Chiral benzylic carbocations: Low-temperature NMR studies and theoretical calculations

Article abstract of DOI:10.1021/jo802296e

(Chemical Equation Presented) The α-chiral secondary and tertiary benzylic carbocations 19-30 were generated from the corresponding benzylic alcohols 1, 2, and 5-14 by treatment with FSO₃H or FSO ₃H/SbF₅ in SO₂ClF as the solvent at -70°C and characterized by one- and two-dimensional NMR spectroscopy. Coupling constants and NOESY measurements suggest a preferred conformation in which the α-hydrogen atom occupies the 1,3-allylic-strain position and the diastereotopic faces of the cations are differentiated by the alkyl substituent and a functional group (FG). The existence of this preferred conformation is further supported by calculations using a DFT method at the B3LYP/6- 311+G** level. Quenching experiments with an arene nucleophile showed a preferential attack from the less shielded diastereotopic face delivering high diastereomeric ratios, supporting the hypothesis that these carbocations are involved as intermediates in previously studied S_N1 reactions. A strong shielding effect at the benzylic carbocationic center is observed for most of the secondary benzylic carbocations (derived from precursors 5-13) investigated, indicating a strong mesomeric distribution of the positive charge to the carbon atom in the para-position of the anisyl substituent. For α-halogen-substituted carbocations (5-7, 12), no neighboring halogen participation leading to halonium ion formation was observed.

Full text of DOI:10.1021/jo802296e

Chiral Benzylic Carbocations: Low-Temperature NMR Studies and
Theoretical Calculations
Daniel Stadler,† Alain Goeppert,‡ Golam Rasul,‡ George A. Olah,‡ G. K. Surya Prakash,*,‡
and Thorsten Bach*,†
Lehrstuhl fu¨r Organische Chemie I, Technische UniVersita¨t Mu¨nchen, 85747 Garching, Germany, and
Loker Hydrocarbon Research Institute and Department of Chemistry, UniVersity of Southern California,
Los Angeles, California 90089-1661
thorsten.bach@ch.tum.de
ReceiVed October 15, 2008
The R-chiral secondary and tertiary benzylic carbocations 19-30 were generated from the corresponding
benzylic alcohols 1, 2, and 5-14 by treatment with FSO3H or FSO3H/SbF5 in SO2ClF as the solvent at
-70 °C and characterized by one- and two-dimensional NMR spectroscopy. Coupling constants and
NOESY measurements suggest a preferred conformation in which the R-hydrogen atom occupies the
1,3-allylic-strain position and the diastereotopic faces of the cations are differentiated by the alkyl
substituent and a functional group (FG). The existence of this preferred conformation is further supported
by calculations using a DFT method at the B3LYP/6-311+G** level. Quenching experiments with an
arene nucleophile showed a preferential attack from the less shielded diastereotopic face delivering high
diastereomeric ratios, supporting the hypothesis that these carbocations are involved as intermediates in
previously studied SN1 reactions. A strong shielding effect at the benzylic carbocationic center is observed
for most of the secondary benzylic carbocations (derived from precursors 5-13) investigated, indicating
a strong mesomeric distribution of the positive charge to the carbon atom in the para-position of the
anisyl substituent. For R-halogen-substituted carbocations (5-7, 12), no neighboring halogen participation
leading to halonium ion formation was observed.
Introduction
dition reactions,4 and rearrangements.5 Possibly because of their
high reactivity, chiral benzylic cations have not been extensively
studied as intermediates in diastereoselective C-C bond forma-
The first secondary benzylic cations were studied by 1H NMR
spectroscopy in solution as early as 1966.1 The first 13C NMR
spectrum of such a cation was obtained in 1971.2 Benzylic
cations have been invoked as intermediates in many reactions,
including Friedel-Crafts alkylation reactions,3 [3 + 2]-cycload-
(4) Angle, S. R.; Boyce, J. P. Tetrahedron Lett. 1994, 35, 6461–6464.
(5) (a) Kita, Y.; Furukawa, A.; Futamura, J.; Ueda, K.; Sawama, Y.;
Hamamoto, H.; Fujioka, H. J. Org. Chem. 2001, 66, 8779–8786. (b) Jung, M. E.;
Anderson, K. L. Tetrahedron Lett. 1997, 38, 2605–2608. (c) Moghaddam, F. M.;
Hoor, A. A.; Dekamin, M. G. J. Sulfur Chem. 2004, 25, 125–130.
(6) (a) Mengel, A.; Reiser, O. Chem. ReV. 1999, 99, 1191–1223. (b) Devant,
R. M.; Radunz, H.-E. In Houben-Weyl Methods of Organic Chemistry; Helmchen,
G., Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart, 1996;
Vol. E21b, pp 1151-1334. (c) Eliel, E. L. In Asymmetric Synthesis; Morrison,
J. D., Ed.; Academic Press: Orlando, 1983; Vol. 2A; pp 125-155.
(7) Reviews: (a) Petrini, M.; Torregiani, E. Synthesis 2007, 2, 159–186. (b)
Vilaivan, T.; Bhanthumnavin, W.; Sritana-Anant, Y. Curr. Org. Chem. 2005, 9,
1315–1392.
† Technische Universita¨t Mu¨nchen.
‡ University of Southern California.
(1) Cupas, C. A.; Comisarow, M. B.; Olah, G. A. J. Am. Chem. Soc. 1966,
88, 361–362.
(2) Olah, G. A.; Porter, R. D.; Kelly, D. P. J. Am. Chem. Soc. 1971, 93,
464–466.
(3) Olah, G. A. J. Org. Chem. 2001, 66, 5943–5957.
312 J. Org. Chem. 2009, 74, 312–318
10.1021/jo802296e CCC: $40.75 2009 American Chemical Society
Published on Web 11/26/2008

Chiral Benzylic Carbocations
SCHEME 1. Diastereoselective Friedel-Crafts Alkylation
Reactions via Chiral Benzylic Cations
FIGURE 1. Set of secondary and tertiary benzylic alcohols 5-14 as
cation precursors.
SCHEME 2. Preparation of the Starting Materials 6, 7, 12,
and 13
tion reactions. The stereoselectivity in reactions of less reactive
electrophiles (carbonyl compounds,6 imines,7 oxonium ions,8
iminium ions9) has been elucidated in much more detail. Our
knowledge about the major factors, which govern the diaste-
reoselectivity in SN1-type reactions10 and in reactions which
involve benzylic carbocations, lags behind the wealth of
information which has been accumulated for, e.g., reactions of
chiral aldehydes or ketones.11
Recently, we were able to show that chiral methoxybenzylic
alcohols such as compounds 1 and 2, which carry a functional
group in the stereogenic R-position, react with various arenes
in a highly selective fashion.12,13 As an example, the reactions
to the 1,1-diarylated products anti-3 and syn-4 are shown in
Scheme 1. Chiral benzylic cations are likely intermediates in
these reactions, and the question of how the selectivity of these
reactions can be explained, led us to investigate the structure
of the intermediates more closely under long-lived stable ion
conditions.14 In the present paper, we disclose full details on
our NMR investigations of chiral benzylic cations, which bear
a stereogenic center in the R-position. Evidence collected from
DFT calculations and experiments suggests that the cations exist
in a preferred conformation.
Results and Discussion
Preparation of the Starting Materials. Our studies were
conducted with the previously depicted benzylic alcohols 1 and
2 (Scheme 1) as cation precursors as well as with the alcohols
5-14 (Figure 1).
The synthesis of alcohols 1, 2, 5, 8-11, and 14 has already
been reported.12 2-Bromoalkanol 6 and 2-fluoroalkanol 7 were
prepared by a straightforward R-halogenation of the correspond-
ing ketone 15 and subsequent NaBH4 reduction (Scheme 2).
For the fluorination, an extended reaction time (72 h) and a
slight excess of Selectfluor (1-chloromethyl-4-fluoro-1,4-
diazoniabicyclo[2.2.2]octanebis-tetrafluoroborate, 1.50 equiv)
were required to reach full conversion. The product was not
separable from the starting material by column chromatography.
Methylmagnesium bromide addition to the known ketone 1615
at room temperature yielded only the undesired trisubstituted
epoxide, whereas methyllithium addition at -78 °C prevented
the epoxide formation and gave the corresponding tertiary
2-chloroalkanol 12 in good chemical yield. Precursor 13 was
synthesized by a Reformatsky-type addition of methyl R-bro-
mopropionate (18)16 to ketone 17.
(8) (a) Schmitt, A.; Reissig, H.-U. Synlett 1990, 40–42. (b) Schinzer, D. In
Organic Synthesis Highlights II; Waldmann, H., Ed.; VCH: Weinheim, 1995;
pp 173-179. (c) Shaw, J. T.; Woerpel, K. A. Tetrahedron 1999, 55, 8747–
8756. (d) Schmitt, A.; Reissig, H.-U. Eur. J. Org. Chem. 2001, 116, 9–1174. (e)
Ayala, L.; Lucero, C. G.; Romero, J. A. C.; Tabacco, S. A.; Woerpel, K. A.
J. Am. Chem. Soc. 2003, 125, 15521–15528. (f) Larsen, C. H.; Ridgway, B. H.;
Shaw, J. T.; Smith, D. M.; Woerpel, K. A. J. Am. Chem. Soc. 2005, 127, 10879–
10884.
(9) Reviews: (a) Maryanoff, B. E.; Zhang, H.-C.; Cohen, J. H.; Turchi, I. J.;
Maryanoff, C. A. Chem. ReV. 2004, 104, 1431–1628. (b) Speckamp, W. N.;
Moolenaar, M. J. Tetrahedron 2000, 56, 3817–3856. (c) de Koning, H.;
Speckamp, W. N. In Methods of Organic Chemistry; Helmchen, G., Hoffmann,
R. W., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart, 1996; Vol. E21b, pp
1953-2010. (d) Schinzer, D. In Organic Synthesis Highlights II; Waldmann,
H., Ed.; VCH: Weinheim, 1995; pp 167-172.
Low-Temperature NMR Studies in Superacidic Media.
Ionization experiments with different superacids (FSO3H, FSO3H/
SbF5, SbF5) in different solvents (SO2ClF, CD2Cl2) were
undertaken to find the optimized conditions for the preparation
(10) For reports on diastereoselective SN1 reactions, see: (a) Klumpp, D. A.;
Rendy, R.; McElrea, A. Tetrahedron Lett. 2004, 45, 7959–7961. (b) Ishikawa,
T.; Aikawa, T.; Mori, Y.; Saito, S. Org. Lett. 2004, 6, 1369–1372. (c) Mu¨hlthau,
F.; Schuster, O.; Bach, T. J. Am. Chem. Soc. 2005, 127, 9348–9349.
(11) (a) No´gra´di, M. StereoselectiVe Synthesis, 2nd ed.; VCH: Weinheim,
1995; pp 135-210. (b) Atta-ur-Rahman; Shah, Z. StereoselectiVe Synthesis in
Organic Chemistry; Springer Verlag: New York, 1993; pp 250-258. (c)
Morrison, J. D.; Mosher, H. S. Asymmetric Organic Reactions; Prentice Hall:
Englewood Cliffs, 1971; pp 84-132.
(13) For related catalytic reactions employing various weak nucleophiles,
see: (a) Rubenbauer, P.; Bach, T. Tetrahedron Lett. 2008, 49, 1305–1309. (b)
Rubenbauer, P.; Bach, T. AdV. Synth. Catal. 2008, 350, 1125–1130.
(14) Muehlthau, F.; Stadler, D.; Goeppert, A.; Olah, G. A.; Prakash, G. K. S.;
Bach, T. J. Am. Chem. Soc. 2006, 128, 9668–9675.
(15) Sonawane, H. R.; Bellur, N. S.; Kulkarni, D. G.; Ayyangar, D. G.
Tetrahedron 1994, 50, 1243–1260.
(16) Smonou, I.; Orfanopoulos, M. Synth. Commun. 1990, 20, 1387–1397.
(12) (a) Stadler, D.; Muehlthau, F.; Rubenbauer, P.; Herdtweck, E.; Bach,
T. Synlett 2006, 2573–2576. (b) Stadler, D.; Bach, T. Chem. Asian J. 2008, 3,
272–284.
J. Org. Chem. Vol. 74, No. 1, 2009 313

Stadler et al.
SCHEME 3. Ionization of Precursors 1,2, and 5-11 and
Generation of Cations 19-27 (Table 1) as a Mixture of
Conformers (E/Z)
TABLE 1. Carbon Shifts for Major and Minor Conformers of
Cations 19-27
FIGURE 2. 13C NMR spectrum of cation 26.
alkyl cations is well precedented.17 The E-conformer is normally
the major diastereoisomer if the cation is secondary. The
rotational barrier around the C-O bond has been used as a probe
for the stabilization of the respective cation by various substit-
uents. The rotational barrier increases if oxygen nonbonded
electron pair assistance is required due to only weak stabilization
by the direct cation substituents. On the other hand, if the cation
stabilization is high, e.g., due to an adjacent cyclopropyl
substituent, the rotational barrier decreases.18 For tertiary
carbocations (vide infra), bearing an additional methyl group
in the benzylic position, both conformations are populated nearly
equally. Interestingly, for all secondary carbocations 19-27 the
carbon atom in the para position of the anisyl substituent (CD)
exhibited the most pronounced downfield shift, which was even
more pronounced than the shift of the benzylic carbon atom
C1. This observation clearly shows that due to the electron-
withdrawing properties of the functional group (FG) and the
resulting destabilization of the positive charge in the benzylic
position, the charge is strongly shifted to the methoxy-stabilized
carbon atom in the para position of the anisyl ring.
C1 (ppm)
CD (ppm)
cation
FG
majora
minora
majora
minora
19
20
21
22
23
24
25
26
27
Cl
Br
F
180.6
179.9
183.9
170.0
170.9
172.1
172.2
167.4
168.1
180.5
179.8
183.7
170.9
170.9
172.1
172.2
167.3
168.1
187.0
186.0
186.0
188.2
188.3
188.1
188.1
188.7
188.5
187.0
186.0
186.0
188.3
188.3
188.1
188.2
188.7
188.6
NO2
CN
CO2Me
PO(OEt)2
SO2Et
SO3Et
a Major and minor conformer with respect to the orientation of the
methoxy group.
of the carbocations. For all benzylic alcohols bearing a methoxy
group in the para position (1, 2, 5-13), it turned out that FSO3H
in SO2ClF was sufficiently strong to quantitatively generate the
cations at -78 °C (Scheme 3). Generation of the carbocations
in CD2Cl2 as the solvent was also successful, although FSO3H
is only poorly soluble at -78 °C and precipitated. Ionization
with FSO3H/SbF5 (Magic Acid) or SbF5 resulted only in
decomposition probably due to protonation of the methoxy
group and destabilization of the benzylic charge. If kept in
SO2ClF at -78 to -70 °C under superacidic conditions, the
cations can be stored for several days without significant
decomposition. Even short warming to higher temperatures (e.g.,
5 to -30 °C) and cooling back to -70 °C did not result in
significant degradation or side product formation indicating the
relatively high stability of these intermediates.
Clean one- and two-dimensional NMR spectra including
DEPT, COSY, NOESY, HMQC, and HMBC were obtained for
the cations 19-27 allowing the full assignment of all signals
(see the Supporting Information). The spectra showed two
unequally populated structures for each carbocation resulting
from the hindered rotation of the methoxy group of the anisyl
substituent. The effect is due to the partial double bond character
of the anisyl-carbon bond and a consequence of mesomeric
stabilization (Table 1). The presence of E/Z-isomers in anisyl-
Figure 2 shows a representative 13C NMR spectrum of cation
26 recorded at -78 °C in SO2ClF as the solvent. The two
conformers are nicely identified in a ratio of 60/40. The aromatic
methoxy-substituted carbon atom (CD) is significantly deshielded
appearing at 188.7 ppm for both conformers, while the benzylic
carbon atom C1 was found at 167.4 ppm in the major and at
167.3 ppm in the minor conformer. Acetone-d6 was used as
external standard (δ ) 29.8 ppm).
In the case of cations 19 (FG ) Cl) and 20 (FG ) Br), no
evidence for the formation of bridged halonium ions by
neighboring halogen participation was observed. The 13C NMR
chemical shift of carbon C2 remains unchanged after ionization,
i.e. by the transformations 5 f 19 and 6 f 20. If halonium ion
formation had occurred the carbon atom would have been
significantly deshielded.19 The result is in agreement with
theoretical predictions and is in line with the fact that substitution
reactions at alcohols 5 and 6 occurred with only modest
diastereoselectivity.12b,20
Conformation Analysis. All 1H NMR spectra showed a large
3J coupling constant for H1/H2, which indicates an antiperiplanar
(18) Jost, R.; Sommer, J.; Engdahl, C.; Ahlberg, P. J. Am. Chem. Soc. 1980,
102, 7663–7667.
(19) (a) Olah, G. A. Halonium Ions; Wiley: New York, 1975. (b) Olah, G. A.;
Westerman, P. W.; Melby, E. G.; Mo, Y. K. J. Am. Chem. Soc. 1974, 96, 3565–
3573.
(17) For examples, see: (a) Servis, K. L.; Shue, F.-F. J. Am. Chem. Soc.
1980, 102, 7233–7240. (b) Siehl, H.-U.; Kaufmann, F.-P.; Hori, K. J. Am. Chem.
Soc. 1992, 114, 9343–9349.
(20) Stadler, D., Bach, T. Unpublished results.
314 J. Org. Chem. Vol. 74, No. 1, 2009

Chiral Benzylic Carbocations
FIGURE 4. NOE contacts for cations 19-29.
FIGURE 3. Newman projection defining the dihedral angle (H1-C1-
C2-H2) and NOE contacts for cations 19-27 (An ) anisyl).
center. The functional group FG resides at one diastereotopic
face, the methyl group at the other, imposing a steric bias for
the approach of a given nucleophile toward the electrophilic
center.
TABLE 2. Observed Chemical Shifts and Calculated Dihedral
Angles for Carbocations 19-27
3JHH (Hz)
calculated angle (°)
Tertiary Carbocations. Upon ionization of alcohols 12 and
13, the tertiary benzylic cations 28 and 29 were obtained. The
cations showed similar NMR-spectroscopic behavior as did their
secondary analogues. Their stability was slightly higher due to
the increased stabilization by the additional methyl substituent.
The increased hyperconjugative stabilization is also responsible
for a shift of the charge density from the methoxy-substituted
aromatic carbon atom CD to the cation center C1. This fact is
substantiated by the 13C NMR chemical shifts of the respective
carbon atoms, with C1 now being more strongly deshielded as
compared to CD. The two conformers, which exist due to the
restricted rotation around the CD-OMe bond and which were
unequally populated for the secondary cations 19-27, are now
equally populated. Relevant individual 13C NMR chemical shift
data are collected in Table 3.
cation
FG
majora
minora
monocation
dication
19
20
22
23
24
25
26
27
Cl
Br
11.1
11.8
9.4
10.3
10.3
b
11.1
11.8
9.4
10.4
10.4
b
177
175
161
175
160
153
156
158
179
176
172
169
165
176
165
171
NO2
CN
CO2Me
PO(OEt)2
SO2Et
SO3Et
10.8
10.3
10.8
10.3
a Major and minor conformer with respect to the orientation of the
methoxy group. b Coupling constant was not extractable due to
3JHP-coupling.
relationship of these atoms. Taking into account that the empty
pz-orbital of the benzylic carbon atom C1 must be parallel to
the pz-orbital of the anisyl ring to allow mesomeric stabilization,
the hydrogen atom H2 should be in the energetically favored
1,3-allylic strain position.21 We have also fully optimized the
structures at the DFT B3LYP/6-311+G** level using the
Gaussian 03 program (see the Experimental Section). 13C NMR
chemical shifts were computed also by using Gaussian 03
program employing the GIAO method at the B3LYP/6-
311+G**// B3LYP/6-311+G** level (vide infra). Indeed,
geometry optimization calculations using the DFT method at
the B3LYP/6-311+G** level showed a dihedral angle
(H1-C1-C2-H2) of 153-177° for carbocations 19-27 (mono-
cations).
TABLE 3. Carbon Shifts for Cations 28 and 29
a
a
cation
FG
Cl
CO2Me
C1 (ppm)
CD (ppm)
28
29
203.5/203.5
191.3/191.5
184.3/184.3
185.9/185.9
a Population of major and minor conformers is approximately 50/50.
On the left side of Figure 3 is depicted the conformation of
cations 19-27 in the Newman projection, and the angle
(H1-C1-C2-H2) is defined relative to the functional group FG
and the methyl group. Indeed, according to the calculations,
the angle as defined above varies in the cations between 156
and 179° (see Table 2) depending on the functional group FG
and on its possible protonation (dication formation, vide infra).
The proposed conformation was further supported by 2D-
NOESY spectra, in which single NOE contacts for H1 and H2
with the two different ortho hydrogen atoms HB and HF were
observed. Typical NOE contacts are depicted on the right side
of Figure 3 for the secondary cations 19-27 (Table 2). Most
importantly, the contact between proton H2 and the aromatic
proton HF supports the fact that the former proton resides in a
1,3-allylic strain position. The strong NOE of H2 and HF on
one hand and of H1 and HB on the other are in accord with the
previously mentioned antiperiplanar arrangement. It is evident
from Figure 3 that the restricted rotation around the carbon-
carbon bonds between cation center C1 and anisyl substituent
and between cation center C1 and R-carbon atom C2 lead to a
differentiation of the diastereotopic faces at the very same cation
The conformational preference concerning the dihedral angle
(CH3 -C1-C2-H2) appearssbased on NOESY datasto be
1
similar to the preference observed for the secondary cations
(Figure 4). The antiperiplanar arrangement of the methyl group
at C1 and the proton H2 at C2 is deduced from strong NOE
contacts of either proton to the ortho protons HB and HF in the
anisyl substituent.
Variation of the Aromatic Substituent. Ionization of
precursor 14 with FSO3H in SO2ClF resulted in incomplete
cation formation due to the weaker stabilizing ability of the
p-tolyl substituent. The red solution did not deliver conclusive
spectra at -78 °C. It was, however, possible to achieve a clean
ionization employing FSO3H/SbF5 in SO2ClF as the acid system.
Side reactions were suppressed due to the quantitative and rapid
protonation by the stronger acid. The 13C NMR spectrum of
the resulting cation 30 (Scheme 4, Figure 5) revealed three
deshielded carbon atoms with chemical shifts at 188.3, 190.2,
and 192.2 ppm.22 The individual signals were assigned to the
carbon atoms COOMe, C1 and CD, respectively. As per our
subsequent discussion, it is highly likely that the carbonyl
oxygen atom of the ester group is protonated and that cation
30 indeed is a dication.
(21) Review: Hoffmann, R. W. Chem. ReV. 1989, 89, 1841–1860.
J. Org. Chem. Vol. 74, No. 1, 2009 315

Stadler et al.
TABLE 4. Chemical Shift Comparison of Functional Groups
chemical shifta (ppm)
sm carbocation
188.6
precursor
FG
acid
FSO3H
FSO3H
FSO3H/SbF5
FSO3H
1
CO2Me
CO2Me
CO2Me
CN
176.1
177.1
176.1
121.0
34.5b
13
14
9
2
7
188.2
188.3 (1H: 12.49)
112.0
31PO(OEt)2 FSO3H
33.9b
19F
FSO3H
-180.3c -175.8c
a Major diastereoisomer (sm ) starting material)/major conformer
b
(carbocation). 31P NMR shift calibrated with PPh3 as external standard.
c
19F-NMR shift calibrated with CFCl3 as external standard.
TABLE 5. Carbon Shifts for Major Conformers of Cations 19-27
calcd shifts C1 included scaling obsd shifts
cation
FG
(ppm)
(X ) 0.86)
C1 (ppm)
FIGURE 5. 13C NMR spectrum of cation 30
19
20
21
22
23
24
25
26
27
28
29
Cl
Br
F
NO2
CN
CO2Me
PO(OEt)2
SO2Et
SO3Et
Cl
195.0
188.2
207.7
197.3
199.6
213.4
205.4
189.7
195.7
220.0
229.7
167.7
161.8
178.6
169.6
171.6
183.5
176.6
163.1
168.2
189.2
197.5
180.6
179.9
183.9
170.0
170.9
172.1
172.2
167.4
168.1
203.5
191.3
SCHEME 4. Ionization and Protonation of Precursor 14
with Magic Acid.
CO2Me
Other data obtained for cation 30 are in accord with
previously studied tolyl cations.22 The cation center at C1 (δ )
190.2 ppm) is more strongly deshielded as compared to the same
atom in the respective anisyl-substituted cation 24 (δ ) 172.1
ppm). The coupling constant between H1 and H2 (3J ) 9.9 Hz)
and the NOESY contacts (see Supporting Information) were
similar to 24 indicating that cation 30 also adopts the preferred
conformation previously discussed. The deshielded 13C NMR
signal for the ester carbonyl carbon atom (δ ) 188.3 ppm)
makes the formation of a dication as depicted in Scheme 4
highly likely.
Investigations of Superelectrophilic Activation/Protona-
tion of Functional Groups/DFT-GIAO Chemical Shift
Calculations. Superacids are known to be sufficiently strong
to generate, in some cases, very reactive dicationic species.23
These systems can undergo reactions which would not be likely
for the corresponding monocationic intermediates. Therefore,
we investigated a possible subsequent protonation of the
functional groups (FG) by comparison of their chemical shifts
with the starting alcohols (Table 4). Typically, the chemical
shift of the indicative atom decreased upon cation formation.
While there is precedence that protonation indeed leads to a
shielding at the former nitrile carbon atom,24 we did not find
any 19F NMR or 31P NMR data related to a possible protonation
of fluorides or phosphonates. The relatively minor shift changes
in cations 25 and 21 relative to their starting materials 2 and 7
make subsequent protonation of the functional group unlikely
in FSO3H, which is a relatively weak superacid. The carbonyl
carbon atom in esters 1, 13, and 14, however, exhibited a
significant increase in 13C chemical shift upon acid treatment,
hinting at the protonation of the ester group. Additional evidence
was based on the 1H NMR of the cation derived from precursor
14, in which an acidic proton was visible at 12.49 ppm, which
would be perfectly in line with a protonated methyl carboxy-
late.25
These findings warranted calculation of the chemical shift
data using the GIAO method at the B3LYP/6-311+G**//
B3LYP/6-311+G** level (see the Experimental Section). The
computed data were compared with the experimentally observed
values. The calculated and experimental 13C NMR chemical
shifts of carbocationic (C1) carbon of 19-27 are listed in Table
5. Calculated chemical shifts are substantially deviated from
the experimental values. For example, 13C NMR chemical shifts
of carbocationic (C1) carbon of 22 is 197.3, about 27 ppm more
deshielded from that of experimental value of 170.0 ppm.
Previous DFT calculations on a series of cumyl cations,
however, indicated that the reasonable prediction of 13C chemical
shifts can be achieved through scaling as reported by Siehl et
al.26 Our present study shows that after scaling by a factor of
0.86, a reasonable correlation between predicted and experi-
mental chemical shifts for a majority of carbocations 21-23
and 25-27 could be obtained. On the other hand, the agreement
between experimental and theoretical values for halo-substituted
carbocations 19-21 as well as carboxy-substituted cation 24 is
rather poor. In ions 19-21, the cationic centers are rather
deshielded, ruling out any adjacent halogen participation. With
the cation 24, it appears that the ester group is also protonated
in the FSO3H medium. In the case of tertiary carbocations, the
agreement between the calculated and experimental 13C NMR
(22) For tolyl-substituted carbocations, see: (a) Kelly, D. P.; Farquharson,
G. J.; Giansiracusa, J. J.; Jensen, W. A.; Huegel, H. M.; Porter, A. P.; Rainbow,
I. J.; Timewell, P. H. J. Am. Chem. Soc. 1981, 103, 3539–3543. (b) Olah, G. A.;
Prakash, G. K. S.; Liang, G. J. Org. Chem. 1977, 42, 2666–2671. (c) Brown,
H. C.; Periasamy, M.; Liu, K.-T. J. Org. Chem. 1981, 46, 1646–1650.
(23) (a) Olah, G. A.; Klumpp, D. A. Acc. Chem. Res. 2004, 37, 211–220.
(b) Olah, G. A. Angew. Chem., Int. Ed. Engl. 1993, 32, 767–788. (c) Olah, G. A.;
Klumpp, D. A. Superelectrophiles and Their Chemistry; Wiley: Hoboken, 2008.
(24) Spear, R. J.; Forsyth, D. A.; Olah, G. A. J. Am. Chem. Soc. 1976, 98,
2493–2500.
(25) (a) Bruck, D.; Rabinovitz, M. J. Am. Chem. Soc. 1976, 98, 1599–1600.
(b) Walspurger, S.; Vasilev, A. V.; Sommer, J.; Pale, P.; Savechenkov, P. Y.;
Rudenko, A. P. Russ. J. Org. Chem. 2005, 41, 1485–1492.
(26) Vrcek, V.; Kronja, O.; Siehl, H.-U. J. Chem. Soc., Perkin Trans. 2 1999,
1317–1321.
316 J. Org. Chem. Vol. 74, No. 1, 2009

Chiral Benzylic Carbocations
SCHEME 5. Results of the Quenching Experiments of
Cations 24 and 25 with Resorcin Dimethyl Ether as a
Representative Arene Nucleophile
conformation, in which the two faces of the cationic center are
shielded differently by the methyl and FG substituents in the
R-position.
Experimental Section
2-Bromo-1-(4′-methoxyphenyl)propane-1-carbenium Ion (20).
1
Major conformer: H NMR (400 MHz, -70 °C, SO2ClF) δ )
3
1.32 (d, J ) 6.2 Hz, 3 H), 3.72 (s, 3 H), 4.84-4.95 (m, 1 H),
3
6.56-6.61 (m, 1 H), 6.74-3.81 (m, 1 H), 7.45 (d, J ) 11.8
3
Hz, 1 H), 7.66 (virt. t, J = 8.6 Hz, 2 H); 13C NMR (100 MHz,
-70 °C, SO2ClF) δ ) 21.7 (q), 39.6 (d), 60.6 (q), 117.8 (d),
125.5 (d), 129.7 (s), 141.9 (d), 157.8 (d), 179.9 (d), 186.0 (s).
1
Minor conformer: H NMR (400 MHz, -70 °C, SO2ClF, e.s.
acetone-d6) δ ) 1.32 (d, 3J ) 6.2 Hz, 3 H), 3.73 (s, 3 H),
4.84-4.95 (m, 1 H), 6.56-6.61 (m, 1 H), 6.74-3.81 (m, 1 H),
chemical shifts of carbocationic (C1) carbon of 29 is slightly
better after scaling by the same factor of 0.86. On the other
hand, halogen-substituted cation 28 does not correlate well at
all even after scaling. It is important to mention that Siehl et
al.26 also showed that different scaling factors are necessary
for different types of carbocations. Carbocations that are
resonance stabilized (such as p-methoxy group substituted
2-phenyl-2-propyl cations) require different scaling factors than
carbocations that are not resonance stabilized (such as alkyl-
substituted carbocations).
Quenching Experiments. To further support the hypothesis
that conformationally restricted carbocations 17-30 are reactive
intermediates in our previously published Friedel-Crafts alky-
lation reactions, quenching experiments were undertaken with
resorcinol dimethyl ether as a representative arene nucleophile
(Scheme 5). Carbocations 24 and 25 were prepared at -78 °C
according to the standard protocol in SO2ClF as the solvent and
were quenched with precooled rescorcin dimethyl ether (10
equiv). The typically strong color of the solution immediately
vanished by addition of the nucleophile indicating a rapid
reaction. Due to the high reactivity of the carbocations, several
side products were formed resulting in only moderate yields
for these reactions. Workup with saturated NaHCO3 solution
and separation by column chromatography gave the desired
products anti-3 and syn-4 in almost identical diastereomeric
ratios relative to the ratios obtained under our usual conditions
(Scheme 1, HBF4 ·OEt2, -78 °C to rt).12 The reaction of cation
24 delivered predominantly product anti-3 with high diastereo-
selectivity, whereas cation 25 gave diastereoisomer syn-4 almost
exclusively.
3
3
7.42 (d, J ) 9.4 Hz, 1 H), 7.45 (d, J ) 11.8 Hz, 1 H), 7.92
3
(dd, J ) 9.6 Hz, 1 H); 13C NMR (100 MHz, -70 °C, SO2ClF)
δ ) 21.7 (q), 39.6 (d), 60.7 (q), 118.4 (d), 124.8 (d), 129.5 (s),
146.3 (d), 152.9 (d), 179.8 (d), 186.0 (s).
2-Methoxycarbonyl-1-(4′-methoxyphenyl)propane-1-carbeni-
um Ion (24). Major conformer: 1H NMR (400 MHz, -70 °C,
3
SO2ClF) δ ) 1.08 (d, J ) 6.6 Hz, 3 H), 3.77 (s, 3 H), 3.78 (s, 3
H), 4.05-4.16 (m, 1 H), 6.61 (d, 3J ) 9.7 Hz, 1 H), 6.77 (d, 3J )
9.6 Hz, 1 H), 7.48 (d, 3J ) 10.3 Hz, 1 H), 7.56 (d, 3J ) 9.7 Hz, 1
3
H), 7.61 (d, J ) 9.6 Hz, 1 H); 13C NMR (100 MHz, -70 °C,
SO2ClF) δ ) 18.4 (q), 41.6 (d), 61.6 (q), 63.5 (q), 118.3 (d), 126.5
(d), 133.9 (s), 142.1 (d), 157.7 (d), 172.1 (d), 188.1 (s), 188.6 (s).
Minor conformer: 1H NMR (400 MHz, -70 °C, SO2ClF, e.s.
acetone-d6) δ ) 1.08 (d, 3J ) 6.6 Hz, 3 H), 3.76 (s, 3 H), 3.78 (s,
3
3
3 H), 4.05-4.16 (m, 1 H), 6.56 (d, J ) 9.5 Hz, 1 H), 6.83 (d, J
) 9.9 Hz, 1 H), 7.39 (d, 3J ) 9.5 Hz, 1 H), 7.48 (d, 3J ) 10.4 Hz,
1 H), 7.81 (d, J ) 9.9 Hz, 1 H); 13C NMR (100 MHz, -70 °C,
3
SO2ClF, e.s. acetone-d6) δ ) 18.6 (q), 41.6 (d), 61.6 (q), 63.5 (q),
119.5 (d), 125.1 (d), 133.7 (s), 146.6 (d), 152.7 (d), 172.1 (d), 188.1
(s), 188.6 (s).
2-Ethylsulfonyl-1-(4′-methoxyphenyl)-propane-1-carbenium Ion
1
(26). Major conformer: H NMR (400 MHz, -70 °C, SO2ClF) δ
3
3
) 0.71 (t, J ) 6.9 Hz, 3 H), 1.09 (d, J ) 5.6 Hz, 3 H), 2.66 (q,
3J ) 6.9 Hz, 2 H), 3.75 (s, 3 H), 4.31-4.41 (m, 1 H), 6.58 (d, J
3
) 9.6 Hz, 1 H), 6.74 (d, 3J ) 9.6 Hz, 1 H), 7.11 (d, 3J ) 10.8 Hz,
1 H), 7.50 (d, J ) 9.6 Hz, 1 H), 7.55 (d, J ) 9.6 Hz, 1 H); 13C
NMR (100 MHz, -70 °C, SO2ClF) δ ) 3.9 (q), 12.3 (q), 46.3 (t),
59.2 (d), 61.9 (q), 118.6 (d), 126.9 (d), 136.9 (s), 142.4 (d), 157.1
3
3
1
(d), 167.4 (d), 188.7 (s). Minor conformer: H NMR (400 MHz,
-70 °C, SO2ClF) δ ) 0.71 (t, 3J ) 6.9 Hz, 3 H), 1.09 (d, 3J ) 5.6
Hz, 3 H), 2.66 (q, 3J ) 6.9 Hz, 2 H), 3.75 (s, 3 H), 4.31-4.41 (m,
3
3
1 H), 6.53 (d, J ) 9.5 Hz, 1 H), 6.81 (d, J ) 9.8 Hz, 1 H), 7.11
3
3
3
(d, J ) 10.8 Hz, 1 H), 7.32 (d, J ) 9.5 Hz, 1 H), 7.74 (d, J )
9.8 Hz, 1 H); 13C NMR (100 MHz, -70 °C, SO2ClF) δ ) 3.9 (q),
12.4 (q), 46.3 (t), 59.3 (d), 62.0 (q), 120.0 (d), 125.4 (d), 136.8 (s),
147.0 (d), 152.2 (d), 167.3 (d), 188.7 (s).
Conclusions
In summary, the conformation of chiral p-methoxybenzylic
cations bearing a stereogenic center of the general structure
-C*HMeFG in the R-position were studied in the superacidic
solution (FSO3H or FSO3H/SbF5 in SO2ClF). NOESY experi-
ments showed that the hydrogen atom at the stereogenic center
resides in the 1,3-allylic strain position with the methyl group
shielding one diastereotopic face, the functional group FG the
other. Such conformations are also supported by DFT theory.
Due to the restricted rotation of the bond between the cationic
carbon atom and the aryl group two rotamers exist, which could
be separately observed. Indications for dication formation in
superacids were found for COOMe as functional group with
the ester carbonyl group likely being protonated. Quenching
experiments strongly support the existence of benzylic carboca-
tions as reactive intermediates in previously conducted Friedel-
Crafts reactions. The diastereoselectivity results from a preferred
3-Methoxycarbonyl-2-(4′-methoxyphenyl)butane-2-carbenium
1
Ion (29). Conformer A: H NMR (400 MHz, -70 °C, SO2ClF)
3
δ ) 1.06 (d, J ) 6.5 Hz, 3 H), 2.11 (s, 3 H), 3.71 (s, 3 H),
3.81 (s, 3 H), 4.41-4.51 (m, 1 H), 6.53-6.60 (m, 1 H),
3
3
6.72-6.79 (m, 1 H), 7.62 (d, J ) 9.7 Hz, 1 H), 8.03 (d, J )
10.0 Hz, 1 H); 13C NMR (100 MHz, -70 °C, SO2ClF): δ )
16.0 (q), 20.7 (q), 46.3 (d), 60.7 (q), 63.9 (q), 117.3 (d), 124.4
(d), 133.1 (s), 142.2 (d), 149.2 (d), 185.9 (s), 188.2 (s), 191.3
(d). Conformer B: 1H NMR (400 MHz, -70 °C, SO2ClF) δ
3
)1.06 (d, J ) 6.6 Hz, 3 H), 2.11 (s, 3 H), 3.71 (s, 3 H), 3.81
(s, 3 H), 4.41-4.51 (m, 1 H), 6.53-6.60 (m, 1 H), 6.72-6.79
3
3
(m, 1 H), 7.78 (d, J ) 9.9 Hz, 1 H), 7.86 (d, J ) 10.0 Hz, 1
H); 13C NMR (100 MHz, -70 °C, SO2ClF) δ ) 16.1 (q), 20.9
(q), 46.3 (d), 60.7 (q), 63.9 (q), 117.7 (d), 124.7 (d), 133.1 (s),
144.7 (d), 146.6 (d), 185.9 (s), 188.2 (s), 191.5 (d).
1-(4′-Methylphenyl)-2-methoxycarbonylpropane-1-carbenium Ion
(30): 1H NMR (400 MHz, -70 °C, SO2ClF) δ ) 1.11 (d, 3J ) 7.0
J. Org. Chem. Vol. 74, No. 1, 2009 317

Stadler et al.
Hz, 1 H), 2.15 (s, 3 H), 3.86 (s, 3 H), 4.20-4.31 (m, 1 H), 7.11 (d,
3J ) 8.7 Hz, 2 H), 7.56 (d, 3J ) 8.7 Hz, 1 H), 7.65 (d, 3J ) 8.7 Hz,
Supporting Information Available: Experimental proce-
dures for the preparation of new compounds and for the
3
1 H), 8.23 (d, J ) 9.9 Hz, 1 H), 12.49 (s, 1 H); 13C NMR (100
1
quenching experiments; H and 13C NMR spectra and data
MHz, -70 °C, SO2ClF) δ ) 19.8 (q), 27.5 (q), 43.4 (d), 65.7 (q),
136.0 (d), 136.7 (d), 137.4 (s), 142.9 (d), 156.3 (d), 188.3 (s), 190.2
(d), 192.1 (s).
of all carbenium ions. Cartesian coordinates and total energies
(hartrees) of the optimized geometries of 19-29 calculated
at the B3LYP/6-311+G**//B3LYP/6-311+G** level. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. This work was supported by supported
by the Deutsche Forschungsgemeinschaft (Ba 1372/12-1) and
by the Fonds der Chemischen Industrie (Frankfurt/Main) in
Germany. Work in the USA was supported by the Loker
Hydrocarbon Research Institute and by the Stauffer Founda-
tion.
JO802296E
318 J. Org. Chem. Vol. 74, No. 1, 2009