Steric isotope effects gauged by the bowl-inversion barrier in selectively deuterated pentaarylcorannulenes

Article abstract of DOI:10.1021/ja073052y

Motivated by a greater bowl depth and barrier to bowl inversion in sym-1,3,5,7,9-pentamanisylcorannulene compared to corannulene, an experimental plan is developed to measure the effective hydrogen/deuterium steric kinetic isotope effect (KIE). Symmetry a

Full text of DOI:10.1021/ja073052y

Published on Web 01/15/2008
Steric Isotope Effects Gauged by the Bowl-Inversion Barrier
in Selectively Deuterated Pentaarylcorannulenes
Tomoharu Hayama, Kim K. Baldridge,* Yao-Ting Wu, Anthony Linden, and
Jay S. Siegel*
Institute of Organic Chemistry, UniVersity of Zurich, Winterthurerstrasse 190,
CH-8057 Zurich, Switzerland
Received May 13, 2007; E-mail: jss@oci.unizh.ch
Abstract: Motivated by a greater bowl depth and barrier to bowl inversion in sym-1,3,5,7,9-pentamanisyl-
corannulene compared to corannulene, an experimental plan is developed to measure the effective
hydrogen/deuterium steric kinetic isotope effect (KIE). Symmetry arguments are used to design orthogonal
isotope labeling patterns so that the barrier for the CD3 compound can be measured in the presence of the
CH3 compound. This scheme eliminates the differential uncertainty in the temperature measurement by
allowing both barriers to be measure in the same sample, which in turn reduces the error in determining
the differential barrier. Ab initio computations corroborate the structure and isotope effect found
experimentally. The predicted and determined steric KIE at 250 K is 1.08 (modified QUIVER at M06-2X/
cc-pVDZ) and 1.22 ( 0.06 (VT-NMR), respectively. The results stem from differences in zero-point energy
of the CH and CD motions; however, the phenomenology makes the CD3 group appear effectively “stickier”
than CH3. The more the C-H‚‚‚X interaction steepens the well, the “stickier” C-D should appear to be
relative to C-Hsan important consideration for molecular recognition and one supported by stronger binding
constants for deuterated substrates.
Introduction
suggested the possibility to predict and measure the relative
attractive steric isotope effect using selectively deuterated
Systematic study of the differences in bowl-inversion barriers
among corannulene (1) and derivatives can serve as a way to
gauge steric or electronic aspects of molecular recognition
normally dealt with in supramolecular chemistry.1 The first
indication that transannulene interactions of substituents might
play a role in the bowl-inversion process came about shortly
after observing a relationship of bowl depth to bowl inversion
using a structure-energy correlation analysis, a la Bu¨rgi and
Dunitz.2 The bowl-inversion barrier for a series of corannulene
derivatives was determined by dynamic variable temperature
NMR (DNMR) techniques and a correlation emerged (Ea ) Cx4)
wherein a deeper bowl depth (x) gave rise to a higher inversion
barrier (Ea). In general, increasing alkyl substitution on the rim
leads to a shallower bowl and lower barrier. This correlation
holds also for monoaryl derivatives of corannulene like mani-
sylcorannulene (2); however, sym-pentamanisylcorannulene3 (3),
a compound with a crown of methyl groups around the rim of
the bowl, showed an anomalously high barrier. Quantum
mechanical calculations suggested that van der Waals (vdW)
attractive forces among the endo methyl groups in 3 could
contribute to this unusual dynamic behavior.4 This hypothesis
derivatives of 3.5
Indications of a van der Waals Stabilizing Effect. Agree-
ment between the computational structure of sym-penta(2,6-
dimethylphenyl)corannulene (4) and the X-ray crystallographic
structure of 36 was initially investigated. On the basis of previous
computational studies, B3LYP/cc-pVDZ was chosen as the
initial level for modeling of 4. Computation of 4 at this level
predicts a classical 5-fold symmetric bowl form with the
dimethylphenyl rings twisted with respect to the rim of the
corannulene placing one methyl group inside the bowl (Me(endo)
)
and one outside (Me(exo)). The bowl is predicted to be slightly
shallower than 1 (depthhub-to-rim ) 0.854 Å calcd vs depth 0.873
Å calcd). This simple structural parameter in combination with
the above-mentioned structure-energy correlation leads to the
prediction that 4 will undergo bowl-inversion more rapidly than
(1) Seiders, T. J.; Baldridge, K. K.; Grube, G. H.; Siegel, J. S. J. Am. Chem.
Soc. 2001, 123, 517-525.
(2) The structure-energy correlation: (a) Bu¨rgi, H. -B.; Dubler-Steudle, K.
C. J. Am. Chem. Soc. 1988, 110, 4953-4957. (b) Bu¨rgi, H. -B.; Dubler-
Steudle, K. C. J. Am. Chem. Soc. 1988, 110, 7291-7299.
(3) Prefix sym- is used here to mean the C5-symmetric substituted corannulene
corresponding to 1,3,5,7,9-pentasubstitution.
(5) (a) Mislow, K.; Graeve, R.; Gordon, A. J.; Wahl, G. H., Jr. Am. Chem.
Soc. 1964, 86, 1733. (b) Mislow, K.; Graeve, R.; Gordon, A. J.; Wahl, G.
H., Jr. J. Am. Chem. Soc. 1963, 85, 1200. (c) Carter, R. E.; Melander, L.
AdV. Phys. Org. Chem. 1973, 10, 1.
(4) Grube, G. H.; Elliott, E. L.; Steffens, R. J.; Jones, C. S.; Baldridge, K. K.;
Siegel, J. S. Org. Lett. 2003, 5, 713.
(6) For the crystallographic data, see Supporting Information (B).
9
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J. AM. CHEM. SOC. 2008, 130, 1583-1591
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A R T I C L E S
Hayama et al.
Table 1. Computed Geometry of 4 Compared to Experimental
Geometry of 3
1, consistent with the notions about a correlation between rim
substitution and bowl depth or inversion barrier, but in sharp
contrast to the experiment measurement.
Deeper analysis of the structure reveals how tricky the
modeling of large organic systems can be. The hub, spoke, flank,
and rim bond lengths display the normal [5]radialene pattern
and are well reproduced by the B3LYP/cc-pVDZ level com-
putations. The bond angles also display no serious anomalies.
In general, the B3LYP/cc-pVDZ geometry of the corannulene
core of 4 reflects crudely what one would expect from a structure
with five aryl-ring substituents locked approximately orthogonal
to the plane of the corannulene at the point of attachment.
Despite the good performance on basic geometric parameters,
the barrier to bowl-inversion at the B3LYP/cc-pVDZ level is
predicted to be 8.84 kcal/mol (ca 3 kcal/mol under the observed
value). Thus in the absence of experiment, this level of theory
would lead to erroneous conclusions about the bowl dynamics,
that is, lower versus higher barrier than the parent corannulene.
Although a single-point energy correction using the MP2
electron correlation treatment will not improve the geometry,
it does provide the insight that inclusion of dispersion/dyamic
correlation is very important to proper modeling of the inversion
barrier. Augmentation of B3LYP/cc-pVDZ single-point energies
with the DFT dispersion correction treatment of Grimme
produced similar results.7 From these results, one can infer that
vdW stabilization of the bowl versus flat structure is at play.
B3LYP/
M06-2X/
parameter
cc-pVDZa
cc-pVDZa
exptl
C-C hub (Å)
C-C spoke (Å)
C-C flank (Å)
1.418
1.385
1.461
1.450
1.399
108.0
123.45
114.77
120.35
0.854
4.62
1.420
1.381
1.455
1.446
1.388
108.0
122.85
115.40
120.56
0.945
4.35
1.413(4)
1.383(4)
1.452(4) leyward
1.446(4) wayward
1.381(8)
108.0(4)
124.3(4)
111.9(4)
122.2(4)
0.91
C-C rim (Å)
angle R (sym) (deg)
angle â (deg)
angle γ (deg)
angle δ (deg)
bowl depth (Å)
Me(endo)(1)-Me(2)(endo) (Å)
Me(endo)(1)-Me(3)(endo) (Å)
Ar-Cor torsion (deg)
4.4
7.1
79
7.60
79.6
7.04
72.2
a Bold values in the theory columns indicate values closer to experimental
results.
predicted bowl-depths (0.854 vs 0.945 Å), Me(endo)/Me(endo)
nonbonded distances (4.62 vs 4.35 Å), and aryl-corannulene
torsion angles (80.3° vs 72.0°).9
X-ray Crystal Structure of 3. Crystals of 3, suitable for
X-ray crystallographic analysis, were grown from a toluene/
isopropanol solution by cooling. Diffraction data was collected
at low temperature and the structure solved by direct methods.
The solution revealed a resolvable whole molecule disorder in
which two molecules of 3 are superposed on one another as
enantiomeric models A and B (Figure 1). Although the idealized
solution structure for 3 would be C5 symmetrical, unsymmetrical
crystal packing distorts the bowl to an unsymmetrical shape
consistent with its general position in the P1 unit cell. The
enantiomers are almost cylindrically symmetric from the
perspective of their external steric presentation and as such pack
into each other’s respective sites virtually interchangeably,
leading to the observed occupational disorder in the crystal. This
phenomenon is common for substituted corannulene structures.
Nonetheless, the disorder model yields respectable R factors
(0.045).
Despite the statistically respectable appearance of the crystal
structure of 3, one should look at the geometry of the
individually derived enantiomeric model conformers with some
degree of skepticism, and not use them as prima facie evidence
for a structural feature that would be otherwise chemically
unreasonable. In order to model the disordered structure, all
chemically equivalent bond lengths and angles within and
between both enantiomers were restrained to be similar during
the refinement. As a result, the spread of values for parameters
such as spoke, rim, hub, and flank bond lengths is very small.
Beyond the issue of overlapping disorder, there is a substantial
Structural Assessment of 3 and 4. Ideally, one would like
to reassess the geometry of these structures with the inclusion
of such dispersion/dynamic correlation effects. At present, even
with access to a very efficient parallel cluster computer, the
memory and CPU requirements of such a job are formidable.
Using the B3LYP/cc-pVDZ optimized structure for the input
to an MP2 optimization looks promising as the gradient was
only 0.0037 (a good guess en route to the 10-6-10-7 criteria
to claim “optimized”); however, each gradient cycle takes 11
days on a Dell PowerEdge 2950 quad core, consuming more
than 30 GB memory and 1.6 TB disk, or 4 days on a dedicated
dual core Itanium HP rx2600. The full optimizations complete
in 47.5 days; however, Hessian analysis would be a second large
investment in cpu time. In such a situation an implementation
of a DFT code either with dispersion correction or functional
parametrization should provide a more effective way to gain
further insight at reasonable computational effort. The M06-
2X functional is such a parametrized functional.8
Geometry optimization of 4 at M06-2X/cc-pVDZ was then
carried out (Table 1). The agreement between B3LYP/cc-pVDZ
and M06-2X/cc-pVDZ optimized structures leaves little to
choose among bond lengths (<0.01 Å difference) and bond
angles (<1° difference). The striking differences comes in the
(9) This comparison demonstrates the disservice done the community by studies
founded only on bond lengths and angles and concluding that basis sets
like 631-G* serve to model structures as well as higher order methods. By
focusing on the trivial aspects of structure, the uninitiated chemist could
be led to unwarranted extrapolation of the model, which would inaccurately
predict important structural parameters, dynamic character, and physical
properties, see: Petrukhina, M. A.; Andreini, K. W.; Mack, J.; Scott, L.T.
J. Org. Chem. 2005, 70, 5713.
(7) Grimme, S. J. Chem. Phys. 2006, 124, 034108.
(8) Zhao, Y.; Truhlar, D.G. Theor. Chem. Acc., 2007, 118, DOI 10.1007/
500214-007-0310-x.
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Steric Isotope Effects in Pentaarylcorannulenes
A R T I C L E S
Figure 1. The molecular structure of 3 showing, separately, the two disordered enantiomeric species, which in the model are super-imposed on one another
with the same center of gravity.
distortion away from 5-fold asymmetric geometry. This distor-
tion has particular influence on the determination of a unique
bowl depth. Although a singular bowl-depthhub-to-rim ) 0.91
Å can be assigned by comparing the best plane of the hub to
that of the rim, as is done for 5-fold symmetric structures, one
finds that these two planes are not parallel in 3 and the individual
rim-atom distances range from 0.86 to 1.05 Å. Given the
expected highly sensitive x4 dependence of barrier to equilibrium
bowl depth, it would be unwise to draw conclusions from such
clearly contextually dependent data alone and/or without deeper
analysis.
Bond lengths and angles are transferable parameters among
cognate structures, but despite a relatively constant set of lengths
and angles in 3 and 4 a wide spectrum of conclusions about
the bowl depth and inversion dynamics are possible.10 The
restraints used during the refinement of the crystallographic
model keep the ranges relatively small, but relevant comparisons
can still be made of the average hub, spoke, flank, and rim bond
lengths, and the R, â, γ, and δ angles (cf. Table 1). The
experimental model presents chemically reasonable bond-length
and angle parameters and appears to corroborate the general
features predicted from theory at levels, which include electron
correlation. For example, the geometry is consistent with the
[5]radialene pattern normally observed in corannulenes. On
average for 3, the experimental bond lengths agree within 0.01
Å and angles within 1° of those predicted by either B3LYP/
cc-pVDZ or M06-2X/cc-pVDZ for the analogue, 4. Thus the
relatively rigid features of the highly restrained crystallographic
model look reliable.
of 4.4 Å, in line with the normal sum of methyl vdW radii, 4.4
Å, and more in line with the M06-2X/cc-pVDZ value of 4.35
Å than the B3LYP/cc-pVDZ value, 4.62 Å, for 4.
Let us return to comment further on the bowl depth, which
represents the minimum of a very soft potential but which cannot
be averaged over several instances in the crystal. The compari-
son value for the bowl-depth in 3 is derived from the diffraction
data (depthhub-to-rim ) 0.912 Å) and sits between the M06-2X/
cc-pVDZ value of 0.945 Å and the B3LYP/cc-pVDZ value of
0.854 Å. The magnitude of the difference alone is not the sole
concern but rather the qualitative trend with regard to the parent
corannulene; the X-ray and M06-2X/cc-pVDZ model suggest
a deeper bowl for the pentaaryl derivative than corannulene,
where as the B3LYP/cc-pVDZ model suggests a shallower bowl.
This difference goes to the heart of whether one would predict
a higher or lower barrier compared to corannulene. Such a large
geometric discrepancy among methods is not found for the
parent corannulene (depthhub-to-rim ) 0.873 Å [B3LYP/cc-
pVDZ]; 0.887 Å [M06-2X/cc-pVDZ]; 0.887 Å [X-ray]). The
deeper bowl depth and the closer positioning of Me(endo) groups
in the crystal structure and M06-2X/cc-pVDZ model correlates
with a cooperative stabilizing network of trans-bowl vdW
interactions; an effect outside the scope of normal HF and
density functional treatments.
Computational Dynamics and Prediction of the Isotope
Effect. The ortho methyl groups of the aryl substituents in the
bowl form of 3 or 4 belong to diasterotopic pentad sets, one
with all members apart (exo) and one with all members
convergent (endo) across the ring. This diasterotopic relationship
provides the 1H NMR probe necessary to measure the inversion
barrier by DNMR methods.
The manisyl groups in 3 are situated more or less orthogonal
to the bowl rim, but with a large spread of torsion angles: 65-
89°. The average value, 79°, is more in line with the B3LYP/
cc-pVDZ model, 80.3°, than the M06-2X/cc-pVDZ model,
72.0°, of 4. The Me(endo)//Me(endo) distances in 3 range from 3.9
to 5.2 Å, reflecting a relatively large variance for the geometrical
features dependent on soft potentials that can be altered by
packing forces. Nonetheless, these values come to an average
Crystal structure analysis of 3 and M06-2X/cc-pVDZ com-
putations of 4 place the neighboring endo methyl groups at
essentially the vdW distance (ca. 4.5 Å), whereas the values
across the ring contacts are about 7.0 Å. The structures of the
exo set are much further separated at 6.5 and 10.5 Å,
respectively. The proximity of the endo methyls in the bowl
form is suspected to account for the unusual dynamic behavior
due to stabilizing van der Waals interactions. In contrast to the
(10) For a discussion of flexible geometry in graphs with rigid distance
relationships, see: Connelly, R. InVent. Math. 1982, 66, 11.
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A R T I C L E S
Hayama et al.
Table 2. Inversion Energies of (4) from Computation
methyl groups also belong to either endo or exo sets (Figure
2). Thus, a scheme of two complementary probe molecules can
be derived from 3 by selective deuterium labeling in either the
methyl hydrogen or aromatic hydrogen positions.
B3LYP/
M06-2X/
cc-pVDZ
B3LYP/
MP2/cc-pVDZ//
barrier
cc-pVDZ
cc-pVDZ
+
GDb
B3LYP/cc-pVDZc
no ZPE
9.05
8.84
8.88
13.15
12.65
12.72
13.83
13.62
13.66
14.09
13.88
13.92
CH3 with ZPEa
CD3 with ZPEa
Deuteration of 3 at the aromatic positions maintains the same
interaction between methyl groups as in the parent compound,
allows the dynamic process to be followed through the
coalescence of the diastereotopic methyl signals, and displays
a ZPE - zero point energy. b GD - dispersion ala Grimme;7 taking the
ZPE correction from the reference geometry. c Taking the ZPE correction
from the reference geometry.
1
no peaks in the aromatic area of the H NMR spectrum. In
contrast, complete deuteration of 3 at the methyl positions
establishes the necessary interaction among deuterated methyl
groups, allows the dynamic process to be followed by coales-
cence of the diastereotopic aromatic protons, but has no peak
in the methyl region of the 1H NMR. Combination of 3-(CD3)10
with 3-(DAr)10 presents the superposition of two “orthogonally”
labeled spectra. As such, coalescence phenomena in the variable
temperature DNMR experiment can be viewed for both com-
pounds simultaneously without worry about the error due to
temperature or the complication of signal overlap. To further
minimize the error, the line shape can be followed over a large
temperature interval and the final energy values reported for a
temperature where the dynamic line shape is active for both
compounds (i.e., in the middle of the temperature range).
Synthesis. Preparation of 3-(CD3)10 and 3-(DAr)10 requires
two basic tasks: (1) creation of the appropriately deuterated
bromomanisyl and (2) effecting an efficient 5-fold aryl-
corannulene coupling over sym-pentachlorocorannulene. Pal-
ladium coupling reactions are often used for the introduction
of aryl (or alkyl) compounds because they normally proceed in
relatively good chemical yield and display broad functional
group tolerance. Such palladium chemistry dovetails well with
the many kinds of halocorannulenes available from literature
procedures (for example, 1,2,7,8-tetraiodocorannulene,11 1,2,7,8-
tetrabromocorannulene,12 bromocorannulene,13 2,3-dichloro-
corannulene,14 sym-pentachlorocorannulene (5),13 and deca-
chlorocorannulene13). Because of the low activity of chloride
in these coupling reactions, the synthetic application of 5
requires some optimization. As no efficient synthesis of sym-
pentabromocorannulene was obtained, optimization efforts were
focused on the catalyst. Simple thermal activation was seen as
the best option and therefore the thermally more stable N-
heterocyclic carbene (NHC)-based catalyst of Nolan was chosen.
This strategy proved effective, and our previously reported
transformation of 5 into 3, via nickel-catalyzed zinc-based
Negishi coupling (7% yield),4 could be improved to 18-35%
by a modified Nolan protocol using the NHC ligand, 1,3-bis-
(2,6-diisopropylphenyl)imidazoliumchloride) (IPr‚HCl) in com-
bination with the zinc-based Negishi reagents (Scheme 1).15,16
The preparations of deuterated bromoanisoles are simple
(Scheme 2). The synthesis of 1-bromo-4-methoxy-2,6-di(methyl-
d3)benzene (6) started from dimethyl-5-methoxyisophthalate (7)
bowl, all the computed transition state models predict a flat form
with the methyls separated from their nearest neighbors by at
least 5-6 Å. At this distance vdW interactions should be greatly
reduced. This analysis and the large difference among computed
barriers to inversion (B3LYP/cc-pVDZ 8.84 kcal/mol vs [M06-
2X/cc-pVDZ 12.65 kcal/mol; B3LYP/cc-pVDZ+Grimme dis-
persion ) 13.62 kcal/mol; and MP2/cc-pVDZ//B3LYP/cc-
pVDZ ) 13.88 kcal/mol]) serve as the basis for the assumption
that the vdW attractive forces play a role in fine-tuning the bowl-
inversion barrier in 3.
Computing the zero-point energy (ZPE) difference between
4-d10 (i.e., 4-[CDAr]10) and 4-d30 (i.e., 4-[CD3]10) at M06-2X/
cc-pVDZ leads to a prediction that the CD3 compound will have
a barrier to inversion ca. 0.074 kcal/mol higher than the parent
(KIE ) 1.16) (Table 2). Despite the clear prediction by
computed ZPE differences and the existence of essential
symmetry conditions needed to measure the barriers in 3-d30,
the paltry value of 70-80 cal/mol for ∆∆Hq between 4-d10 and
4-d30 presents serious precision issues for a reliable experimental
assessment of this prediction. An additional issue is the validity
of using a simple ZPE argument for predicting the isotope effects
in these systems. Thus came about the motivation to investigate
more sophisticated theoretical methods for predicting the steric
deuterium isotope effect.
Experimental Design. As mentioned above, the predicted
small difference in energy creates a serious challenge to the
design of an experiment that distinguishes a meaningful
difference from random error. In the DNMR technique, the
largest source of error comes from uncertainty in the measured
temperature, not only in the precision of the temperature
measure, but also the accuracy of the temperature measurement
in the sample; placement of the sample relative to the thermo-
couple and rates of nitrogen gas flow can have a substantial
influence. The amount of solvent and degree of equilibration
time can also introduce problems when extremely accurate
results are desired. Even when good calibration methods are
used, there are still some errors that make it difficult to reduce
the reproducibility error below 75 cal/mol for independent
experiments, and if one considers three times the error as a
significant difference, one would need error limits on the order
of ( 25 cal/mol to test the prediction made above by H vs D
ZPE analysis.
One solution for this problem would be to measure both
molecules in the same tube at the same time, thus eliminating
differences in temperature as a major source of error. To
accomplish this, each of the compounds must have signals that
decoalesce upon cooling of the sample, but do not overlap with
any other signals in the mixture. Consideration of the equilib-
rium equation for the bowl inversion of 3 reveals that the methyl
signals are not the only signals representing diastereotopic sets
of protons; the signals for the aromatic protons neighboring the
(11) Xu, G.; Sygula, A.; Marcinow, Z.; Rabideau, P. W. Tetrahedron Lett. 2000,
41, 9931-9934.
(12) Sygula, A.; Rabideau, P. W. J. Am. Chem. Soc. 2000, 122, 6323-6324.
(13) Seiders, T. J.; Baldridge, K. K.; Elliott, E. L.; Grube, G. H.; Siegel, J. S.
J. Am. Chem. Soc. 1999, 121, 7439-7440.
(14) Seiders, T. J.; Elliott, E. L.; Grube, G. H.; Siegel, J. S. J. Am. Chem. Soc.
1999, 121, 7804-7813.
(15) Stille coupling: Grasa, G. A.; Nolan, S. P. Org. Lett. 2001, 3, 119-122.
Suzuki coupling: Navarro, O.; Kelly, R. A., III; Nolan, S. P.; J. Am. Chem.
Soc. 2003, 125, 16194-16195.
(16) The synthesis of IPr‚HCl: (a) Arduengo, A. J., III; Krafczyk, R.;
Schmutzler, R.; Tetrahedron 1999, 55, 14523-14534. (b) Jafarpour, L.;
Stevens, E. D.; Nolan, S. P. J. Organomet. Chem. 2000, 606, 49-54.
9
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Steric Isotope Effects in Pentaarylcorannulenes
A R T I C L E S
Figure 2. The equilibrium equation of 3, 3-(CD3)10, and 3-(DAr)10.
Scheme 1. Synthesis of 3 and Deuterated Derivatives, 3-(CD3)10
and 3-(DAr)10
five times until all aromatic protons were exchanged for
deuteriums.19 Then the deuterated phenol was methylated with
iodomethane and potassium carbonate to give 12 followed by
bromination with NBS to yield 9.
Having easy access to 6 and 10 meant the deuterated
compounds 3-(CD3)10 and 3-(DAr)10 could be readily synthesized
using the reaction conditions described above in Scheme 1.
Mixing 3-(CD3)10 and 3-(DAr)10 created the necessary two-
component probe for the DNMR experiment.
Results and Discussion
NMR Measurement of Isotope Effect. From the mixture
of 3-(CD3)10 and 3-(DAr)10 (3-(CD3)10/3-(DAr)10 ) 1/2.14) the
1
variable temperature H NMR spectra in dichloromethane-d2
were obtained (Figure 3). For the evaluation of rate parameters,
line-shape analysis of the aromatic protons of 3-(CD3)10 and
the aromatic methyl protons of 3-(DAr)10 were used.20 The
inversion energies were compared at 250 K and at the respective
coalescence temperatures.
The inversion energy of 3-(CD3)10 is found to be 0.1 ( 0.026
kcal/mol larger than that of 3-(DAr)10 at 250 K, the midrange
temperature where dynamic effects can be seen in the NMR
(Table 3). This difference in inversion energy is greater than
three times the sum of individual errors, placing it well above
the 99% confidence limit as statistically significant. Under these
statistical conditions, one would conclude that the experiment
by the reduction with lithium aluminum deuteride (LAD)
(Scheme 2a). Then the diol 8 was mesylated with methane-
sulfonyl chloride and 4-(dimethylamino)pyridine (DMAP) and
reduced with LAD again to form 9. Finally the anisole was
selectively brominated with N-bromosuccinimide (NBS) of the
aromatic proton to afford 6.17
The second deuterated bromoanisole 1-bromo-4-methoxy-2,6-
dimethylbenzene-3,5-d2 (10) was prepared with base-catalyzed
hydrogen-deuterium exchange-reaction (Scheme 2b). First of
all, the aromatic protons of 3,5-dimethylphenol (11) were
deuterated using D2O and NaOD.18 This process was repeated
Scheme 2.
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A R T I C L E S
Hayama et al.
Figure 3. The aromatic proton peaks of 3-(CD3)10 (left) and the methyl
proton peaks of 3-(DAr
)
10
(right) at different temperatures.
Table 3. The Inversion Energies of 3-(CD3)10 and 3-(DAr)10 from
Line-Shape Analysis in Dichloromethane-d2
Tc (K)
∆
GT250‡ (kcal/mol)
∆
GTc‡ (kcal/mol)
3-(DAr
)
10 (CH3)a
266.1
251.0
11.62 ( 0.015
11.72 ( 0.011
11.60 ( 0.011
11.72 ( 0.010
Figure 4. Differential ZPE for C-D and C-H in the bowl and flat forms.
3-(CD3)10 (CD3)b
(KIE/ip).22 This treatment provides KIE for individual sites of
deuterium substitution. Treating these single-site KIEs as
energetically additive requires one to take the product over the
30 methyl C-H sites together to obtain a value for 4-(CD3)10;
similarly, one must take the product over the 10 aryl C-H sites
to obtain a value for 4-(DAr)10. Such an analysis gives 1.071
for the KIE/ip of 4-(CD3)10 and 0.996 for 4-(DAr)10. The ratio
of these KIE/ip values is suitable for comparison with experi-
ment.
The comparison can be conducted either by converting the
∆∆Gq of experiment into a KIE ratio or converting the
theoretical KIE ratio into a ∆∆Gq. The former leads to an
experimental KIE of 1.22 ( 0.06 which compares qualitatively
with the 1.08 obtained from the ratio just described. The
equivalent analysis based on ∆∆Gq yields a theoretical value
of 0.04 kcal/mol in comparison with the 0.10 ( 0.026 kcal/
mol reported from the variable temperature NMR experiments
above.
These values are determined for 250 K to match the midrange
temperature at which the experimental determination was made.
With many low-energy vibration/libration modes as in 4, it is
likely that entropic effects will alter the KIE with temperature.
Model for Interpreting the Isotope Effect. Independent of
the statistical success of these results, one would like a physical
model to understand steric isotope effects. The prevailing model
from quantum mechanics is that, although hydrogen and
deuterium give rise to the same potential-energy surface, the
ZPE for the motions of deuterium sits lower in the well than
hydrogen. The result is that in a competition between two states
with wells of different steepness, the deuterium ZPE favors the
steeper well energetically (Figure 4). In principle, all H/D
isotope effects can be interpreted in this way as a first
approximation. Other considerations such as tunneling come into
the full treatment, as described above.
a Calculated from methyl proton peaks. b Calculated from aromatic proton
peaks.
demonstrates a clear direction and magnitude of the isotope
effect (cf. Table 1), thus dealing with one of the main issues of
this study. It also happens that the value found experimentally
matches qualitatively that predicted by simple ZPE analysis;
however, a proper analysis of the theoretical isotope effect is
instructive.
Computation of Isotope Effect. Proper values for the kinetic
isotope effect (KIE) were calculated using a modified version
of the QUIVER software package, utilizing the optimized
ground and transition-state structure vibrational analyses of 4.
On the basis of statistical mechanics and classical transition state
theory, reduced partition functions of the various isotopomers
are calculated from the force constants using the Biegeleisen-
Mayer formalism:21
kH κHσHσ/
)
H (mmi)(exc)(zpe)
κDσDσ/D
kD
where mmi is the mass and moment of inertia, exc is the
excitation factor, zpe is the zero-point energy, and σ* refers to
the transition state. Using standard assumptions (mmi ) 1; κ
and σ unchanged in the various isotopomers), one then applies
the Redlich-Teller product rule and substitutes explicit terms
for the partition functions, using the ratios of the Biegeleisen-
Mayer functions, (s2/s1) f(2/1) for the various isotopomers. The
predicted KIE, without any tunneling correction, is simply
kH V/H
(s2/s1) f(2/1)
)
VD/
kD
(s2/s1) f(2/1)*
The ZPE interpretation of steric isotope effects has precedence
in the recent literature regarding cyclohexane inversions23 and
host-guest chemistry.24 Historically, there have been notions
of the CD3 group being smaller than CH3. From the asymmetric
bonding potential-energy well of the C-H bond, the lower C-D
for all ratios and frequency values. To include effects of
tunneling, thermally averaged transmission coefficients for an
infinite parabolic barrier are calculated as approximated by Bell
(17) Edwards, J. D., Jr.; Cashaw, J. L. J. Am. Chem. Soc. 1956, 78, 3821-
3824.
(18) Wa¨ha¨la¨, K.; Ma¨kela¨, T.; Ba¨ckstro¨m, R.; Brunow, G.; Hase, T. J. Chem.
Soc., Perkin Trans. 1 1986, 1, 95-98.
(22) Bell, R.P. The Tunnel Effect in Chemistry; Chapman and Hall: New York,
1980, pp 60-63.
(23) Saunders, M.; Wolfsberg, M.; Anet, F. A. L.; Kronja, O. J. Am. Chem.
Soc. 2007, 129, 10276.
(19) From H-NMR, 99% deuterium displacements were confirmed.
(20) For the detail of the line shape analysis, see Supporting Information (A).
(21) Bigeleisen, J.; Mayer, M. G. J. Chem. Phys. 1947, 51, 1369-1374.
9
1588 J. AM. CHEM. SOC. VOL. 130, NO. 5, 2008

Steric Isotope Effects in Pentaarylcorannulenes
A R T I C L E S
stretch yields a shorter req for C-D than for C-H. Therefore,
the vdW radii for CD3 is presumed to be smaller than for
CH3.5,25,26 This notion focuses only on the effect of the stretching
modes; however, the isotope effect comes from the sum over
all modes involving H/D motion, including wags, librations,
and rotations and is sensitive to the steepness of the potential
in all dimensions.
flat transition state; deuterium favors the bowl form and
manifests a higher barrier.
The conclusion that the methyl interactions contribute in an
attractive way comes from the observation that the C20 bowl in
3 and 4 is deeper than in 1, and the barrier to inversion of 3
and 4 is higher than 1. “Normal” repulsive steric effects at the
rim of 1 would work in the opposite direction structurally and
energetically. Thus the trans-bowl interactions provide insight
to the nature of noncovalent interactions and a gauge of their
energetic magnitude.
The issue of changing the steepness of the potential-energy
surface is important in molecular recognition. First, consider
the case in which the neighboring CH3//CH3 distance would be
shorter than the sum of the vdW radii. Then the resting position
of the corannulene bowl would be holding the methyls of the
manisyl groups inside the sum of vdW radii to overcome a
repulsion between methyl groups and arrive at a higher energy
(strained) equilibrium geometry. Therefore, shorter distances
between methyl groups would lead to a compression that should
increase the steepness of the C-H potential. If the changes in
that mode dominate, then the bowl with CD3 would be lower
in energy compared to the flat transition state, where such
interactions are much less important. The barrier for 3-(CD3)10
should be higher than the barrier for 3-(DAr)10.
Conclusions
An anomalous barrier height in the bowl-inversion of 3 leads
to the hypothesis that attractive vdW interactions are at play in
the dynamics of 3. Computational results supporting this
hypothesis stimulated the idea that study of the dynamics in
isotopomers of 3 could result in an estimate of an attractive
deuterium steric isotope effect. To this end, an isotope-based
symmetry analysis leads to the design of an experiment in which
the dynamics of two orthogonally labeled isotopomers of 3 could
be measured simultaneously to enable a variable temperature
NMR determination of ∆∆Gq values with high accuracy. These
energies correlate with KIE ratios. Analysis of the KIE using
quantum mechanical optimized structures for the ground and
transition states in combination with a computational KIE
prediction (modified QUIVER) leads to values in reasonable
agreement with those obtained experimentally. The isotope
effect is seen to come from a differential ZPE between flat and
bowl forms owing to the general increase in the steepness of
the interaction potential between methyl groups in a crowded
environment.
In the course of this work, it was necessary to develop a
synthetic methodology for pentasubstitution of sym-pentachlo-
rocorannulene. This was achieved in relatively good chemical
yield using Negishi reagents and palladium with Nolan’s NHC
ligands. This result shows the usefulness of the NHC ligand
even for the coupling reaction with multichlorides.
Transannulene interactions in bowl-shaped compounds should
provide a general arena for studying molecular recognition.
Other sym-substituted corannulenes may be anticipated as model
compounds for the investigation other interactions.
Second, consider the case in which the neighboring CH3//
CH3 distance would be longer than the sum of vdW radii for
CH3. In this case, the resting position of the corannulene bowl
would favor placement of the methyl groups outside the sum
of vdW radii and an attraction between the methyls helps
establish the equilibrium geometry. Key here is not the attractive
or repulsive component between the methyls, but rather the
affect their proximity has on the steepness of the potential.
Indeed, long before the methyl groups come to the point of vdW
contact, their vibrations interact, leading to a steepening of the
well and an enegetic bias for deuterium in the bowl form. This
model is supported by the detailed analysis of the KIE
prediction, which says that on the endo methyl groups, the CH
bond vector pointing into the bowl favors a KIE > 1, whereas
the one pointing away from the bowl favors KIE e 1.
The simple ZPE difference analysis is consistent with the
barrier for 3-(CD3)10 being higher than the barrier for 3-(DAr)10.
Nonetheless, the phenomenology suggests that the vdW attrac-
tion of CD3//CD3 is larger, which could lead to the notion of
CD3 being “stickier” (i.e., more tightly bound). A parallel to
this concept can be found in the higher binding constants
measured for deuterated host-guest systems.24
As both of these scenarios can be rationalized by a ZPE effect
in the same direction, the isotope effect as sole factor cannot
indicate whether the trans-bowl methyl interaction is attractive
or repulsive. Both situations can be approximated by a vibrating
C-H oscillator such that when two or more such oscillators
come into proximity, their space becomes restricted and the
potential-energy well becomes steeper. The larger energy
spacings for the steeper well makes a ZPE bias for C-D over
C-H. The shape of quantum mechanical potential-energy
surface is identical for C-H and C-D. In short, the bowl form
of 3 presents a more congested methyl environment than the
Methods
Computational Methods. The conformational analyses of the
molecular systems described in this study, including structural and
orbital arrangements as well as property calculations, were carried out
using the Gaussian 9827 and GAMESS28 software packages. Structural
computations of all compounds were performed using hybrid density
functional methods (HDFT). The HDFT method employed Becke’s 3
parameter functional29 in combination with nonlocal correlation pro-
vided by the Lee-Yang-Parr expression30,31 with both local and
nonlocal terms, B3LYP, as well as the new M06-2X functional of
Truhlar et al.8 Dunning’s correlation consistent basis set, cc-pVDZ, a
[3s2p1d] contraction of a (9s4p1d) primitive set was employed.32 Full
(27) Frisch, M. J.; et. al. Gaussian 98, Revision A.6, Gaussian, Inc.: Wallingford,
CA, 1998.
(28) Schmidt, M. W.; Baldridge, K. K.; Boatz, J. A.; Elbert, S. T.; Gordon, M.
S.; Jensen, J. H.; Koseki, S.; Matsunaga, N.; Nguyen, K. A.; Su, S.; Windus,
T. L.; Elbert, S. T. J. Comp. Chem. 1993, 14, 1347.
(29) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652.
(30) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
(31) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H. Chem. Phys. Lett 1989, 157,
200.
(24) (a) Zhao, Y.-L.; Houk, K. N.; Rechavi, D.; Scarso, A.; Rebek, J., Jr. J.
Am. Chem. Soc. 2004, 126, 11426. (b) Laughrey, Z. R.; Upton, T. G.; Gibb,
B. C. J. Chem. Soc., Chem. Commun. 2006, 970. (c) Liu, Y.; Warmuth, R.
Org. Lett. 2007, 9, 2883.
(25) Ubbelohde, A. R. Trans. Farady Soc. 1936, 32, 525.
(26) Pauling, L. The Nature of the Chemical Bond; Graphic Reproductions
Ltd: London, 1952; Chapter 5.
(32) Dunning, T. H. J. Chem. Phys. 1989, 90, 1007.
9
J. AM. CHEM. SOC. VOL. 130, NO. 5, 2008 1589

A R T I C L E S
Hayama et al.
geometry optimizations were performed with an ultrafine grid and tight
criteria and uniquely characterized via second derivatives (Hessian)
analysis to determine the number of imaginary frequencies (0 ) minima;
1 ) transition state), zero point contributions. Additionally, deuterium
isotopic difference effects were determined from selective deuterium
substitutions made on the aryl and methyl groups as described in the
text. From the fully optimized structures, single point energy and
gradient computations were performed using the MP2 dynamic cor-
relation treatment,33 providing more accurate energy barriers and insight
into the difference from optimization, respectively. We have established
these levels of theory to be reliable for structural and energetic
determinations in these types of compounds in several previous
publications.34 Analysis using the Grimme DFT dispersion method was
accomplished by implementation of the recently developed methodology
of Grimme into our GAMESS software. More sophisticated kinetic
analysis was done using a modified version of QUIVER (frequency
scaling factor 0.9614 and temperature ) 250 K),35 which provides
calculation of the kinetic isotope effect corrected for tunneling with a
one-dimensional tunneling approximation, as proposed by Bell.22
Corrections were introduced in accord with a recent book chapter by
M. Wolfsberg.36 Molecular orbital and electrostatic contour plots, used
as an aid in the analysis of results, were generated and depicted using
the programs 3D-PLTORB37 and QMView.38
mL, 90 mmol) was added dropwise with stirring at 0 °C under nitrogen.
The mixture was stirred at 0 °C for 10 min under nitrogen. The reaction
was quenched with the addition of water (150 mL). The organic layer
was separated, dried with Na2SO4, and evaporated to yield a pale yellow
oil (10.1 g). To a suspension of LAD (5.67 g, 135 mmol) in THF (80
mL), the crude mixture in THF (120 mL) was added dropwise over a
period of 30 min at rt under nitrogen. The mixture was heated at 60
°C for 2 h under nitrogen. After the mixture was cooled to 0 °C, an
aqueous solution of H2SO4 (300 mL, 1 M) was added. The mixture
was diluted with ethylacetate (50 mL), filtered, separated, washed with
saturated aqueous NaCl (100 mL), dried with Na2SO4, and evaporated
to yield a yellow oil (2.95 g). The product was purified by column
chromatography on silica gel eluted with hexane. The solvent was
evaporated to yield a colorless oil (1.50 g; 35%) of 9 [Rf ) 0.85 (SiO2,
hexane/ethyl acetate ) 16:1)]. IR (KBr): ν cm-1 ) 1610, 1592, 1453,
1
1433, 1327, 1299, 1196, 1164, 1073, 1046, 908, 785, 678, 580. H
3
NMR (300 MHz, CDCl3): δ ppm ) 3.77 (s, 3H), 6.53 (d, J ) 1.5
Hz, 2H), 6.60 (t, 3J ) 1.5 Hz, 1H). 13C NMR (75.5 MHz, CDCl3, plus
DEPT): δ ppm ) 20.5 (septet, 1J ) 19.1 Hz, CD3), 55.0 (CH3), 111.7
(CH), 122.4 (CH), 139.0 (C), 160.0 (C). MS (EI), m/z (%): 142 (M+),
124 (M+ - CD3), 111 (M+ - OCH3).
1-Bromo-4-methoxy-2,6-di(d3-methyl)benzene (6). A solution of
NBS (1.69 g, 9.5 mmol) in acetonitrile (15 mL) was added dropwise
to 9 (1.42 g, 10 mmol) in acetonitrile (5 mL) at 0 °C. After warming
to rt and stirring for 17 h, water (20 mL) was added. The mixture was
extracted with hexane (50 mL × 4), dried with Na2SO4, and evaporated
to yield a yellow oil (1.96 g; 89%) of 6. IR (KBr) ν cm-1: 1584, 1448,
1427, 1413, 1326, 1584, 1448, 1427, 1413, 1326, 1198, 1168, 1049,
1014, 826. 1H NMR (300 MHz, CDCl3) δ ppm: 3.76 (s, 3H), 6.64 (s,
2H). 13C NMR (75.5 MHz, CDCl3, plus DEPT) δ ppm: 23.1 (septet,
1J ) 19.5 Hz, CD3), 55.2 (CH3, 113.8 (C), 122.4 (CH), 138.9 (C),
Experimental Methods. General. Data were collected on the
following instruments: 1H and 13C NMR, Bruker AMX 300 (300 and
75.5 MHz); IR, Bruker IFS 66 (FT-IR); EI-MS, Finnegan MAT 95
spectrometer (70 eV). High-resolution mass data (HRMS) were obtained
by preselected-ion peak matching at R ≈ 10000 to be within ( 3 ppm
of the exact mass. Crystallographic data was recorded using a Non´ıus
Kappa CCD diffractometer with Mo KR radiation (λ ) 0.71073 Å).
Chromatography was performed using Merck silica gel 60 (230-400
mesh) or Fluka neutral alumina (Brockmann I, Activity II). Tetrahy-
drofuran (THF) was distilled from sodium/benzophenone. Solvents for
chromatography were technical grade and freshly distilled before use.
sym-Pentachlorocorannulene4 and IPr‚HCl16 were prepared according
to the literature procedures. Other compounds, which are not mentioned
in the experimental section and Supporting Information, are com-
mercially available.
158.0 (C). MS (EI), m/z (%): 221 (M+), 141 (M+ - Br), 111 (M+
-
OCH3 - Br). HRMS (EI): calcd for C9H5D6BrO. 220.0370; found,
220.0367.
3,5-Dimethylphen-2,4,6-d3-ol (11-d3). 3,5-Dimethylphenol (6.11 g,
50 mmol), deuterium oxide (8.94 mL, 500 mmol), and sodium
deuteroxide (1 mL, 40 wt % solution in D2O) were placed in a pressure
tube (Ace pressure tube from Aldrich). After the nitrogen flush, the
tube was sealed and heated at 100 °C for 22 h. After cooling to 0 °C,
the reaction mixture was acidified with concentrated H2SO4 (3 mL) in
D2O (7 mL). The resulting precipitate was filtered and washed with
D2O (2 mL × 5). This process was repeated an additional four times
to yield a brown solid (5.01 g; 79%) of 11-d3: mp 51-52 °C. IR (KBr)
5-Methoxybenzenebis(methane-R,R-d2)-ol (8). To a suspension of
LAD (4.62 g; 110 mmol) in THF (100 mL), dimethyl-5-methoxyiso-
phthalate (11.2 g, 50 mmol) in THF (150 mL) was added dropwise.
The mixture was stirred at room temperature (rt) for 17 h under nitrogen.
After cooling to 0 °C, an aqueous solution of H2SO4 (175 mL, 1 M)
was added. The mixture was diluted with ethylacetate (100 mL),
separated, washed with saturated aqueous NaCl (100 mL), dried with
Na2SO4, and evaporated to yield a white solid (7.50 g; 87%) of 8: mp
79 °C. IR (KBr) ν cm-1: 3330, 3203, 1596, 1460, 1429, 1339, 1296,
1200, 1173, 1102, 1056, 966, 856, 816, 800, 690. 1H NMR (300 MHz,
CDCl3): δ ppm: 1.62 (s, 2H), 3.83 (s, 3H), 6.86 (d, 3J ) 1.5 Hz, 2H),
1
ν cm-1: 3275, 2434, 1597, 1575, 1448, 1390, 1311, 1053, 547. H
NMR (75.5 MHz, CDCl3, plus DEPT) δ ppm: 2.60 (s, 6H). 13C NMR
1
(75.5 MHz, CDCl3, plus DEPT) δ ppm: 21.0 (CH3), 112.7 (t, J )
1
21.8 Hz, CD), 122.1 (t, J ) 23.3 Hz, CD), 139.3 (C), 155.2 (C). MS
(EI), m/z (%): 126 (M+), 111 (M+ - CH3). HRMS (EI): calcd for
C8H6D4O, 126.0983; found, 126.0980.
3
6.96 (t, J ) 1.5 Hz, 1H). 13C NMR (75.5 MHz, CDCl3, plus DEPT):
1-Methoxy-3,5-dimethylbenzene-2,4,6-d3 (12). To a suspension of
11-d3 (5.01 g, 40 mmol) in acetone (90 mL), potassium carbonate (22.2
g, 160 mmol) and iodomethane (12.5 mL, 200 mmol) were added. The
mixture was heated at 75 °C for 33 h. After cooling to rt, the solvent
was evaporated. Water (70 mL) was added, and the mixture was
extracted with ethylacetate (100 mL). The organic layer was washed
with water (70 mL) and saturated aqueous NaCl (70 mL), dried with
MgSO4, and evaporated to yield 12 as a brown oil (3.36 g; 60%). IR
(KBr) ν cm-1: 2955, 2926, 2874, 2861, 826, 724. 1H NMR (300 MHz,
CDCl3) δ ppm: 2.84 (s, 6H), 3.71 (s, 3H). 13C NMR (75.5 MHz, CDCl3,
δ ppm: 55.2 (CH3), 64.1 (quint, 1J ) 22.2 Hz, CD2), 111.5 (CH), 117.5
(CH), 142.6 (C), 159.8 (C). MS (EI), m/z (%): 172 (M+), 139 (M+
-
CD2OH). HRMS (EI): calcd for C9H8D4O3, 172.1038; found, 172.1038.
1-Methoxy-3,5-di(d3-methyl)benzene (9). To a solution of 8 (5.17
g, 30 mmol), DMAP (750 mg, 6 mmol), and triethylamine (12.6 mL,
90 mmol) in dichloromethane (300 mL), methanesulfonyl chloride (6.9
(33) Moller, C.; Plesset, M. S. Phys. ReV. 1934, 46, 618-622.
(34) For example, see Seiders, T. J.; Baldridge, K. K.; Grube, G. H.; Siegel, J.
S. J. Am. Chem. Soc. 2001, 123, 517-525.
1
plus DEPT) δ ppm: 21.3 (CH3), 55.0 (CH3), 111.5 (t, J ) 23.9 Hz,
(35) Saunders, M.; Laidig, K. E.; Wolfsberg, M. J. Am. Chem. Soc. 1989, 111,
8989-8994.
CD), 122.2 (t, 1J ) 23.9 Hz, CD), 139.0 (C), 159.6 (C). MS (EI), m/z
(%): 139 (M+), 124 (M+ - CH3), 108 (M+ - OCH3).
(36) Wolfsberg, M. Comments on Selected Topics in Isotope Theoretical
Chemistry. In Isotope Effects in Chemistry and Biology; Amnon Kohen,
A., Hans-Heinrich Limbach, H.-H., Eds.; CRC Press/Taylor & Francis:
Boca Raton, FL, 2005; Chapter 3.
1-Bromo-4-methoxy-2,6-dimethylbenzene-3,5-d2 (10). A solution
of NBS (3.63 g, 20.4 mmol) in acetonitrile (30 mL) was added dropwise
to 12 (2.92 g, 21 mmol) in acetonitrile (10 mL) at 0 °C. After warming
to rt and stirring for 16 h, water (30 mL) was added. The mixture was
(37) 3D-PLTORB, Version 3D; San Diego Supercomputer Center: San Diego,
CA, 1997.
(38) Baldridge, K. K.; Greenberg, J. P. J. Mol. Graphics 1995, 13, 63.
9
1590 J. AM. CHEM. SOC. VOL. 130, NO. 5, 2008

Steric Isotope Effects in Pentaarylcorannulenes
A R T I C L E S
extracted with hexane (20 mL × 5), dried with MgSO4, and evaporated
to yield an orange oil (4.03 g; 24%) of 10. IR (KBr) ν cm-1: 1566,
sym-Penta(4-methoxy-2,6-dimethylphenyl-3,5-d2)corannulene (3-
(DAr)10). The similar procedure to the synthesis of 3 yielded a yellow
solid (35%) of (3-(DAr)10): mp >350 °C. IR (KBr) ν cm-1: 3441, 1589,
1
1456, 1437, 1378, 1320, 1110, 1013. H NMR (300 MHz, CDCl3) δ
ppm: 2.38 (s, 6H), 3.76 (s, 3H). 13C NMR (75.5 MHz, CDCl3, plus
1467, 1400, 1310, 1107. H NMR (75.5 MHz, CDCl3, plus DEPT) δ
1
1
DEPT) δ ppm: 23.9 (CH3), 55.2 (CH3), 113.5 (t, J ) 24.2 Hz, CD),
ppm: 1.98 (s, 30H), 3.81 (s, 15H), 7.09 (s, 5H). 13C NMR (75.5 MHz,
118.1 (CH), 138.9 (C), 158.0 (C). MS (EI), m/z (%): 217 (M+), 202
(M+ - Br - CH3), 137 (M+ - Br), 107 (M+ - Br - OCH3). HRMS
(EI): calcd for C9H9D2BrO, 216.0119; found, 216.0115.
CDCl3, plus DEPT) δ ppm: 21.3 (CH3), 55.1 (CH3), 112.3 (t, J )
1
19.1 Hz, CD), 125.8 (CH), 130.4 (C), 131.4 (C), 134.9 (C), 138.1 (C),
140.0 (C), 158.5 (C). MS (EI), m/z (%): 931 (M+).
sym-Pentamanisylcorannulene (3). 4-Bromo-3,5-dimethylanisole
(153 mg, 0.71 mmol) in THF (10 mL) was cooled to -78 °C in a dry
ice/acetone bath and n-butyllithium (0.52 mL, 0.78 mmol) was added
as a 1.5 M solutions in hexane. After 30 min, a freshly prepared solution
of ZnCl2 (146 mg, 1.07 mmol) in THF (5 mL) was transferred to the
solution. The mixture was stirred in the dry ice/acetone bath for 10
min and the bath was removed. After an additional 20 min, the resulting
aryl-zinc chloride solution was transferred to a flask containing a
suspension of sym-pentachlorocorannulene (30 mg, 0.071 mmol), Pd-
(OAc)2 (16 mg, 0.071 mmol), and IPr‚HCl (30 mg, 0.071 mmol) in
THF (5 mL). The mixture was refluxed at 110 °C in an oil bath for 4
days. The cooled mixture was filtered over celite and washed with
dichloromethane. The mixture was evaporated. The product was purified
by column chromatography on aluminum oxide (5% deactivated with
water) eluted with hexane/dichloromethane at 3/1, 2/1, and 1.5/1. The
solvent was evaporated to yield 3 as a yellow solid (0.16 g; 89%) 3 [Rf
) 0.35 (Al2O3, hexane/dichloromethane ) 3:1)]. The spectroscopic data
were identical with those reported.4
sym-Penta(4-methoxy-2,6-di(methyl-d3)phenyl)corannulene (3-
(CD3)10). The similar procedure to the synthesis of 3 yielded a yellow
solid (18%) of (3-(CD3)10): mp >350 °C. IR (KBr) ν cm-1: 3444,
1600, 1465, 1420, 1320, 1196, 1170, 1046. 1H NMR (75.5 MHz, CDCl3,
plus DEPT) δ ppm: 3.81 (s, 15H), 6.66 (s, 10H), 7.10 (s, 5H). 13C
NMR (75.5 MHz, CDCl3, plus DEPT) δ ppm: 20.5 (septet, 1J ) 19.5
Hz, CD3), 55.1 (CH3), 112.6 (CH), 122.4 (CH), 130.4 (C), 131.4 (C),
134.9 (C), 138.1 (C), 140.0 (C), 158.6 (C). MS (EI), m/z (%): 951
(M+).
Acknowledgment. This work was supported by the Swiss
NFP grant. Dr. Eli Zysman-Colman (University of Zurich) is
acknowledged for helpful discussion. We are grateful to Don
Truhlar for graciously allowing us to use facilities at the
Minnesota Supercomputer Center enabling computations involv-
ing the M06-2X functional, which is not yet distributed to the
public. We thank Martin Saunders for the latest version of
QUIVER.
Note Added in Proof: Through discussions with Jack Dunitz,
a question has been raised concerning the role of entropy on
the kinetic isotope effect. Entropic considerations could stem
from low energy librational modes, the higher-order modes of
which would become populated with increasing temperature.
This could result in the existence of a temperature dependence
and a sublte isoselective relationship similar to that found more
drammatically for dihalocarbene selectivities, see: Giese, B.;
Meister, J. Angew. Chem. Int. Ed. Engl. 1978, 17, 595.
Supporting Information Available: Complete ref 27; the
details of the line shape analysis and the crystal structure data
of 2. This material is available free of charge via the Internet at
http://pubs.acs.org.
JA073052Y
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J. AM. CHEM. SOC. VOL. 130, NO. 5, 2008 1591