Reactions of [aryloxy(phenyl)carbene]pentacarbonylchromium(0) complexes with thiolate ions. Decreasing reactivity with increasing basicity of the nucleophile

Article abstract of DOI:10.1021/jo701422z

(Chemical Equation Presented) A kinetic study of the reactions of thiolate ions with three Fischer-type [aryloxy(phenyl)carbene]-pentacarbonyl chromium(0) complexes in 50% MeCN-50% water (v/v) is reported. Bronsted plots of the second-order rate constants are biphasic with an initial steep rise for weakly basic thiolate ions (β_nuc ≈ 1.0) followed by a slightly descending leg with a negative slope (β_nuc ≈ -0.2) for strongly basic thiolate ions. This indicates a change from rate-limiting leaving group departure at low pK_a^RSH to rate-limiting nucleophilic attachment at high pK_a^RSH. The negative β_nuc values result from a combination of minimal progress of C-S bond formation at the transition state and the requirement for partial desolvation of the nucleophile before it enters the transition state. Possible factors that may affect the degree of bond formation in reactions of Fischer carbene complexes as well as reactions of other unsaturated electrophiles with thiolate ions are discussed.

Full text of DOI:10.1021/jo701422z

Reactions of [Aryloxy(phenyl)carbene]pentacarbonylchromium(0)
Complexes with Thiolate Ions. Decreasing Reactivity with Increasing
†
Basicity of the Nucleophile
Claude F. Bernasconi,* Mois e´ s P e´ rez-Lorenzo, and Sara J. Codding
Department of Chemistry and Biochemistry, UniVersity of California, Santa Cruz, California 95064
bernasconi@chemistry.ucsc.edu
ReceiVed June 29, 2007
A kinetic study of the reactions of thiolate ions with three Fischer-type [aryloxy(phenyl)carbene]-
pentacarbonyl chromium(0) complexes in 50% MeCN-50% water (v/v) is reported. Brønsted plots of
the second-order rate constants are biphasic with an initial steep rise for weakly basic thiolate ions (ânuc
≈
1.0) followed by a slightly descending leg with a negative slope (ânuc ≈ -0.2) for strongly basic
RSH
a
thiolate ions. This indicates a change from rate-limiting leaving group departure at low pK
to rate-
RSH
limiting nucleophilic attachment at high pKa . The negative ânuc values result from a combination of
minimal progress of C-S bond formation at the transition state and the requirement for partial desolvation
of the nucleophile before it enters the transition state. Possible factors that may affect the degree of bond
formation in reactions of Fischer carbene complexes as well as reactions of other unsaturated electrophiles
with thiolate ions are discussed.
Introduction
are many factors that affect the reactivity of nucleophiles such
as its basicity, size, polarizability, charge, solvation, and the
nature of the electrophile, just to name the most important ones.
The situation becomes much simpler when nucleophiles within
the same family, i.e., bases with the same nucleophilic atom
and similar structural features, are compared with each other
and all the reactions are conducted in the same solvent. In such
cases, there is generally a good correlation between rate
constants and the basicity of the nucleophile, with the rate
Nucleophilic reactivity is a subject that has received a great
deal of attention over several decades and is discussed in
considerable detail in most books on physical organic chemistry
and many reviews.1-13 The subject is complex because there
†
Physical Organic Chemistry of Transition Metal Carbene Complexes. 35.
Part 34: Bernasconi, C. F.; Zoloff Michoff, M. E.; de Rossi, R. H.; Granados,
A. M. J. Org. Chem. 2007, 72, 1285.
constants typically increasing with increasing basicity. This is
(
1) Ingold, C. K. Structure and Mechanism in Organic Chemistry; Cornell
University Press: Ithaca, NY, 1953.
2) Hammett, L. P. Physical Organic Chemistry; McGraw-Hill: New
York, 1940.
NucH
commonly expressed by the Brønsted eq 1 where pKa
is the
(
NucH
logknuc ) ânucpKa
+ c
(1)
(
(
3) Hine, J. Physical Organic Chemistry; McGraw-Hill: New York, 1962.
4) Leffler, J. E., Grunwald, E. Rates and Equilibria of Organic
Reactions; Wiley & Sons: New York, 1963.
5) Kosower, E. M. Physical Organic Chemistry; McGraw-Hill: New
York, 1968.
pKa of the conjugate acid of the nucleophile and ânuc is equal
(
NucH
to the slope of a plot of logknuc versus pKa
and represents
NucH
(6) Jencks, W. P. Catalysis in Chemistry and Enzymology; McGraw-
the sensitivity of the rate to changes in pKa ; typically 1 >
ânuc > 0.
Hill: New York, 1969.
(
7) Alder, R. W.; Baker, R.; Brown, J. M. Mechanisms in Organic
Chemistry; Wiley-Interscience: New York, 1971.
8) Hudson, R. F. In Chemical ReactiVity and Reaction Paths; Klopman,
G., Ed.; Wiley & Sons: New York, 1974.
(
(11) Pross, A. Theoretical and Physical Principles of Organic ReactiVity;
McGraw-Hill: New York, 1995.
(
9) Harris, M. J.; McManus, S. P., Eds. AdV. Chem. Ser. 1957, 215
Nucleophilicity).
10) Isaacs, N. S. Physical Organic Chemistry; McGraw-Hill: New York,
981.
(12) Carroll, F. A. Structure and Mechanism in Organic Chemistry;
Brooks/Cole: New York, 1998.
(13) Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic
Chemistry; University Science Books: Sausalito, CA, 2006.
(
(
1
10.1021/jo701422z CCC: $37.00 © 2007 American Chemical Society
9
456
J. Org. Chem. 2007, 72, 9456-9463
Published on Web 11/15/2007

Reactions of Thiolate Ions with Fischer-Type Cr Complexes
A common interpretation of the numerical values of ânuc is
that they represent an approximate measure of the degree of
bond formation between the nucleophile and the electrophilic
center of the substrate at the transition state. This interpretation
4
goes back to the seminal contributions by Leffler and Grunwald
and is in keeping with the Hammond postulate.14
and 4-Cr-NO2 in 50% aqueous acetonitrile. The reactions follow
However, a number of cases have been reported where the
ânuc value was close to zero or even negative; in such cases
this interpretation cannot be correct. Examples where negative
the typical two-step mechanism for nucleophilic substitution at
22
the carbene carbon (eq 5). Depending on the basicity of the
thiolate ion, either the k1 or the k2 step is rate limiting. For the
reactions where the k1 step is rate limiting, the ânuc values are
again negative but not as strongly negative as for the reaction
ânuc values were found include the reaction of quinuclidines
with aryl phosphates,15 of amines with carbocations,
16,17
of
18
oximate ions with electrophilic phosphorus centers, of thiolate
21
of 4-Cr-NO2 with aryloxide ions.
19
19
ions with Fischer carbene complexes such as 1-M, 2-M, and
3
-M,20
Results
and of aryloxide ions with [p-nitrophenoxy(phenyl)carbene]-
pentacarbonylchromium(0) (4-Cr-NO2).2
-
-
Rates were determined with CH3CH2CH2S , HOCH2CH2S ,
0,21
-
-
-
-
MeOCOCH2CH2S , MeOCOCH2S , CF3CH2S , PhS , 3,4-Cl2-
-
-
C6H3S , and C6F5S as the nucleophiles in 50% MeCN-50%
water at 25 °C and an ionic strength of 0.1 M maintained with
KCl in most cases. The reactions were conducted under pseudo-
first-order conditions, with the carbene complex as the minor
component, and at constant pH corresponding to the pKa values
RSH
According to Jencks et al.,15 negative ânuc values result from a
combination of minimal progress of bond formation at the
transition state and the requirement for partial desolvation of
the nucleophile before it enters the transition state. In a first
approximation ânuc may be expressed by eq 2 where âd and
â′nuc are defined by eqs 3 and 4, respectively;
of the respective thiol (pK
). The kinetic runs were moni-
a
tored in a stopped-flow spectrometer at 390 nm for X ) H and
CH3, and at 400 nm for X ) NO2, respectively. Rates were
determined at six thiolate ion concentrations ranging from 5 ×
-
4
-3
-
10 to 5 × 10 M in all cases except for C6F5S where the
range was from 0.01 to 0.5 M due to the low reactivity of this
thiolate ion.
ânuc ) â + â′
(2)
(3)
(4)
d
nuc
Representative plots of pseudo-first-order rate constants (kobsd)
versus thiolate ion concentration are shown in Figure 1. The
slopes of these plots yield kRS, the second-order rate constants
for the overall reaction. Table 1 summarizes all kRS values
determined in this study.
NucH
a
â ) d logK /d pK
d
d
NucH
â′nuc ) d logk′ /d pKa
1
Kd represents the equilibrium constant for partial desolvation
of the nucleophile while k′1 is the rate constant for nucleophilic
attack by the partially desolvated nucleophile. Since desolvation
becomes more difficult with increasing basicity of the nucleo-
phile, âd < 0 which, along with a small â′nuc value, can lead to
a negative ânuc value. A more elaborate treatment of this problem
has been presented elsewhere.19
Discussion
Mechanism. Generally, nucleophilic substitution at the
carbene carbon of Fischer carbene complexes involves a two-
step mechanism as shown in eq 5 for the reactions studied in
the present work. Some of the most compelling evidence for
the stepwise nature of the mechanism has come from the study
2
2
19,20,24,25
of systems where the intermediate is directly detectable,
We now report a kinetic study of the reactions of a series of
thiolate ions with the Fischer carbene complexes 4-Cr-CH3,
including cases where the reaction is intramolecular.26 Recently,
4
-Cr-H,
(22) (a) D o¨ tz, K. H.; Fischer, H.; Hofmann, P.; Kreissl, F. R.; Schubert,
U.; Weiss, K. Transition Metal Carbene Complexes; Verlag Chemie:
Deerfield Beach, FL, 1983. (b) Bernasconi, C. F. Chem. Soc. ReV. 1997,
26, 299. (c) Bernasconi, C. F. AdV. Phys. Org. Chem. 2002, 37, 137.
(23) A referee has raised the question as to whether eq 5 might be
reversible. We did not find any evidence of reversibility and, in view of
the higher nucleophilicity of thiolate ions compared to aryloxide ions and
(
(
14) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334.
15) Jencks, W. P.; Haber, M. T.; Herschlag, D.; Nazaretian, K. L. J.
Am. Chem. Soc. 1986, 108, 479.
(
16) Richard, J. P. J. Chem. Soc., Chem. Commun. 1987, 1768.
(17) McClelland, R. A.; Kanagasabapathy, V. M.; Banait, N. S.; Steenken,
-
S. J. Am. Chem. Soc. 1992, 114, 1816.
18) (a) Terrier, F.; Le Gu e´ vel, E.; Chatrousse, A. P.; Moutiers, G.;
the very low concentrations of XC6H4O being formed during the reaction,
no measurable reversibility is expected.
(
Buncel, E. Chem. Commun. 2003, 600. (b) Terrier, F.; Rodriguez-Dafonte,
P.; Le, Gu e´ vel, E.; Moutiers, G. Org. Biomol. Chem. 2006, 4, 4352.
(24) Lam, C. I.; Senoff, C. V.; Ward, J. E. H. J. Organomet. Chem.
1974, 70, 273.
(25) (a) Bernasconi, C. F.; Flores, F. X.; Gandler, J. R.; Leyes, A. E.
Organometallics 1994, 13, 2186. (b) Bernasconi, C. F.; Garc ´ı a-R ´ı o, L. J.
Am. Chem. Soc. 2000, 122, 3821.
(19) Bernasconi, C. F.; Kittredge, K. W.; Flores, F. X. J. Am. Chem.
Soc. 1999, 121, 6630.
(20) Bernasconi, C. F.; Ali, M. J. Am. Chem. Soc. 1999, 121, 11384.
(
21) Bernasconi, C. F.; Zoloff Michoff, M. E.; de Rossi, R. H.; Granados,
(26) Bernasconi, C. F.; Ali, M.; Lu, F. J. Am. Chem. Soc. 2000, 122,
1352.
A. M. J. Org. Chem. 2007, 72, 1285.
J. Org. Chem, Vol. 72, No. 25, 2007 9457

Bernasconi et al.
FIGURE 1. Representative plots of kobsd versus thiolate ion concentra-
-
-
tionforreactionsof4-Cr-H: (0)CH CH CH S ;(9)MeOCOCH CH S ;
3 2 2 2 2
-
-
(
O) MeOCOCH S ; and (b) PhS .
2
it was shown that even with exceptionally good leaving groups
such as p-nitrophenoxy the reaction of aryloxide ions with 4-Cr-
NO2 is still stepwise.21 This contrasts with nucleophilic substitu-
tions on carboxylic acid esters where the reactions become
27,28
concerted for aryloxy leaving groups.
The reason for this
contrast is that the intermediates in the reaction of the Fischer
carbenes are both thermodynamically and kinetically much more
stable than the corresponding tetrahedral intermediates in the
2
1,22b
ester reactions.
FIGURE 2. Brønsted plot for the reactions of 4-Cr-X with thiolate
ions.
The results of the present study confirm the stepwise nature
of the reaction of 4-Cr-X with thiolate ions because the data
indicate a change in the rate-limiting step as the basicity of the
nucleophile changes. This change manifests itself in the biphasic
nature of the Brønsted plots for 4-Cr-H and 4-Cr-Me (Figure
We note that the break in the Brønsted plots of Figure 2A,B
RSH
which correspond to k2 ) k-1 occurs at pKa
around 8. This
implies that the leaving group abilities of aryloxide ions with
ArOH
a
2
A,B). For the reaction of 4-Cr-NO2 (Figure 2C), the kinetic
pK
values of 11.6 (X ) H) or 11.9 (X ) Me) are
RSH
stopped-flow traces for the reactions with the two least basic
thiolate ions were erratic and irreproducible and hence no kRS
values could be determined; the reason for the erratic behavior
is unclear.
The Brønsted plots in Figure 2A,B show a steep initial rise
that is followed by a straight line with a small negative slope.
The slope values (ânuc) are summarized in Table 2.
The biphasic nature of the Brønsted plots can be understood
based on the rate law for eq 5, which, using the steady state
approximation for the intermediate, yields eq 6 for the second-
order rate constant kRS. For weakly basic thiolate ions the
breakdown of the intermediate back to
comparable to that of a thiolate ion with pKa ≈ 8.0. Or,
stated differently, aryloxide ions are much better leaving groups
than thiolate ions of similar basicities.
A similar conclusion was reached by Douglas and Alborz,29
who showed that aryloxide ions depart from acetoacetate anions
3
5 × 10 times faster than thiolate ions of the same basicity,
and 79 times faster from fluorene-9-carboxylic acid ester anions.
On the other hand, in the reactions of thiolate ions with
arylacetates, eq 9,
k k
1
2
kRS
)
(6)
k-1 + k2
the leaving group ability of the aryloxide ions is comparable or
even somewhat less than that of thiolate ions of similar
the reactants is faster than its conversion to products (k-1 >
(.) k2) and hence eq 6 simplifies to eq 7.
(27) (a) Ba-Saif, S.; Luthra, A. K.; Williams, A. J. Am. Chem. Soc. 1987,
1
09, 6362. (b) Ba-Saif, S.; Luthra, A. K.; Williams, A. J. Am. Chem. Soc.
kRS ) K1k2
(7)
1989, 111, 2647.
(
28) (a) Stefanidis, D.; Cho, S.; Dhe-Pagenon, S.; Jencks, W. P. J. Am.
For strongly basic thiolate ions the opposite is true (k-1 < (,)
k2) and nucleophilic attack becomes rate limiting, eq 8.
Chem. Soc. 1993, 115, 1650. (b) Hengge, A. C.; Hess, R. A. J. Am. Chem.
Soc. 1994, 116, 11256. (c) Fernandez, M. A.; de Rossi, R. H. J. Org. Chem.
1
999, 64, 6000.
29) Douglas, K. T.; Alborz, M. J. Chem. Soc., Chem. Commum. 1981,
551.
(
kRS ) k1
(8)
9458 J. Org. Chem., Vol. 72, No. 25, 2007

Reactions of Thiolate Ions with Fischer-Type Cr Complexes
TABLE 1. Summary of the Second-Order Rate Constants, kRS, for the Reactions of Thiolate Ions with 4-Cr-X (X ) CH3, H, NO2) in 50%
a
MeCN-50% Water at 25 °C
RS-
pKa
RSH
10-3kRS(CH3), M-1 s-1
10-3kRS(H), M-1 s-1
10-3kRS(NO2), M-1 s-1
-
CH3CH2CH2S
HOCH2CH2S
11.94
10.79
10.69
9.45
9.07
7.84
3.34 ( 0.06
3.87 ( 0.10
4.30 ( 0.07
4.90 ( 0.10
9.19 ( 0.10
11.55 ( 0.09
15.4 ( 0.1
46.3 ( 1.8
38.1 ( 0.2
76.8 ( 1.6
121 ( 2.1
147 ( 3
-
-
CH3OCOCH2CH2S
7.42 ( 0.14
-
CH3OCOCH2S
8.97 ( 0.04
-
CF3CH2S
PhS
13.9 ( 0.04
-
8.81 ( 0.17
20.6 ( 0.6
294 ( 6
-
3
,4-Cl2-C6H3S
6.60
3.97
0.307 ( 0.013
0.00097 ( 0.00004
0.93 ( 0.07
0.00162 ( 0.0007
-
C6F5S
a
-
-
µ
)
0
.
1
m
a
i
n
t
a
i
n
e
d
w
i
t
h
K
C
l
e
x
c
e
p
t
f
o
r
t
h
e
r
e
a
c
t
i
o
n
s
w
i
t
h
C
6
F
5
S
w
h
e
r
e
µ
)
0
.
5
M
w
a
s
u
s
e
d
d
u
e
t
o
t
h
e
h
i
g
h
e
r
c
o
n
c
e
n
t
r
a
t
i
o
n
r
a
n
g
e
o
f
[
C
6
F
5
S
]
.
basicity.30 Specifically, the break in the Brønsted plots (k-1 )
of oxyanions implies that their partial desolvation is energetically
more demanding, which may translate into a more negative âd
value.
RSH
k2) for these reactions occurs at pK
≈ 10.1 for X ) H
a
ArOH
RSH
a
ArOH
a
(pKa
) 9.86), pK
≈ 7.8 for X ) 4-NO2 (pK
)
RSH
ArOH
Regarding the ânuc(K1k2) values for the reaction of thiolate
7
.14), and pKa ≈ 5.0 for X ) 2,4-(NO2)2 (pK
) 5.20).
a
2
9
ions with 4-Cr-Me (ca. 1.01) and 4-Cr-NO (ca. 1.06), they
As discussed in more detail by Douglas and Alborz, the
relative leaving group abilities of oxyanions and thiolate ions
clearly depends strongly on the specific reaction system.
Brønsted Coefficients. The ânuc values determined in the
present study as well as those referring to the reactions of other
Fischer carbene complexes are summarized in Table 2. As
discussed in the Introduction, the negative values for ânuc(k1)
must result from a combination of minimal progress of C-S
bond formation at the transition state and the impact of having
to partially desolvate the nucleophile as it enters the transition
state, i.e., eq 2 applies with âd < 0 and |âd| > â′nuc.
2
may be broken down into ânuc(K1k2) ) âeq + âpush where âeq
RSH
describes the dependence of K1 on the pKa
and âpush refers
to the electronic push by the lone pairs of the sulfur atom that
arises from the resonance development in the product. These
ânuc(K1k2) values are quite similar to those reported by Hupe
3
0
and Jencks for eq 9.
Regarding the dependence of ânuc(k1) on the carbene complex
the following points are noteworthy.
Reactivity. The k1 values for the reaction of 4-Cr-H
(1) For the three carbene complexes with aryloxy leaving
-
3
-1 -1
with HOCH2CH2S (4.90 × 10 M s ) are about 4.5-fold
groups (4-Cr-X with X ) CH3, H, and NO2) the ânuc(k1) values
are all around -0.20, i.e., there is no dependence on the aryl
substituent. This implies that either both âd and â′nuc are constant
or that any change in âd is offset by an equal but opposite change
lower than for the reaction of 1-Cr with the same nucleophile.
For the reaction with OH the reactivity difference is a
factor of 11 in favor of 1-Cr relative to 4-Cr-H. As pointed
-
2
1
2
1
out before, based on electronic effects alone 4-Cr-H should
be more reactive because the PhO group is more electron
withdrawing than the MeO group and the methoxy group is a
stronger π-donor than the PhO group, which lowers the
reactivity of 1-Cr. The results imply that the steric effect of
the larger PhO group more than offsets the electronic effects
and is responsible for the lower reactivity of 4-Cr-H. That steric
effects in reactions of nucleophiles with carbene complexes are
14
4
in â′nuc. For example, according to the Hammond -Leffler
postulate the increase in reactivity in the order 4-Cr-Me <
-Cr-H , 4-Cr-NO2 may lead to a decrease in C-S bond
4
formation at the transition state, thereby reducing â′nuc. This
would require a corresponding increase in âd, making it less
negative and implying less desolvation of the thiolate ion at
the transition state.
(
2) For the other carbene complexes with alkoxy and
31
important has also been shown by Zoloff Michoff et al. and
methyl thio leaving groups the ânuc(k1) values are slightly
more negative, i.e., between -0.25 and -0.30. It is not clear
whether the differences within this set or even relative to
the set for 4-Cr-X are significant or just the result of
experimental uncertainty. In any case, there is no obvious
correlation between the ânuc(k1) values and the reactivity of the
carbene complexes as measured by k1 for the standard thiolate
2
0,21
others.
Hammett Plots. Figure 3 shows Hammett plots for the
-
-
reactions with CH3CH2CH2S , HOCH2CH2S , CH3OCOCH2-
-
-
-
CH2S , CH3OCOCH2S , and CF3CH2S . These are the nu-
cleophiles for which kRS is clearly equal to k1, so F ) F(k1).
The F(k1) values are 1.24 ( 0.10, 1.08 ( 0.08, 1.10 ( 0.09,
1
.22 ( 0.10, and 1.13 ( 0.15, respectively, i.e., they are all the
-
ion HOCH2CH2S (last column in Table 2). If the ânuc(k1) values
same within the experimental uncertainties with an average value
of 1.15. The fact that the F values are independent of the
nucleophile is not only consistent with the observation that
the ânuc(k1) values are independent of the leaving group
substituent, they are a required consequence. This is because
for this second set are truly slightly more negative than for the
first, it is not clear whether this is because â′nuc is smaller or âd
is more negative.
(3) For the reaction of 4-Cr-NO2 with aryloxide ions there
is little doubt that the ânuc(k1) value (-0.39 ( 0.03) should
be regarded as significantly more negative than ânuc(k1) for the
reaction of the same carbene complex with thiolate ions (-0.21
RSH
the dependence of F on pKa and the dependence of ânuc(k1)
on σ are coupled through the cross-correlation coefficient,
3
2,33
pxy (eq 10).
Our results indicate that pxy ≈ 0, which is
(
0.04). This difference is most plausibly interpreted in terms
of differences in solvation energies of thiolate versus oxy-
anions. Specifically, the stronger hydrogen bonding solvation
(
31) Zoloff Michoff, M. E.; de Rossi, R. H.; Granados, A. M. J. Org.
Chem. 2006, 71, 2395.
2
RSH
2
BH
a
(
32) pxy ) (d log k1)/(dσ dpK ) ) (d log)/(dpK dσ).
a
(30) Hupe, D. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 451.
(33) Jencks, D. A.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 7948.
J. Org. Chem, Vol. 72, No. 25, 2007 9459

Bernasconi et al.
TABLE 2. Brønsted ânuc Values for Reactions of Fischer Carbene Complexes with Thiolate Ions in 50% MeCN-50% Water at 25 °C
a
Errors are standard deviations. b This work. c Reference 19. d Reference 20. e Reference 21.
a reasonable result for a reaction where leaving group departure
is decoupled from the nucleophilic attachment step.
the F value should be enhanced because k2 is expected to show
a much stronger dependence on the leaving group substituent
than k1.
dF
d pKa
dânuc(k1)
A comparison of F(k1) for the reactions of thiolate ions with
4-Cr-X with F(k1) values for nucleophilic attachment to other
Fischer carbenes is instructive. These latter are summarized in
Table 3. The most obvious interpretation of the positive F(k1)
values is that they indicate stabilization of the developing
negative charge at the transition state by electron-withdrawing
substituents. However, the fact that there are large variations
in these F(k1) values suggests that other factors come into play
p )
)
(10)
xy
RSH
dσ
-
The Hammett plot for the reaction of PhS (not shown) has
a F value of 1.57 ( 0.10. The somewhat higher value than for
the more basic thiolate ions may be attributed to a transition
from k2 . k-1 to k2 > k-1 so that kRS is no longer strictly equal
to k1 but given by eq 6 where k2 makes a small contribution to
-
kRS. The fact that the point for PhS on the Brønsted plot for
(34) (a) Bernasconi, C. F.; Ali, M. Organometallics 2001, 20, 3383. (b)
4
-Cr-Me shows a small negative deviation is consistent with
Bernasconi, C. F.; Bhattacharya, S. Organometallics 2003, 22, 1310.
3
6
this notion. As a consequence of the contribution of k2 to kRS,
(35) σR ) -0.43 and -0.15 for MeO and MeS, respectively.
9460 J. Org. Chem., Vol. 72, No. 25, 2007

Reactions of Thiolate Ions with Fischer-Type Cr Complexes
3
5
(
which is particularly strong with alkoxy groups, e.g., 6 , but
weaker for alkylthio groups (5 ).
(
35
(
Electron-withdrawing substituents destabilize 6 , which en-
hances the reactivity of the carbene complex and hence renders
F(k1) more positive. This is believed to be the main reason why
F(k1) is larger for alkoxy carbenes (nos. 2-5, 8) than for
alkylthio carbenes (nos. 6, 7, 9).
The reactions reported in the current study (no. 1) differ from
all the others in that the substituents are on the aryloxy leaving
group rather than on the phenyl group directly attached to the
carbene carbon. This increases the distance between the sub-
stituent and the site of negative charge development at the
transition state, thereby strongly reducing the contribution of
transition state stabilization to the F(k1) value, assuming a
comparable degree of bond formation at the transition state. The
fact that the F(k1) value (1.15) is as large as it is and larger
than for most reactions where the leaving group is an alkylthio
group suggests that here, too, the π-donor effect plays a
dominant role. However, the fact that the substituents are on
the aryloxy group leads to a somewhat different situation
regarding the influence of the π-donor effect. The oxygen in 7
FIGURE 3. Hammett plots for the reactions of 4-Cr-X with
-
-
-
-
2
CH
MeOCOCH
3
CH
2
CH
2
S
(4), HOCH
2
CH
2
S
(2), MeOCOCH
2
CH
S
(0),
-
-
2
S
(9), CF
3
2
CH S
(O), and PhS (b).
TABLE 3. Representative Hammett G(k1) Values for Reactions of
Fischer Carbene Complexes with Nucleophiles in 50% MeCN-50%
Water (v/v) at 25 °C
is less basic than that in 6, which should reduce its π-donor
strength and hence the stabilization of the carbene complex.
On the other hand, the closer proximity of the substituents to
the π-donor atom in 7 should enhance the substituent effect on
the π-donor effect. The overall result appears to be a positive
contribution to the F(k1) values.
Comparison with Other Reactions. Irrespective of the
precise breakdown of ânuc(k1) into â′nuc and âd, it is reasonable
to conclude that C-S bond formation in the reactions of thiolate
ions with Fischer carbene complexes has made very little
progress at the transition state. How do these ânuc(k1) values
compare with those for the attachment of thiolate ions to other
electrophiles such as esters, aromatic compounds, and vinylic
substrates? Table 4 summarizes some representative ânuc(k1)
values. The table includes rate constants for the reaction with
thiophenoxide ion; these rate constants provide a crude measure
of the relative reactivities of the various electrophiles although
they do not allow a distinction to be made between cases where
k1 is high mainly because of a large thermodynamic driving
force (large K1) and cases where k1 is high mainly because of
a low Marcus intrinsic barrier or high intrinsic rate constant.37
The range of these ânuc(k1) values from -0.30 to 0.65 is
remarkably large. As is the case for the comparison of ânuc(k1)
values for the reactions within the family of carbene complexes
a
b
Average value for first five thiolate ions in Table 1. This work.
c
d
Reference 25b. F includes dependence of acidity constant of the OH
group. Ali, M.; Bernasconi, C. F.; Biswas, S. J. Organomet. Chem. 2006,
91, 3477. Reference 34a. Reference 20. Bernasconi, C. F.; Whitesell,
C.; Johnson, R. A. Tetrahedron 2000, 56, 4917. Reference 34b.
e
(Table 2), there is no clear correlation between ânuc(k1) and the
f
g
h
6
reactivity of the electrophiles. For example, within the ester
i
(
36) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165.
(37) The Marcus intrinsic barrier (intrinsic rate constant) is the barrier
as well. One important factor identified previously is the π-donor
o
for a reaction without thermodynamic driving force, i.e., ∆G ) 0 (the rate
constant when the equilibrium constant is unity).
34
38,39
effect of the leaving group on the stabilization of the reactant,
J. Org. Chem, Vol. 72, No. 25, 2007 9461

Bernasconi et al.
TABLE 4. Representative ânuc(k1) Values for the Attachment of Thiolate Ions to Electrophiles
a
b
Crampton, M. R.; Willison, M. J. J. Chem. Soc., Perkin Trans. 2 1974, 238. Bartoli, G.; Di Nunno, L.; Forlani, L; Todesco, P. E. Int. J. Sulfur Chem.,
c
d
e
C 1971, 6, 77. Reference 30. Bernasconi, C. F.; Ketner, R. J.; Chen, X.; Rappoport, Z. J. Am. Chem. Soc. 1998, 120, 7461. Bernasconi, C. F.; Ketner,
f
R. J.; Chen, X.; Rappoport, Z. Can. J. Chem. 1999, 77, 584. Bernasconi, C. F.; Fassberg, J.; Killion, R. B., Jr.; Rappoport, Z. J. Am. Chem. Soc. 1990, 112,
g
h
3
169. Extrapolated value. This work. i Reference 20.
family, ânuc(k1) is constant (0.27) despite a reactivity range of
orders of magnitude. Furthermore, the esters as a group are
the least reactive electrophiles except for p-nitrofluoro and
p-nitrochlorobenzene yet the ânuc(k1) values are close to the
midrange. On the other hand, the reactivity of the benzylidene
Meldrum’s acid derivatives is quite comparable to that of the
respective carbene complexes but the ânuc(k1) values are much
smaller for the latter.
4
9462 J. Org. Chem., Vol. 72, No. 25, 2007

Reactions of Thiolate Ions with Fischer-Type Cr Complexes
One factor that does seem to play a role in the trend of the
ânuc(k1) values is steric crowding at the transition state. This
crowding is particularly severe in the reactions of the carbene
at the transition state is a factor in retarding the C-S bond
formation at the transition state and lowering ânuc(k1).
2
0,40
complexes due to the large size of the (CO)5Cr group;
it is
Experimental Section
also quite considerable in the reactions of the benzylidene
Meldrum’s acid derivatives.41 It appears then that the crowding
Materials. The carbene complexes 4-Cr-H and 4-Cr-NO
2
were
21
available from a previous study while 4-Cr-Me was prepared as
leads to transition states in which C-S bond formation has made
less progress in order to avoid excessive steric strain. However,
what is still lacking is a comprehensive theory that encompasses
all possible factors that contribute to the degree of bond
formation at the transition state of nucleophilic attachment
reactions.
4
2
described by Pulley et al. and identified by NMR (500 MHz,
1
CDCl
and OC
6 4
57.8 (Ph and OC H
3
) as follows: H NMR δ 2.44 (3H, s), 7.11-7.44 (9H, Ph
13
6
H
4
); C NMR δ 121.3, 124.8, 128.0, 130.2, 137.6, 154.7,
), 215.4 (cis CO), 225.1 (trans CO), 351.7
1
(Cd). Thiols were obtained from commercial vendors in the highest
available purity and distilled under argon prior to use. KOH
solutions were prepared from DILUT-IT analytical concentrates (J.
T. Baker). ACS high-purity HPLC acetonitrile was used without
purification. Ultrapure water was obtained from a Millipore
MILLI-Q Plus water system.
Conclusions
(1) The reaction of thiolate ions with the Fischer-type carbene
Kinetic Experiments. All kinetic experiments were conducted
complexes 4-Cr-X is stepwise (eq 5) as evidenced by the sharp
in 50% MeCN-50% water (v/v) at 25 °C. The ionic strength was
break in the Brønsted plots, indicating a change from rate-
-
6 5
maintained at 0.1 M with KCl except for the reactions with C F S
RSH
limiting leaving group expulsion (k2) at low pKa
to rate-
where the ionic strength was 0.5 M because the low reactivity of
this thiolate ion required the use of higher concentrations. All rates
were measured in a stopped-flow spectrophotometer. In most cases
the reactions were initiated by mixing equal volumes of an
acetonitrile solution of the carbene complex with an aqueous
solution of the thiolate buffer. In this way hydrolysis of the carbene
complex prior to its reaction with the thiolate ion could be avoided.
RSH
limiting nucleophilic attachment (k1) at high pKa
.
(
2) The fact that the break in the Brønsted plots where k2 )
RSH
a
k-1 occurs at a pK
value (∼8.0) that is much lower than the
ArOH
pKa
of the aryloxy leaving groups means that the aryloxide
ions are much better leaving groups than the thiolate ions of
comparable basicities. However, this conclusion does not
necessarily apply to other reaction systems such as, e.g., eq 9.
-
-
2 6 5 6 5
For the reactions with 3,4-Cl C H S and C F S the reactions were
initiated by mixing equal volumes of 50% aqueous acetonitrile
solutions of carbene complex and thiolate buffer because of the
relatively low solubility of the respective thiols in water. Since these
buffer reactions were conducted at low pH hydrolysis was minimal.
Special caution was required for the preparation of the aromatic
thiolate ion buffers due to their facile oxidation. They were prepared
by injecting the freshly distilled thiol into the appropriate KOH
solution that had been degassed for 1 h in an ultrasonic bath while
under a stream of argon bubbling through the solution. Transfer
into the stopped-flow syringe was carried out under argon.
Rates were monitored at 390 nm for 4-Cr-Me and 4-Cr-H and
(3) The ânuc(k1) values for the three carbene complexes are
around -0.2. The negative values result from a combination of
minimal progress of bond formation at the transition state and
the requirement for partial desolvation of the thiolate ion before
it enters the transition state. The ânuc(k1) values for the reactions
of aryloxide ions with 4-Cr-NO2 are even more negative than
those for the reactions of thiolate ions with 4-Cr-X. This is
probably the result of the stronger solvation of the aryloxide
ions, which makes their partial desolvation energetically more
demanding.
2
at 400 nm for 4-Cr-NO . Typical substrate concentrations were
-5
(4) The Hammett F(k1) values are independent of the thiolate
3-5 × 10 M while thiol and thiolate concentrations were always
in large excess over the substrate. All pH measurements were carried
out on an Orion 611 pH meter equipped with a glass electrode and
a Sure-Flow (Corning) reference electrode and calibrated with
standard aqueous buffers. The pH in 50% MeCN-50% water (v/
v) was determined according to Allen and Tidwell.43 The pH of
the reaction solutions for the stopped-flow runs was measured in
ion (average 1.15). This implies a pxy ≈ 0 and is consistent
with the ânuc(k1) values being independent of the X-substituent.
(5) The main factor responsible for the positive F values is
the increase in the reactivity of 4-Cr-X with electron-withdraw-
ing substituents, which reduces the stabilization of the carbene
complex by the π-donor effect of the oxygen atom. Transition
state stabilization plays a minor role due to the large distance
of the substituent from the site of negative charge development.
mock-mixing experiments that simulated the kinetic runs. The pK
a
values of the thiols were determined by measuring the pH of 1:1
or 9:1 buffer solutions under the reaction conditions.
(
6) In comparing ânuc(k1) values for the reaction of thiolate
ions with other unsaturated electrophiles no clear correlation
with reactivity exists. However, it appears that steric crowding
Acknowledgment. This research was supported by Grant
CHE-046622 from the National Science Foundation. Support
of S.J.C. by NSF-REU-CHE-0552641 is also gratefully
acknowledged.
(38) Marcus, R. A. J. Phys. Chem. 1968, 72, 891.
(
39) Keeffe, J. R.; Kresge, A. J. In InVestigation of Rates and Mechanisms
JO701422Z
of Reactions; Bernasconi, C. F., Ed.; Wiley-Interscience: New York, 1986;
Part 1, p 747.
(
40) Bernasconi, C. F.; Bhattacharya, S. Organometallics 2003, 22, 426.
41) Bernasconi, C. F.; Ketner, R. J.; Ragains, M. L.; Chen, X.;
(42) Pulley, S R.; Sen, S.; Vogorushin, A.; Swanson, E. Org. Lett. 1999,
1, 1721.
(
Rappoport, Z. J. Am. Chem. Soc. 2001, 123, 2155.
(43) Allen, A. D.; Tidwell, T. T. J. Am. Chem. Soc. 1987, 109, 2774.
J. Org. Chem, Vol. 72, No. 25, 2007 9463