Sulfonyl transfer mechanism in C-S coupling of phenylmagnesium bromide with phenyl arenesulfonates

Article abstract of DOI:10.1016/j.jorganchem.2009.09.044

The kinetics of C-S coupling of phenylmagnesium bromide with phenyl arenesulfonates has been studied in THF:toluene (7:10) at 90 °C. Kinetic data and Hammett relationship are consistent with an asynchronous S_Na mechanism in which rate determini

Full text of DOI:10.1016/j.jorganchem.2009.09.044

Journal of Organometallic Chemistry 695 (2010) 267–270
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Sulfonyl transfer mechanism in C–S coupling of phenylmagnesium bromide
with phenyl arenesulfonates
a
b
a,*
Fatma Ero g˘ lu , Didem Kâhya , Ender Erdik
a
Ankara University, Science Faculty, Be ßs evler, Ankara 06100, Turkey
Ankara University, Biotechnology Institute, Be ßs evler, Ankara 06100, Turkey
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 May 2009
Received in revised form 15 September
The kinetics of C–S coupling of phenylmagnesium bromide with phenyl arenesulfonates has been studied
in THF:toluene (7:10) at 90 °C. Kinetic data and Hammett relationship are consistent with an asynchro-
N
nous S a mechanism in which rate determining thiophilic attack of carbanion takes place much ahead of
2
009
phenoxy group departure.
Accepted 26 September 2009
Available online 5 October 2009
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
C–S coupling
Grignard reagents
Aryl arenesulfonates
Hammett plot
1
. Introduction
Sulfones are useful intermediates in organic synthesis [1,2] and
There are various mechanistic possibilities for S–O bond cleav-
age in aryl arenesulfonates and there has been considerable inter-
est in the kinetics and mechanism of the sulfonyl transfer reactions
of oxygen, sulfur and nitrogen anionic nucleophiles [28–33]. How-
ever, no work has been published on the mechanism of the reac-
tions of organolithiums and Grignard reagents with sulfonates at
sulfur center.
also in medicine as drugs [3,4]. They can be synthesized by a vari-
ety of methods [5,6]. However, the use of organometallic methods
are quite limited and a few papers have been published on sulfony-
lation of carbanions with sulfonyl chlorides [7–9] and sulfonates
[
[
[
10–12]. Sulfonates are useful partners in C–C coupling reactions
13] of organolithium [8], -copper [14–16] and -zinc reagents
17–19] (Scheme 1, pathway a). Grignard reagents can react either
In order to gain some insight into the mechanism of thiophilic
attack of carbon nucleophiles at S on the sulfonates, we have
undertaken a detailed kinetic and mechanistic study [34]. We pro-
posed a mechanism for C–S coupling of aryl Grignard reagents with
aryl arenesulfonates, which is consistent with kinetic data, activa-
tion parameters and Hammett relationship for the substituent ef-
fects of aryl nucleophile. In order to provide another support for
the mechanism, herein we wish to report the results of a Hammett
study for the substituent effects of the electrophile, i.e. arenesulfo-
nyl groups in the aryl arenesulfonates.
by C–O bond cleavage [7,20–22] or C–S bond cleavage [23–25]
Scheme 1, pathway a and pathway b, respectively) to give C–C
coupling products. Organolithiums [10] and Grignard reagents
11,12] are also known to react with arenesulfonates to give C–S
coupling leading to the formation of sulfones by S–O bond cleavage
(
[
(
Scheme 1, pathway c).
Although synthetic and mechanistic aspects of C–C coupling of
sulfonates are well known, C–S coupling of sulfonates have not
been investigated in detail. In our long term investigation on the
C-heteroatom coupling of organometallic reagents, we already
found that aryl Grignard reagents 1 attack phenyl tosylate 2a to
give only sulfones 3, i.e. S–O bond cleavage takes place (Scheme
2
. Results and discussion
We have already discussed the kinetics of phenylmagnesium
bromide 1a with phenyl tosylate 2a in THF:toluene (7:10) at
6
2) [26,27].
0 °C [34]. The reaction obeys clean second order kinetics:
d½PhOTosꢁ
ꢀ
¼ k ½PhMgBrꢁ ½PhOTosꢁ
ð1Þ
dt
*
Corresponding author. Address: Ankara Üniversitesi Fen Fakültesi, Kimya
The first order kinetics in aryl Grignard reagent and in phenyl
tosylate seems consistent with thiophilic attack of aryl carbonions
at sulfonate sulfur to give C–S coupling products.
Bölümü, Be ßs evler, Ankara 06100, Turkey. Tel.: +90 312 212 67 20x1031; fax: +90
12 223 23 95.
3
E-mail address: erdik@science.ankara.edu.tr (E. Erdik).
0
022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.09.044

2
68
F. Ero g˘ lu et al. / Journal of Organometallic Chemistry 695 (2010) 267–270
6 4 2
reaction between 1a and Y–C H SO OPh 2a,c–e (Y = H a, 3-Me c,
4
-t-Bu d, 4-MeO e) obey the second order as the reaction between
1
a and phenyl tosylate 2b (Y = 4-Me b) [34]. For this purpose, we
carried out reactions under pseudo-first order conditions by using
variable concentration of phenylmagnesium bromide 1a in excess
and varied to find the reaction order in phenyl arenesulfonates
2
a,c–e and phenylmagnesium bromide 1a. As we already found
that the use of directly measured [PhOTos] values, i.e. the concen-
t
tration of phenyl tosylate 2b at time t give minimum error in the
evaluation of rate data, we followed the kinetics by measuring the
concentration of remaining arenesulfonates 2a,c–e. By keeping
the initial concentration of arenesulfonate 2 constant and chang-
ing the concentration of phenylmagnesium bromide 1a between
5
and 15 times than that of 2a,c–e, we obtained pseudo-first order
plots which are linear up to 60–80% completion of the reaction.
Pseudo-first order plot for the sulfonation of phenylmagnesium
bromide 1a with phenyl 3-toluenesulfonate 2c is given in Fig. 1.
Scheme 1. Sulfonates as C–C and C–S coupling partners in reactions with
organometallic reagents.
Pseudo-first order rate constants k
1
were calculated by linear
values with ex-
regression analysis (r P 0.99). The linearity of k
1
cess concentration of phenylmagnesium bromide 1a for the sulfo-
nation with phenyl 4-methoxybenzenesulfonate 2e is illustrated
Reactions of nucleophiles with aryl arenesulfonates at S atom
are known to take place generally by stepwise S
concerted S 2(S) mechanism (Scheme 3) [28–33]. S
involves a pentacoordinate intermediate [29,33] and S
N
a mechanism or
a mechanism
2(S) mech-
in Fig. 2. Plots of log k
a,c–e yielded a slope between 0.94 and 1.19 (r P 0.97) confirm-
ing the first order reaction in phenylmagnesium bromide 1a. We
calculated the second order rate constants k as k = k / [C MgBr]
1
versus log[PhMgBr] for sulfonation with
N
N
2
N
anism proceeds via a transition state in which bond formation and
bond breaking occur synchronously.
1
6 5
H
In order to propose a mechanism for the C–S coupling of Grig-
nard reagents with aryl arenesulfonates, we applied Hammett
methodology for the substituent effects of the nucleophile, i.e. aryl
6 4
Grignard reagents X–C H MgBr in the sulfonation with phenyl tos-
ylate 2b and also calculated activation parameters for the sulfona-
tion of phenylmagnesium bromide [34]. Kinetic data, solvent
effect, Hammett relationship and activation parameters suggest
that the C–S bond formation at the transition state is significantly
advanced than S–O bond cleavage or at least the reaction process
involves thiophilic attack of carbanion on the sulfonate. However,
this results did not seem to help us to make a clear distinction be-
N N
tween a concerted S 2(S) mechanism and S a mechanism in which
Scheme 3. Reactions of nucleophiles with aryl arenesulfonates by S–O bond
cleavage. S a: Addition-elimination reaction, S 2(S): Concerted mechanism.
addition is the rate determining step. Nevertheless, it seemed us
conceivable to propose a nucleophilic addition mechanism involv-
ing a rate determining attack of solvated Grignard reagent to sulfo-
nyl group followed by a fast phenoxide group leaving (Scheme 4).
The coordination of ester with Mg occurs by replacement of donor
THF coordinated to Grignard reagent and replacement of THF with
toluene results in a more favorable complex formation leading to
observed reactivity of Grignard reagent in S–O bond cleavage.
In order to find another support for the proposed mechanism,
we tried Hammett treatment of substituent effects on the arene-
sulfonyl groups of the sulfonate esters. We expect that the reactiv-
ity of arenesulfonates 2 changes depending on the substituents on
N
N
1
the arenesulfonyl group, R and the transition state of the reaction
will be more stabilized by the presence of electron withdrawing
substituents. In this work, we found the rate constants of the reac-
tions of phenylmagnesium bromide 1a with phenyl substituted
benzenesulfonates Y–C
6
H
4
SO
2
OPh 2 in the THF:toluene (7:10) at
of Hammett q–r
9
0 °C and calculated the reaction constant
q
correlation. However, before evaluating the Hammett relationship,
Scheme 4. Proposed mechanism for C–S coupling of aryl Grignard reagents with
we first carried out kinetic studies to check that the kinetics of the
aryl arenesulfonates.
Scheme 2. Reaction of aryl Grignard reagents with phenyl tosylate to give sulfones.

F. Ero g˘ lu et al. / Journal of Organometallic Chemistry 695 (2010) 267–270
269
2
.5
1
SO
2
OPh
-
1
Y
2
-
-
-
1.2
1.4
1.6
Y
1
0
H a
4
-CH
3
3
b
c
3
-CH
-1.8
4
-(CH
3
)
3
C d
-2
4
-CH
3
O e
-
2.2
.5
0
-0.2
-0.1
0
0.1
0.2
ρ
Fig. 3. Variation of rate constants with Hammett substituent constants for the
sulfonation of phenylmagnesium bromide 1 with phenyl esters of substituted
benzenesulfonates 2a–e in THF:toluene (7:10) at 90 °C.
0
50
100
15
200
t, min
Fig. 1. Typical first order plots for the reaction of phenylmagnesium bromide 1 with
phenyl 3-toluenesulfonate 2c in THF:toluene (7:10) at 90 °C, c = [3-MeC
6 4-
H
was not used. However, a number of deviations have been already
SO
2
OPh]
t
[PhMgBr]
0
= 0.040 M, [3-MeC
6
H
4
SO
2
OPh]
0
= 0.520 M.
reported with 4-CH
3
O containing reactants in the Hammett plots
value indicates that
for Grignard reactions [36–38]. The high
q
the reactivity of the arenesulfonates is significantly increased by
the electron withdrawing effect of the substituents, as expected.
As the electron withdrawing substituent on the arenesulfonyl
group can decrease the electron density of the reaction center,
the attack of the nucleophilic carbanion will be easier and the rate
of C–S bond formation will increase resulting in a large positive va-
lue for reaction constant q. However, we may think that the elec-
tron withdrawing substituent on the arenesulfonyl group can also
decrease the leaving ability of the phenoxide group. Then, the
4
3
2
1
0
opposing effect of substituent Y of Y–C
bond formation and on the S–O bond cleavage might cause a low
positive value or even a negative value of reaction constant if
6 4 2
H SO OPh 2 on the C–S
q
0
100
200
300
400
500
600
the leaving group departure is involved in the rate determining
step [39]. In our study, the large positive value of reaction constant
3
[
C H MgBr], 10 M
6 5
q
indicates the absence of the contribution of leaving group ability
Fig. 2. Effect of phenylmagnesium bromide 1a concentration on the pseudo-first
order rate constants in the reaction of phenylmagnesium bromide 1a with phenyl
in the transition state and excludes a single step concerted mech-
anism. This result supports that C–S formation between Grignard
reagents and aryl arenesulfonates proceeds by a stepwise mecha-
nism in which the rate determining step is the thiophilic attack
of carbanion on the arenesulfonate or at least carbanion attack pos-
sibly takes place much ahead of phenoxy group departure in the
transition state. The present study of substituent effects on the
C–S coupling of Grignard reagents with aryl arenesulfonates pro-
4
-methoxybenzenesulfonate 2e in toluene.
Table 1
Rate constants for the sulfonation of phenylmagnesium bromide 1 with phenyl esters
of substituted benzenesulfonates 2a–e in THF:toluene (7:10) at 90 °C
N
vides another support for asynchronous S a mechanism.
In our continuing work, we will study to provide another sup-
port for the mechanism of the sulfonyl transfer reactions of aryl
Grignard reagents.
.
a
103 k, M min
ꢀ1
ꢀ1b
Compound
Y
r
2
2
2
2
2
d
b
e
c
4-(CH
3
)
3
C
ꢀ0.15
ꢀ0.14
ꢀ0.12
ꢀ0.06
0.00
10.8
13.0c
7.9
21.3
22.3
4-CH
4-CH
3-CH
H
3
3
. Experimental
3
O
3
3.1. General methods
a
a
Substituent constants are taken from Ref. [35].
Second order rate constants were calculated under pseudo-first order
All reactions were carried out under a nitrogen atmosphere in
b
oven-dried glassware reagents and solvents were handled using
standard syringe-rubber septum techniques [40]. Quantitative GC
analysis were performed on a Thermo-Focus gas chromatograph
equipped with a ZB-1 capillary column (immobilized with poly-
dimethylsiloxane) and a flame ionization detector using internal
standard techniques.
conditions.
c
Rate constant is taken from Ref. [34].
and taking the average of k values with the uncertainty of 5–10%,
which is in the error limit of GC analysis.
The kinetic reactions of phenylmagnesium bromide 1a with all
substituted benzenesulfonates 2a–e obeyed second order kinetics.
The second order rate constants are given in Table 1 and the
3.2. Reagents
plot of the rate constants against Hammett
in Fig. 3. As seen, a reasonably good correlation with a value
of = 2.13 (r = 0.954) was obtained. For the correlation, the point
for the 4-CH O substituent lying significantly of the linear plot
r
constants is shown
Magnesium 99.9% pure and purified bromobenzene were used.
THF was distilled over sodium benzophenone dianion and toluene
was distilled over sodium. Phenylmagnesium bromide 1a was pre-
pared in THF by standard method and its concentration was found
q–r
q
3

2
70
F. Ero g˘ lu et al. / Journal of Organometallic Chemistry 695 (2010) 267–270
by titration prior to use [41]. Phenyl arenesulfonates 2a–e were
prepared by the published procedures using arenesulfonyl chlo-
rides and phenol and were confirmed by melting points, IR and
Acknowledgment
We thank the University Research Fund Grant No. BAP 2007-10-
05-09 for financial support.
1
H NMR spectroscopy [25,33,42–44] as follows:
3.3. C
6
H SO OC
5 2 6
H
5
2a
References
Mp 34–35 °C (lit. [44] mp 34–35 °C); IR (KBr) V cmꢀ1: 1618,
[1] M.S. Simpkins, Sulfones in Organic Synthesis, Pergamon Press, Oxford, 1993.
[
2] P. Page, Organosulfur Chemistry, Academic Press, New York, 1998.
1
1
489, 1384 (SO
2
), 1170 (SO
2
), 619 (S–O); H NMR (400 MHz, CDCl
3
)
[3] M.S. Mitchell, Biological Interaction of Sulfur Compounds, CRC Press, Florida,
1996.
d ppm: 7.82 (2H, d, J = 7.2 Hz), 7.66 (1H, t, J = 7.6 Hz), 7.52 (2H, t,
J = 7.6 Hz), 7.23–7.31 (3H, m), 6.97 (2H, d, J = 7.2 Hz).
[
4] S. Oaie, T. Okuyama, Organic Sulfur Chemistry: Biochemical Aspects, CRC Press,
Florida, 1992.
[
5] R.C. Larock, Comprehensive Organic Transformations. A Guide to Functional
Group Preparations, Wiley, New York, 1999.
3
.4. 4-CH
3 6 4 2 6 5
C H SO OC H 2b
[
[
6] C.M. Rayner, Contemp. Org. Synth. 2 (1995) 409.
7] B.J. Wakefield, Organomagnesium Methods in Organic Synthesis, Academic
Press, New York, 1995 (Chapter 13.2).
Mp 50–53 °C (lit. [33] mp 76 °C, lit. [25] 93–94 °C, lit. [44] 96–
ꢀ1
[8] B.J. Wakefield, Organolithium Methods, Academic Press, London, 1990
(Chapter 12.3).
[
[10] W.E. Baachers, Can. J. Chem. 54 (1976) 3056.
11] A.I. Meyers, A. Nebay, H.W. Adrekers, I.R.J. Politzer, Am. Chem. Soc. 91 (1969)
63.
12] H. Gilman, N.J. Beaber, C.H.J. Meyers, Am. Chem. Soc. 47 (1925) 2047.
13] A. Meijere, F. Diederich (Eds.), Metal Catalyzed Cross Coupling Reactions,
Wiley, Chichester, 2004 (Chapter 1).
14] B.H. Lipshutz, S. Sengupta, Org. React. 41 (1992) 135.
15] N. Krause (Ed.), Modern Organocopper Chemistry, Wiley-VCH, Weinheim,
2001.
9
7 °C); IR (KBr) V cm : 1597, 1510, 1355 (SO
2
), 1182 (SO
) d ppm: 7.70 (2H, d, J = 8.4 Hz),
.24–7.31 (5H, m), 7.03 (2H, d, J = 7.2 Hz), 2.44 (3H, s).
2
), 810
1
(
S–O); H NMR (400 MHz, CDCl
3
9] P. Sun, L. Wang, Y. Zhang, Tetrahedron Lett. 38 (1997) 5549.
7
[
7
3
3 6 4 2 6
.5. 3-CH C H SO OC H5. 2c
[
[
Oil form, IR (KBr) V cmꢀ1: 1618, 1489, 1384 (SO
19 (S–O); H NMR (400 MHz, CDCl
2
2
), 1170 (SO ),
[
[
1
6
3
) d ppm: 7.65 (1H, s), 7.60
(
7
1H, d, J = 6.8 Hz), 7.43 (1H, d, J = 7.4 Hz), 7.37 (1H, t, J = 7.3 Hz),
.22–7.29 (3H, m), 6.97 (2H, d, J = 7.2 Hz), 2.37 (3H, s).
[
[
16] R.J.K. Taylor, Organocopper Reagents, Oxford University Press, Oxford, 1994.
17] E. Erdik, Organozinc Reagents in Organic Synthesis, CRC Press, Florida, 1996
(
Chapter 7).
[
[
18] P. Knochel, P. Jones (Eds.), Organozinc Reagents. A Practical Approach, Oxford
University Press, Oxford, 1999.
19] Z. Rappoport, I. Marek (Eds.), Patai’s the Chemistry of Organozinc Compounds,
Wiley, Chichester, 2007.
3
3 3 6 4 2 6 5
.6. 4-(CH ) CC H SO OC H 2d
Mp 50–55 °C, IR (KBr) V cmꢀ1: 1618, 1488, 1384 (SO
), 1170
) d ppm: 7.76 (2H, d,
2
1
(
SO
2
), 619 (S–O); H NMR (400 MHz, CDCl
3
[20] G.A. Silverman, P.E. Rakita (Eds.), Handbook of Grignard Reagents, Marcel
Dekker, New York, 1996 (Chapter 29).
[
[
J = 8.4 Hz), 7.53 (2H, d, J = 8.4 Hz), 7.24–7.31 (3H, m), 7.01 (2H, d,
J = 7.2 Hz), 1.34 (9H, s).
21] D. Zim, Y.R. Lando, J. Dupon, A.L. Monteiro, Org. Lett. 3 (2001) 3049.
22] D.H. Burns, J.D. Miller, H.K. Chan, H.-D.J. Delaney, Am. Chem. Soc. 119 (1997)
2125.
[
[
[
23] C.-H. Cho, M. Sun, K. Park, Bull. Korean Chem. Soc. 26 (2005) 1410.
24] C.-H. Cho, M. Sun, Y.-S. Sen, C.-B. Kim, K.J. Park, Org. Chem. 70 (2005) 1482.
25] C.-H. Cho, H.-S. Yun, K.J. Park, Org. Chem. 68 (2003) 3017.
3
3 2 6 5
.7. 4-CH OSO OC H 2e
Mp 60–63 °C (lit. [44] 62–63 °C), IR (KBr) V cmꢀ1: 1592, 1495,
), 670 (S–O); 1H NMR (400 MHz, CDCl
369 (SO ), 1158 (SO ) d
[26] E. Erdik, T. Da sß kapan, Synth. React. Inorg. Metal-Org. Comp. 25 (1995) 1517.
[27] E. Erdik, F. Ero g˘ lu, Synth. React. Inorg. Metal-Org. Comp. 30 (2000) 955.
[
1
2
2
3
28] I.M. Gordon, H. Maskill, M.F. Ruasse, Chem. Soc. Rev. 18 (1989) 123.
ppm: 7.73 (2H, d, J = 8.4 Hz), 7.23–7.31 (3H, m), 6.98 (2H, d,
J = 7.2 Hz), 6.96 (2H, d, J = 8.0 Hz), 3.88 (3H, s).
[29] M.J. Pregel, E.J. Dunn, E.J. Buncel, Am. Chem. Soc. 113 (1991) 3545. and
references cited therein.
[
30] I.-H. Um, S.-J. Lee, J.-J. Kim, D.-S. Kwon, Bull. Korean Chem. Soc. 15 (1994) 473.
and references cited therein.
Kinetic procedure for the reaction of phenylmagnesium bro-
mide 1a with phenyl arenesulfonates 2a–e: The kinetics were fol-
lowed by measuring concentration of remaining phenyl
arenesulfonate by GC analysis. Phenyl arenesulfonate, toluene
and internal standard were thermostated at 90 °C in a jacketed
two necked reaction vessel of approximately 25 ml capacity
equipped with a reflux condenser and a magnetic stirrer. THF solu-
tion of phenylmagnesium bromide was added rapidly to initiate
the reaction. Aliquots (7–13) were withdrawn from the homoge-
neous solution at 15 min intervals by syringe and were added to
[31] S.D. Yoh, J.-H. Park, D.-Y. Cheong, J.-H. Park, Y.-D. Lee, K.-T.J. Howang, Phys.
Org. Chem. 12 (1998) 319. and references cited therein..
[
32] S. Thea, C. Carpanelli, G. Cevasco, Eur. J. Org. Chem. 2001 (2001) 151. and
references cited therein.
[
33] J.H. Choi, B.C. Lee, H.W. Lee, I.J. Lee, Org. Chem. 67 (2002) 1277.
[34] E. Erdik, F. Ero g˘ lu, Cent. Eur. J. Chem. 6 (2008) 237.
[
[
35] N.S. Isaacs, Physical Organic Chemistry, Longman, Harlow, 1987 (Chapter 4).
36] H. Yanataka, N. Miyano, T.J. Hanafusa, Org. Chem. 56 (1991) 2573. and
references cited therein.
[37] E. Erdik, Ö. Ömür, Appl. Organomet. Chem. 19 (2005) 887.
[
38] E. Erdik, F. Ero g˘ lu, D.J. Kâhya, Phys. Org. Chem. 18 (2005) 950.
[
39] P. Zuman, R.C. Patel, Techniques in Organic Reaction Kinetics, Wiley, New York,
4
a vial containing a quenching solution of aqueous NH Cl for hydro-
1984 (Chapter 3.7).
lysis and diethyl ether. The vial was capped and shaken. Extraction
of the remaining phenyl arenesulfonate and products sulfone and
phenol was found to be essentially quantitative. The ethereal phase
was analyzed by GC analysis. Generally self consistent data could
be obtained for 2 or 3 half lives. Reproducibility of the rate con-
stants was generally ±5%.
[40] J. Leonard, B. Lygo, G. Procter, Advanced Practical Organic Chemistry, Blackie,
London, 1995.
[
[
41] C.H. Watson, J.F.J. Eastham, Organomet. Chem. 9 (1967) 167.
42] F. Drahovzol, D. Klaman, Monatsh 82 (1951) 452.
[43] R.S.J. Tipson, Org. Chem. 9 (1944) 235.
[
44] B.S. Nader, C.E. Povlowski, C.L. Powell, C.F. O’Brien, M.P. Arrington, Ind. Eng.
Chem. Res. 34 (1995) 981.