Activation of pentafluorophenylsilanes by Weak Lewis bases in reaction with iminium cations

Article abstract of DOI:10.1021/jo0606812

The Lewis base mediated carbon-carbon bond forming reactions between pentafluorophenylsilanes and iminium cations were studied theoretically and experimentally. The complexation of silanes with anionic Lewis bases was analyzed computationally using DFT me

Full text of DOI:10.1021/jo0606812

Activation of Pentafluorophenylsilanes by Weak Lewis Bases in
Reaction with Iminium Cations
Alexander D. Dilman,*,† Vitalij V. Levin,† Miriam Karni,‡ and Yitzhak Apeloig‡
N. D. Zelinsky Institute of Organic Chemistry, Leninsky prosp. 47, 119991 Moscow, Russian Federation,
and The Lise Meitner MinerVa Center for Computational Quantum Chemistry,
Technion-Israel Institute of Technology, Technion City, 32000 Haifa, Israel
dilman@ioc.ac.ru
ReceiVed March 30, 2006
The Lewis base mediated carbon-carbon bond forming reactions between pentafluorophenylsilanes and
iminium cations were studied theoretically and experimentally. The complexation of silanes with anionic
Lewis bases was analyzed computationally using DFT methods at the B3LYP/6-31+G(d) level. The
pentafluorophenyl group was found to exhibit a significant stabilizing effect on the formation of
pentacoordinate silicon species, with (C6F5)3SiF and C6F5SiF3 being the strongest Lewis acids. Comparison
of geometrical isomers of trigonal bipyramidal siliconates R2(C6F5)SiXY- (R ) Me, F, Cl; X, Y ) F,
Cl, ClO4) revealed that the heteroatoms and the C6F5 group prefer to occupy apical and equatorial positions,
respectively. Calculations of C6F5 group transfer processes from silanes to N,N-dimethyliminium cation
lead to the following conclusions: (1) when employing weak Lewis bases X- ) Cl-, ClO4- as activators,
R2(C6F5)SiF are more reactive than R2(C6F5)SiX (X ) Cl, ClO4); (2) the C6F5 group is much more reactive
in an apical position than in an equatorial position of the siliconate; (3) a solvent greatly increases the
reaction barrier by stabilizing the reactants; and (4) the efficiency of C-C bond formation can be improved
by rendering the process intramolecular. It was shown experimentally that reactions of (C6F5)3SiF with
+
PhCHdNMe2 TfO- can be promoted by a series of weak Lewis bases, from which the chloride anion
was the most effective. Even more facile was the reaction of N-(silyloxyethyl)iminium ion
(C6F5)3SiOCH2CH2N(Me)dCHPh+TfO-, likely proceeding via intramolecular transfer of a C6F5 group.
The optimal conditions for pentafluorophenylation of iminium ions involved the use of benzyltriethyl-
ammonium chloride in refluxing dichloroethane.
Introduction
the carbon-silicon bond becomes more polarized, rendering the
nucleophilic leaving group more reactive (Scheme 1, path a).
The fluoride and alkoxide anions have turned out to be the
most commonly used Lewis bases for activation of carbon-
silicon bonds.2a,3,4 Their efficiency originates from very strong
bonds between silicon and fluoride and oxygen, respectively.
The major synthetic applications of organosilicon compounds
correspond to the transfer of the organic group from the silicon
atom to an electrophile.1 However, the organosilanes are in-
trinsically moderately reactive, and an additional activator is
required to initiate the electrophile-nucleophile coupling. One
of the methods to effect such activation involves the employment
of a Lewis base, which binds to the silicon atom, generating a
five-coordinate siliconate intermediate.2 In the latter species,
(2) (a) Chuit, C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Chem. ReV.
1993, 93, 1371. (b) Kost, D.; Kalikhman, I. In The Chemistry of Organic
Silicon Compounds; Apeloig, Y., Rappoport, Z., Eds.; Wiley: Chichester,
U.K., 1998; Vol. 2, p 1339. (c) Holmes, R. R. Chem. ReV. 1996, 96, 927.
(3) (a) Furin, G. G.; Vyazankina, O. A.; Gostevsky, B. A.; Vyazankin,
N. S. Tetrahedron 1988, 44, 2675. (b) Hosomi, A.; Shirahata, A.; Sakurai,
H. Tetrahedron Lett. 1978, 3043. (c) Lettan, R. B., II; Scheidt, K. A. Org.
Lett. 2005, 7, 3227. (d) Busch-Petersen, J.; Bo, T.; Corey, E. J. Tetrahedron
Lett. 1999, 40, 2065.
† N. D. Zelinsky Institute of Organic Chemistry.
‡ Technion-Israel Institute of Technology.
(1) (a) Weber, W. P. Silicon Reagents for Organic Synthesis; Springer:
New York, 1983. (b) Fleming, I.; Barbero, A.; Walter, D. Chem. ReV. 1997,
97, 2063.
10.1021/jo0606812 CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/12/2006
7214
J. Org. Chem. 2006, 71, 7214-7223

ActiVation of Pentafluorophenylsilanes
SCHEME 1
C6F5 group is a strong electron withdrawer and a variety of
pentafluorophenyl silanes can be readily synthesized by con-
ventional organometallic synthesis.11 As electrophiles, the
iminium cations were chosen since they constitute an important
class of carbocationic electrophiles. The iminium cations can
be obtained as stable isolable salts or can be generated in situ
using known protocols.12 Moreover, amines resulting from the
addition of a C6F5 group onto an iminium cation may be
interesting as potential pharmaceutical and agrochemical agents.13
We first performed quantum mechanical analysis of the C6F5
group transfer process in order to identify the most efficient
combination of the reagents required for C-C bond forming
reaction. Subsequently, the results of theory were verified
experimentally.
However, besides significant affinity toward silicon, these Lewis
bases serve as extremely strong nucleophiles and therefore are
incompatible with reactive electrophiles, such as carbocations
(Scheme 1, path b). As a consequence, only poorly electrophilic
neutral reagents, such as aldehydes, Michael acceptors, and
imines, have been employed in Lewis base mediated C-C bond
forming reactions.3 In this regard, an important question
arises: what are the optimal conditions for Lewis base activation
of silicon reagents and for transferring a nucleophilic leaving
group from the activated intermediate onto a carbocationic
electrophile? To solve this problem for a specific combination
of a leaving group and an electrophile, it is necessary to find a
proper combination of silicon substituents and a Lewis base.
In particular, the following criteria have to be fulfilled: (a) the
silicon atom of the reagent should be prone to an interaction
with the Lewis base for the formation of a five-coordinate
siliconate; (b) the five-coordinate intermediate should readily
transfer the leaving group to the electrophile; and (c) the reaction
of the Lewis base with the silane must compete efficiently with
its reaction with the electrophile. Correspondingly, a selection
of a weaker Lewis base and increasing the silicon Lewis acidity
appears as a major direction which should be pursued.
While considering trimethylsilyl derivatives, the acetate anion
is the weakest competent activating Lewis base employed so
far, as was demonstrated by Mukaiyama and co-workers for
the transfer of a trifluoromethyl group onto aldehydes and
electron-poor imines.5-7 On the other hand, we have recently
reported that an increase of silicon Lewis acidity can be achieved
by introducing the electron-withdrawing pentafluorophenyl
groups.8-10 In this respect, it becomes interesting to find optimal
conditions for the application of weak Lewis bases for activating
silicon reagents in C-C bond forming reactions.
Selection of the Theoretical Method
All computations were carried out using the Gaussian 03
program.14 The stationary points were verified by vibrational
analysis, and the thermodynamics was calculated at 298.15 K.
The B3LYP hybrid density functional method15 and ab initio
second-order perturbation theory16 (MP2) were selected for the
initial evaluation.17,18 The interaction of fluorotrimethylsilane
(8) (a) Dilman, A. D.; Belyakov, P. A.; Korlyukov, A. A.; Struchkova,
M. I.; Tartakovsky, V. A. Org. Lett. 2005, 7, 2913. (b) Dilman, A. D.;
Arkhipov, D. E.; Belyakov, P. A.; Struchkova, M. I.; Tartakovsky, V. A.
Izv. Russ. Chem. Bull. 2006, 55, 517 [Engl. transl. of IzV. Acad. Nauk.,
Ser. Khim. 2006, 498]. (c) Dilman, A. D.; Gorokhov, V. V.; Belyakov, P.
A.; Struchkova, M. I.; Tartakovsky, V. A. Tetrahedron Lett. 2006, 47, 6217.
(9) For acetate ion induced C6F5 group transfer processes, see: (a)
Dilman, A. D.; Levin, V. V.; Belyakov, P. A.; Struchkova, M. I.;
Tartakovsky, V. A. Synthesis 2006, 447. (b) Levin, V. V.; Dilman, A. D.;
Belyakov, P. A.; Korlyukov, A. A.; Struchkova, M. I.; Antipin, M. Y.;
Tartakovsky, V. A. Synthesis 2006, 489.
(10) For the enhanced reactivity of silyl enol ethers bearing a (C6F5)3Si
fragment in aldol reaction, see: Dilman, A. D.; Belyakov, P. A.; Korlyukov,
A. A.; Tartakovsky, V. A. Tetrahedron Lett. 2004, 45, 3741.
(11) (a) Dilman, A. D.; Arkhipov, D. E.; Korlyukov, A. A.; Ananikov,
V. P.; Danilenko, V. M.; Tartakovsky, V. A. J. Organomet. Chem. 2005,
690, 3680. (b) Whittingham, A.; Jarvie, A. W. P. J. Organomet. Chem.
1968, 13, 125.
(12) (a) Kantlehner, W. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 6, p 485. (b)
Rehn, S.; Ofial, A. R.; Mayr, H. Synthesis 2003, 1790. (c) Kleinman, E. F.
In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 2, p 893.
Herein we present our theoretical and experimental studies
in an attempt to address the latter problem. The pentafluoro-
phenyl silanes were selected as model compounds because the
(13) Kim, C.-Y.; Chang, J. S.; Doyon, J. B.; Baird, T. T., Jr.; Fierke, C.
A.; Jain, A.; Christianson, D. W. J. Am. Chem. Soc. 2000, 122, 12125.
(14) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K.
N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich,
S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A.
D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A.
G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03, revision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
(4) At the same time, allylic trichlorosilanes undergo coupling with
aldehydes in the presence neutral Lewis bases, such as amides, phosphor-
amides, and pyridine-N-oxides, but the efficiency of these reactions is likely
associated with concerted character of transition state. See: (a) Kobayashi,
S.; Nishio, K. J. Org. Chem. 1994, 59, 6620. (b) Denmark, S. E.; Fu, J.
Chem. Commun. 2003, 167. (c) Malkov, A. V.; Dufkova, L.; Farrugia, L.;
Kocovsky, P. Angew. Chem., Int. Ed. 2003, 42, 3674.
(5) (a) Mukaiyama, T.; Kawano, Y.; Fujisawa, H. Chem. Lett. 2005, 34,
88. (b) Kawano, Y.; Fujisawa, H.; Mukaiyama, T. Chem. Lett. 2005, 34,
422. (c) Kawano, Y.; Mukaiyama, T. Chem. Lett. 2005, 34, 894. (d) For an
example of an application of acetate ion as Lewis base for activation of
Me3SiAr, see: Effenberger, F.; Spiegler, W. Chem. Ber. 1985, 118, 3872.
(6) Trifluoromethylation of carbonyl compounds with Me3SiCF3 using
neutral Lewis bases was reported. (a) Trimethylamine-N-oxide showed
moderate activity, while HMPA and pyridine-N-oxide were ineffective:
Prakash, G. K. S.; Mandal, M.; Panja, C.; Mathew, T.; Olah, G. A. J. Fluor-
ine Chem. 2003, 123, 61. (b) DMSO as solvent: Iwanami, K.; Oriyama, T.
Synlett 2006, 112. (c) P(t-Bu)3 was noted to be an active catalyst, but its
ability to behave as silicon-specific activator is arguable: Mizuta, S.; Shibata,
N.; Sato, T.; Fujimoto, H.; Nakamura, S.; Toru, T. Synlett 2006, 267.
(7) For reviews on Lewis base promoted trifluoromethylation reactions,
see: (a) Prakash, G. K. S.; Yudin, A. K. Chem. ReV. 1997, 97, 757. (b)
Prakash, G. K. S.; Mandal, M. J. Fluorine Chem. 2001, 112, 123. (c) Singh,
R. P.; Shreeve, J. M. Tetrahedron 2000, 56, 7613. (d) Langlois, B. R.;
Billard, T.; Roussel, S. J. Fluorine Chem. 2005, 126, 173.
(15) (a) Becke, A. D. Phys. ReV. A 1988, 38, 3098. (b) Lee, C.; Yang,
W.; Parr, R. G. Phys. ReV. B 1988, 37, 785. (c) Becke, A. D. J. Chem.
Phys. 1993, 98, 5648.
(16) Moller, C.; Plesset, M. S. Phys. ReV. 1934, 46, 618.
(17) For a review of earlier quantum chemical treatment of hypercoor-
dinate silicon species, see: Apeloig, Y. In The Chemistry of Organic Silicon
Compounds; Patai, S., Rappoport, Z., Eds. John Wiley & Sons: New York,
1989; p 57.
J. Org. Chem, Vol. 71, No. 19, 2006 7215

Dilman et al.
TABLE 1. Calculated Energies of Siliconate Formation (kcal/mol,
at 298.15 K)a
SCHEME 2
entry
silane (R3SiF)
∆E
∆H
∆G
∆G (CH2Cl2)
(Me3SiF) with a fluoride anion to give difluorotrimethylsili-
conate was selected as the reference for our calculations since,
for this reaction, experimental thermochemical data in the gas
phase are available (∆H ) -38.2 kcal/mol, ∆G ) -31.6
kcal/mol).19 Variation of method and basis set demonstrated that
the B3LYP/6-31+G(d) level of theory is the most suitable
(∆Hcalc ) -40.4 kcal/mol, ∆Gcalc ) -33.6 kcal/mol). Further
expanding the basis set to triple-ú and addition of polarization
functions did not lead to higher accuracy (see Supporting
Information for details). Of special note is the fact that the use
of diffuse functions is essential for reproducing the experimental
results.18 Accordingly, all further calculations were performed
at the B3LYP/6-31+G(d) level.
To take into account the solvent effect, the polarizable
continuum model (PCM)20 was employed as implemented in
Gaussian 03. The single-point PCM calculations for gas-phase
geometries were performed, and obtained solution energies were
augmented with thermochemical corrections taken from gas-
phase vibrational analysis. Dichloromethane was selected as a
typical organic solvent of moderate polarity (ꢀ ) 8.93), which
is routinely used in synthesis.
1
2
3
4
5
6
7
8
9
Me3SiF
-39.8
-58.1
-72.5
-85.5
-47.4
-57.4
-72.1
-76.9
-63.2
-42.2
-44.5
-58.0
-40.4
-58.7
-73.0
-86.1
-48.0
-58.0
-72.7
-77.5
-63.8
-42.8
-45.1
-58.6
-33.6
-51.1
-64.7
-75.6
-39.9
-49.8
-64.9
-68.7
-54.4
-34.8
-37.1
-50.2
1.8
-7.5
-16.0
-23.6
-6.9
-17.9
-32.2
-26.5
-18.3
0.0
Me2(C6F5)SiF
Me(C6F5)2SiF
(C6F5)3SiF
Me2SiF2
MeSiF3
SiF4
C6F5SiF3
PhSiF3
Me2(MeO)SiF
(CH2)3Si(Me)F
Me2(C6F5)2Si
10
11b
12c
-0.8
1.2
a The two fluorines are located in apical positions of the trigonal
bipyramidal structure of 2 unless mentioned otherwise. ∆ ) energy(2) -
[energy(1) + energy (F-)]. b One fluorine in apical and another in equatorial
position of the siliconate. c Fluorine and C6F5 in the apical positions of the
siliconate.
One can see that a C6F5 group significantly stabilizes the
formation of the siliconate anion, and in the gas phase, this effect
is noticeably stronger than that of fluoride substituent (cf. entries
2 and 5, ∆∆G ) 11.2 kcal/mol). However, solvent greatly
reduces this difference, making them almost equally effective
(∆∆Gsol ) 0.6 kcal/mol). Not surprisingly, the C6F5 group is a
more efficient stabilizing group than a methoxy substituent or
a silacyclobutyl ring even in solution (entry 2 vs 10 and 11).
Of special note is the comparison of fluoride ion affinities
of Me2(C6F5)SiF and Me2(C6F5)2Si (entries 2 and 12). For these
silanes, the gas-phase energies are similar, while in solution,
they differ by 8.7 kcal/mol, with Me2(C6F5)SiF furnishing a
more stable siliconate. This effect is likely associated with
significant charge delocalization within the C6F5 group com-
pared to that in the small fluoride that causes a weaker solvation
of Me2(C6F5)2SiF-.
Results and Discussion
Calculations. The C6F5 group transfer reaction between the
silane and the iminium cation includes two steps: genera-
tion of the five-coordinate siliconate and the subsequent C-C
bond forming event (Scheme 2). In principle, the formation of
covalent species Me2NCH2X from the iminium ion and
Lewis base may occur.21 However, this is unlikely to affect
our analysis of the reaction mechanism. Thus, iminium chlor-
ides exist in solution as ionic hydrogen bonded aggregates
R2NdC(R)-H‚‚‚Cl, whereas weaker counterions, which are most
interesting from an experimental point of view, exist completely
in the ionic form.22
The interaction of the silane with a Lewis base constitutes
the first step of the process, and it is necessary to understand
the effect of the C6F5 group on the efficiency of the generation
of five-coordinate siliconate species. Table 1 lists the calculated
energies for the reactions of fluorosilanes with a fluoride anion
in the gas phase, as well as the calculated free energy in
dichloromethane solution.
Among the studied silanes containing a C6F5 group, (C6F5)3-
SiF and C6F5SiF3 produced the most stable pentacoordinate
complexes in solution.23
Though fluoride is known to be the strongest activator with
respect to silicon, weaker Lewis bases compatible with car-
bocationic electrophiles have to be considered. The anions of
strong protic acids HX (e.g., X ) OTf, ClO4, CF3CO2, or Cl)
would be attractive activators, relying on the greater bond energy
of silicon-heteroatom versus carbon-heteroatom.24 The silicon
derivatives bearing such substituents are frequently employed
as silylating agents and as Lewis acids.25 Mechanistically, all
these processes proceed through the nucleophilic substitution
at the silicon atom, and the reactivity of silanes increases in
the following order: R3SiF < R3SiOMe < R3SiOAc < R3SiCl
≈ R3SiOC(O)CF3 < R3SiBr < R3SiOTf ≈ R3SiOClO3.25
To evaluate the ability of a particular anion X to serve as
Lewis base in the C6F5 group transfer reaction from a particular
silyl group (e.g., R2(C6F5)SiY), we have to compare various
(18) For recent calculations of siliconates, see: (a) Damrauer, R.; Crowell,
A. J.; Craig, C. F. J. Am. Chem. Soc. 2003, 125, 10759. (b) Ignatyev, I. S.;
Schaefer, H. F., III. J. Phys. Chem. A 2001, 105, 7665. (c) Ignatyev, I. S.;
Schaefer, H. F., III. Organometallics 2001, 20, 3113. (d) Krouse, I. H.;
Wenthold, P. G. J. Am. Soc. Mass Spectrom. 2005, 16, 697. (e) Krouse, I.
H.; Wenthold, P. G. Organometallics 2004, 23, 2573. (f) Feng, S.;
Feng, D.; Li, M.; Zhou, Y.; Wang, P. J. Mol. Struct. (THEOCHEM) 2002,
618, 51.
(19) Larson, J. W.; McMahon, T. B. J. Am. Chem. Soc. 1985, 107, 766.
(20) Tomasi, J.; Mennucci, B.; Cammi, R. Chem. ReV. 2005, 105, 2999.
(21) For example, covalent compounds R2NCH2F were described, but
they serve as a source of naked fluoride anion. See: (a) Bo¨hme, H.; Hilp,
M. Chem. Ber. 1970, 103, 104. (b) Knunyants, I. L.; Delyagina, N. I.;
Igumnov, S. M. IzV. Akad. Nauk SSSR Ser. Khim. 1981, 857 [Bull. Acad.
Sci. USSR DiV. Chem. Sci. 1981, 30, 637 (Engl. Transl.)].
(23) The preparation of salts with C6F5SiF4- was reported. Frohn, H. J.;
Bardin, V. V. J. Organomet. Chem. 1995, 501, 155.
(24) Walsh R. In The Chemistry of Organic Silicon Compounds;
Rappoport, Z., Apeloig, Y., Eds.; John Wiley & Sons: Chichester, U.K.,
1998; Vol. 2, Chapter 4, p 153.
(22) Mayr, H.; Ofial, A. R.; Wu¨rthwein, E.-U.; Aust, N. C. J. Am. Chem.
Soc. 1997, 119, 12727.
(25) Dilman, A. D.; Ioffe, S. L Chem. ReV. 2003, 103, 733.
7216 J. Org. Chem., Vol. 71, No. 19, 2006

ActiVation of Pentafluorophenylsilanes
TABLE 2. Calculated Energies of Siliconate Formation (kcal/mol,
at 298.15 K)a
TABLE 3. Relative Energies of Geometrical Isomers of
-
Me2(C6F5)SiF2 (kcal/mol, at 298.15 K)
∆E
∆H
∆G
∆G (CH2Cl2)
apical, apical
∆E
∆H
∆G
∆G (CH2Cl2)
X- + Me2(C6F5)SiF f
F, F
0.0
5.0
8.1
9.9
10.9
0.0
5.0
8.1
9.9
10.9
0.0
5.1
8.1
10.0
10.7
0.0
6.2
8.1
10.0
10.7
Me2(C6F5)Si(F)(X)-
F, C6F5
F, Mea
C6F5, Mea
Me, Me
X-
MeO-
AcO-
Cl-
-50.6
-26.3
-17.7
-15.8
-10.8
-51.2
-26.9
-18.3
-16.4
-11.4
-40.3
-15.0
-12.0
-4.7
-11.5
11.2
13.9
16.1
11.7
-
a The data of constraint geometry optimization are given since on relaxed
search the geometry spontaneously changes to a more stable isomer.
CF3CO2
-
ClO4
-2.5
X- + Me2(C6F5)SiX f
-
Me2(C6F5)SiX2
TABLE 4. Reaction Energies (kcal/mol, at 298.15 K)
X-
MeO-
AcO-
Cl-
-42.6
-27.5
-21.1
-26.0
-17.7
-43.2
-28.1
-21.7
-26.6
-18.3
-30.5
-16.6
-14.4
-13.5
-8.1
0.9
11.8
13.6
11.9
13.9
-
CF3CO2
-
ClO4
∆E
58.1
0.0
-76.8
-65.5
-130.8
∆H
58.7
0.0
-77.4
-66.1
-130.8
∆G
51.1
0.0
-66.3
-53.9
-129.8
∆G (CH2Cl2)
X- + C6F5SiF3 f
C6F5SiF3X-
X-
reactantsa
siliconate
local min
TS1
7.5
0.0
3.9
Cl-b
CF3CO2
-28.3
-28.5
-13.5
-28.9
-29.1
-14.1
-20.8
-15.8
-2.6
7.2
4.0
15.8
-b
24.4
-48.1
-b
ClO4
products
X- + C6F5SiCl3 f
+
a Me2(C6F5)SiF + F- + CH2dNMe2
.
C6F5SiCl3X-
X-
Cl-
-25.9
-24.7
-8.3
-26.4
-25.3
-8.9
-18.7
-12.5
2.4
11.9
9.3
22.9
10.8
-
-c
electrophiles. The difluorosiliconate Me2(C6F5)SiF2 was se-
lected as a simplest hypercoordinate nucleophile, and its struc-
ture was examined in greater detail.
CF3CO2
-c
ClO4
Cl- + (C6F5)3SiF-
f
-34.7
-35.3
-24.2
(C6F5)3SiFCl-
The trigonal bipyramidal arrangement of pentacoordinate
silicon requires the consideration of five isomers differing in
relative position of substituents (Table 3). The structure with
two fluorines in apical positions is the most stable, whereas the
molecule bearing, at apical sites, fluorine and a C6F5 group is
6.2 kcal/mol higher in energy. Other possible species are even
higher in energy. It is interesting to note that solvent has only
a very small effect on the relative energies of the geometrical
isomers.
a Two heteroatomic substituents were located in apical positions of the
trigonal bipyramidal structure of siliconate. ∆ ) energy(Me2(C6F5)SiXY-)
- [energy(Me2(C6F5)SiY) + energy (X-)]. b The most stable isomer with
fluorine and X in apical positions. c Chlorine and X in apical positions.
siliconates of general formula R2(C6F5)SiYX-. If we select the
perchlorate anion as the weakest Lewis base, then all siliconates
are expected to fall within the range between two extreme
structures possessing fluoride and perchlorate substituents,
namely, R2(C6F5)SiFClO4- and R2(C6F5)Si(ClO4)2-. In general,
for some anion X-, the siliconate containing fluoride at silicon
The interaction of the most stable isomer of difluorosili-
-
conate Me2(C6F5)SiF2 with N,N-dimethyliminium ion was
-
R2(C6F5)SiFX- and symmetric species R2(C6F5)SiX2 have to
investigated as a model system. The calculated energies are
referenced relative to the sum of energies of siliconate and
iminium ions (Table 4). Figure 1 shows the free energy sur-
faces for the reaction in the gas phase and in dichloromethane
solution.
The salient feature of this process is the extremely high
thermodynamic driving force in the gas phase (overall ∆G )
-180.9 kcal/mol), which comes from the formation of strong
Si-F and C-C bonds replacing a weak Si-C bond. As can be
anticipated, the solvent dramatically reduces the exothermicity
(by 125 kcal) since the reactants are charged, while the products
are neutral. Furthermore, the solvation contributes to the increase
of transition structure energy, making it higher than the sum of
the reactants.
The transition structure and its key bond lengths and angles
are given in Figure 2. A concerted transfer of the C6F5 group
from silicon to the iminium carbon was observed with one
imaginary frequency of -249.0i, which was validated by
forward (to products) and backward (to the pentacoordinate
silicon intermediate) IRC calculations. A σ-complex of the type
characteristic for conventional aromatic electrophilic attack26
could not be detected.
be studied.
We first investigated computationally the interaction of silanes
Me2(C6F5)SiY, C6F5SiY3, and (C6F5)3SiY with different Lewis
bases (Table 2). In the gas phase, the complex formation is
exothermic and is favored according to the negative Gibbs free
energy for all calculated systems. However, in dichloromethane,
the formation of five-coordinate siliconates with weak Lewis
bases is unfavorable by about 10-15 kcal/mol. Even in the case
of highly Lewis acidic C6F5SiX3 and (C6F5)3SiX (X ) F, Cl),
complex formation should not occur owing to the loss of
solvation energy of the smaller anion X relative to the solvation
energy of larger siliconates. Nevertheless, pentacoordinate
siliconate species may exist in very small equilibrium concen-
tration and serve as competent nucleophiles.
Another important conclusion can be drawn from Table 2.
Thus, comparison of the complexing abilities of pairs of si-
lanes R3SiF versus R3SiX (i.e., Me2(C6F5)SiF vs Me2(C6F5)SiX;
C6F5SiF3 vs C6F5SiX3) suggests that in CH2Cl2 solution the
fluorinated derivatives R3SiF usually bind stronger the anionic
Lewis bases (smaller positive free energy of complexation),
thereby providing higher equilibrium concentrations of sili-
conates.
A local minimum preceding the transition structure was
identified in the gas phase, representing a hydrogen bonded
complex between the fluorine of difluorosiliconate and an
To compare the reactivity of siliconates, it is necessary to
analyze the potential energy surface for their reactions with
J. Org. Chem, Vol. 71, No. 19, 2006 7217

Dilman et al.
FIGURE 1. Free energy profiles of fluoride-activated reactions in the gas phase and dichloromethane solution.
in apical (-0.73 e) than in the equatorial isomer (-0.63 e; NAO
charges27).
We next examined the performance of chloride and perchlo-
rate anions as activators for the C6F5 group transfer from fluoro-,
chloro-, and perchlorate-substituted dimethylpentafluorophenyl
silanes Me2(C6F5)SiY, Y ) F, Cl, ClO4. For the reaction of
unsymmetrical siliconate Me2(C6F5)SiFCl-, two different transi-
tion structures were considered, corresponding to the approach
of the electrophile to the C6F5 group from the fluorine side (TS2)
or from the chlorine atom (TS3). The calculations show that
the fluorine side approach is 1.4 kcal/mol lower in energy.
Consequently, transition structures for reactions of other sili-
conates were calculated only for fluoride side approach. The
intermediate hydrogen bonded local minima similar to that
observed for Me2(C6F5)SiF2- were excluded from consideration
since these stationary points do not affect the final conclusion,
while their identification requires considerable computational
resources. Table 5 shows the calculated energies referenced
relative to the sum of starting silane, Lewis base, and iminium
ions because in solution the formation of siliconates is ener-
getically unfavorable. At the same time, the barriers for the
generation of siliconates were not considered.28
FIGURE 2. Transition structure TS1. Selected bond lengths (Å) and
angles (deg).
It should be noted that the thermodynamics of chloride initi-
ated reactions are very close, but the free energies of activation
differ by 5.7 kcal/mol (i.e., TS2 vs TS4). This means that C6F5
group transfer triggered by a chloride ion will proceed ap-
proximately 104 times faster at room temperature when fluo-
rosilane rather than chlorosilane is used! A similar trend was
observed for perchlorate-activated processes, with Me2(C6F5)-
iminium hydrogen. In solution, this complex is higher in energy
than the parent siliconate and iminium ions and may not be a
detectable intermediate.
It is interesting to analyze also the reaction of siliconate
Me2(C6F5)SiF2- containing apical C6F5 and fluorine substituents.
In this case, a barrierless transfer of the C6F5 fragment onto the
electrophile was observed. The greater reactivity of the apical
versus the equatorial group may be associated with higher
polarization of the apical bonds. Thus, in the structure with an
equatorial C6F5 group, the Si-CC F bond distance is 1.98 Å,
(27) (a) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. ReV. 1988, 88,
899. (b) Foster J. P.; Weinhold, F. J. Am. Chem. Soc. 1980, 102, 7211.
(28) Indeed, the generation of siliconate from a reaction of the Lewis
base and the silane is energetically favored (and barrierless) in the gas phase
but is disfavored in solution (see Table 2). This means that in solution there
exists an activation barrier which is probably due to solvent reorganization
(a process which we have not studied). For a similar situation for SN2
reaction, see: (a) Shaik, S. S.; Schlegel, H. B.; Wolfe, S. Theoretical Aspects
of Physical Organic Chemistry, The SN2 Mechanism; John Wiley and
Sons: New York, 1992. (b) Chandrasekhar, J.; Smith, S. F.; Jorgensen W.
L. J. Am. Chem. Soc. 1984, 106, 3049. (c) Chandrasekhar, J.; Smith, S. F.;
Jorgensen, W. L. J. Am. Chem. Soc. 1985, 107, 154. (d) Chandrasekhar, J.;
Jorgensen W. L. J. Am. Chem. Soc. 1985, 107, 2974.
6
5
while for the isomer with an apical C6F5 group it is 2.21 Å. In
addition, the charge located on the C6F5 group is more negative
(26) (a) Taylor, R. Electrophilic Aromatic Substitution; John Wiley &
Sons: Chichester, U.K., 1990. (b) Hubig, S. M.; Kochi, J. K. J. Org. Chem.
2000, 65, 6807. (c) For recent detailed computational studies of aromatic
electrophilic addition, see: Esteves, P. M. Carneiro, J. W. M.; Cardoso, S.
P.; Barbosa, A. G. H.; Laali, K. K.; Rasul, G.; Prakash, G. K. S.; Olah, G.
A. J. Am. Chem. Soc. 2003, 125, 4836.
7218 J. Org. Chem., Vol. 71, No. 19, 2006

ActiVation of Pentafluorophenylsilanes
TABLE 5. Reaction Energies (kcal/mol, at 298.15 K)
TABLE 6. Relative Energies of Geometrical Isomers of
C6F5SiY3X- (kcal/mol, at 298.15 K)
reaction
∆E
∆H
∆G
∆G (CH2Cl2)
apical, apical
∆E
∆H
∆G
∆G (CH2Cl2)
Me2(C6F5)SiF + Cl-+
+
-
CH2dNMe2
C6F5SiF4
reactants
siliconate
0.0
0.0
0.0
0.0
13.9
52.7
54.1
-22.0
F, F
0.0
1.9
0.0
1.9
0.0
2.1
0.0
3.6
-17.7 -18.3 -12.0
-72.4 -73.6 -52.7
-71.5 -72.7 -51.8
-139.2 -139.8 -131.3
F, C6F5
C6F5SiF3Cl-
F, Cl
F, F
F, C6F5
Cl, C6F5
C6F5SiF3ClO4
F, ClO4
ClO4, C6F5
F, F
F, C6F5
C6F5SiCl4
TS2 (F side)
TS3 (Cl side)
products
0.0
1.7
3.9
2.5
0.0
1.7
3.9
2.5
0.0
2.3
4.2
2.9
0.0
2.0
5.5
3.9
Me2(C6F5)SiCl + Cl-+
+
CH2dNMe2
-
reactants
siliconate
TS4
0.0
0.0
0.0
0.0
13.6
58.4
-21.1 -21.7 -14.4
-67.0 -68.2 -47.1
-138.6 -139.2 -130.6
0.0
3.0
4.6
8.5
0.0
3.0
4.6
8.5
0.0
3.5
5.4
0.0
3.7
5.0
products
-21.2
-
a
Me2(C6F5)SiF + ClO4
+
11.6
11.9
+
-
CH2dNMe2
reactants
siliconate
TS5
products
0.0
0.0
0.0
-2.5
0.0
11.7
62.1
-3.7
Cl, Cl
Cl, C6F5
0.0
8.3
0.0
8.3
0.0
10.5
0.0
9.6
a
-10.8 -11.4
-51.6 -52.7 -30.0
-109.4 -110.0 -98.9
a The unconstrained optimization provided structure with one imaginary
frequency corresponding to the movement toward the more stable isomer.
-
Me2(C6F5)SiClO4 + ClO4
+
+
CH2dNMe2
reactants
siliconate
TS6
0.0
0.0
0.0
-8.1
0.0
13.9
68.4
-0.9
dimethyliminium carbocation. Surprisingly, upon forming the
C-C bond, the C6F5 group spontaneously moves from an
equatorial to an apical position. The calculated data for a series
of C-C bond forming reactions are given in Table 7. The
energies were referenced to the species, which exist in high
concentration, that is relative to the siliconate and iminium ions
in the case of fluoride activation or relative to the starting silane,
anion, and iminium cation for weaker Lewis bases.
-17.7 -18.3
-51.0 -52.2 -26.8
-107.5 -108.1 -96.5
products
SiF being significantly more reactive than silyl perchlorate
Me2(C6F5)SiClO4 (∆∆Gq ) 6.3 kcal/mol; see Table 5, TS5
sol
vs TS6).
To verify the applicability of the B3LYP functional for
the description of transition structures, the calculations for
TS1-TS4 at the MP2/6-31+G(d)//B3LYP/6-31+G(d) level
were performed and provided identical trends (see Supporting
Information for details).
These computational results suggest a general guide for the
synthetic work aimed at the application of weakly nucleophilic
Lewis bases, which can be formulated as follows: silyl fluorides
should be used to proVide fastest reactions; at the same time,
silanes containing good leaVing groups (such as ClO4) will be
less reactiVe.
Since fluorine has such a profound activating effect on nucleo-
philic transfer of a C6F5 fragment, we decided to study the per-
formance of a fully fluorinated derivative, namely, C6F5SiF3.
First of all, the geometrical isomers of the trigonal bipyramid
of five-coordinate complexes of C6F5SiF3 with fluoride, chloride,
and perchlorate anions were calculated (Table 6). The energy
differences between geometrical isomers of these siliconates
usually do not exceed 5 kcal/mol; that is lower than that in
siliconates derived from Me2(C6F5)SiF (cf. Table 3). Conse-
quently, if the barrier for the transition of the C6F5 group from
an equatorial to an apical position is low, the reaction of such
siliconates with an electrophile may be very fast owing to the
significant elongation and polarization of the bond between
silicon and the apical substituent.
Comparison of chloride ion promoted C6F5 group transfer
reactions from C6F5SiF3 and C6F5SiCl3 suggests that in dichlo-
romethane solution the transition structure for the trifluorosilyl
derivative is 10.4 kcal/mol lower than that for the trichlorosilyl
counterpart (TS8 vs TS9). A similar trend is observed for
perchlorate-activated processes (∆∆Gqsol ) 10.0 kcal/mol, TS10
vs TS11). The trifluoroacetate anion showed similar reactivity
to that of the chloride anion.
It is also interesting to compare the reactions of dimeth-
ylfluorosilyl and trifluorosilyl derivatives (Figure 3). In the case
-
of fluoride activation, the methylated siliconate Me2(C6F5)SiF2
is more reactive than tetrafluorosiliconate C6F5SiF4-, even
despite the fact that in the transition structures of the reaction
of Me2(C6F5)SiF2 the C6F5 group is transferred from an
-
equatorial position, while for C6F5SiF4-, it is from an apical
position. On the other hand, for chloride- and perchlorate-
initiated processes, the reverse trend is observed, with trifluo-
rosilane C6F5SiF3 being more reactive than dimethylsilane
Me2(C6F5)SiF. In the latter case, the faster reactions of trifluo-
rosilane are associated both with more effective siliconate
formation and with higher population of the isomer with an axial
C6F5 group. Indeed, comparison of data from Tables 3 and 6
suggests that siliconates derived from C6F5SiF3 have a smaller
energy difference between geometrical isomers than those of
Me2(C6F5)SiF2-. Furthermore, the barrier for the apical/equato-
rial interconversion is known to be lower for more halogenated
siliconates,2b thereby rendering the most reactive species with
the axial C6F5 group more accessible for siliconates C6F5SiF3X-.
These data allow one to formulate an important generaliza-
tion for the group transfer processes from a series of silanes
R2RtSiX (Rt ) transferable group, X ) heteroatom, R ) any
substituent): Upon employment of strong actiVators forming
stable fiVe-coordinate siliconates, those silanes with substituents
proViding the least stabilization of the siliconate species will
be the more reactiVe. When using weak actiVators, thus
The relative energies for the isomers of chlorinated siliconate
-
C6F5SiCl4 are also given in Table 6. The complex with the
C6F5 group in an apical position corresponds to the transition
structure toward rearrangement to a more stable isomer with a
barrier height of about 10 kcal/mol. This means that, for a
reaction of C6F5SiCl4- requiring positioning of the C6F5 group
in an apical arrangement, additional energy will be needed to
reach the transition structure.
We attempted to locate the transition structure for the
interaction of siliconates C6F5SiY3X- (Y, X ) F, Cl) with a
J. Org. Chem, Vol. 71, No. 19, 2006 7219

Dilman et al.
FIGURE 3. Free energy profiles of fluoride (left) and chloride (right) assisted reactions in dichloromethane solution (in kcal/mol).
TABLE 7. Reaction Energies (kcal/mol, at 298.15 K)
reaction
∆E
76.9
0.0
-63.6
-108.2
∆H
77.5
0.0
-64.1
-108.2
∆G
68.7
0.0
-50.6
-106.5
∆G (CH2Cl2)
+
C6F5SiF3 + F- + CH2dNMe2
reactants
siliconate
TS7
26.5
0.0
27.8
products
-22.6
+
C6F5SiF3 + Cl- + CH2dNMe2
reactants
siliconate
TS8
0.0
-28.3
-87.8
-134.8
0.0
-28.9
-89.0
-135.4
0.0
-20.8
-68.0
-126.0
0.0
7.2
36.8
products
-16.0
C6F5SiCl3 + Cl- + CH2dNMe2
+
reactants
siliconate
TS9
0.0
-25.9
-74.5
-136.6
0.0
-26.4
-75.7
-137.2
0.0
-18.7
-55.5
-128.5
0.0
11.9
47.2
products
-18.8
C6F5SiF3 + ClO4- + CH2dNMe2
+
reactants
siliconate
TS10
0.0
-13.5
-62.1
-101.8
0.0
-14.1
-63.3
-102.4
0.0
-2.6
-37.7
-90.5
0.0
15.8
54.1
6.0
products
C6F5SiCl3 + ClO4- + CH2dNMe2
+
reactants
siliconate
TS11
0.0
-8.3
-48.7
-104.6
0.0
-8.9
-49.9
-105.2
0.0
2.4
-25.7
-93.6
0.0
22.9
64.1
2.5
products
C6F5SiF3 + CF3CO2- + CH2dNMe2
+
reactants
siliconate
TS12
0.0
-28.5
-82.6
-123.7
0.0
-29.1
-83.8
-124.3
0.0
-15.8
-57.1
-110.9
0.0
4.0
35.5
products
-14.4
generating a fiVe-coordinate intermediate in low equilibrium
concentration, the silanes haVing substituents with the strongest
anion-stabilizing effect will be the most reactiVe.
As was demonstrated in Table 1, among different substituents,
fluoride and pentafluorophenyl groups provide the most sig-
nificant stabilizing effect for the formation of siliconate anion.
In this respect, the silanes of general formula (C6F5)nSiF4-n, n
) 1-4, should be first evaluated experimentally in Lewis base
mediated reactions. However, tetrakis(pentafluorophenyl)silane
(C6F5)4Si is expected to be the least reactive in solution since,
7220 J. Org. Chem., Vol. 71, No. 19, 2006

ActiVation of Pentafluorophenylsilanes
TABLE 8. Energies for Intramolecular Reaction (kcal/mol, at
298.15 K)
triethylamine. The standard ratio of reagents was used through-
out (3:silane:activator ) 1:1.1:1.2, [3] ) 0.25 M), and reactions
were performed either in methylene chloride at room temper-
ature or in 1,2-dichloroethane at reflux (82 °C). After mixing
the reagents and exposure for a certain period of time (45 min,
3 h, 15 h), the mixture was worked up and amine 4 was isolated
by flash column chromatography. The results of variation of
Lewis base and silane are presented in Table 9.
The mixture of acetic acid (pKa ) 4.76) and triethylamine
induced the pentafluorophenylation of 3 with (C6F5)3SiF,
whereas C6F5SiF3 proved to be noticeably less reactive. Lower-
ing the Lewis basicity of the activator by using 3-cyanobenzoate
anion (pKa ) 3.64) insignificantly affected the reaction effi-
ciency furnishing amine 4 in 44% yield after 15 h at room
temperature. Further decrease of anion basicity to 3,5-dinitro-
and 2,4-dinitrobenzoates (pKa 2.82 and 1.42, respectively)
retarded the reaction, though the yields of 48-52% were
achieved at elevated temperature (Table 9, entries 6 and 7).
Subsequently, we tested the anions of strong protic acids,
such as trifluoroacetic (pKa ) -0.26), methanesulfonic (pKa )
-1.89), HBr (pKa ) -9.00), and HCl (pKa ) -8.00). It was
rewarding to find that these activators are able to promote the
pentafluorophenylation in refluxing dichloroethane (Table 9,
entries 8-17). To the best of our knowledge, these are the first
examples when the poorly nucleophilic trifluoroacetate, mesy-
late, chloride, and bromide anions trigger C-C bond formation
by nucleophilic activation of a silicon atom! Of special note is
the high yield of product (85%) in experiment with the chloride
ion serving as Lewis base (Table 9, entry 17). Heating of
iminium triflate 3 with (C6F5)3SiF without any additives did
not give any product, thereby demonstrating that triflate anion
(pKa of TfOH equals -14) cannot be exploited as a competent
Lewis base.
∆E
0.0
-112.5
-110.7
-182.7
∆H
0.0
-113.1
-111.3
-183.3
∆G
0.0
-105.3
-101.0
-176.2
∆G (CH2Cl2)
X- ) F-
reactants
siliconate
TS13
product
X- ) Cl-
reactants
siliconate
TS14
0.0
-3.8
11.3
-57.5
0.0
-65.3
-61.7
-134.3
0.0
-65.9
-62.3
-134.9
0.0
-58.7
-50.4
-127.3
0.0
22.1
43.1
product
-24.5
in its structure, there are no silicon-heteroatom bonds, necessary
for the silicon to exhibit sufficient Lewis acidity for complexing
weak Lewis bases.
The overall efficiency of Lewis base mediated processes
results from the interplay of two steps: complexation of silicon
reagent with Lewis base and C6F5 group transfer. The variation
of environment around the silicon atom mainly facilitates the
first step. At the same time, the C-C bond forming event can
also be accelerated by rendering the process intramolecular. In
particular, we have recently reported a method for the synthesis
of pentafluorophenylated amino alcohols, where the key step
involves the acetate ion induced C6F5 group transfer from N-(2-
silyloxyethyl)iminium cation [RCHdN+(Me)CH2CH2OSi-
(C6F5)3].9b
Different pentafluorophenylsilanes were combined with imi-
nium salt 3 under optimal conditions (Table 9, entries 18-24).
On the basis of the yield of the product, it can be concluded
that the reactivity of silanes decreases in the order: (C6F5)3SiF
> C6F5SiF3 > (C6F5)3SiOMe . other silanes. Fluorosilanes
were considerably more active than analogous chlorosilanes (cf.
entries 17 and 22; 18 and 19), which is in full agreement with
theoretic predictions.
Though no mechanistic studies to confirm the intramolecular
character of the transformation have been performed, the
reaction proceeded smoothly under very mild conditions.9b As
a mechanistic probe to distinguish between inter- and intramo-
lecular C6F5 group transfer, we calculated the energy profiles
for the fluoride and chloride ion promoted reactions of N-methyl-
N-(2-silyloxyethyl)methyleneiminium ion (Table 8).
Concerning intramolecular reactions, iminium salt 5, ob-
tained from benzylidenemethylamine and 2-silyloxyethyltriflate
according to our recent procedure,9b was treated with a series
of Lewis bases to afford amino alcohol 6, and the results are
collected in Table 10.
All activators, which worked for salt 3, also were applicable
for the synthesis of amino alcohol 6. As a rule, siloxyeth-
yliminium salt 5 reacted more readily compared to the combina-
tion of 3/(C6F5)3SiF. For example, amino alcohol 6 can be
obtained by using 3,5-dinitrobenzoate anion at room temperature
(Table 10, entry 2), whereas system 3/(C6F5)3SiF is absolutely
ineffective under similar conditions (Table 9, entry 5). Employ-
ment of a chloride anion as activator also provided good yield
of 6. Interestingly, the latter reaction slowly proceeds even at
room temperature (Table 10, entry 10). The efficiency of the
C6F5 group transfer from salt 5, as well as the results of
calculations, testifies in favor of intramolecular mechanism of
the process.
Comparison of these data with those for the reaction of
dimethyliminium cation with Me2(C6F5)SiF suggests that in
solution both fluoride- and chloride-mediated reactions pro-
ceed considerably faster intramolecularly (F-, ∆∆Gqsol ) 13.1
kcal/mol, TS1 vs TS13; Cl-, ∆∆Gq ) 9.6 kcal/mol, TS2 vs
sol
TS14). This means that for intramolecular processes milder
conditions may be used in synthetic experiments.
Experimental Studies. To validate the theoretical consider-
ations, we performed a series of Lewis base promoted reactions
between an iminium electrophile and various pentafluorophen-
ylsilanes. N,N-Dimethylbenzylideneiminium triflate (3), obtained
from benzylidenemethylamine and methyl triflate, was selected
as model electrophile. As basic activators, the anions of protic
acids were tested, which were employed either in the form of
quaternary ammonium salts or generated in situ from acid and
Conclusion
We demonstrated both theoretically and experimentally that
a pentafluorophenyl group exerts a considerable stabilizing effect
J. Org. Chem, Vol. 71, No. 19, 2006 7221

Dilman et al.
TABLE 9. Lewis Base Activated C6F5 Group Transfer Reactions
yield of
entry
silane
X-
AcOH/NEt3
solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
temp
rt
rt
rt
rt
rt
time
4 (%)a
1
2
3
4
5
6
7
8
C6F5SiF3
45 min
45 min
15 h
15 h
45 min
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
3 h
15 h
3 h
3 h
3 h
<5
35
58
44
<5
48
52
19
35
41
12
48
65
38
<5
8
85
39
<5
21
<5
<5
<5
15
(C6F5)3SiF
(C6F5)3SiF
(C6F5)3SiF
(C6F5)3SiF
(C6F5)3SiF
(C6F5)3SiF
C6F5SiF3
AcOH/NEt3
AcOH/NEt3
3-NC-BzOH/NEt3
3,5-(NO2)2-BzOH/NEt3
3,5-(NO2)2-BzOH/NEt3
2,4-(NO2)2-BzOH/NEt3
CF3CO2H/NEt3
CF3CO2H/NEt3
CF3CO2 NBu4
CF3CO2 NBu4
MsO NBu4
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
CH2Cl2
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
82 °C
82 °C
82 °C
82 °C
82 °C
82 °C
82 °C
82 °C
82 °C
82 °C
rt
82 °C
82 °C
82 °C
82 °C
82 °C
82 °C
82 °C
82 °C
9
(C6F5)3SiF
(C6F5)3SiF
C6F5SiF3
(C6F5)3SiF
(C6F5)3SiF
C6F5SiF3
(C6F5)3SiF
(C6F5)3SiF
(C6F5)3SiF
C6F5SiF3
C6F5SiCl3
(C6F5)3SiOMe
C6F5Si(OEt)3
(C6F5)3SiCl
(C6F5)4Si
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Bu4NBr
Bu4NBr
-
BnNEt3Cl
BnNEt3Cl
BnNEt3Cl
BnNEt3Cl
BnNEt3Cl
BnNEt3Cl
BnNEt3Cl
BnNEt3Cl
BnNEt3Cl
3 h
3 h
3 h
3 h
(C6F5)3SiMe
3 h
a Isolated yield.
TABLE 10. Intramolecular Lewis Base Activated C6F5-group
Transfer Reactions
promoters for the transfer of a pentafluorophenyl group from
silicon to the iminium carbocation. Given the ample opportuni-
ties for the generation of electrophilic species by protonation
of organic substrates with hydrochloric or trifluoroacetic acids
with concomitant appearance of corresponding conjugate bases,
the data presented in this work pave the way for the development
of new carbon-carbon bond forming processes employing
silicon reagents. The results of our investigations along these
lines will be reported in forthcoming publications.
yield of
entry
LB
solvent
CH2Cl2
temp
rt
rt
rt
rt
rt
time
6 (%)a
1b AcOH/NEt3
2
3
4
5
6
7
8
9
20 min
45 min
45 min
3 h
75
64
38
53
31
50
43
54
77
32
<5
Experimental Section
3,5-(NO2)2-BzOH/NEt3 CH2Cl2
2,4-(NO2)2-BzOH/NEt3 CH2Cl2
2,4-(NO2)2-BzOH/NEt3 CH2Cl2
Cl2CHCO2H/NEt3
CF3CO2 NBu4
Bu4NOMs
Bu4NBr
Fluorotris(pentafluorophenyl)silane was obtained according to
modified procedure.29 Fluorosulfonic acid (4.0 mL, 70 mmol) was
added dropwise through the reflux condenser to a suspension of
tris(pentafluorophenyl)phenylsilane11a (18.2 g, 30 mmol) in dichlo-
roethane (20 mL). The exothermic reaction occurred accompanied
by the dissolution of starting silane. After stirring for 10 min, the
reaction flask was heated at 50 °C for additional 1.5 h, and the
solvent was evaporated under vacuum (finally applying oil pump
at 50 °C to ensure complete removal of dichloroethane). The residue
was treated with hexane (40 mL) that provided a two-phase mixture.
The upper layer containing most of the product was decanted, and
the lower layer was extracted with hot hexane (10 mL). The
combined hexane layers were heated to reflux, and sodium fluoride
(0.25 g, 6 mmol) was added. The solution was filtered while hot
and allowed to cool to 5 °C that caused precipitation of clear
colorless needles. Filtration and drying in vacuum afforded 14.5 g
of (C6F5)3SiF (88% yield).
CH2Cl2
3 h
ClCH2CH2Cl 82 °C 3 h
ClCH2CH2Cl 82 °C 3 h
ClCH2CH2Cl 82 °C 3 h
ClCH2CH2Cl 82 °C 3 h
CH2Cl2
ClCH2CH2Cl 82 °C 3 h
BnNEt3Cl
BnNEt3Cl
-
10
11
rt
15 h
a Isolated yield. b From ref 9b.
on a pentacoordinate silicon intermediate, and the magnitude
of this effect is comparable to that of fluorine. However, in
addition to having the role of an electron-withdrawing group, a
pentafluorophenyl substituent may also serve as a transferable
nucleophilic group toward carbon electrophiles.
By varying the character of other substituents on silicon, it
is possible to achieve a suitable energetic balance between the
generation and subsequent reaction of the pentacoordinate silicon
intermediate so that very weak Lewis base activators can be
used. Indeed, under certain conditions, even chloride and tri-
fluoroacetate anions exhibited noticeable activity as nucleophilic
Pentafluorophenyltrifluorosilane. The mixture of sodium hexa-
fluorosiliconate (16.6 g, 50 mmol) and pentafluorophenyltrichlo-
rosilane30 (7.54 g, 25 mmol) was refluxed for 1 h and then distilled
(29) Frohn, H. J.; Lewin, A.; Bardin, V. V. J. Organomet. Chem. 1998,
568, 233.
7222 J. Org. Chem., Vol. 71, No. 19, 2006

ActiVation of Pentafluorophenylsilanes
at 105-109 °C (ambient pressure) to give 5.36 g of C6F5SiF3 (85%
yield).
of silane (1.1 mmol) and a solution of acid (1.2 mmol) and
triethylamine (167 µL, 1.2 mmol) in 1 mL of solvent. After
completion, the mixture was worked up as described above.
N,N-Dimethylbenzylideneiminium triflate (3). Benzylidene-
methylamine (2.5 g, 21 mmol) was added to the solution of methyl
triflate (2.5 mL, 22.1 mmol) in benzene (15 mL) that caused an
exothermic reaction and formation of a biphasic mixture. After
stirring for 2 min, the mixture was allowed to cool slowly without
stirring. After crystallization of the lower layer, the benzene was
decanted, and the residue was washed with benzene (2 × 10 mL).
Drying in vacuum provided 5.82 g of colorless crystals (98% yield).
Mp 77-78 °C. 1H NMR (300 MHz, CD3CN) δ: 3.76 (d, 3H, J )
1.2 Hz, Me), 3.86 (d, 3H, J ) 1.2 Hz, Me) 7.69-7.94 (m, 5H,
Ph), 8.99 (s, 1H, CH). 13C NMR (50 MHz, CD3CN) δ: 45.1, 52.8,
131.2, 133.9, 137.3, 174.0.
Dimethyl(pentafluorophenylphenylmethyl)amine (4). Chro-
matography in hexanes-EtOAc, 10:1, Rf ) 0.32; bp 144-150
°C/15 Torr (bath temperature). 1H NMR (300 MHz, CDCl3) δ: 2.29
(s, 6H, NMe2), 4.84 (s, 1H, CH), 7.24-7.39 (m, 3H, Ph), 7.47-
7.55 (m, 2H, Ph). 13C NMR (75.5 MHz, CDCl3) δ: 44.0, 66.0,
115.1 (tm, J ) 15.3 Hz, i-C6F5), 127.3, 127.7, 128.6, 137.6 (dm, J
) 252.6 Hz), 139.9, 140.2 (dm, J ) 253.3 Hz), 144.8 (dm, J )
249.5 Hz). 19F NMR (188 MHz, CDCl3) δ: -162.79 (td, 2F, J )
22.2, 8.3 Hz, meta), -156.62 (t, 1F, J ) 20.8 Hz, para), -140.14
(dm, 2F, J ) 22.8 Hz, ortho). Anal. Calcd for C15H12F5N: C, 59.80;
H, 4.01; N, 4.65. Found: C, 59.64; H, 3.91; N, 4.53.
Lewis Base Activated Reactions. To the iminium triflate (1
mmol) were successively added 4 mL of dry solvent, silane (1.1
mmol), and quaternary ammonium salt (1.2 mmol). The mixture
was stirred either at room temperature or at gentle reflux for the
time indicated in Table 9 or 10. For the workup, saturated aqueous
Na2CO3 (0.8 mL) was added at 10 °C, and the resulting suspension
was diluted with 15 mL of ether/hexane (1:1), filtered through
anhydrous Na2SO4, and concentrated in vacuum. The residue was
chromatographed on silica gel.
N-Methyl-N-(pentafluorophenylphenylmethyl)-2-aminoetha-
nol (6).9b Chromatography in hexane/EtOAc 3:1, Rf ) 0.36.
Acknowledgment. This work was supported by INTAS
(project # 2003-55-1185) and the Ministry of Science (project
MK-2235.2005.3).
Supporting Information Available: Cartesian coordinates and
absolute energies for calculated structures. This material is available
free of charge via the Internet at http://pubs.acs.org.
For experiments using an acid/NEt3 mixture, 3 mL of solvent
was added to the iminium triflate (1 mmol) followed by addition
(30) Frohn, H. J.; Giesen, M.; Klose, A.; Lewin, A.; Bardin, V. V. J.
Organomet. Chem. 1996, 506, 155.
JO0606812
J. Org. Chem, Vol. 71, No. 19, 2006 7223