.
In other words, kinetics of mixed diorganocuprates would
possibly provide another support for the commonly accepted
hypothesis. For this purpose, we investigated the reaction of mixed
diorganocuprates, n-Bu(FG-C6H4)CuMgBr and homocuprate,
n-Bu2CuMgBr with n-alkyl bromides in THF at 25 ꢁC using
competitive kinetics [28] and recently, direct kinetic study [29]. We
found that in the second order reaction, the n-Bu group transfer
rate to n-pentyl bromide in THF at 25 ꢁC, is much lower in the mixed
cuprate n-BuPhCuMgBr [36] than that in the homocuprates,
n-Bu2CuMgBr. In addition, n-Bu group transfer rate is well
correlated with Hammett substituent constants of residual
FG-C6H4 groups (FG ¼ 3-Me, 4-Me, 3-MeO, 4-MeO, 4-Br) and
we evaluated the unexpected positive sign of the Hammett
reaction constant depending on the reaction mechanism.
However, in the reactions of catalytic mixed diorganocuprate
n-BuPhCuMgBr derived in situ from CuI catalyzed reaction of mixed
zincate, n-BuPh2ZnMgBr with n-pentyl bromide in THF at 65 ꢁC, Ph
group is the transferable group [35] and its transfer rate to n-pentyl
bromide is higher in the mixed catalytic cuprate, n-BuPhCuMgBr
than that in the catalytic homocuprates Ph2CuMgBr.
As seen group selectivity in the mixed n-BuPhCuMgBr reagents
also depends on the organometallic reagent to be transmetallated,
i.e. Grignard reagent or bromomagnesium zincate and/or tem-
perature. Then we thought that it would be of interest to carry out
similar kinetic studies using mixed halozinc diorganocuprates,
RRRTCuZnCl with the aims of (i) determining the kinetic order and
finding the difference between the reaction rate of transferable
group RT in mixed and homocuprates, RRRTCuZnCl and
(RT)2CuZnCl, respectively, (ii) offering a reaction pathway and also
(iii) evaluating the dependence of the reaction rate of transferable
group, RT on the residual group, RR. Due to the unreactivity of
halozinc cuprates toward n-alkyl electrophiles, we used acylation
2. Results and discussion
For acylation reactions of mixed halozinc diorganocuprates we
used iodozinc n-BuPhCuZnI as a model halozinc mixed cuprate
aiming a comparison with our previous results on the group
selectivity of n-BuPhCuq nucleophiles.
On our recent work [39], optimal conditions showed that the
acylation of n-BuPhCuZnI 1ab with benzoyl chloride 2 can take
place at room temperature with an acylation yield of 78% and n-Bu
group:Ph group transfer ration of 76:24e64:36 (Scheme 2).
2.1. Kinetics of the acylation of n-BuPhCuZnI and n-Bu2CuZnI with
benzoyl chloride
For the kinetic and mechanistic study of n-butyl selective acyl-
ation of mixed cuprate n-BuPhCuZnI 1ab and acylation of homo-
cuprate n-Bu2CuZnI 1a2 with benzoyl chloride 2 in THF, we focused
on the determining of
(i) the reaction order and rate constant of acylation of mixed
cuprate 1ab
(ii) the reaction order and rate constant of acylation of homo-
cuprate 1a2 and
(iii) activation parameters for acylation of 1ab.
In the evaluation of the rate data, we used the method that we
already developed and successfully used for the evaluation of the
rate data in the alkylation of stoichiometric mixed cuprates,
R1R2CuMgBr [29], catalytic mixed cuprates derived from mixed
zincates, R1(R2)2ZnMgBr [35] and also in the allylation of mixed
diorganozincs, R1R2Zn [34].
In the coupling with homocuprate 1a2, benzoyl chloride 2 gives
only 3a as product whereas 3a and 3b are formed in the case of
coupling with mixed cuprate 1ab. While applying this method, we
used calculated value for c ¼ [benzoyl chloride]t, i.e. the concen-
tration of benzoyl chloride 2 at time t rather than directly measured
value due to the hydrolysis of 2 during the work-up of aliquots.
c can be calculated as
c ¼ ½Benzoyl chlorideꢂ0 ꢀ ½n ꢀ BuCOPhꢂt
for the acylation of 1a2 (Method A) and
(1a)
Á
c ¼ ½Benzoyl chlorideꢂ0 ꢀ ½n ꢀ BuCOPhꢂt þ ½PhCOPhꢂt 1b
(1b)
for the acylation of 1ab (Method B). The disappearance of the
benzoyl chloride 2 and the formation of the products 3a and 3b
were monitored relative to an internal standard using gas chro-
matographic analysis of quenched aliquots.
The preparation method for halozinc diorganocuprates seemed
important to collect the reproducible kinetic data. So, for the

646
Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
Scheme 2. Acylation reactions of mixed cuprate n-BuPhCuZnI 1ab with benzoyl chloride 2.
preparation of halozinc n-butyl phenyl cuprate, n-BuPhCuZnX 1ab
(X ¼ I, Cl) we used four different methods A, B, C and D starting
from Grignard reagents. As outlined in Scheme 3, we carried out
first Mg / Zn transmetallation [30,40,41] and then Zn / Cu
transmetallation in Methods AeC. We carried out Mg / Zn
transmetallation of bromomagnesium n-butylphenylcuprate n-
BuPhCuMgBr in Method D.
In the in situ Methods A1 and A2, n-BuZnCl prepared by trans-
metallation of n-BuMgBr was allowed to react with PhMgBr and
then with CuI (Method A1) or similarly, PhZnCl prepared by
transmetallation of n-BuMgBr was allowed to react with n-BuMgBr
and then with CuI (Method A2). Mg / Zn transmetallation gives n-
BuPhZn and Zn / Cu transmetallation gives n-BuPhCuZnI. Mixing
equimolar amounts of homocuprates n-Bu2CuZnI 1a2 and Ph2CuZnI
1b2 also leads to formation of n-BuPhCuZnI (Method B). In Methods
C1 and C2, we mixed equimolar amounts of n-BuZnCl and PhCu or
PhZnCl and n-BuCu, respectively to give n-BuPhCuZnCl.
For evaluating the effect of preparation method of n-BuPhCuZnI
1ab on the group selectivity in its coupling with benzoyl chloride,
total acylation yield and 3a:3b product ratios were found in a re-
action carried out with equimolar amounts of coupling partners in
THF at 25 ꢁC in 2 h.
Scheme 3. Preparation methods for mixed halozinc diorganocuprates, n-BuPhCuZnX (X ¼ I, Cl) 1ab.

Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
647
Table 1
First, we tested Method A1 and Method A2 to see if the organyl
group originally bonded to Zn could make a change in the total yield
and in the relative transfer ability of n-Bu or Ph groups. As expected,
Methods A1 and A2 gave almost equal total yields (71e78%) and
3a:3b product ratios (58:42e76:24) and the original bonding of n-
Bu or Ph group to Zn was found not to be important. We tried
Method B to see if the organyl group transfer ability would be
affected by the possible equilibrium between homocuprates n-
Bu2CuZnI 1a2 and Ph2CuZnI 1b2 to form mixed cuprate n-BuPhCuZnI
1ab the total yield of 76% and 3a:3b product ratio of 56:44 showed
that Methods A1 and A2 and Method B give possibly the same re-
agents. Methods C1 and C2 also resulted in similar total yields (76e
84%) and not much different 3a:3b product ratios (59:41e69:31).
The use of Methods D1 and D2 gave erratic values in the products
yields. Comparison of the yields and 3a:3b product yields obtained
in Methods A and Methods C reveals that either in situ trans-
metallation of R1R2Zn reagents with CuI (Method A) or trans-
metallation of R1ZnX reagent with prepared R2Cu reagent (Method
C) lead to the same mixed diorganozinc cuprate R1R2CuZnX. How-
ever, we found one pot successive Mg / Zn and Zn / Cu trans-
metallation reactions (Methods A1 and A2) more practical for the
preparation of halozinc mixed diorganocuprates and in addition, we
wanted to avoid the equilibrium on the formation of the mixed
diorganocuprate (Method B). So, we prepared the mixed cuprate
1ab according to Method A2 for kinetic experiments.
For the acylation of mixed cuprate 1ab and homocuprate 1a2,
we collected the rate data under pseudo-first order conditions,
i.e. in the presence of excess and varied concentration of
diorganocuprate 1ab or 1a2 reagent to find the reaction order in
benzoyl chloride 2 and in diorganocuprate 1ab or 1a2. The initial
concentration of benzoyl chloride 2 was kept constant and con-
centration of mixed cuprate 1ab or homocuprate 1a2 was
changed between 6 and 12 times than that of 2. We obtained
pseudo-first order plots which are linear up to 70e90% comple-
tion of the reaction for both mixed cuprate 1ab and homocuprate
1a2.
Effect of n-butylphenylcuprate 1ab concentration on the pseudo-first order rate
constants, k0 of benzoylation of 1ab with benzoyl chloride 2 in THF at 0 ꢁC and third
order rate constants, k.
[n-BuPhCuZnI], (M)
k0, minꢀ1a
k, Mꢀ2 minꢀ1b
0.095
0.110
0.126
0.142
0.158
0.173
0.189
0.027
0.035
0.042
0.057
0.064
0.087
0.111
3.0
2.9
2.6
2.8
2.6
2.9
3.1
a
[PhCOCl] ¼ 0.0158 M.
b
k ¼ k0/[n-BuPhCuZnI]2.
values versus log [mixed cuprate] gave a slope of 1.997
(r2 ¼ 0.973) (Fig. 2) confirming the second order reaction in
mixed cuprate 1ab.
Thus, the total rate law for the benzoylation of mixed cuprate
1ab in THF can be written as:
Rate ¼ ꢀd½PhCOClꢂ ¼ k½n ꢀ BuPhCuZnClꢂ2½PhCOClꢂ
dt
(2)
¼ k0½PhCOClꢂ
The third order rate constants were calculated as k ¼ k0/[n-
Bu(PhCuZnI]2 for acylation of mixed cuprate 1ab and taking the
average led to rate constant of k ¼ 2.9 ꢄ 0.1 Mꢀ2 minꢀ1 in THF at
0 ꢁC with the uncertainty of max. 7% which is in the error limit of GC
analysis (Table 1).
Pseudo-first order rate constants, k’ were calculated by linear
regression analysis (r2 ꢃ 0.980).
(ii) In the second set of experiments, we found the pseudo-first
rate constants, k0 of homocuprate 1a2 in a similar way used in
the pseudo-first order rate experiments of mixed cuprate
1ab. Due to the instantaneous reaction at 0 ꢁC, we could
collect the rate data only for the reaction at ꢀ15 ꢁC.
(i) In the first set of experiments, we found the pseudo-first
order rate constant, k0 of mixed cuprate 1ab and we chose
acylation at 0 ꢁC in a model kinetic run. As an example, a
pseudo-first order plot is given in Fig. 1. Pseudo-first order
rate constants, k’ in the presence of excess concentration of
mixed cuprate 1ab are listed in Table 1. The plot of log k0
As an example, a pseudo-first order plot is given in Fig. 3. Then,
we determined the pseudo-first order rate constants, k’ in the
presence of excess concentration of homocuprate 1a2 (Table 2).
log 103 k', min-1 2,1
log c, M -1,8
-2,0
r2 = 0,997
1,9
-2,2
r2 = 0,973
1,7
-2,4
-2,6
-2,8
-3,0
1,5
1,3
1,95
2
2,05
2,1
2,15
2,2
2,25
2,3
0
2
4
6
8
10 12 14 16 18 20 22
t, min
log 103 [n -BuPhCuZnI], M
Fig. 1. Typical first-order plot for the reaction of n-butylphenylcuprate 1ab with
benzoyl chloride in THF at 0.189 M,
ꢁC; [n-Butylphenylcuprate]0
[PhCOCl]0 ¼ 0.0158 M, c ¼ [PhCOCl]0 ꢀ ([n-BuCOPh]t þ [PhCDPh]t).
Fig. 2. Effect of n-butylphenylcuprate 1ab concentration on the pseudo-first order rate
constant k0 for the reaction of 1ab with benzoyl chloride 2 in THF at 0 ꢁC. Data are from
Table 1.
2
0
¼

648
Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
Table 2
-1,8
-2,0
-2,2
-2,4
-2,6
-2,8
log c, M
Effect of din-butylcuprate 1a2 concentration on the pseudo-first order rate con-
stants, k0 of benzoylation of 1a2 with benzoyl chloride 2 in THF at ꢀ15 ꢁC and third
order rate constants, k.
r2 = 0,993
[n-Bu2CuZnI], (M)
k0, minꢀ1a
k, Mꢀ2 minꢀ1b
0.095
0.110
0.126
0.142
0.158
0.173
0.29
0.39
0.59
0.65
0.90
0.96
32.1
32.2
37.1
32.2
36.1
32.1
0,0
0,5
1,0
1,5
2,0
2,5
3,0
3,5
4,0
t, min
Fig. 3. Typical first-order plot for the reaction of di-n-butylcuprate 1a2 with benzoyl
chloride 2 in THF at ꢀ15 ꢁC; [di-n-Butylcuprate]0 ¼ 0.142 M, [PhCOCl]0 ¼ 0.0158 M,
c ¼ [PhCOCl]0 ꢀ [n-BuCOPh]t.
a
[PhCOCl] ¼ 0.0158 M.
b
k ¼ k0/[n-Bu2CuZnI]2.
Plotting of log k0 values versus log [homocuprate] gave a slope of
1.940 (r2 ¼ 0.980) confirming again the second order reaction in the
homocuprate (Fig. 4). The total rate law for the acylation of
homocuprate 1a2 is also expressed using Eq. (3).
ꢀ
ꢁ
k02½PhCOClꢂ0
0
½PhCOPhꢂt ¼ ½PhCOPhꢂ0 þ
1 ꢀ eꢀk t
(4b)
k0
For the model pseudo-first order reaction given above (Fig. 1), we
0
plotted [n-BuCOPh]t versus (1 ꢀ eꢀk t) and also [PhCOPh]t versus
Rate ¼ ꢀd½PhCOClꢂ ¼ k½n ꢀ Bu2CuZnClꢂ2½PhCOClꢂ
0
(1 ꢀ eꢀk t) (Fig. 5). As [PhCOCl]0 ¼ 0.0158 M and pseudo-first order
dt
(3)
total rate constant, k0 ¼ 0.111 minꢀ1 are known, separate pseudo-first
order rate constants k01 and k02 rate constants, can be calculated. We
determined that k01 ¼0.091 minꢀ1 and k02 ¼ 0.020 minꢀ1 and the sum
of the separate rate constants, k0 ¼ k01 þ k02 ¼ 0.111 minꢀ1 were found
not to be different from the total pseudo-first order rate constant.
To see the dependence of separate pseudo-first order rate con-
stants, k’1 and k’2 on the excess concentration of mixed cuprate, we
first determined these values for all total k’ values listed in Table 1.
However, as the initial concentration of products equals zero, i.e.
[n-BuCOPh]0 ¼ 0 and [PhCOPh]0 ¼ 0, we also used another possi-
bility for determining k01 and k02 values [42] and we found the ratio
of [n-BuCOPh]t/[PhCOPh]t after a chosen time interval:
¼ k’½PhCOClꢂ
The third order rate constants for acylation of homocuprate 1a2
were calculated as above for the acylation of mixed cuprate 1ab and
taking the average led to rate constant of k ¼ 33.7 ꢄ 2.1 Mꢀ2 minꢀ1
in THF at ꢀ15 ꢁC (Table 2).
The first order reaction for acyl halide in the acylation reactions
of homocuprate 1a2 and mixed cuprate 1ab is an expected result.
However, the second order reaction for the cuprate seemed
surprising.
The problem in the acylation kinetics of mixed n-BuPhCuZnI 1ab
seemed that the coupling yield of residual group, i.e. Ph group, is
not low enough to be ignored and more important, it does not
remain constant, i.e. increases during a kinetic run. Then we
thought that evaluating the acylation reaction of mixed cuprate
n-BuPhCuZnI 1ab as two parallel reactions, i.e. acylation of n-Bu
group and acylation of Ph group rather than selective acylation of
n-Bu group would be better Eq. (4).
½n ꢀ BuCOPhꢂt=½PhCOPhꢂt ¼ k01=k20
(5)
Finding this ratio in at least seven cases, taking the average of
similar values and using the total rate constant, k’, we listed the
calculated separate k01 and k02 values in Table 3.
It was pleasant that plotting of log k01 values and log k02 values
versus log [n-BuPhCuZnI] gave again slopes of 2.3 (r2 ¼ 0.868) and
1.71 (r2 ¼ 0.983), respectively and confirmed the second order
ð4Þ
log 103 k', min-1 3,1
2,9
As we could determine the concentrations of the products of
both reactions, it seemed possible to separate values of reaction
rate constants k1 and i2 for the benzoylation of n-Bu and Ph groups,
respectively. In this evaluation, we used the valid relationships to
measure the time dependence of concentration of 3a and 3b [42].
Under the pseudo-first order rate conditions, i.e. in the excess of
mixed cuprate these equations can be written as follows to find the
k01 and k02 constants:
2,7
r2 = 0,980
2,5
2,3
1,95 2,00 2,05 2,10 2,15 2,20 2,25 2,30
log 103 [n -Bu2CuZnI], M
ꢀ
ꢁ
k01½PhCOClꢂ0
0
½n ꢀ BuCOPhꢂt ¼ ½n ꢀ BuCOPhꢂ0 þ
1 ꢀ eꢀk t
Fig. 4. Effect of di-n-butylcuprate 1a2 concentration on the pseudo-first order rate
constant k0 for the reaction of 1a2 with benzoyl chloride 2 in THF at ꢀ15 ꢁC. Data are
from Table 2.
k0
(4a)

Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
649
2,1
1,9
1,7
1,5
a
14
12
10
8
r2 = 0,972
r2 = 0,997
1,3
1,1
0,9
0,7
r2 = 0,979
6
4
2
1,95
2
2,05
2,1
2,15
2,2
2,25
2,3
log 103 [n -BuPhCuZnI], M
0
0,00
0,20
0,40
0,60
0,80
1,00
Fig. 6. Effect of n-butylphenylzinc cuprate 1ab concentration on the pseudo-first order
rate constants k01 (C) and k02 (:) for the product formation n-BuCOPh 3a and PhCOPh
3b, respectively in the reaction of 1ab with benzoyl chloride in THF at 0 ꢁC.
1 - e-k't
b
4
3,5
3
and homocuprate, n-Bu2CuZnCl 1a2. In THF, at ꢀ15 ꢁC, we deter-
mined that the reaction rates of mixed cuprate 1ab and homo-
cuprate 1a2 are 1.8 Mꢀ2 minꢀ1 and 33.7 Mꢀ2 minꢀ1, respectively. As
seen, acylation rate of mixed cuprate, n-BuPhCuZnCl is much lower
than that of homocuprate, n-Bu2CuZnCl being similar to the lower
alkylation rate of n-BuPhCuMgBr than that of n-Bu2CuMgBr (in THF,
0.77 Mꢀ1 minꢀ1 for mixed cuprate at 25 ꢁC, 0.83 Mꢀ1 minꢀ1 for
homocuprate at 0 ꢁC) [36].
2,5
2
r2 = 0,997
1,5
1
0,5
0
(iii) To calculate the activation parameters, the acylation reaction
of mixed cuprate 1ab was studied at 15e(ꢀ15)ꢁC tempera-
tures. The third order rate constants are given in Table 4.
Eyring plot of ln (k/T) versus 1/T was found linear (r2 ¼ 0.942)
0,00
0,20
0,40
0,60
0,80
1,00
1 - e-k't
0
Fig. 5. Plots of [n-BuCOPh]t (C) and [PhCOPh] (:) versus 1 ꢀ eꢀk t in the reaction of n-
and activation parameters,
D
D
Hs ¼ 38.7 ꢄ 8.4 kJ molꢀ1 and
butylphenylcuprate 1ab with benzoyl chloride
2
in THF at
0
ꢁC; [n-
Ss ¼ ꢀ93.3 ꢄ 16.0 Jmolꢀ1 Kꢀ1 were determined.
Butylphenylcuprate] ¼ 0.189 M, [PhCOCl] ¼ 0.0158 M, k0 ¼ 0.111 minꢀ1
.
Low value of
D D
Hs and relatively low negative value of Ss is
consistent with an associative process involving the development
of charge separation in the transition state. As the activation en-
tropy is relatively small, the reaction rate is mainly controlled by
enthalpy factor. This result, together with the significant
exothermic character of the reaction might possibly point to a
transition state occurring rather early in the reaction profile.
reaction both in the n-Bu group transfer and Ph group transfer of n-
BuPhCuZnI reagent in acylation with benzoyl chloride (Fig. 6).
In evaluating the rate data, we can consider either total rate
constants, k which depend on benzoyl chloride 2 disappearance
rate or separate rate constants k1 and k2, which depend on product
formation rate for n-BuCOPh 3a and PhCOPh 3b, respectively.
However, we could simply note that there is little difference be-
tween the k1/k ratios for the transfer of n-Bu group acylation of
n-BuPhCuZnI, i.e. k1/k ¼ 0.79e0.80. So, due to a lower error, we
preferred to use the total rate constants, k for the comparison of the
transfer rate of n-Bu group in the mixed cuprate, n-BuPhCuZnCl 1ab
2.2. Reaction pathway for the acylation reaction of halozinc
diorganocuprates in THF
In order to propose a reaction pathway for the reaction of
halozinc diorganocuprates with acyl halides which appears to be
consistent with the kinetic data, we assumed a contact ion
pair such as a homodimer 4 or a heteroaggregate 5 (CIP) in
equilibrium with solvent-separated ion pair (SSIP) 6 for their
structure similar to lithium homo and mixed diorganocuprates
Table 3
Pseudo-first order rate constants, k01 and k02 of n-Bu group and Ph group transfer
rate in the acylation of n-BuPhCuZnCl 1ab with benzoyl chloride 2a in THF at 0 ꢁC in
the presence of excess 1ab.
[n-BuPhCuZnI], k01, minꢀ1a k02, minꢀ1a k1, Mꢀ2 minꢀ1b k2, Mꢀ2 minꢀ1c
(M)
Table 4
Temperature dependence of the third order rate constants for the acylation of mixed
cuprate, n-BuPhCuZnI 1ab with benzoyl chloride 2 in THF.
0.095
0.110
0.126
0.142
0.158
0.173
0.189
0.021
0.025
0.036
0.045
0.049
0.070
0.091
0.006
0.008
0.009
0.012
0.015
0.017
0.020
2.22
2.07
2.28
2.23
1.96
2.34
2.55
0.77
0.70
0.60
0.60
0.60
0.57
0.56
a
[PhCOCl] ¼ 0.0158 M.
k1 ¼ k01/[n-BuPhCuZnI]2.
k2 ¼ k02/[n-BuPhCuZnI]2.
T, K
288
7.4
283
6.7
278
3.5
273
2.9
268
2.3
258
1.8
b
c
k, Mꢀ2 minꢀ1

650
Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
ð6Þ
Scheme 4. Plausible equilibria for CIP and SSIP structures for halozinc dio-
rganocuprates in solution.
For the acylation of diorganocuprates with acyl halides we pro-
pose the pathway given in Scheme 7, which is similar to the mecha-
nism reported by Nakamura et al. (Scheme 5) [38]. We thinkthat, first,
the diorganocuprate can form similarly a complex through the ZneO
interaction and complexation between Cu atom and C]O bond gives
the oxidative addition transition state D. ZneO complexation is ex-
pected to affect the simultaneous formation of C]O bond and CeCl
bond cleavage. In the R-acyl coupling reaction of R1R2CuZnCl reagent,
both R1 and R2 groups are expected to react in the same pathway. The
discussion that follows is expected to relate the kinetic data in our
work to the acylation reaction of homo or mixed diorganocuprates.
A pathway for the formation of the acylation product by reacting
two molecules of zinc cuprate with one molecule of acyl halide
could involve first formation of acyl halide e zinc cuprate complex
A by ZneO interaction Eq. (7a) and then reaction of A with acyl
halide Eq. (7b).
[2,3,23,43e47] and Grignard reagent derived homocuprates
[23,45,47] (Scheme 4).
It is known that it is essentially only CIP structures of a cuprate
which undergoes the reaction and the reactions proceed with a
small equilibrium concentration of CIP in solution and SSIP is the
much less or even unreactive species [3,23,44,48e54].
Nakamura et al. recently suggested a mechanism for the reac-
tion of lithium organocuprates with acyl halides depending on
theoretical calculations and experimental studies [38]. First, the
diorganocuprate dimer forms a complex A through the LieO
interaction and charge transfer from the diorganocuprate dimer to
the C]O bond leads to the formation of a
p-complex B. Rear-
rangement of the complex gives a more stable oxidative addition
transition state C. Li assisted CeCl bond cleavage and CeC bond
formation occur simultaneously in the reductive elimination step to
give the ketone (Scheme 5).
For the reactions of acyl chlorides with Grignard reagent derived
catalytic organocuprates, six-centered transition state in which
chloride is displaced without addition to the carbonyl group by
catalytic cuprate RCu(Cl)MgX (X ¼ Br, Cl) was already offered [37]
(Scheme 6).
Six-centered transition states [55e57] and formation of ketone-
dimeric Grignard reagent complexes [58] have been also reported
for the mechanism of Grignard reagent addition to ketones.
In fact, the literature on the acylation reactions of alcohols
[59,60] and amines [61] in aprotic solvents also show a third order
kinetic term. In the alcoholysis Eq. (6), methanol first gives a
tetrahedral intermediate (nucleophilic catalysis), this intermediate
reverts to reactants or it is deprotonated with a second molecule of
methanol to give a new tetrahedral intermediate which collapses to
product [59,60].
ð7aÞ
ð7bÞ
We think that steady-state kinetics provide a straightforward
explanation for the rate laws expressed by Eqs. (1) and (2).
We assume that the concentration of halide-cuprate complex A
does not change with time as an intermediate since it is used up as
Scheme 5. Mechanism for the acylation of lithium diorganocuprates with acyl halides.

Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
651
Scheme 8. Acylation reactions of mixed halozinc cuprates n-Bu(FG-C6H4)CuZnI 1abe
ag with benzoyl chloride 2.
Scheme 6. Six-centered mechanism for acylation of catalytic organocuprate reagents
in situ derived from RMgX and CuCl.
all mixed halozinc cuprates n-Bu(FG-C6H4)CuZnI in THF at 0 ꢁC. The
third order reaction rates, k were determined depending on ben-
zoyl halide 2 disappearance under pseudo-first order conditions
and they were listed in Table 5.
In the alkylation of n-Bu selective n-BuPhCuMgBr with n-pentyl
bromide in THF at 25 ꢁC, we already correlated [29] n-Bu group
transfer rate to electronic affects of substituents on the FG-C6H4
fast as is formed, giving either cuprate 1 and PhCOCl 2 in step a or
ketone 3 in step b.
d½Aꢂ
O ¼
¼ k1½cuprateꢂ½PhCOClꢂ ꢀ k ½Aꢂ ꢀ k2½Aꢂ½cuprateꢂ (8)
ꢀ1
dt
The value for [A] is inserted into the original rate expression
depending on the benzoyl halide disappearance and
group using Hammett
s values [62e65]. We evaluated the positive
reaction constant as a quite important support for our hypothesis
that the residual group RR affects the reaction rate of transferable
group, RT in mixed cuprates, RRRTCuM (M ¼ Li, MgX, ZnX).
Expecting a similar substituent effect of residual FG-C6H4 group
on the acylation rate of n-Bu group, we plotted the rate constants of
d½PhCOClꢂ
dt
k1k2½cuprateꢂ2½PhCOClꢂ
Rate ¼ ꢀ
¼ k2½Aꢂ½cuprateꢂ ¼
k
ꢀ1 þ k2½cuprateꢂ
(9)
n-Bu(FG-C6H4)CuZnI 1abeag in THF at 0 ꢁC against Hammett
s
is obtained.
values (Fig. 7). It is clear that there is a good linear correlation with a
If we consider the first step as a rapid attainment of equilibrium
followed by rate determining acylation step, we can write
positive reaction constant
3-MeO may be attributed to the inadequacy of applying the stan-
r
¼ 1.95 (r2 ¼ 0.946). The deviations for
dard
s constants of the H-bond accepting substituents for the re-
k1k2
Rate ¼
½cuprateꢂ2½PhCOClꢂ
(10)
actions carried in a polar aprotic solvents and these deviations
related to the reactions of Grignard reagents and cuprates were
already reported [66e69]. The finding of correlation between the
reaction rate of transferable n-Bu group and electronic effects of
substituents on the residual seemed us another important support
for our hypothesis.
For the interpretation of the result of Hammett study, we
checked the consistency of the correlation with our proposed
mechanism for acylation reaction of halozinc cuprates
(Scheme 6). We concentrated on the effect of the strength of FG-
C6H4eCu bond for the formation of transition state D in the re-
action of benzoyl chloride e cuprate complex A with cuprate,
k
ꢀ1
as the rate expression which shows the first order reaction in acyl
halide 2 and second order reaction in cuprate 1.
2.3. Dependence of the n-Bu transfer rate on the FG-C6H4 group in
the acylation reaction of n-Bu(FG-C6H4)CuZnI with benzoyl chloride
In order to evaluate the dependence of the reaction rate of
transferable n-Bu group on the residual group we screened a series
of FG-C6H4 (FG ¼ 4-Me c, 3-Me d, 4-MeO e, 3-MeO f, 4-Br g) groups
as residual groups (Scheme 8). We determined the reaction rate of
Scheme 7. Reaction pathway for the acylation of halozinc diorganocuprates, R1 ¼ R2 or R1 s R2.

652
Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
Table 5
withdrawing ability of the FG substituents of residual FG-C6H4
groups resulting in a lower reaction rate of mixed cuprates n-Bu
(FG-C6H4)CuZnCl than that of homocuprate, n-Bu2CuZnCl.
In summary, these findings support our hypothesis and also
provide a kinetic explanation for the commonly accepted hypoth-
esis regarding the dependence of the RT group transfer ability on
the strength of RReCu bond in mixed cuprates, RRRTCuLi.
Rate constants of acylation of iodozinc n-butyl (substituted phenyl) cuprates 1abeag
with benzoyl chloride 2 in THF at 0 ꢁC.
FG
H, b
4-Me, c
3-Me, d
4-MeO, e
3-MeO, f
4-Br, g
k, Mꢀ2 minꢀ1
2.9
1.1
2.0
0.8
1.8
4.6
4. Experimental
All reactions were carried out under dry nitrogen atmosphere
using oven dried glassware. Reagents and solvents were handled by
using standard syringe-septum cap techniques [70]. Quantitative
GLC analysis were performed on a Thermo Finnigan gas chro-
matograph equipped with a ZB-5 capillary column packed with
phenylpolysiloxane using internal standard technique. THF was
distilled from sodium benzophenone dianion. n-Butyl bromide,
bromobenzene, and 4-methyl-, 3-methyl-, 4-methoxy-, 3-
methoxy-, 4-bromo- and 3-bromobenzenes were obtained
commercially and purified. Mg turnings for Grignar reagents was
used without further purification. ZnCl2 (Aldrich) was dried under
reduced pressure at 100 ꢁC for 2 h and used as a THF solution. CuI
was purified according to the literature procedure, dried under
reduced pressure at 60e90 ꢁC for at least 1 h and kept under ni-
trogen [71]. Benzoyl chloride was obtained commercially and pu-
rified. Grignard reagents n-BuMgBr and FG-C6H4MgBr (FG ¼ H b, 4-
Me c, 3-Me d, 4-MeO e, 3-MeO f, 4-Br g, 3-Br h) were prepared in
THF by standard methods and their concentration were found by
titration prior to use [72].
Typical procedure for the preparation of mixed diorganozinc
cuprate, n-BuPhCuZnI 1ab using Method A2 is given below: To
1 mol equiv of ZnCl2 in THF at ꢀ15 ꢁC, first,1 mol equiv of PhMgBr in
THF and after stirring for 20 min at that temperature, 1 mol equiv of
n-BuMgBr in THF was added. The gray-colored heterogenous so-
lution of n-BuPhZn was stirred at ꢀ15 ꢁC for 20 min and a sus-
pension of 1 mol equiv of CUI in THF at ꢀ15 ꢁC and dark yellow
heterogeneous solution of n-BuPhCuZnI was stirred at that tem-
perature for another 20 min.
which is rate determining step. An electrostatic interaction be-
tween R2 ¼ FG-C6H4 group and Zn atom might cause a stronger
coordination and increase the stability of the transition state.
Inductive and resonance effects of FG groups are expected to
affect this interaction leading to a lower activation energy and
easier transfer of R1 ¼ n-Bu group to carbonyl group. However,
the electronic charge of R2 ¼ FG-C6H4 group is expected to in-
crease not only the strength of R2eZn bond, but also the strength
of R2eCu bond due to similar electronegativities of Zn and Cu. If
this is true, simultaneous formation of C]O bond and CeCl bond
cleavage in the transition state will be easier resulting in a higher
coupling rate of R1 ¼ n-Bu group with C]O group. This result
allows us to conclude that our proposed reaction mechanism for
the acylation of halozinc diorganocuprates, R2CuZnI is also sup-
ported by the Hammett study of reaction rates of transferable
alkyl groups to correlate with the substituent effect of residual
substituted phenyl groups, n-Bu(FG-C6H4)CuZnI. Of course,
a detailed mechanism which explains both the acylation of
cuprates and the dependence of transferable group rate on the
residual group are not clear at this time.
3. Conclusions
We introduced this work to confirm our hypothesis that the
reaction rate of transferable group, RT changes depending on the
residual group, RR in mixed cuprates, RRRTCuM (M ¼ Li, MgX, ZnX).
For this purpose, we have reported a detailed kinetic study of
the acylation of n-Bu(FG-C6H4)CuZnCl with benzoyl chloride in THF
at 15 e (ꢀ15)ꢁC. We have determined the kinetic law to be rate ¼ k
[acyl halide] [cuprate]2. We offered a reaction mechanism for the
acylation of halozinc diorganocuprates depending on the kinetic
data and activation parameters. Correlation of the reaction rate of
transferable group, n-Bu to the Hammett substituent constants of
residual group, FG-C6H4 gave a positive reaction constant which is
in accordance with the proposed mechanism and also shows the
dependence of n-Bu group transfer ability on the electron
Homo di-n-butylzinc cuprate n-Bu2CuZnI 1a2 reagent was pre-
pared by addition of 2 mol equiv of n-BuMgBr reagent in THF to a
solution of 1 mol equiv of ZnCl2 in THF at ꢀ15 ꢁC, stirring at that
temperature for 20 min and adding 1 mol equiv of CuI in THF to
Ph2Zn and then stirring again at ꢀ15 ꢁC for 30 min.
A typical kinetic procedure for reaction of n-BuPhCuZnI 1ab
with benzoyl chloride 2 in THF at 15 e (ꢀ15)ꢁC under pseudo-first
order conditions in the presence of excess 1ab is given below:
In a flame-dried, two-necked flasks with septum caps and stir-
ring bars, n-BuPhCuZnI 1ab (10 mmol) was prepared using THF
solution of ZnCl2 (10 mmol), PhMgBr (10 mmol) in THF, n-BuMgBr
(10 mmol) in THF and CuI (10 mmol) at ꢀ15 ꢁC as explained above.
To the stirred mixture, internal standard nonane (1 mmol) and
PhCOCl 2 (1 mmol) was 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 chlo-
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
n -Bu
r2 = 0,946
CuZnI
FG
H
4-Me
4-MeO
4-Br
3-Me
ride 2 constant. The mixture was quickly thermostated by
immersing the flask cooling bath at constant temperature on a
magnetic stirrer. Aliquots (10e16) were withdrawn from the
mixture by syringe under nitrogen atmosphere at 5 or 5 min in-
tervals and were hydrolyzed in a vial containing saturated NH4Cl
solution containing 20% NH3. The aqueous phase was extracted
with ether and the ethereal phase was analyzed by GC. The rate
data were collected by measuring the concentration of coupling
products 3a and 3b in each sample. Self consistent data could be
obtained for two-four half lives. Reproducibility of the rate
-0,1
-0,2
3-MeO
σ
-0,4
-0,2
0
0,2
0,4
Fig. 7. Hammett study showing correlation of reaction rate of transferable n-Bu group
with values of the residual FG-C6H4 group substituents in the acylation reaction of n-
Bu(FG-C6H4)CuZnI in THF at 0 ꢁC. Substituent constants are taken from Ref. [71].
s

Ö.Ö. Pekel, E. Erdik / Journal of Organometallic Chemistry 751 (2014) 644e653
653
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Acknowledgments
[38] N. Yoshikai, R. Iida, E. Nakamura, Adv. Synth. Catal. 350 (2008) 1063.
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We thank Turkish Scientific and Technical Research Council
(Grant No. TBAG 112T676) for the financial support.
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