Inverse solvent effects in carbocation carbanion combination reactions: The unique behavior of trifluoromethylsulfonyl stabilized carbanions

Article abstract of DOI:10.1021/ja072135b

Second-order rate constants for the reactions of the trifluoromethylsulfonyl substituted benzyl anions 1a-e (CF₃SO ₂CH-C₆H₄-X) with the benzhydrylium ions 2f-j and structurally related quinone methides 2a-e have

Full text of DOI:10.1021/ja072135b

Published on Web 07/18/2007
Inverse Solvent Effects in Carbocation Carbanion
Combination Reactions: The Unique Behavior of
Trifluoromethylsulfonyl Stabilized Carbanions
Stefan T. A. Berger, Armin R. Ofial, and Herbert Mayr*
Contribution from the Department Chemie und Biochemie, Ludwig-Maximilians-UniVersita¨t
Mu¨nchen, Butenandtstr. 5-13 (Haus F), 81377 Mu¨nchen, Germany
Received March 27, 2007; E-mail: herbert.mayr@cup.uni-muenchen.de
Abstract: Second-order rate constants for the reactions of the trifluoromethylsulfonyl substituted benzyl
anions 1a-e (CF3SO2CH--C6H4-X) with the benzhydrylium ions 2f-j and structurally related quinone
methides 2a-e have been determined by UV-vis spectroscopy. The reactions proceed approximately
10-40 times faster in methanol than in DMSO leading to the unique situation that these carbocation
carbanion combinations are faster in protic than in dipolar aprotic media. The pKa values of some benzyl
trifluoromethylsulfones were determined in methanol (1c-H, 17.1; 1d-H, 16.0; 1e-H, 15.0) and found to be
5 units larger than the corresponding values in DMSO. Rate and equilibrium measurements thus agree
that the trifluoromethylsulfonyl substituted benzyl anions 1a-e are more effectively solvated by ion-dipole
interactions in DMSO than by hydrogen bonding in methanol. Brønsted correlations show that in DMSO
the trifluoromethylsulfonyl substituted carbanions 1 are less nucleophilic than most other types of carbanions
of similar basicity, indicating that in DMSO the intrinsic barriers for the reactions of the localized carbanions
1 are higher than those of delocalized carbanions, including nitroalkyl anions. The situation is reversed in
methanol, where the reactions of the localized carbanions 1 possess lower intrinsic barriers than those of
delocalized carbanions as commonly found for proton-transfer processes. As a consequence, the relative
magnitudes of intrinsic barriers are strongly dependent on the solvent.
Relationships between nucleophilicity (i.e., relative rates of
reactions of electron-pair donors with a given electrophile) and
basicity (i.e., relative affinities for a proton in acid-base
equilibria) play a central role for our understanding of organic
reactivity.1-5 While it is well-known that good correlations
between nucleophilic reactivities and the pKa values of the
conjugate acids can only be obtained when the nature of the
reaction center remains unchanged,6 in some cases anomalous
rate equilibrium relationships have been observed, even
within families of closely related compounds.7 The most
prominent example for an untypical Brønsted correlation is the
so-called “nitroalkane anomaly” which implies that the rates
of protonation of nitronate anions decrease with increasing
basicity.8
There is ample evidence that nitro-stabilized carbanions are best
described by the resonance structure with a CN double bond,
as indicated in Scheme 1.9,10
A completely different type of anion stabilization is exerted
by the CF3SO2 group, which has been known to be one of the
strongest electron acceptor groups in organic chemistry since
the pioneering investigations by Sheppard11 and Yagupol’skii.12
(8) (a) Fukuyama, M. P.; Flanagan, W. K.; Williams, F. T., Jr.; Frainier, L.;
Miller, S. A.; Shechter, H. J. Am. Chem. Soc. 1970, 92, 4689-4699. (b)
Bordwell, F. G.; Boyle, W. J., Jr.; Yee, K. C. J. Am. Chem. Soc. 1970, 92,
5926-5932. (c) Bordwell, F. G.; Boyle, W. J., Jr. J. Am. Chem. Soc. 1975,
97, 3447-3452. (d) Bernasconi, C. F.; Wiersema, D.; Stronach, M. W. J.
Org. Chem. 1993, 58, 217-223. (e) Yamataka, H.; Ammal, S. C. ArkiVoc
2003, 10, 59-68. (f) Eliad, L.; Hoz, S. J. Phys. Org. Chem. 2002, 15,
540-543. (g) Yamataka, H.; Mustanir; Mishima, M. J. Am. Chem. Soc.
1999, 121, 10223-10224. (h) Beksic, D.; Betran, J.; Lluch, J. M.; Hynes,
J. T. J. Phys. Chem. A 1998, 102, 3977-3984. (i) Erden, I.; Keefe, J. R.;
Xu, F. P.; Zheng, J. B. J. Am. Chem. Soc. 1993, 115, 9834-9835. (j)
Bernasconi, C. F.; Paschalis, P. J. Am. Chem. Soc. 1989, 111, 5893-5902.
(k) Albery, W. J.; Bernasconi, C. F.; Kresge, A. J. J. Phys. Org. Chem.
1988, 1, 29-31. (l) Pross, A.; Shaik, S. S. J. Am. Chem. Soc. 1982, 104,
1129-1130. (m) Agmon, N. J. Am. Chem. Soc. 1980, 102, 2164-2167.
(n) Keeffe, J. R.; Morey, J.; Palmer, C. A.; Lee, J. C. J. Am. Chem. Soc.
1979, 101, 1295-1297. (o) Kresge, A. J. Can. J. Chem. 1974, 52, 1897-
1903. (p) Goumont, R.; Magnier, E.; Kizilian, E.; Terrier, F. J. Org. Chem.
2003, 68, 6566-6570. (q) Terrier, F.; Moutiers, G.; Pelet, S.; Buncel, E.
Eur. J. Org. Chem. 1999, 1771-1774. (r) Moutiers, G.; Peignieux, A.;
Terrier, F. J. Chem. Soc., Perkin Trans. 2 1998, 2489-2495. (s) Moutiers,
G.; Thuet, V.; Terrier, F. J. Chem. Soc., Perkin Trans. 2 1997, 1479-
1486. (t) Marcus, R. A. J. Am. Chem. Soc. 1969, 91, 7224-7225.
(9) (a) Bernasconi, C. F.; Ali, M.; Gunter, J. C. J. Am. Chem. Soc. 2003, 125,
151-157. (b) Bernasconi, C. F. Acc. Chem. Res. 1987, 20, 301-308. (c)
Bernasconi, C. F. J. Phys. Org. Chem. 2004, 17, 951-956. (d) Bernasconi,
C. F. Acc. Chem. Res. 1992, 25, 9-16.
Transition state imbalances, due to the extensive π-delocal-
ization of nitro stabilized carbanions, have been claimed to be
responsible for the high intrinsic barriers of these reactions.9
(1) Williams, A. Free Energy Relationship in Organic and Bio-organic
Chemistry; The Royal Society of Chemistry: Cambridge, U.K., 2003.
(2) Brønsted, J. N.; Pedersen, K. Z. Phys. Chem. 1924, 108, 185-235.
(3) Hammett, L. P. J. Am. Chem. Soc. 1937, 59, 96-103.
(4) Eigen, M. Angew. Chem. 1963, 75, 489-508; Angew. Chem., Int. Ed. Engl.
1964, 3, 1-19.
(5) Nucleophilicity ; Harris, J. M., McManus, S. P., Eds.; Advances in
Chemistry Series 215; American Chemical Society: Washington, DC, 1987.
(6) Bordwell, F. G.; Cripe, A.; Hughes, D. L. In Nucleophilicity; Harris, J.
M., McManus, S. P., Eds.; Advances in Chemistry Series 215; American
Chemical Society: Washington, DC, 1987; Chapter 9.
(7) Jencks, W. P. In Nucleophilicity; Harris, J. M., McManus, S. P., Eds.;
Advances in Chemistry Series 215; American Chemical Society: Wash-
ington, DC, 1987; Chapter 10.
(10) Nielsen, A. T. In Nitrones, Nitronates and Nitroxides; Breuer, E., Aurich,
H. G., Nielsen, A. T., Eds.; Wiley: New York, 1989.
9
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J. AM. CHEM. SOC. 2007, 129, 9753-9761
9753

A R T I C L E S
Berger et al.
Scheme 1. Nitro- and Triflinate Stabilized Carbanions
Table 1. Quinone Methides 2a-e and Benzhydrylium Ions 2f-j
Employed in This Work
Scheme 2. Preparation of the 4-X-Benzyl Trifluoromethyl Sulfones
(1a-e)-H According to the Hendrickson Method and Generation of
the Corresponding R-Triflinate Stabilized Carbanions 1a-e
The pKa values of substituted benzoic acids indicate that the
CF3SO2 group (σp ) 0.96)12,13 is a stronger electron acceptor
than the nitro group (σp ) 0.81).13
Comparison of the pKa values of substituted anilinium ions
and phenols also showed the greater electron-accepting power
of CF3SO2 (σp ) 1.63 or 1.65)12,13 compared to NO2 (σp
)
-
-
1.24).13,14 NMR spectroscopic investigations of triflinate sub-
stituted carbanions revealed that the carbanion center is sp3-
hybridized and that resonance stabilization is unimportant,
resulting in the high weight of the resonance structure on the
left side of Scheme 1.15 In line with this interpretation is the
unusual solvent dependence of the pKa values of the benzyl
trifluoromethyl sulfones. In contrast to the behavior of most
CH acids, their acidities decrease with increasing water content
of DMSO/H2O mixtures.8p,15
a Electrophilicity parameters E for 2a-e from ref 22a and for 2f-j from
b
c
from ref 16d. In DMSO, from ref 23. From ref 24.
in orderto determine the nucleophilicity parameters N and s
(eq 1)16 of 1a-e in DMSO and in methanol.
In this work we have studied the rates of the reactions of the
R-CF3SO2-substituted 4-X-benzyl anions 1a-e (Scheme 2) with
a set of reference electrophiles (quinone methides 2a-e and
the structurally analogous benzhydrylium ions 2f-j, Table 1)
log k20°C ) s(N + E)
(1)
E ) electrophilicity parameter
N ) nucleophilicity parameter
(11) Sheppard, W. A.; Taft, R. W. J. Am. Chem. Soc. 1972, 94, 1919-1923.
(12) Yagupol’skii, L. M.; Yagupolskaya, L. N. Proc. Acad. Sci. USSR (Eng.
Transl.) 1960, 134, 1207; Dokl. Akad. Nauk SSSR, 1960, 135, 377.
(13) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165-195.
(14) Sheppard, W. A. J. Am. Chem. Soc. 1963, 85, 1314-1318.
(15) (a) Terrier, F.; Kizilian, E.; Goumont, R.; Faucher, N.; Wakselman, C. J.
Am. Chem. Soc. 1998, 120, 9496-9503. (b) Goumont, R.; Kizilian, E.;
Buncel, E.; Terrier, F. Org. Biomol. Chem. 2003, 1, 1741-1748. (c) Terrier,
F.; Magnier, E.; Kizilian, E.; Wakselman, C.; Buncel, E. J. Am. Chem.
Soc. 2005, 127, 5563-5571.
(16) (a) Mayr, H.; Patz, M. Angew. Chem. 1994, 106, 990-1010; Angew. Chem.,
Int. Ed. Engl. 1994, 33, 938-957. (b) Mayr, H. In Cationic Polymeriza-
tion: Mechanisms, Synthesis and Applications; Matyjaszewski, K., Ed.;
Marcel Dekker: New York, 1996; pp 51-136. (c) Mayr, H.; Kuhn, O.;
Gotta, M. F.; Patz, M. J. Phys. Org. Chem. 1998, 11, 642-654. (d) Mayr,
H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.;
Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am. Chem. Soc.
2001, 123, 9500-9512. (e) Mayr, H.; Kempf, B.; Ofial, A. R. Acc. Chem.
Res. 2003, 36, 66-77. (f) Ofial, A. R.; Mayr, H. Macromol. Symp. 2004,
215, 353-367. (g) Mayr, H.; Ofial, A. R. In Carbocation Chemistry; Olah,
G. A.; Prakash, G. K. S., Eds.; Wiley: Hoboken, NJ, 2004; Chapter 13,
pp 331-358. (h) Mayr, H.; Ofial, A. R. Pure Appl. Chem. 2005, 77, 1807-
1821.
s ) nucleophile-specific slope parameter
We will show that the comparison of the reactivities of nitro-
and trifluoromethylsulfonyl substituted carbanions in DMSO and
methanol provides significant new insights in the origin of
intrinsic barriers.
Preparation and Deprotonation of Benzyl Trifluoromethyl
Sulfones. A variety of methods have been developed for the
(17) (a) Hendrickson, J.; Skipper, P. L. Tetrahedron 1976, 32, 1627-1635. (b)
Hendrickson, J.; Bair, K. W. J. Org. Chem. 1977, 42, 3875-3877. (c)
Eugene, F.; Langlois, B.; Laurent, E. J. Fluorine Chem. 1994, 66, 301-
309. (d) Zhu, S.; Chu, Q.; Xu, G.; Qin, C.; Xu, Y. J. Fluorine Chem. 1998,
91, 195-198. (e) Goumont, R.; Faucher, N.; Moutiers, G.; Tordeux, M.;
Wakselman, C. Synthesis 1997, 691-695. (f) Hendrickson, J. B.; Sternbach,
D. D.; Bair, W. W. Acc. Chem. Res. 1977, 10, 306-312.
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9754 J. AM. CHEM. SOC. VOL. 129, NO. 31, 2007

Reactivity of Trifluoromethylsulfonyl Stabilized Carbanions
A R T I C L E S
Scheme 3. Reactions of the Potassium Salts of the
Trifluoromethylsulfonyl Stabilized Carbanions 1a-e with the
Benzhydrylium Tetrafluoroborates 2f-j in DMSO
Table 2. 1H NMR Chemical Shifts (in ppm) and Coupling
Constants 3J (in Hz) for 1-H and 2-H of the Products 3a
entry
nucleophile
Ar2CH+
product
δ(1-H)
δ
(2-H)
3J
1
2
3
4
5
6
7
8
9
1a (X ) CH3)
1b (X ) H)
2f
2f
2d
2g
2f
2h
2i
2f
3af
3bf
3bd
3cg
3df
3dh
3di
3ef
5.15
5.16
5.17
5.22
5.21
5.21
5.18
5.27
5.28
5.27
5.25
4.74
4.76
4.86
4.68
4.71
4.77
4.70
4.74
4.68
4.81
4.73
10.2
10.2
9.8
Figure 1. UV-vis-spectroscopic monitoring of the reaction of benzyl
triflinate (1b, 6.29 × 10-4 mol L-1) with the quinone methide 2b (3.16 ×
10-5 mol L-1) at 500 nm in DMSO at 20 °C.
1b (X ) H)
1c (X ) CF3)
1d (X ) CN)
1d (X ) CN)
1d (X ) CN)
1e (X ) NO2)
1e (X ) NO2)
1e (X ) NO2)
1e (X ) NO2)
9.3
10.1
10.2
9.8
10.1
9.6
2g
2h
2i
3eg
3eh
3ei
10
11
10.2
9.9
a Assignments not confirmed.
synthesis of the benzyl trifluoromethyl sulfones (1a-e)-H.17 We
used the procedure described by Hendrickson and co-workers,18
which combines benzyl bromides with potassium triflinate19 in
boiling acetonitrile in the presence of catalytic amounts of
potassium iodide (Scheme 2).
Solutions of 1a-e were obtained by treatment of the benzyl
trifluoromethyl sulfones (1a-e)-H with 1.05 equiv of either
Schwesinger’s P2-tBu phosphazene base [(Me2N)3PdNs
P[NMe2]2NtBu]20,21 or KOtBu in DMSO. The potassium salts
(1d-e)-K precipitated when the benzyl trifluoromethyl sulfones
(1d-e)-H were combined with 1 equiv of KOtBu in dichlo-
romethane under a nitrogen atmosphere. Only partial deproto-
nation was achieved when the sulfones (1a-e)-H were treated
with 1 equiv of sodium methoxide in methanol.
Reaction Products. As shown in Scheme 3, the triflinate
stabilized benzyl anions 1a-e react with the benzhydrylium ions
2f-j to give the addition products 3, several of which have
been characterized by 1H and 13C NMR spectroscopy (for
details, see the Supporting Information).
Evidence for the formation of the compounds 3 comes from
their 1H NMR spectra, which show doublets (J ) 9.3-
10.2 Hz) in the range of δ ) 5.15-5.28 ppm (1-H) and δ )
4.65-4.81 ppm (2-H) as summarized in Table 2.
We also studied the reaction of the quinone methide 2d with
the triflinate stabilized carbanion 1b by 1H NMR spectroscopy
(entry 3 in Table 2). In contrast to our expectation, only one
pair of doublets was observed for 1-H and 2-H indicating the
formation of only one diastereoisomer.
Figure 2. Determination of the second-order rate constant k2 ) 8.85 L
mol-1 s-1 for the reaction of benzyl triflinate (1b) with the quinone methide
2b in DMSO at 20 °C from a plot of the first-order rate constants k1Ψ vs
the triflinate concentration. Counterions were K+ or protonated Schwesing-
er’s phosphazene base tBu-P2H+ (ref 20).
Kinetic Investigations in DMSO. The kinetic investigations
in DMSO were performed at 20 °C. All reactions proceeded
quantitatively, and the rates were determined photometrically
by following the decrease of the absorbances of the electrophiles
2 at their absorption maxima (Table 1), as shown in Figure 1.
All reactions were studied under pseudo-first-order conditions
using 10 to 100 equiv of the benzyl triflinate ions 1. The
concentrations of 1 (10-3-10-4 mol L-1) were thus kept almost
constant throughout the kinetic measurements, resulting in an
exponential decay of the concentrations of the colored electro-
philes (eq 2).
-d[2]/dt ) k1Ψ[2]
(2)
The pseudo-first-order rate constants k1Ψ () k2[1]0) were
obtained by least-squares fitting of the single-exponential At )
A0 exp(-k1Ψt) + C to the time-dependent absorbance A of the
electrophile. Plots of k1Ψ versus the nucleophile concentration
[1]0 give straight lines with the slope k2 (Table 3), as shown
for one example in Figure 2 and for all other experiments in
the Supporting Information.
(18) Hendrickson, J. B.; Giga, A.; Wareing, J. J. Am. Chem. Soc. 1974, 36,
2275-2276.
(19) Potassium triflinate was obtained from commercially available CF3SO2Cl
and potassium iodide in cold acetone (see ref 18 for details).
(20) P2-t-Bu: 1-(tert-butylimino)-1,1,3,3,3-pentakis(dimethylamino)-1λ5, 3λ5-
diphosphazene, pKBH+ ) 21.4 (in DMSO), CAS Registry No. 111324-
03-9.
(21) Schwesinger, R.; Schlemper, H.; Hasenfratz, C.; Willaredt, J.; Dambacher,
T.; Breuer, T.; Ottaway, C.; Fletschinger, M.; Boele, J. Liebigs Ann. Chem.
1996, 1055-1081.
In several k1Ψ vs [1]0 plots, k1Ψ values obtained with the
potassium and the phosphazenium salts of 1 were used side by
9
J. AM. CHEM. SOC. VOL. 129, NO. 31, 2007 9755

A R T I C L E S
Berger et al.
Table 3. Second-Order Rate Constants k2 for the Reactions of the Quinone Methides 2a-e and Benzhydrylium Ions 2f-j with the
R-Triflinate Stabilized Carbanions 1a-e (DMSO, 20 °C)
b
a Nucleophilicity parameters N and s derived by eq 1. Characteristic product signals identified by proton NMR in CDCl3.
side. The fact that first-order rate constants obtained with
different counterions are on the same correlation line (see Figure
2) demonstrates the independence of the rate constants of the
nature of the counterion. In line with these observations, the
same rate constants within experimental error were obtained,
when the rate of the reaction of 1d with 2f was studied with a
solution of the isolated potassium salt 1d-K or with a solution
of the corresponding sulfone 1d-H and 1.05 equiv of KOtBu.
When solutions of the triflones (1c-e)-H were combined with
KOtBu in DMSO, limiting values of the absorbances of the
colored carbanions 1c-e were reached after the addition of 1
equiv of KOtBu indicating that 1 equiv of KOtBu is sufficient
for a complete deprotonation of the benzyl trifluoromethyl
sulfones.
Kinetic Investigations in Methanol. The analysis of the
kinetic experiments in methanol is more complicated because
of the presence of different nucleophiles. Because most of the
reference electrophiles 2 listed in Table 1 react readily with
methanol, it was not possible to prepare solutions of these
electrophiles in methanol and mix them with methanolic
solutions of the triflinates 1a-e in order to determine the rate
constants for the reactions of 1a-e with 2 in pure methanol.
However, we were able to measure the kinetics of the reactions
of the CF3SO2-substituted benzyl anions 1c-e with benzhydryl
cations 2 in methanol/acetonitrile mixtures (91:9, v/v) in a
stopped-flow instrument by mixing 10 volume parts of metha-
(23) Lucius, R. Dissertation, Ludwig-Maximilians-Universita¨t, Mu¨nchen, Ger-
many, 2001.
(24) Remennikov, G. Y.; Mayr, H., unpublished results.
(25) In order to be consistent with the quoted literature, we also use the term
KMeOH to designate the ion product of methanol: Schaal, A. R.; Lamber,
G. J. Chim. Phys. Phys.-Chim. Biol. 1962, 1153-1163; (b) Rochester, C.
H. Acidity Functions; Academic Press: London, 1970; p 246.
(22) (a) Lucius, R.; Loos, R.; Mayr, H. Angew. Chem. 2002, 114, 97-102;
Angew. Chem., Int. Ed. 2002, 41, 91-95. (b) Lucius, R.; Mayr, H. Angew.
Chem. 2000, 112, 2086-2089; Angew. Chem., Int. Ed. 2000, 39, 1995-
1997.
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9756 J. AM. CHEM. SOC. VOL. 129, NO. 31, 2007

Reactivity of Trifluoromethylsulfonyl Stabilized Carbanions
A R T I C L E S
Table 4. Deprotonation of the Benzyl Trifluoromethyl Sulfones
(1c-e)-H by Sodium Methoxide (20 °C, MeOH)
1
triflone
λ
max (nm)a
K
CH (M-
)
pKa
1c-H (X ) CF3)
1d-H (X ) CN)
1e-H (X ) NO2)
305
345
476
0.600
8.24
76.1
17.1
16.0
15.0
a Absorption maxima of the R-triflinate stabilized carbanions (λmax for
1c, 1d, and 1e in DMSO reported in ref 15b: 316, 347, and 476 nm,
respectively).
nolic solutions of the triflones 1-H and methoxide with one part
-
of a solution of Ar2CH+ BF4 (2) in acetonitrile.
As previously reported by Terrier,15 the 4-X-benzyl trifluo-
romethyl sulfones (1a-e)-H are weaker acids in water than in
DMSO. In line with this observation, even the acceptor
substituted sulfones (1c-e)-H cannot completely be deproto-
nated by sodium methoxide in methanol, and the equilibrium
(eq 3) has to be considered.
Figure 3. Determination of the second-order rate constant k2,C ) 2.35 ×
105 L mol-1 s-1 for the reaction of 2f with benzyl triflinate 1e in MeOH/
CH3CN (91:9, v/v) at 20 °C.
Table 5. Second-Order Rate Constants k2,MeO for the Reactions of
Methoxide Anion and First-Order Rate Constants k1,MeOH for the
Reactions of Methanol with Benzhydrylium Ions 2f-k in MeOH/
CH3CN (91:9, v/v) at 20 °C (from ref 26)
KCH
CH + MeO- y z C- + MeOH
KCH ) [C-]/([CH][MeO-])
(3)
(4)
1
1
electrophile
k
2,MeO (M-1 s-
)
k )
1,MeOH (s-
2f
2g
2h
2i
1.17 × 103
2.48 × 103
7.41 × 103
1.56 × 104
4.80 × 104
6.14 × 10-3
3.16 × 10-2 a
2.13 × 10-1 a
2.17 × 10-1
9.32 × 10-1
pKMeOH ) -log{[MeO-][H+]} ) 16.92 (at 20 °C)25
pKa ) -(log KCH) + pKMeOH
(5)
(6)
2j
a Calculated according to eq 1.
For the trifluoromethyl sulfones (1c-e)-H neither the pKa
nor the KCH values in methanol have been reported. The
equilibrium constants KCH (eq 4) were, therefore, determined
photometrically at the absorption maxima of the carbanions by
titration of (1c-e)-H with sodium methoxide (Table 4). Because
quantitative deprotonation of the triflones could not be achieved,
the acid dissociation constants KCH (eq 4, Table 4) were obtained
by least-squares fitting of calculated and experimental concen-
trations of C- () 1c-e) as described in the Supporting
Information. The pKa values were then calculated according to
eq 6.
sodium methoxide in methanol yielded the equilibrium con-
centrations of 1c-e in less than 2 ms, the dead time of our
stopped-flow instrument.
According to eq 7, the pseudo-first-order rate constants kobsd
determined in methanol reflect the sum of the reactions of the
electrophile with the carbanion (k2,C[C-]), with methoxide
(k2,MeO[MeO-]), and with methanol (k1,MeOH).
kobsd ) k2,C[C-] + k2,MeO[MeO-] + k1,MeOH
(7)
Phan and Mayr have reported that the ionization constants
of p-cyanophenylnitromethane in pure methanol and in MeOH/
CH3CN (91:9, v/v) agree within experimental error.26 The pKa
values for (1c-e)-H in pure MeOH (Table 4) have, therefore,
been used for the calculation of the carbanion concentrations
during the kinetic experiments in MeOH/CH3CN (91:9, v/v).
Because of the low acidities of 1a-H and 1b-H, we were not
able to determine their equilibrium constants KCH in methanol,
and therefore we have not performed kinetic investigations with
these carbanions in methanol.
As a consequence of the incomplete deprotonation of the
triflones (1c-e)-H in many of the kinetic experiments, it was
often not possible to achieve a high excess of the carbanions 1
over the electrophiles 2. However, even in the case [1] ≈ [2]
pseudo-first-order conditions were warranted when [1-H] . [2]
because the proton transfer between the carbanions 1c-e and
methanol is much faster than the reaction of 1c-e with the
electrophiles used in these investigations. Fast proton transfer
from 1-H to methoxide, as expected for the formation of
carbanions with little rehybridization, was proven by the
observation that treatment of 1c-H (2.24 × 10-4 mol L-1), 1d-H
(2.36 × 10-4 mol L-1), and 1e-H (2.21 × 10-4 mol L-1) with
The second-order rate constants k2,MeO for the reactions of
methoxide ion with benzhydrylium ions and the relevant first-
order rate constants for the reactions of benzhydrylium ions with
methanol, which have previously been reported,26 are sum-
marized in Table 5.
Rearrangement of eq 7 gives eq 8,
k
1Ψ ) kobsd - k2,MeO[MeO-] ) k2,C[C-] + k1,MeOH (8)
which implies that the second-order rate constants k2,C can be
derived from the slopes of plots of k1Ψ vs [C-] as shown in
Figure 3 for the reaction of 2f with benzyl triflinate 1e. The
intercepts of these correlations correspond to the reactions of
the electrophiles 2 with the solvent MeOH. In agreement with
the entries in the right column of Table 5, these intercepts are
small and can be neglected.
In all kinetic experiments, the term k2,C[C-] was the major
contribution to kobsd, which excludes major errors in the
determination of the carbanion reactivities. For the reaction of
1d with 2i, it was furthermore shown that almost the same rate
constants k1Ψ were obtained when variable ratios of [1d-H]/
[MeO-] were employed, as required by the suggested kinetic
formalism (Supporting Information).
(26) Phan, T. B.; Mayr, H. Can. J. Chem. 2005, 83, 1554-1560.
9
J. AM. CHEM. SOC. VOL. 129, NO. 31, 2007 9757

A R T I C L E S
Berger et al.
Table 6. Second-Order Rate Constants k2,C for the Reactions of
the R-Triflinate Stabilized Carbanions 1c-e with the
(with most of the negative charge residing on the oxygen atoms,
Scheme 1), can also be seen in the different slopes of the
Hammett-type correlations in Figure 7. In contrast to the good
correlation between N of the triflinate anions 1a-e with
Benzhydrylium Ions 2f-j in MeOH/CH3CN (91:9, v/v) at 20 °C
1
nucleophilea
Nb
sb
electrophile
k
2,C (M-1 s-
)
1c (X ) CF3)
20.72
0.58
2f
2g
2h
2i
2j
2f
2g
2h
2i
2j
2f
2g
2h
2i
1.55 × 106
4.09 × 106
9.85 × 106
2.20 × 107
3.50 × 107
8.52 × 105
1.99 × 106
5.44 × 106
1.22 × 107
2.50 × 107
2.35 × 105
7.98 × 105
1.31 × 106
3.85 × 106
9.83 × 106
-
Hammett’s σp the corresponding correlation with σp is of
considerably lower quality (R2 ) 0.8919).
Unusual solvent effects, as previously reported for the
basicities of carbanions 1a-e,15 have now been found for their
nucleophilicities. Because the stabilization of most carbanions
occurs to a large extent through hydrogen bonding, the basicities
as well as the nucleophilicities of carbanions are usually smaller
in protic than in aprotic solvents. In line with the observation
that the acidities of benzyl triflones are higher in DMSO than
in DMSO/water mixtures,15 Figure 8 shows that also the
nucleophilic reactivities of the benzyl triflinates 1c-e are higher
in methanol than in DMSO. The differences of s for the triflinate
anions 1 in methanol and DMSO imply that the relative
nucleophilic reactivities in the two solvents depend on the
electrophile. The direct comparison of the rate constants in
Tables 3 and 6 shows that the triflinate-stabilized carbanions
studied in this work react 10 to 40 times faster (!) with
benzhydrylium ions in methanol than in DMSO.
This unusual solvent dependence of the pKaH values has been
explained by the electronic structure of the triflinates 1. Terrier
has shown that the negative charge of the triflinates 1 is localized
on the benzylic carbon atom and is highly polarizable.15 For
that reason, the carbanions 1 are better solvated in the highly
polarizable and dielectric solvent DMSO (ꢀ ) 47)30 than in
methanol (ꢀ ) 33).30 The higher acidities of fluorenes in DMSO
than in methanol have analogously been rationalized by the high
polarizabilities of the resulting carbanions.31 Because the CC-
coupling step of Scheme 3 must be preceded by the destruction
of the ion-dipole interactions which prevail in DMSO, the
kinetic phenomena observed in this work can also be explained
by the fact that the highly polarizable triflinate stabilized
carbanions 1a-e are better solvated in DMSO.
The dominant role of ion-dipole forces for the solvation of
the trifluoromethylsulfonyl substituted carbanions 1 is further
confirmed by the observation that the reactivity of 1e (X )
NO2) toward the carbocations 2f-j (Table 8) is considerably
higher in the less dipolar solvent acetonitrile (ꢀ ) 38)30 than in
DMSO (Figure 9).
Figure 10 shows that the Brønsted plot for the reactions of
the triflinate stabilized carbanions 1a-e with the benzhydrylium
ion 2f has a slope of 0.36, comparable to that for substituted
R-nitrobenzyl anions in DMSO.28 Because only a small number
of carbanions have been studied with respect to a single
reference electrophile, more comprehensive nucleophilicity-
basicity correlations shall be based on the nucleophilicity
parameters N.
1d (X ) CN)
1e (X ) NO2)
19.49
18.24
0.63
0.66
2j
a Generated from the corresponding triflones (1c-e)-H and NaOMe.
bNucleophilicity parameters N and s derived by eq 1.
Discussion
As previously shown for many other nucleophile electrophile
combinations,16,22,26-28 the second-order rate constants given in
Tables 3 and 6 correlate well with the electrophilicity parameters
E of the benzhydrylium ions 2f-j and quinone methides 2a-e
(Figures 4 and 5).
Figures 4 and 5 as well as the nucleophilicity parameters N
in Table 7, which were determined by eq 1, show the expected
substituent effects on the reactivities of the carbanions. Donors
(methyl) increase the nucleophilicities of the triflinate ions 1,
whereas acceptors (trifluoromethyl, cyano, nitro) decrease their
reactivity. The similarities of the slopes of the linear correlations
in Figures 4 and 5, which are numerically expressed by the
parameters s in Table 7, imply that the relative nucleophilicities
of the triflinate stabilized benzyl anions depend only slightly
on the electrophilicity of the reaction partner.
Comparison of the nucleophilicity parameters of R-nitro28 and
R-triflinate substituted benzyl anions (Figure 6) shows that both
classes of carbanions possess similar nucleophilicities in DMSO
but that variation of the para-substituents has a much larger
effect on the triflinate than on the nitro substituted benzyl anions.
This effect, which can be explained by the localization of
the negative charge on carbon in the triflinate stabilized
carbanions and the charge delocalization in the nitronate anions
(27) (a) Mayr, H.; Lang, G.; Ofial, A. R. J. Am. Chem. Soc. 2002, 124, 4076-
4083. (b) Kempf, B.; Hampel, N.; Ofial, A. R.; Mayr, H. Chem.sEur. J.
2003, 9, 2209-2218. (c) Bug, T.; Hartnagel, M.; Schlierf, C.; Mayr, H.
Chem.sEur. J. 2003, 9, 4068-4076. (d) Loos, R.; Kobayashi, S.; Mayr,
H. J. Am. Chem. Soc. 2003, 125, 14126-14132. (e) Remennikov, G. Y.;
Kempf, B.; Ofial, A. R.; Polborn, K.; Mayr, H. J. Phys. Org. Chem. 2003,
16, 431-437. (f) Minegishi, S.; Kobayashi, S.; Mayr, H. J. Am. Chem.
Soc. 2004, 126, 5174-5181. (g) Tokuyasu, T.; Mayr, H. Eur. J. Org. Chem.
2004, 2791-2796. (h) Kempf, B.; Mayr, H. Chem.sEur. J. 2005, 11, 917-
927. (i) Dilman, A. D.; Mayr, H. Eur. J. Org. Chem. 2005, 1760-1764.
(j) Terrier, F.; Lakhdar, S.; Boubaker, T.; Goumont, R. J. Org. Chem. 2005,
70, 6242-6253. (k) Dulich, F.; Mu¨ller, K.-H.; Ofial, A. R.; Mayr, H. HelV.
Chim. Acta 2005, 88, 1754-1768. (l) Phan, T. B.; Mayr, H. Eur. J. Org.
Chem. 2006, 2530-2537. (m) Phan, T. B.; Mayr, H. J. Phys. Org. Chem.
2006, 19, 706-713. (n) Phan, T. B.; Breugst, M.; Mayr, H. Angew. Chem.
2006, 118, 3954-3959; Angew. Chem., Int. Ed. 2006, 45, 3869-3874. (o)
Lakhdar, S.; Westermaier, M.; Terrier, F.; Goumont, R.; Boubaker, T.; Ofial,
A. R.; Mayr, H. J. Org. Chem. 2006, 71, 9088-9095. (p) Brotzel, F.;
Kempf, B.; Singer, T.; Zipse, H.; Mayr, H. Chem.sEur. J. 2007, 13, 336-
345. (q) Tumanov, V. V.; Tishkov, A. A.; Mayr, H. Angew. Chem. 2007,
119, 3633-3636; Angew. Chem., Int. Ed. 2007, 46, 3563-3566. (r) Brotzel,
F.; Chu, Y. C.; Mayr, H. J. Org. Chem. 2007, 72, 3679-3688. (s) For a
database of reactivity parameters E, N, and s, see: www.cup.uni-
muenchen.de/oc/mayr/DBintro.html.
A correlation of low quality is obtained, when the nucleo-
philicities of carbanions of variable structure (N in DMSO) are
plotted against their pKaH values in DMSO (Figure 11). The
most remarkable feature of this correlation is that the triflinate
substituted carbanions 1 are at the lower edge of this “correlation
(29) Bordwell, F. G.; Bausch, M. J.; Branca, J. C.; Harrelson, J. A., Jr. J. Phys.
Org. Chem. 1988, 1, 225-241.
(30) Reichardt, C. SolVent Effects in Organic Chemistry; Wiley-VCH: Wein-
heim, 2003.
(31) Ritchie, C. D. In Solute-SolVent Interactions; Coetzee, J. F.; Ritchie, C.
D., Eds.; Marcel Dekker: New York, 1969; Chapter 4, p 232.
(28) Bug, T.; Lemek, T.; Mayr, H. J. Org. Chem. 2004, 69, 7565-7576.
9
9758 J. AM. CHEM. SOC. VOL. 129, NO. 31, 2007

Reactivity of Trifluoromethylsulfonyl Stabilized Carbanions
A R T I C L E S
Figure 4. Plots of log k2 for the reactions of the triflinate stabilized anions 1a-e (from Table 3) with the quinone methides 2a-e and benzhydryl cations
2f-j in DMSO at 20 °C versus their electrophilicity parameters E.
Figure 6. Comparison of the nucleophilicities N of triflinate stabilized
carbanions (1a-e) and nitronate anions in DMSO.
Figure 5. Plots of log k2,C for the reactions of the triflinate stabilized anions
1c-e (from Table 6) with the benzhydryl cations 2f-j in MeOH at 20 °C
versus their electrophilicity parameters E.
Table 7. Nucleophilicity Parameters N and s and pKaH Values of
the Triflinate Stabilized Carbanions 1a-e in DMSO and MeOH
in DMSO
N
in MeOH
N
nucleophile
pKaH
s
pKaH
s
1a (X ) CH3)
1b (X ) H)
1c (X ) CF3)
1d (X ) CN)
1e (X ) NO2)
15.4a
14.62b
11.95b
10.7a
9.46b
19.35
18.67
17.33
16.28
14.49
0.67
0.68
0.74
0.75
0.86
-
-
-
-
-
-
17.1
16.0
15.0
20.72
19.49
18.24
0.58
0.63
0.66
b
a From ref 29. From ref 15b.
corridor”, i.e., that their nucleophilic reactivities are lower than
those of most other carbanions of comparable pKaH values,
indicating low intrinsic reactivities.9b,32,33 On the other hand,
the resonance-stabilized nitronates are in the center or on the
upper edge of this correlation band, indicating high intrinsic
reactivities of the anions 4. These findings were in contrast to
our expectation, because we had assumed that in analogy to
the behavior of cyano substituted carbanions34-37 the low
Figure 7. Correlations of the nucleophilicity parameters N (in DMSO)
with the Hammett σp- values for triflinates (b: N ) -3.12σp- + 18.9, R2
) 0.9557, n ) 5) and nitronates (9: N ) -1.42σp- + 18.2, R2 ) 0.9792,
n ) 4).
reorganization energies of the localized triflinate anions 1, which
had been derived from their fast proton-transfer reactions, and
the high reorganization energies for the nitronate ions 4 which
had been derived from their slow proton-transfer reactions38
(Table 9) should also be reflected in the reactions with carbon
(32) (a) Marcus, R. A. Annu. ReV. Phys. Chem. 1964, 15, 155-196. (b) Marcus,
R. A. J. Phys. Chem. 1968, 72, 891-899.
(33) Richard, J. P.; Amyes, T. L. Acc. Chem. Res. 2001, 34, 981-988.
(34) Bug, T.; Mayr, H. J. Am. Chem. Soc. 2003, 125, 12980-12986.
(35) Wiberg, K. B.; Castejon, H. J. Org. Chem. 1995, 60, 6327-6334.
(36) (a) Richard, J. P.; Williams, G.; Gao, J. J. Am. Chem. Soc. 1999, 121,
715-726. (b) Abbotto, A.; Bradamante, S.; Pagani, G. A. J. Org. Chem.
1993, 58, 449-455.
(37) Fleming, F. F.; Shook, B. C. Tetrahedron 2002, 58, 1-23.
(38) (a) Bernasconi, C. F.; Kliner, D. A. V.; Mullin, A. S.; Ni, J. X. J. Org.
Chem. 1988, 53, 3342-3351. (b) Bernasconi, C. F.; Ni, J. X. J. Am. Chem.
Soc. 1993, 115, 5060-5066.
9
J. AM. CHEM. SOC. VOL. 129, NO. 31, 2007 9759

A R T I C L E S
Berger et al.
Figure 10. Plot of log k2 for the reactions of the triflinate substituted
carbanions 1a-e with the benzhydrylium ion 2f in DMSO at 20 °C versus
their pKaH values.
Figure 8. Comparison of the nucleophilicity parameters N of the benzyl
triflinates 1c-e in DMSO and MeOH.
Table 8. Second-Order Rate Constants k2 for the Reactions of 1e
with the Electrophiles 2f-h (CH3CN, 20 °C)a
1
electrophile
k
2 (M-1 s-
)
2f
2g
2h
2j
9.41 × 104 b
3.79 × 105
6.34 × 105
5.04 × 106
a Carbanion 1e was generated by mixing 1e-H with 1.0 equiv of
Verkade’s
base
(2,8,9-triisopropyl-2,5,8,9-tetraaza-1-
phosphabicyclo[3.3.3]undecane). bA second-order rate constant of k2 ) 8.28
× 104 M-1 s-1 was obtained when 1e was generated from 1e-H by
deprotonation with potassium tert-butoxide.
Figure 11. Brønsted plot for the reactions of different carbanions with
benzhydrylium ions and quinone methides in DMSO (nucleophilicity
parameters N and pKaH values used for this diagram are compiled in the
Supporting Information)
Table 9. Intrinsic Rate Constants log k0 for Deprotonation of
Some Carbon Acids by Primary and Secondary Amines in
DMSO/Water (50:50, v/v) at 25 °C unless Indicated Otherwise
carbon acid
log k0
C6H5CH2NO2
CH3NO2
-0.25b
0.73b
2.75b
g5a
acetylacetone
1c-H (X ) CF3)
1d-H (X ) CN)
1e-H (X ) NO2)
NC-CH2-CN
g5a
g5a
Figure 9. Comparison of the rate constants of the reactions of the
carbocations 2f-j with the carbanion 1e in DMSO, acetonitrile, and
methanol (cosolvent: 9 vol % acetonitrile).
∼7c
a Reference 15b. bAt 20 °C, from ref 41. cIn water at 20 °C, from ref 41.
electrophiles.39,40 Why are carbanions 1 and 4 on the “wrong”
edges of the “correlation corridor”?
A solution of this paradox came from consideration of the N
vs pKaH correlation in methanol (Figure 12). In methanol, the
correlation between nucleophilicity42 and basicity27l,43 is even
worse than that in DMSO, but the triflinate substituted carban-
ions 1 are now found on the upper rim of the correlation
corridor, while the nitronate ions are found on the lower edge.
In methanol, the intrinsic reactivities of the localized triflinate
substituted carbanions 1 are high and those of the delocalized
(43) Acidity constants pKaH in methanol: (a) Cox, J. P. L.; Crampton, M. R.;
Paul, W. J. Chem. Soc., Perkin. Trans. 2 1988, 25-29. (b) Belokon, Y.
N.; Faleev, N. G.; Belikov, V. M. IzV. Akad. Nauk SSSR, Ser. Khim. 1969,
1039-1046; Bull. Acad. Sci. USSR 1969, 949-955. (c) Gandler, J. R.;
Saunders, O. L.; Barbosa, R. J. Org. Chem. 1997, 62, 4677-4682. (d)
Crampton, M. R.; Stevens, J. A. J. Chem. Soc., Perkin. Trans. 2 1991,
1715-1720.
(39) Guthrie, J. P. Can. J. Chem. 2005, 83, 1-8.
(40) Guthrie, J. P. ChemPhysChem 2003, 4, 809-816.
(41) Bernasconi, C. F.; Stronach, M. W. J. Am. Chem. Soc. 1990, 112, 8448-
8454.
(42) Nucleophilicities N of carbanions in methanol: ref 27l.
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9760 J. AM. CHEM. SOC. VOL. 129, NO. 31, 2007

Reactivity of Trifluoromethylsulfonyl Stabilized Carbanions
A R T I C L E S
conclusions that the nitroalkane anomaly8 only shows up in
protic solutions, and not in the gas phase8g or DMSO.8n While
nitronate ions (resonance stabilized carbanions) show low
intrinsic reactivities in protic solvents and high or normal
intrinsic reactivities in DMSO, we have now found that the
opposite holds for the highly polarizable carbanions 1. Thus,
nitro and triflinate substituted carbanions represent two different
extremes: while transition state imbalances for reactions of
nitronate anions are found in protic solvents, where hydrogen
bridging has to be abandoned prior to rehybridization, analogous
imbalances for reactions of triflinate substituted carbanions 1
are found in the highly polarizable, dipolar solvent DMSO,
where ion-dipole interactions have to be removed prior to bond
formation.
Acknowledgment. Dedicated to Professor George A. Olah
on the occasion of his 80th birthday. We thank the Deutsche
Forschungsgemeinschaft (Ma 673/17) and the Fonds der Che-
mischen Industrie for support of this work and Oliver Kaumanns
for performing the kinetic measurements in acetonitrile. Helpful
suggestions by Professor Franc¸ois Terrier and Professor J. Peter
Guthrie are gratefully acknowledged.
Figure 12. Nucleophilicity parameters N (in methanol) for different types
of carbanions versus their acidity constants pKaH in methanol (data
compilation in the Supporting Information).
nitronate anions are low as expected from earlier work, where
the high reorganization energy of the resonance stabilized
nitronate anions was accounted for by the high intrinsic barriers
of the reactions of nitronate anions.9
Our observation that nitronate anions do not have low intrinsic
reactivities in DMSO (Figure 11) is in agreement with earlier
Supporting Information Available: Details of the product
characterization, kinetic experiments, and determination of
equilibrium constants (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JA072135B
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J. AM. CHEM. SOC. VOL. 129, NO. 31, 2007 9761