Tautomerism and atropisomerism in free-base (meso)-strapped porphyrins: Static and dynamic aspects

Article abstract of DOI:10.1002/chem.201403881

We report herein some outstanding examples of atropisomerism and tautomerism in five (meso-)strapped porphyrins. Porphyrins S0-S4 have been synthesised, characterised and studied in detail by spectroscopic and spectrometric techniques, and their isomeric purity verified by HPLC analysis. In particular, they exhibit perfectly well-defined NMR spectra that display distinct patterns depending on their average symmetry at room temperature: C_2v D_2d, C_2h, C_2v and D_2h for S0-S4, respectively. NH tautomerism was evidenced by variable-low-temperature ¹H NMR experiments in [D₂]dichloromethane performed on S0 (δG^?_298K = 48± 1 kJmol^-1) and S1 (δG^?_298K = 55±3 kJmol^-1), which has led to an understanding of the average spectra observed for the five porphyrins at room temperature. On the other hand, S2 and S3 are stable atropisomers at room temperature, easily separated and characterised, as a result of restricted rotation of their strapped bridges due to their high rotational barrier energies. Upon heating to 82 °C, they slowly equilibrate to a thermodynamic ratio of 64:36 in favour of the more stable S2 isomer. This atropisomerisation process was evidenced by ¹H NMR spectroscopy and monitored by HPLC, from which high rotational energy barriers of 115.2 (δG^?_S3) and 116.9 kJ mol^-1 (δG^?_S3) were deduced.

Full text of DOI:10.1002/chem.201403881

DOI: 10.1002/chem.201403881
Full Paper
&
Thermodynamics
Tautomerism and Atropisomerism in Free-Base (meso)-Strapped
Porphyrins: Static and Dynamic Aspects
Maxence Urbani*[a, b] and Tomꢀs Torres*[a, b]
Abstract: We report herein some outstanding examples of
atropisomerism and tautomerism in five (meso-)strapped
porphyrins. Porphyrins S0–S4 have been synthesised, charac-
terised and studied in detail by spectroscopic and spectro-
metric techniques, and their isomeric purity verified by HPLC
analysis. In particular, they exhibit perfectly well-defined
NMR spectra that display distinct patterns depending on
their average symmetry at room temperature: C2v, D2d, C2h,
C2v, and D2h for S0–S4, respectively. NH tautomerism was evi-
to an understanding of the average spectra observed for the
five porphyrins at room temperature. On the other hand, S2
and S3 are stable atropisomers at room temperature, easily
separated and characterised, as a result of restricted rotation
of their strapped bridges due to their high rotational barrier
energies. Upon heating to 828C, they slowly equilibrate to
a thermodynamic ratio of 64:36 in favour of the more stable
S2 isomer. This atropisomerisation process was evidenced by
1H NMR spectroscopy and monitored by HPLC, from which
high rotational energy barriers of 115.2 (DGꢀS2!S3) and
116.9 kJmolꢁ1 (DGSꢀ2!S3) were deduced.
1
denced by variable-low-temperature H NMR experiments in
[D2]dichloromethane performed on S0 (DGꢀ298K =48ꢀ
1 kJmolꢁ1) and S1 (DG2ꢀ98K =55ꢀ3 kJmolꢁ1), which has led
thesis,[37–39] ZnII–Pors has been used as a template for rotax-
anes,[40] conjugated molecular tapes,[41] a host for fullerene,[42]
self-assembled materials,[43–46] and H2–Pors has been used as
a multi-dentate polynucleating ligand[47] and template for viol-
ogen rotaxanes.[48,49] Because their molecular structures mimic
macroscopic objects, many strapped porphyrins have received
diverse names such as “gyroscope”, “basket handle”, “pocket”,
“picnic basket”, “coronet” or “capped”.[28,50] The preparation
and isolation of strapped porphyrins as (stereo)isomerically
pure compounds in reasonable yields remains an important
challenge that often hampers further studies and applications.
Two different synthetic approaches are used: the post-func-
tionalisation of a porphyrin scaffold (“post-strapping”) and the
direct synthesis by using a pre-functionalised strapped alde-
hyde (“pre-strapping”).[50] We have synthesised and studied five
meso-strapped porphyrins S0–S4 by following this latter strat-
egy (Table 1). Continuing our interest in phthalocyanine, por-
phyrin and other related porphyrinoid macrocycle ana-
logues,[2,51] we report herein a detailed study of the revisited
synthesis and characterisation of five “meso-strapped” porphyr-
ins, providing some outstanding examples of isomerism, tauto-
merism and atropisomerism in these peculiar yet fascinating
macrocycles.
Introduction
Besides their exceptional optical, photophysical and electro-
chemical properties extensively exploited for decades in
donor–acceptor systems[1] and molecular photovoltaics,[2–4] por-
phyrins (Pors) have also proved to be extraordinary supra-
molecular scaffolds in the design of sophisticated 1D-, 2D- and
3D-dimensional architectures,[5–9] covalently or self-assem-
bled,[10–14] including chiral materials[15–17] or sensors,[18] molecu-
lar cages,[19–23] turnstiles,[24] tweezers[25,26] and dendrimer
cores.[9] Since the first reported example in 1969,[27] atropiso-
merism in porphyrins has been a concept widely exploited in
these kinds of architectures (and, in particular, in tetra-meso-ar-
ylporphyrins).[28–30] For example, “picket-fence” and ansa-like
“strapped” designs have been widely used for the preparation
of many synthetic metallo- and free-base porphyrin complexes.
RuII–Pors[31] or FeII–Pors[32,33] that bind O2, CO, and/or N2 mim-
icking haem-containing proteins have been used in synthetic
peptide models[34–36] and as chiral catalysts for asymmetric syn-
[a] Dr. M. Urbani, Prof. T. Torres
Departamento de Quꢀmica Orgꢁnica
Universidad Autꢂnoma de Madrid
Cantoblanco, 28049 Madrid (Spain)
Fax: (+34)914973966
E-mail: maxence.urbani@uam.es
tomas.torres@uam.es
Results and Discussion
[b] Dr. M. Urbani, Prof. T. Torres
Synthesis
Instituto MadrileÇo de Estudios Avanzados (IMDEA)-Nanociencia
c/Faraday, 9, Cantoblanco, 28049 Madrid (Spain)
Porphyrins S1–S3 were synthesised by BF3-catalysed condensa-
tion of dialdehyde 1 and pyrrole in CHCl3 under an inert at-
mosphere, followed by oxidation with 2,3-dichloro-5,6-dicyano-
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403881. Detailed synthetic procedures
1
and characterisation, H and 13C NMR, UV/Vis, MS and HRMS spectra.
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Table 1. meso-Strapped porphyrins S0–S4 studied in this work.
S0 S1
S2
S3
S4
molecular
structure
schematic
cartoon
minimised
equilibrium
geometry in
the ground
state (PM6
method)
estimated
dipole
n/a
0.8
1.1
6.5
n/a
moment, m
[D]
Rf[a] [%]
76–82[b]
(78)[c]
C2v
43–54[b]
(49)[c]
D2d
39–46[b]
(43)[c]
C2h
17–22[b]
(20)[c]
C2v
59–69[b]
(67)[c]
D2h
average
symmetry at
RT[d]
[a] The retention factors (Rf , in %) were determined on TLC plates (5ꢂ5 cm, SiO2; eluent: CHCl3/hexanes, 3:2) are given have an error of ꢀ3%. [b] Start-to-
end. [c] Centre. [d] Average “pseudo” symmetries due to fast dynamic processes, observed by NMR spectroscopy (see the discussion in the main text).
1,4-benzoqinone (DDQ) at room temperature under the opti-
mised conditions previously reported in the literature[52]
(Scheme 1). Porphyrins S1–S3 have been synthesised previous-
ly under different conditions giving different yields.[53] Porphyr-
ins S0 and S4 were readily obtained by [2+1] condensation of
5-mesityldipyrromethane[54] and
1
or the tetraoxa-
[12.12]metacyclophane dialdehyde 3b, respectively.
Characterisation
Porphyrins S0–S4 were characterised by MS and HRMS spec-
trometry (MALDI-TOF); their spectra display the [M]+ and/or
[M+H]+ molecular ions peaks (Figure 1). Their isomeric purity
was determined by HPLC analysis (Figure 2) and found to be in
the range of 98.5–100% (mol%).
Room-temperature NMR spectra
1
Scheme 1. Synthesis of S0–S4. Reagents and conditions: i) 5-mesityldipyrro-
methane; ii) pyrrole; iii) CHCl3, BF3·OEt2, RT, Ar, 1.5–3 h, followed by DDQ, RT,
1 h. (*Denotes the estimated yields before chromatographic separation,
based on the relative 1H NMR integration and the amount of pre-purified
product.)
Partial H NMR spectra of porphyrins S0–S4 recorded in CDCl3
at 300 K are presented in Figure 3 (full-range H and 13C NMR
1
spectra are provided in the Supporting Information). For S1–
S3, AMX and AMNX (ca. AM2X) patterns are observed for the
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Figure 2. HPLC traces (SiO2 Cosmosil; mobile phase: toluene) of S0–S4 and
a mixture of S1–S3 (test control). The isomeric purities of S0–S4, determined
by the relative integrations of the HPLC peaks, are given. (* Denotes signals
arising from residual porphyrin impurities; detection wavelength: 420 nm
(Soret band), ref: 800 nm.)
at 300 K. In turn, both S2 and S3 display two distinct singlets
for the b-pyrrolic protons (b1 and b2), consistent with average
C2h and C2v symmetry, respectively. The relative dipole orienta-
tion of the phenoxy groups in each isomer (anti/syn for S2 or
all-syn for S3) causes significant differences in the chemical
shifts of their proton signals, in particular, for the b-pyrrolic
(slightly) and the A-H protons (more pronounced). Although
some attempts to distinguish the cis-a/a from the cis-a/b iso-
mers based on these observations have been made previously
for other porphyrin systems,[50] no clear conclusion was drawn
that allowed us to distinguish them simply and in a straightfor-
ward manner by NMR spectroscopic methods (nor by other
spectrometric methods as they are two constitutional isomers.
To discriminate these two isomers, we performed computa-
tional studies at the semi-empirical level (PM6 method). Based
on our calculations, the dipole moment increases in the order
S1<S2 !S3 (see Table 1). Although these formal values have
Figure 1. MALDI-TOF mass spectra of S0–S4 (the most abundant molecular
ion peak [M]+ or [M+H]+ is denoted).
A, B, C and D protons of the four magnetically equivalent
o-substituted meso-phenyl rings with relatively strong de-
shielding in comparison with their parent dialdehyde 1 due to
the ring current effect of the porphyrin moiety. Notably, S1 dis-
plays a single singlet for the eight magnetically equivalent b-
pyrrolic protons, in agreement with an average D2d symmetry
1
Figure 3. Partial H NMR spectra (300 MHz, 300 K) in CDCl3 of 1, 3b, crude S1–S3[a] and S0–S4. Left: aromatic proton region; right: methoxy proton region.
([a] Estimated yields of isomers S1–S3 before chromatographic separation are noted, based on the relative integration of the A-H proton signals in the
1H NMR spectrum. *S denotes the residual solvent peak of CDCl3.)
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1
1
Figure 4. Labelling of the hydrogen atoms (left) and 2D COSY H/1H NMR spectrum (right) of S0 (CDCl3, 300 MHz, 300 K). The 1D H NMR spectrum of S0 is de-
picted in horizontal and vertical traces.
to be interpreted carefully (because they strongly depend on
the relative orientation of the phenoxy-strapped bridges in the
calculations: “in–in”, “in–out” and “out–out”, all equivalent in
the case of S1), this trend matches perfectly the order of elu-
tion (S1<S2 !S3) from a chromatography column (SiO2) ob-
served experimentally (Rf =49 (S1), 43 (S2), and 20% (S3), de-
termined on TLC plates (SiO2); eluent: CHCl3/hexanes, 3:2). This
order of elution is in agreement with that previously proposed
by Momenteau et al.[53] In agreement with their respective
average symmetries at room temperature, the OCH2 methoxy
protons (a-H) appear as equivalents in S0, S1 and S4, display-
ing a relatively well-resolved triplet in each case. In contrast,
these protons become diastereotopic in S2 and S3, which re-
sults in more complex but characteristic AA’XX’ systems for the
four sets of methoxy protons (a-H/a’-H). S0 displays an average
C2v 1H NMR spectrum at room temperature (see Figures 3–5). In
particular, an AB quartet is observed for the four sets of b-pyr-
rolic protons (b1/b2), magnetically equivalent due to the two
average sv planes and the C2 axis of symmetry. The non-equiv-
alency of the two porphyrin faces of S0 can be clearly attested
by the presence of three distinct singlets in a 1:1:1 ratio for
the ArCH3 methyl protons m-H, n-H and n’-H (see Figure 5). In
turn, for S4 with both porphyrin faces equivalent, the n-H pro-
tons appear as a unique singlet due to an average D2h symme-
try. In addition, S4 displays a perfectly well-defined AX2 system
for the aromatic protons X-H and Y-H of the two equivalent
o,o’-substituted meso-phenyl rings. As illustrated in the 2D
COSY spectrum of S0 (Figure 4), all the CH2 methylene protons
b–f-H are clearly distinguishable. The drastic shielding of these
protons between 1 and ꢁ1.5 ppm lays witness to their proxi-
mal location inside the shielding cone of the porphyrin ring (a
maximum distance of 4–5 ꢃ between the farthest f-H protons
and the centre of the macrocycle core was estimated based on
molecular modelling).
Variable-temperature NMR experiments
Of course, the relatively simple NMR spectra observed for S0–
S4 at room temperature result from average symmetries. To
explain these average spectra, some criteria must be satisfied.
First, the fast tautomerism of the NH protons that is ubiquitous
to free-base porphyrins. Next, molecular modelling studies sug-
gested that the lowest-energy conformers possess the strap
bent to one side of the porphyrin core. Therefore it can be an-
ticipated that a “swinging bridge”[55] motion of the strap(s)
must also be fast on the NMR timescale, as exemplified for S0
in Figure 6. To gain insights into these dynamic exchange phe-
nomena and conformational processes, and to support our hy-
1
Figure 5. Mesityl proton region of the H NMR spectra of S0 (bottom) and
1
pothesis, we performed variable-temperature (VT) H NMR ex-
S4 (top; CDCl3, 300 MHz, 300 K; proposed assignment, inversion between
the n-H and n’-H protons is possible).
periments (500 MHz).
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Figure 6. Fast “swinging” motion of the strap as exemplified for S0.
We first studied S0 as a lead compound at various high tem-
peratures in [D2]tetrachloroethane. As representative examples,
selected partial VT NMR spectra of S0 are depicted in Figure 7
(see full-range spectra in the Supporting Information). Upon
heating, all the peaks sharpened slightly, but no significant
changes can be observed, with the exception of slight shifts in
the methyl PhCH3 (Figure 7) and NH pyrrolic proton signals
(see below). At 1248C, the limit temperature of our NMR appa-
ratus and close to the boiling point of the C2D2Cl4 solvent, two
sharp singlets can still be clearly observed for the n-H and n’-H
protons, which shows that rotation around all the phenyl axes,
including the (bis)phenoxy-strapped bridge and the two mesi-
tyl groups, are sterically hindered in S0 (Figure 7, top inset).
This is not surprising because the ortho-substituted meso-
phenyl groups are known to exhibit barriers to rotation in
excess of 100–110 kJmolꢁ1 (OH<OMe, CH3, CN)[56] and signifi-
cantly higher for o,o’-disubstituted phenyl groups.[57] These
statements could not be directly verified by variable-high-tem-
perature NMR spectroscopy in the cases of S1 and S4 as both
of their porphyrin faces are equivalent. However, considering
the restricted rotation in S0, it is clear that the “flip-flap”
motion of the doubly trans-strapped bridge in S4, in a “gyro-
scope-like” fashion, must also be hindered, as well as those of
the two cross-linked trans-strapped bridges in S1, for obvious
steric reasons. Next, variable-low-temperature NMR experi-
ments were performed on S0 and S1 in [D2]dichloromethane
(500 Hz; Figures 8 and 9). Upon cooling, coalescence of the b-
pyrrolic protons signals was observed for both S0 (TC =240ꢀ
2 K) and S1 (TC =263ꢀ10 K). For S0, the b-pyrrolic proton sig-
Figure 7. Top: representation of hindered rotation processes in S0. Bottom:
selected partial H NMR spectra (500 MHz; C2D2Cl4) of the mesityl proton
region of S0 (proposed assignment, inversion between n-H and n’-H protons
is possible).
1
nals split into two sets of doublets at 193 K, which has been
ascribed to the slow equilibrium of two (identical) trans tauto-
mers of lower symmetry (C2). It is now accepted that hydrogen
tautomerism in free-base porphyrins occurs through an asyn-
chronous two-step pathway,[58–65]] the interconversion between
the two most stable trans tautomers involving cis-tautomeric
transition state(s) as metastable intermediate(s) (trans![cis]!
trans conversion, see Scheme 2). Note, the b’-H proton signals
(b’1/b’2) are significantly broader than those of b’’-H (b’’1/b’’2),
Scheme 2. Schematic energy diagrams for the NH tautomerism process in S0 and S1 ([TS]*=Transition State). For the sake of clarity, only one of the two cis
tautomer intermediates of S0 is represented (both being identical in the case of S1).
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1
Figure 8. Top: symmetries observed at RT and low temperature and H NMR nomenclature for S0 and S1 (note that only one of the two (identical) trans tau-
1
tomers is represented in each case). Bottom: variable-low-temperature H NMR spectra (CD2Cl2; 500 MHz) of the b-pyrrolic proton region of S0 (left) and S1
(right).
1
Figure 9. Variable-temperature H NMR spectra (500 MHz) of the NH proton region of S0 (left) and S1 (right).
4
indicative of long-range couplings J(N-H/b’-H) for the former,
as previously reported in other cases.[66]
rolic proton signals, which was not observed experimentally).
To rule out this possibility in S0 we studied the ZnII-metallated
analogue Zn-S0 by VT NMR spectroscopy (Figure 10; see de-
tails of the synthesis of Zn-S0 in the Supporting Information).
In principle, the loss of symmetry C2v!C2 in only the case of
S0 could also be explained by a slow “swinging” motion of the
strapped bridge at low temperature (this hypothesis is exclud-
ed in S1 as this would imply a set of (pseudo) enantiomers
and hence result in a four- to eight-fold splitting of the b-pyr-
1
Although the H NMR spectrum in [D2]dichloromethane is less
defined at room temperature than that recorded in CDCl3, it
quickly sharpened upon cooling.
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Figure 10. Left: 1H NMR spectrum in CDCl3 (300 MHz, 298 K; upper trace) and VT NMR spectra in CD2Cl2 (500 MHz; lower traces) of Zn-S0. Right: 1H NMR spec-
tra of Zn-S0 and S0 for comparison in different solvents and at different temperatures.
It can be clearly attested that there are no significant
changes in the NMR spectrum at low temperatures as two
well-resolved doublets are still observed for the b1-H and b2-H
pyrrolic protons. As NH tautomerism is excluded in Zn-S0, we
can attribute the occurrence of this dynamic process to S0.
1
However, close inspection of the H NMR spectrum of Zn-S0 at
193 K reveals the beginning of the loss of equivalency of the
b-pyrrolic protons, which appear as slightly split doublets. This
suggests that the “swinging bridge” motion starts to be slow
enough on the NMR timescale to be observed in the case of
Zn-S0. Nevertheless, we assume that the “swinging bridge”
motion is still faster than the NMR timescale at 193 K in the
!
*
Figure 11. Eyring plots for S0 ( ) and S1 ( ) with the corresponding linear
fitting curves (solid lines). k (sꢁ1) is the rate constant for NH proton exchange
determined by following the coalescence of the b-pyrrolic protons in low-VT
1H NMR experiments in CD2Cl2 (see Figure 8), T (K) is the temperature and r
is the correlation coefficient for the fitting curves.
case of S0 as the b’1-H and b’2-H proton signals appear as two
sets of doublets perfectly well-resolved at this temperature. A
plausible explanation of the lower activation energy for this
process in Zn-S0 than in S0 can be explained in terms of the
zinc metallation effect. Indeed, the porphyrin core of metallo-
porphyrins is known to display more distortion and deforma-
tion modes than their free-base analogues (the latter most
usually having a flatter structure than the former) in order to
accommodate the metal ion into the cavity, which impacts on
the Gibbs activation energies (DGꢀ) of conformational process-
es, such as rotations.[67–71] Similarly to S0, the b-pyrrolic proton
signal of S1 splits from one (room temperature) into two dis-
tinct singlets at 203 K (D2d!D2 symmetry), which has also
been attributed to the slowing down of the NH tautomerism
process (Figure 8, right). Also in this case, the signal of the b’
protons is broader than that of the b’’ protons (full width at
half maximum, FWHM=5.4 and 3.8 Hz, respectively), which is
responding Gibbs activation energies at 298 K were calculated
from the Gibbs–Helmholtz equation as 48ꢀ1 kJmolꢁ1 for S0
and 55ꢀ3 kJmolꢁ1 for S1 (Table 2, see details in the Support-
ing Information), which are in the range of experimental and/
or predicted values reported in the literature for free-base por-
phyrins.[55,58–65]
In parallel to the evolution of the b-pyrrolic proton signals,
the chemical shifts (dNH) and line shapes (FWHM) of the NH
proton signals also strongly depend upon both the tempera-
ture and the solvent (Figures 9 and 12A–D). First, the evolution
of dNH versus T for S0 and S1 follows a perfect linear depend-
ence (Figure 12A and B, respectively): constant shielding upon
cooling and deshielding upon warming/heating. Although
little information can be found in the literature concerning this
behaviour, it is known for porphyrins and other related por-
phyrinoid analogue systems that both the steric effects of
bridge substitution[62] and the degree of planarity of the mac-
rocycle[60] strongly influence the tautomeric transition states
through core deformations: the more planar the macrocycle,
4
indicative of long-range couplings J(N-H/b’-H) in the former.
By monitoring the coalescence of the b-pyrrolic proton signals
by VT NMR experiments in CD2Cl2, and assuming a first-order
reaction, the rate constant (k) for exchange[72] of the NH pro-
tons could be determined as a function of the temperature (T)
and used to prepare Eyring plots (ln(k/T) vs 1/T, see Figure 11).
The associated activation parameters DHꢀ and DSꢀ[73–75] could
be determined from the Eyring plots and, accordingly, the cor-
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More counter-intuitive is the broadening of these signals at
temperatures below around 220–230 K. As discussed above,
this might be associated with a reduced rate of the second dy-
namic process, the “swinging motion” of the strap(s) that
under the limit of solubility of the compounds and the freez-
ing point of the CD2Cl2 solvent could not be evidenced. Others
have previously evidenced such phenomena, but in more con-
strained quinone cyclophane strapped porphyrins, for which
coalescence temperatures have been reported below 190 K.[55]
In comparison with our more flexible -O(C12H25)O- strap(s), we
assume that the swinging motion in S0 and S1 is always faster
than the NMR timescale in the temperature range of our ex-
periments (from room temperature to 193–203 K). In contrast,
variable-high-temperature NMR experiments on S0 in C2D2Cl4
primarily revealed a slight narrowing of the NH proton signal
upon heating in the 300–340 K range, followed by a drastic
broadening in the 340–397 K range. The NMR spectra recorded
before (298 K) and after (300 K) heating being exactly similar,
they attest to the full reversibility of any other hypothetical dy-
namic process and exclude any chemical transformation or
degradation reactions at high temperatures.
Table 2. Calculated activation parameters for the NH tautomerism pro-
cess for S0 and S1 in CD2Cl2.
[b]
DHꢀ[a]
[kJmolꢁ1
DSꢀ[a]
[JKꢁ1 molꢁ1
DGꢀ298K
DGꢀT [b,c]
DGꢀT [c,d]
c
c
]
]
[kJmolꢁ1
]
[kJmolꢁ1
]
[kJmolꢁ1
]
S0 45.(4)ꢀ1
ꢁ10.1ꢀ0.3
48.(4)ꢀ1
47.(9)ꢀ1
~47.7
(10.9ꢀ0.3)[e] (ꢁ2.42ꢀ0.06)[f] (11.6ꢀ0.3)[e] (11.5ꢀ0.3)[e]
(11.4)[e]
~52.4
S1 34ꢀ2
ꢁ70ꢀ4
55ꢀ3
52ꢀ3
(8.1ꢀ0.4)[e]
(ꢁ17ꢀ1)[f]
(13.1ꢀ0.7)[e] (12.5ꢀ0.7)[e]
(12.5)[e]
[a] Calculated from Eyring plot parameters. [b] Calculated from the
Gibbs–Helmholtz equation. [c] Coalescence temperatures: TC =240ꢀ2 K
for S0 and 263ꢀ10 K for S1. [d] DGꢀ values estimated by using VT NMR
data and simplification of the Eyring equation at coalescence tempera-
ture. [e] Values expressed in kcalmolꢁ1
.
[f] Values expressed in
calKꢁ1 molꢁ1 (errors in DHꢀ, DSꢀ and DGꢀ were calculated by using stan-
dard formula for propagation, see the Supporting Information for details).
the more shielded are the NH protons. Hence, we have as-
cribed the shielding effect of these protons to reduced distor-
tion modes of the macrocycle upon lowering of the tempera-
ture. In contrast, the line shapes do not show a linear depend-
ence on cooling, but bear witness to changes in the porphyrin
environment associated with a dynamic process. Upon cooling
to around 220–230 K, a strong narrowing of the NH proton
signal is observed for both S0 and S1 that is associated with
a reduced rate of NH proton migration (tautomerism process).
Atropisomerisation of S2 and S3
In contrast with the more constrained trans-strapped bridge(s)
of porphyrins S0, S1 and S4, for which the “flip-flap” motion(s)
*
Figure 12. Temperature-dependence of A,B) the chemical shift (dNH) and C,D) the FWHM of the NH proton signal (left: S0; right: S1; : experimental values;
solid lines: linear fitting curves; r=correlation coefficients.
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is sterically fully hindered (at least up to 1248C), the more flexi-
ble cis-linked straps in S2 and S3 allow the interconversion of
these two atropisomers upon heating as a result of the simul-
taneous rotation of the two strapped phenoxy groups of one
bridge around the porphyrin core. This atropisomerisation pro-
cess was studied in toluene by heating solutions of isomerical-
ly pure samples of S2 or S3 at 75 or 1108C, recording their
1H NMR spectra at room temperature before and after heating
(CDCl3, 300 MHz; Figure 13). After heating S2 (or S3) new sig-
itor accurately the atropisomerisation process in two experi-
ments carried out in parallel. Initially, pure samples of S2 or S3
were heated separately in toluene at 82ꢀ28C. Aliquots were
taken at different intervals of time and analysed directly by
HPLC at room temperature (stationary phase: SiO2, Cosmosil;
mobile phase: toluene). The quantities of S2 (ctS2(%)) and S3
(ctS3(%)) at any time (t) of isomerisation in each experiment
were determined by relative integration of the HPLC chroma-
togram peaks. The results of the two experiments and defini-
tions of the kinetic and thermodynamic terms referred to in
this study are summarised in Figure 14 [Eqs. (1) and (2)]. As-
Figure 14. Overview of the two experiments monitored by HPLC at room
temperature and the associated Equations (1) and (2). Kiso1 and Kiso2 are de-
fined as the thermodynamic equilibrium constants of experiments 1 and 2,
respectively, k23 and k32 are defined as the first-order kinetic rate constants
eq
for the conversion of S2 into S3, and of S3 into S2, respectively, cSn is the
mole fraction of Sn, and [Sn]eq is the concentration of S2 (n=2) or S3 (n=3)
at the thermodynamic equilibrium.
Figure 13. Atropisomerisation of S2 and S3 in hot toluene evidenced by
1H NMR spectroscopy (300 MHz) at 300 K in CDCl3 (b-pyrrolic (b-H) and A-H
proton regions) a) before heating, b) after heating at 758C for 3 h and
suming reversible and first-order reactions[74] for the intercon-
version of two atropisomers of different stability,[78–82] the inte-
grated rate law of the atropisomerisation process led to Equa-
tion (3) (see Figure 15), adapted from the equations previously
reported by Carlier and co-workers for the epimerisation of
diastereoisomers with different configurational stability.[76] As
seen in Figure 16, the plots of ct(%) versus time for the two ex-
periments are perfectly fitted by first-order exponential curves
(decaying or growing) with a non-zero end-point (see the fit-
ting model equation in Figure 15) with the correlation coeffi-
cients r=0.99962 and 0.99968 for experiments 1 and 2, respec-
tively, matching perfectly the integrated rate law. The quanti-
ties of S2 and S3 at thermodynamic equilibrium were extrapo-
~
*
c) after heating at 1108C for 3 h (same after 1.5 h). and denote the sig-
nals of S2 and S3, respectively.
nals appeared in the b-pyrrolic and A-H proton regions of the
1H NMR spectrum corresponding to the formation of the other
(S3 or S2) atropisomer. Upon heating S2 at 758C, the reaction
evolved to give a ratio of S2/S3 of around 3:1 (i.e., ꢁ25% of
starting material) after 3 h, whereas heating S3 under the
same conditions and for the same time led to a ratio of S3/S2
of around 2:1 (i.e., ꢁ33% of the starting material). After heat-
ing either S2 or S3 at reflux in toluene for 1.5 h, the same S2/
S3 ratio of around 2:1 was achieved that did not evolve further
on prolonged heating (3 h). These observations clearly indicate
that upon heating the two atropisomers equilibrate in favour
of the thermodynamically more stable S2 isomer, which recip-
rocally implies that the forward and backward kinetic constants
of isomerisation are not identical.[74–77]
In view of these primary results and observations it can be
anticipated that the interconversion between S2 and S3 is an
intrinsically reversible (intramolecular level) but macroscopical-
ly irreversible and thermodynamically driven process involving
two (achiral) atropisomers of different conformational stability.
We chose HPLC analysis as a known and powerful tool to mon-
Figure 15. Integrated rate law [Eq. (3)] and the fitting model equation. A1,
T1 and y0 are constants, X and y are variables, cSn is the mole fraction of S2
(n=2) or S3 (n=3) at any time (t), at the thermodynamic equilibrium (eq)
and initially (0).
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Figure 16. Analysis and curve fitting of the evolution of mole fractions of S2
and S3 versus isomerisation time. Data points obtained from experiments 1
Figure 18. Curve fitting (linear regression) of plots A–D used for the graphi-
cal determination of the rate constants of atropisomerisation (slope=k). Ex-
~ !
* *
, ) and 2 ( , ), the corresponding exponential fitting (solid lines) and ex-
(
~ !
* *
, ) and 2 ( , ), and the corre-
perimental points from experiments 1 (
trapolated (dashed lines) curves. Correlation coefficients for the fitting:
sponding linear fitting (solid lines) and extrapolated (dashed lines) curves.
Correlation coefficients for the linear fitting: r=0.99971 (A,B) and 0.99980
(C,D)
r=0.99962 and 0.99968 for experiments 1 and 2, respectively.
lated from each fitting curve at infinite time (y0 parameter),
and average values of the two experiments were determined
terconversion S3!S2 takes place almost twice as fast (1.77) as
the interconversion S2!S3 (see Table 3). From the Eyring–Po-
lanyi equation [see Figure 19; Eqs. (8) and (9) in which R is the
gas constant (8.314 JKꢁ1 molꢁ1), h is Planck’s constant (6.626ꢂ
10ꢁ34Js), kB is Boltzmann’s constant (1.381ꢂ10ꢁ23JKꢁ1) and T is
the temperature of isomerisation (355 K)], average values of
the Gibbs free energy of activation for the atropisomerisation
process were calculated to be DGꢀ23 =116.9ꢀ0.8 kJmolꢁ1 and
DGꢀ32 =115.2ꢀ0.7 kJmolꢁ1, in agreement with the value of
1.7ꢀ0.2 kJmolꢁ1 for the difference in the Gibbs free energy of
the two interconversions (DrGS3/S2) calculated by inserting the
thermodynamic equilibrium constant (Keq =[cS2]eq/[cS3]eq) into
eq
eq
as c =64ꢀ2 and c =36ꢀ2%.
S2
S3
To determine readily the k values and simplify the calcula-
tions of errors, we used Equations (4)–(7) (see Figure 17), ob-
tained by combining Equations (1)–(3). By inserting the previ-
ous constants c0, ceq and Kiso into these equations, the rate
constants k23 and k32 could be determined graphically (slope=
k) by linear regression of the corresponding plots A–D of
Figure 18 and the associated marginal errors obtained directly
by the fitting analysis (Dk =Dslope). Average values of k23 =
(4.6ꢀ0.3)ꢂ10ꢁ5sꢁ1 and k32 =[8.1(5)ꢀ0.1(5)]ꢂ10ꢁ5sꢁ1 were ob-
tained from the two experiments, which evidence that the in-
the
Van’t Hoff
equation
[Figure 19, Eq. (10)].
Equations (8)–(10) were de-
rived from the general Eyring–
Polanyi equation and used to
calculate the Gibbs energy of ac-
tivation for the atropisomerisa-
tion processes S2!S3 (DGꢀ23)
and S3!S2 (DGꢀ32). Equation (10)
was derived from the linear
Van’t Hoff equation and used to
calculate the difference in the
Gibbs free energy.
Although activation barriers
for rotation can most often be
easily predicted by computation-
al studies (calculating the poten-
tial energy as a function of the
dihedral angle),[83–86] the phen-
oxy groups in S2 and S3 do not
act as independent entities, but
partially interdependent entities,
because they are connected to
Figure 17. Equations (4)–(7) used for plots A–D in Figure 18 (all terms have been defined previously in Figures 14
and 15).
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Table 3. Thermodynamic, kinetic and activation parameters for the atro-
pisomerisation of S2 and S3 in toluene at 355ꢀ2 K.
Parameters
Expt 1
Expt 2
Average
Relative
error [%][a]
eq
cS2 [%]
62.7ꢀ0.5
64.7ꢀ0.6
64ꢀ2
2.4(5)
4.3
6.1
eq
cS3 [%]
37.3ꢀ0.5
1.68ꢀ0.03
4.90ꢀ0.04
8.25ꢀ0.06
116.8ꢀ0.7
115.2ꢀ0.7
35.3ꢀ0.6
1.83ꢀ0.04
4.39ꢀ0.02
36ꢀ2
[b]
Keq
1.8ꢀ0.1
4.6ꢀ0.3
k23 [10ꢁ5 sꢁ1
k32 [10ꢁ5 sꢁ1
]
]
6.1
8.05ꢀ0.04 8.1(5)ꢀ0.1(5) 1.9
DGꢀ23 [kJmolꢁ1
DGꢀ32 [kJmolꢁ1
]
]
117.1ꢀ0.7 116.9ꢀ0.8
115.3ꢀ0.7 115.2ꢀ0.7
0.70
0.59
11
DrGS3/S2 [kJmolꢁ1
]
ꢁ(1.54ꢀ0.06) ꢁ(1.79ꢀ0.06) ꢁ(1.7ꢀ0.2)
[a] Maximum relative errors on average values. [b] For Keq, see Equa-
tion (10).
Scheme 3. Energy diagram for the atropisomerisation of S2 and S3 at 355 K
energy barriers to rotation. Thus, assuming DGꢀ to be inde-
pendent of the temperature (with DGꢀT =DHꢀꢁTDSꢀ and DSꢀ
ꢂ0) gives DGꢀ ꢂDHꢀ, and the values of DGꢀ of 115.2 and
116.9 kJmolꢁ1 for S2 and S3, respectively, at 355 K should be
roughly the same as those at room temperature, which corre-
sponds to a half-life in the range of months to a year at room
temperature. These high activation energy barriers to rotation
largely exceed the minimum value required to enable atro-
pisomers to be physically separated at a given temperature
Figure 19. Equations (8)–(10).
each other by a strap, which, in addition to the high degree of
freedom of the dodecyl chains, rendered our calculations, so
far, unsuccessful for such predictions. In other words, the (re-
stricted) rotations of the two phenoxy groups of one bridge
are mutually influenced by each other through the long and
flexible strap.
(DG3ꢀ50K =109 kJmolꢁ1, DG3ꢀ00K =93.5 kJmolꢁ1 [92,93]
in agreement
,
with our experimental observations: conformational atro-
pisomers S2 and S3 stable for a long time were easily separa-
ble as isomerically pure compounds at room temperature, and
manipulated and characterised without atropisomerisation on
the laboratory timescale (weeks to a month) and under labora-
tory conditions (temperature range from room temperature to
408C, 408C being the usual temperature of our water bath for
rotary evaporation of sample solutions).
It can be concluded from our experiments that each reaction
evolves irreversibly at the macroscopic level to a thermodynam-
ically driven equilibrium (Keq), imposed by the difference in ac-
tivation Gibbs free energy (DGꢀ) between the two atropisom-
ers of different conformational stability, which reciprocally gov-
erns the rate constants (k23 and k32) of the reversible and first-
order reaction of the atropisomerisation process at the (intra)-
molecular level (microscopic reversibility principle).[73,74] The
energy diagram for the atropisomerisation is depicted in
Scheme 3. Although some significant variations in the entropy
of atropisomerisation processes have been reported for some
cases, for example, in push–pull-type biphenyl atropisomers
(DSꢀ up to ꢁ120 Jmolꢁ1),[85,86] the DSꢀ values of pure dynamic
conformational processes are most often negligible and usually
do not exceed a few Jmolꢁ1, which lies within experimental
error.[84–89] Moreover, considering the same symmetry
number[90] (s=2) for S2 (average C2v) and S3 (average C2h), and
assuming the distortion modes and planarity to be similar for
both porphyrin macrocycles, there is no obvious reason to
expect any significant difference between the entropy energies
of S2 and S3 (although the significant difference in their
dipole moments may influence their entropy and/or enthalpy
through solvation effects).[76,91] It is therefore reasonable to
assume that, in our case, the variation in entropy for the inter-
conversion of the S2 and S3 atropisomers must be at least
negligible with respect to the highly enthalpic-dependent
Conclusion
Five meso-strapped porphyrins (S0–S4) have been synthesised,
characterised and studied in detail by NMR spectroscopy, mass
spectrometry and HPLC. NH tautomerism was evidenced in
free-base porphyrins S0 and S1 by VT NMR experiments, from
which were deduced Gibbs free energies (298 K) of 48ꢀ1 and
55ꢀ3 kJmolꢁ1, respectively. On the other hand, S2 and S3 are
stable atropisomers at room temperature that interconvert
upon heating in favour of the thermodynamically more stable
S2 isomer. This atropisomerisation process was evidenced by
1H NMR spectroscopy and monitored accurately by HPLC upon
heating a toluene solution of each isomer. High energy barriers
of 115.2 (DGꢀS3!S2) and 116.9 kJmolꢁ1 (DGꢀS2!S3) at 355 K were
deduced from these experiments.
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[18] Y. Furusho, T. Kimura, Y. Mizuno, T. Aida, J. Am. Chem. Soc. 1997, 119,
5267–5268.
Experimental Section
1H NMR spectra (300 MHz) were obtained on a Bruker TopSpin AV-
[19] T. Nakamura, H. Ube, M. Shiro, M. Shionoya, Angew. Chem. 2013, 125,
748–751; Angew. Chem. Int. Ed. 2013, 52, 720–723.
[20] L. Baldini, P. Ballester, A. Casnati, R. M. Gomila, C. A. Hunter, F. Sansone,
R. Ungaro, J. Am. Chem. Soc. 2003, 125, 14181–14189.
[21] S. Singh, A. Aggarwal, C. Farley, B. A. Hageman, J. D. Batteas, C. M.
Drain, Chem. Commun. 2011, 47, 7134–7136.
[22] J. Taesch, V. Heitz, F. Topic, K. Rissanen, Chem. Commun. 2012, 48, 5118–
5120.
[23] K. Tashiro, T. Aida, J.-Y. Zheng, K. Kinbara, K. Saigo, S. Sakamoto, K. Ya-
maguchi, J. Am. Chem. Soc. 1999, 121, 9477–9478.
[24] A. Guenet, E. Graf, N. Kyritsakas, M. W. Hosseini, Chem. Eur. J. 2011, 17,
6443–6452.
[25] X. Huang, B. H. Rickman, B. Borhan, N. Berova, K. Nakanishi, J. Am.
Chem. Soc. 1998, 120, 6185–6186.
[26] J. Rosenthal, D. G. Nocera, Acc. Chem. Res. 2007, 40, 543–553.
[27] L. K. Gottwald, E. F. Ullman, Tetrahedron Lett. 1969, 10, 3071–3074.
[28] A. C. Tomꢇ, A. M. S. Silva, I. Alkorta, J. Elguero, J. Porphyrins Phthalocya-
nines 2011, 15, 1–28.
1
300 spectrometer. Variable-temperature H NMR (500 MHz) experi-
ments were performed on a Bruker TopSpin AV-500 spectrometer.
Molecular modellings were performed with the Spartan 10 soft-
ware package for Windows.[94] Minimised geometry-optimised
structures and calculations were performed at the semi-empirical
level (PM6 method). HPLC experiments were performed on an Agi-
lent 1200 infinity LC instrument (stationary phase: SiO2; column:
Agilent Prep-Sil column, 4.6ꢂ250 nm, 5 mm particle size; mobile
phase: 100% toluene (Carlo Erba, HPLC-isocratic grade); flow:
0.5 mLminꢁ1; detector: UV/Vis lamp). Curve fitting, statistics and
data analysis were performed by using the OriginPro 8 software
package for Windows.[95] Chromatographic purifications were per-
formed by using silica gel 60 SDS (particle size: 0.040–0.063 mm).
Analytical TLC was performed by using Merck TLC silica gel 60
F254.
[29] S. Arai, D. Niwa, H. Nishide, S. Takeoka, Org. Lett. 2006, 9, 17–20.
[30] T. Hayashi, T. Asai, F. M. Borgmeier, H. Hokazono, H. Ogoshi, Chem. Eur.
J. 1998, 4, 1266–1274.
[31] J. P. Collman, J. I. Brauman, J. P. Fitzgerald, J. W. Sparapany, J. A. Ibers, J.
Am. Chem. Soc. 1988, 110, 3486–3495.
Acknowledgements
Financial support is acknowledged from the European Union
within the FP7-ENERGY-2012-1 framework, GLOBALSOL project
(Proposal No 309194-2) and the Spanish MEC and MICINN
(CTQ2011-24187/BQU and PRI-PIBUS-2011-1128). We thank
Maite Alonso Pascual (MS), Marꢄa Luz Gallego Adamuz (MS),
and Ana Poveda (VT-NMR) of the Servicio Interdepartamental
de Investigaciꢅn (SIdI) at the Autonoma University of Madrid
for MS, HRMS, and VT NMR experiments as well as helpful dis-
cussions.
[32] J. E. Baldwin, T. Klose, M. Peters, J. Chem. Soc. Chem. Commun. 1976,
881–883.
[33] J. Li, B. C. Noll, A. G. Oliver, C. E. Schulz, W. R. Scheidt, J. Am. Chem. Soc.
2013, 135, 15627–15641.
[34] M. Momenteau, C. A. Reed, Chem. Rev. 1994, 94, 659–698.
[35] R. Popescu, J. L. Mispelter, J. Gallay, L. Mouawad, J. Phys. Chem. B 2005,
109, 2995–3007.
[36] A. Lombardi, F. Nastri, V. Pavone, Chem. Rev. 2001, 101, 3165–3190.
[37] K. Gopalaiah, Chem. Rev. 2013, 113, 3248–3296.
[38] E. Rose, E. Gallo, N. Raoul, L. Bouchꢇ, A. Pille, A. Caselli, O. Lequin, J. Por-
phyrins Phthalocyanines 2010, 14, 646–659.
[39] R. Young, C. K. Chang, J. Am. Chem. Soc. 1985, 107, 898–909.
[40] K. M. Mullen, M. J. Gunter, J. Org. Chem. 2008, 73, 3336–3350.
[41] T. Ikeda, J. M. Lintuluoto, N. Aratani, Z. S. Yoon, D. Kim, A. Osuka, Eur. J.
Org. Chem. 2006, 3193–3204.
Keywords: atropoisomerism
tautomerism · thermodynamics
· kinetics · porphyrinoids ·
[42] J.-B. Giguꢈre, J.-F. Morin, Org. Biomol. Chem. 2012, 10, 1047–1051.
[43] V. Rauch, J. A. Wytko, M. Takahashi, Y. Kikkawa, M. Kanesato, J. Weiss,
Org. Lett. 2012, 14, 1998–2001.
[44] J. Brandel, A. Trabolsi, H. Traboulsi, F. Melin, M. Koepf, J. A. Wytko, M. El-
habiri, J. Weiss, A.-M. Albrecht-Gary, Inorg. Chem. 2009, 48, 3743–3754.
[45] T. Ikeda, M. Asakawa, K. Miyake, M. Goto, T. Shimizu, Langmuir 2008, 24,
12877–12882.
[46] X.-B. Shao, X.-K. Jiang, X. Zhao, C.-X. Zhao, Y. Chen, Z.-T. Li, J. Org. Chem.
2004, 69, 899–907.
[47] F. Eckes, E. Deiters, A. Mꢇtivet, V. Bulach, M. W. Hosseini, Eur. J. Org.
Chem. 2011, 2531–2541.
[48] R. G. E. Coumans, J. A. A. W. Elemans, P. Thordarson, R. J. M. Nolte, A. E.
Rowan, Angew. Chem. 2003, 115, 674–678; Angew. Chem. Int. Ed. 2003,
42, 650–654.
[49] A. E. Rowan, P. P. M. Aarts, K. W. M. Koutstaal, Chem. Commun. 1998,
611–612.
[1] D. M. Guldi, Chem. Soc. Rev. 2002, 31, 22–36.
[2] M. V. Martꢄnez-Dꢄaz, G. de La Torre, T. Torres, Chem. Commun. 2010, 46,
7090–7108.
[3] L.-L. Li, E. W.-G. Diau, Chem. Soc. Rev. 2013, 42, 291–304.
[4] S. Mathew, A. Yella, P. Gao, R. Humphry-Baker, B. F. E. Curchod, N.
Ashari-Astani, I. Tavernelli, U. Rothlisberger, M. K. Nazeeruddin, M. Grꢆt-
zel, Naure Chem. 2014, 6, 242–247.
[5] J. Yang, M.-C. Yoon, H. Yoo, P. Kim, D. Kim, Chem. Soc. Rev. 2012, 41,
4808–4826.
[6] A. K. Burrell, D. L. Officer, P. G. Plieger, D. C. W. Reid, Chem. Rev. 2001,
101, 2751–2796.
[7] E. Iengo, E. Zangrando, E. Alessio, Acc. Chem. Res. 2006, 39, 841–851.
[8] I. Beletskaya, V. S. Tyurin, A. Y. Tsivadze, R. Guilard, C. Stern, Chem. Rev.
2009, 109, 1659–1713.
[9] W. Maes, W. Dehaen, Eur. J. Org. Chem. 2009, 4719–4752.
[10] C. M. Drain, A. Varotto, I. Radivojevic, Chem. Rev. 2009, 109, 1630–1658.
[11] J. H. Fuhrhop, Langmuir 2014, 30, 1–12.
[50] R. W. Wagner, T. E. Johnson, J. S. Lindsey, Tetrahedron 1997, 53, 6755–
6790.
[51] G. Bottari, G. de La Torre, D. M. Guldi, T. Torres, Chem. Rev. 2010, 110,
6768–6816.
[12] F. Sguerra, V. Bulach, M. W. Hosseini, Dalton Trans. 2012, 41, 14683–
14689.
[52] J. S. Lindsey, Acc. Chem. Res. 2010, 43, 300–311.
[53] M. Momenteau, J. Mispelter, B. Loock, E. Bisagni, J. Chem. Soc. Perkin
Trans. 1 1983, 189–196.
[54] B. J. Littler, Y. Ciringh, J. S. Lindsey, J. Org. Chem. 1999, 64, 2864–2872.
[55] C. Krieger, M. Dernbach, G. Voit, T. Carell, H. A. Staab, Chem. Bern 1993,
126, 811–821.
[13] X. Shi, K. M. Barkigia, J. Fajer, C. M. Drain, J. Org. Chem. 2001, 66, 6513–
6522.
[14] H. Ohkawa, A. Takayama, S. Nakajima, H. Nishide, Org. Lett. 2006, 8,
2225–2228.
[15] D. B. Amabilino in Organic Nanomaterials, (Eds. T. Torres, G. Bottari)
Wiley, Hoboken, 2013, pp. 59–77.
[16] S. Yamamoto, H. Iida, E. Yashima, Angew. Chem. 2013, 125, 6987–6991;
Angew. Chem. Int. Ed. 2013, 52, 6849–6853.
[56] J. W. Dirks, G. Underwood, J. C. Matheson, D. Gust, J. Org. Chem. 1979,
44, 2551–2555.
[17] P. Iavicoli, H. Xu, L. N. Feldborg, M. Linares, M. Paradinas, S. Stafstrçm, C.
Ocal, B. Nieto-Ortega, J. Casado, J. T. Lꢅpez Navarrete, R. Lazzaroni, S. D.
Feyter, D. B. Amabilino, J. Am. Chem. Soc. 2010, 132, 9350–9362.
[57] S. S. Eaton, G. R. Eaton, J. Am. Chem. Soc. 1975, 97, 3660–3666.
[58] X. Lu, Y. He, J. Chen, J. Wang, H. Shi, J. Phys. Chem. A 2010, 114, 12731–
12738.
Chem. Eur. J. 2014, 20, 16337 – 16349
www.chemeurj.org
16348
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[59] E. A. Ermilov, B. Bꢉge, S. Jasinski, N. Jux, B. Rçder, J. Chem. Phys. 2009,
[79] B. Paul, G. L. Butterfoss, M. G. Boswell, M. L. Huang, R. Bonneau, C. Wolf,
K. Kirshenbaum, Org. Lett. 2012, 14, 926–929.
130, 134509.
[60] P. Wacker, K. Dahms, M. O. Senge, E. Kleinpeter, J. Org. Chem. 2008, 73,
[80] M. W. Ghosn, C. Wolf, J. Org. Chem. 2011, 76, 3888–3897.
[81] C. Wolf, G. E. Tumambac, J. Phys. Chem. A 2003, 107, 815–817.
[82] J. E. Davoren, M. W. Bundesmann, Q. T. Yan, E. M. Collantes, S. Mente,
D. M. Nason, D. L. Gray, ACS Med. Chem. Lett. 2012, 3, 433–435.
[83] F. Ajamaa, T. M. Figueira Duarte, C. Bourgogne, M. Holler, P. W. Fowler,
J.-F. Nierengarten, Eur. J. Org. Chem. 2005, 3766–3774.
[84] L. Lunazzi, M. Mancinelli, A. Mazzanti, J. Org. Chem. 2007, 72, 5391–
5394.
2182–2190.
´
[61] H. Cybulski, M. Pecul, T. Helgaker, M. Jaszunski, J. Phys. Chem. A 2005,
109, 4162–4171.
[62] H. Garcꢄa-Ortega, J. Crusats, M. Feliz, J. M. Ribꢅ, J. Org. Chem. 2002, 67,
4170–4176.
[63] J. Braun, H.-H. Limbach, P. G. Williams, H. Morimoto, D. E. Wemmer, J.
Am. Chem. Soc. 1996, 118, 7231–7232.
[64] A. Ghosh, T. Wondimagegn, H. J. Nilsen, J. Phys. Chem. B 1998, 102,
10459–10467.
[65] J. Baker, P. M. Kozlowski, A. A. Jarzecki, P. Pulay, Theor. Chem. Acc. 1997,
97, 59–66.
[66] C. B. Storm, Y. Teklu, E. A. Sokoloski, Ann. N. Y. Acad. Sci. 1973, 206, 631–
640.
[67] P. G. Plieger, A. K. Burrell, G. B. Jameson, D. L. Officer, Dalton Trans. 2004,
319–326.
[85] J. Rotzler, H. Gsellinger, A. Bihlmeier, M. Gantenbein, D. Vonlanthen, D.
Haussinger, W. Klopper, M. Mayor, Org. Biomol. Chem. 2013, 11, 110–
118.
[86] J. Rotzler, H. Gsellinger, M. Neuburger, D. Vonlanthen, D. Haussinger, M.
Mayor, Org. Biomol. Chem. 2011, 9, 86–91.
[87] M. A. Cremonini, L. Lunazzi, G. Placucci, R. Okazaki, G. Yamamoto, J. Am.
Chem. Soc. 1990, 112, 2915–2921.
[88] P. C. H. Lam, P. R. Carlier, J. Org. Chem. 2005, 70, 1530–1538.
[89] L. Lunazzi, M. Mancinelli, A. Mazzanti, J. Org. Chem. 2008, 73, 5354–
5359.
[68] Z. Zhou, X. Zhang, Q. Liu, Z. Yan, C. Lv, G. Long, Inorg. Chem. 2013, 52,
10258–10263.
[69] Z. Zhou, C. Cao, Q. Liu, R. Jiang, Org. Lett. 2010, 12, 1780–1783.
[70] Z. Zhou, Q. Liu, Z. Yan, G. Long, X. Zhang, C. Cao, R. Jiang, Org. Lett.
2013, 15, 606–609.
[71] Z. Zhou, M. Shen, C. Cao, Q. Liu, Z. Yan, Chem. Eur. J. 2012, 18, 7675–
7679.
[90] S.-K. Lin, J. Chem. Inf. Comput. Sci. 1996, 36, 367–376.
[91] N. Deora, P. R. Carlier, J. Org. Chem. 2010, 75, 1061–1069.
[92] G. Bringmann, A. J. Price Mortimer, P. A. Keller, M. J. Gresser, J. Garner, M.
Breuning, Angew. Chem. 2005, 117, 5518–5563; Angew. Chem. Int. Ed.
2005, 44, 5384–5427.
¯
[72] F. P. Gasparro, N. H. Kolodny, J. Chem. Educ. 1977, 54, 258–261.
[73] H. Eyring, Chem. Rev. 1935, 17, 65–77.
[93] M. Oki, Recent Advances in Atropisomerism in Topics in Stereochemistry,
(Eds.: N. L. Allinger, E. L. Eliel, S. H. Wilen), Wiley, Hoboken, 1983; Vol. 14,
[74] K. A. Connors, Chemical Kinetics. The Study of Reaction Rates in Solution,
VCH, Weinheim, 1990, pp. 480.
[75] D. J. Winzor, C. M. Jackson, J. Mol. Recognit. 2006, 19, 389–407.
[76] M. Gao, N. N. Patwardhan, P. R. Carlier, J. Am. Chem. Soc. 2013, 135,
14390–14400.
pp. 1–81.
[94] Spartan 10, Wavefunction Inc. (Irvine, CA, USA), 1991–2011.
[95] OriginPro 8, OriginLab Corporation (Northampton, MA, USA), 1991–
2007.
[77] P. Beak, D. R. Anderson, M. D. Curtis, J. M. Laumer, D. J. Pippel, G. A. Wei-
senburger, Acc. Chem. Res. 2000, 33, 715–727.
[78] J. Clayden, S. P. Fletcher, J. J. W. McDouall, S. J. M. Rowbottom, J. Am.
Chem. Soc. 2009, 131, 5331–5343.
Received: June 9, 2014
Published online on October 15, 2014
Chem. Eur. J. 2014, 20, 16337 – 16349
www.chemeurj.org
16349
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