Preparation of Carbodiimides with One-Handed Axial Chirality

Article abstract of DOI:10.1021/jacs.8b08969

The axial chirality of carbodiimide was proposed in 1932, but the synthesis of carbodiimide with one-handed axial chirality has not been achieved because of the low barrier of racemization. This work presents a strategy to use a conformationally restrained cyclic structure for creating carbodiimides whose biases of the axial chirality (labeled as S_NCN/R_NCN) are higher than 100:1, as determined by vibrational circular dichroism spectroscopy and density functional theory calculations.

Full text of DOI:10.1021/jacs.8b08969

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Preparation of Carbodiimides with One-Handed Axial Chirality
Tohru Taniguchi, Takahiro Suzuki, Haruka Satoh, Yukatsu Shichibu, Katsuaki Konishi, and Kenji Monde
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Tohru Taniguchi,* Takahiro Suzuki, Haruka Satoh, Yukatsu Shichibu, Katsuaki Konishi, Kenji
Monde*
,
†
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Frontier Research Center for Advanced Material and Life Science, Faculty of Advanced Life Science, and Graduate School
of Life Science, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan
§Faculty of Environmental Earth Science, Hokkaido University, Kita 10 Nishi 5, Sapporo 060-0810, Japan
Supporting Information Placeholder
performed an extensive computational study on car-
bodiimides with various ring sizes. Both studies sug-
gested little influence of the ring structures on the isom-
erization barriers. Although a few reports claimed isola-
tions of chiral carbodiimides, their validity has been
questioned by other studies. Thus, creation of a car-
bodiimide with one-handed axial chirality, which should
open up a new research field involving chiral car-
bodiimides, remains to be accomplished.
ABSTRACT: The axial chirality of carbodiimide was pro-
posed in 1932, but the synthesis of carbodiimide with
one-handed axial chirality has not been achieved because
of the low barrier of racemization. This work presents a
strategy to use a conformationally-restrained cyclic struc-
ture for creating carbodiimides whose biases of the axial
chirality (labeled as SNCN/RNCN) are higher than 100:1, as
determined by vibrational circular dichroism spectros-
copy and density functional theory calculations.
6
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6
-8
Carbodiimide (R−N=C=N−R) is an important class of
molecules in life science for its reactivity to form amide
and ester linkages and in polymer science for its utility as
1
monomers for polycarbodiimide synthesis. Despite the
daily use of carbodiimides worldwide, little is known
about the nature of their axial chirality analogous to the
chirality of allenes (C=C=C). Axially chiral allenes were
predicted to exist by van’t Hoff in 1875 and were first
obtained in 1935, which led to the development of broad
research areas such as asymmetric synthesis and drug de-
velopment. In contrast, since the first proposal of the
possibility of optically active carbodiimides by Roll and
Adams in 1932, no studies have been considered suc-
2
3
4
Figure 1. Studies on the axial chirality of carbodiimides.
Both (A) acyclic carbodiimides and (B) cyclic carbodiimides
exist as inseparable racemic mixture. (C) Acyclic car-
bodiimides with chiral substituents were studied in our pre-
liminary study. See the Supporting Information for details.
(D) Carbodiimides with conformational restraint.
5
cessful in obtaining carbodiimides with one-handed axial
6
chirality.
Access to axially chiral carbodiimides has been ham-
pered by the low barrier of racemization. In 1970, Anet et
al. performed a low-temperature NMR measurement of
diisopropylcarbodiimide down to −150 °C and estimated
In an initial attempt at enriching the axial chirality of
carbodiimide (labeled as SNCN/RNCN), we have synthe-
sized several acyclic carbodiimides with chiral substitu-
ents (Figure 1C). The SNCN : RNCN ratios of prepared car-
bodiimides were studied by vibrational circular dichroism
VCD) spectroscopy in combination with density func-
tional theory (DFT) calculations. As VCD spectroscopy
detects all the structural isomers that interconvert slower
7
the barrier height to be ca. 7 kcal/mol (Figure 1A). Sim-
ilar values were proposed using intermediate neglect of
differential overlap method for H−N=C=N−H by Gordon
and Fischer in 1968 and for dimethylcarbodiimide by
Williams and Damrauer in 1969 and 1971. These values
are much lower than a threshold for isolability of stereoi-
(
8
12
than a picosecond, it enabled us to analyze the diastere-
omeric ratio of chiral acyclic carbodiimides. However,
none of the prepared acyclic carbodiimides showed a high
9
somers at room temperature (ca. 20 kcal/mol). Damrauer
and co-workers later experimentally studied a 9-mem-
bered cyclic carbodiimide 1 (Figure 1B),10 and recently
S
NCN : RNCN ratio, with the highest value being 4:1, and
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thus we have abandoned our initial approach using acy- angles are deviated from the values predicted for the most
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clic carbodiimides (Figure S1). Having seen slightly
greater biases in the SNCN : RNCN ratio for bulkier chiral
substituents, we envisioned the possibility to bias the ax-
ial chirality by using steric interactions between two sub-
stituents. To enhance such interactions, we sought to con-
nect two substituents and form carbodiimides with con-
formationally-restrained cyclic structures (Figure 1D).
Here, we report the synthesis and structural analysis of
several cyclic carbodiimides, some of whose SNCN : RNCN
ratio is higher than 100:1.
stable conformers of dimethylcarbodiimide (±96.0°)
(Figure S2). Importantly, (Snap)-(SNCN)-2 was 4.3 kcal/mol
15
more stable than (Snap)-(RNCN)-2, which corresponds to
a SNCN : RNCN ratio of approximately 1000:1. The validity
of the computational results was evaluated by comparison
of the measured VCD/IR spectra of (Snap)-2 and the cal-
culated ones for (Snap)-(SNCN)-2 and (Snap)-(RNCN)-2. Both
(Snap)-(SNCN)-2 and (Snap)-(RNCN)-2 were predicted to
show a strong IR absorption originating from the N=C=N
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stretching vibration at around 2100 cm , with their loca-
-1
tions separated by more than 25 cm (Figure 2b). Signif-
A chiral 1,1′-binaphthyl structure with varied ring sizes
was chosen as a cyclic framework.13 The chirality of
icantly, the signs of the corresponding theoretical VCD
signals were negative for (Snap)-(SNCN)-2 and positive for
binaphthyl and biphenyl units is labeled as Snap/Rnap and
(Snap)-(RNCN)-2. The experimental spectra of (Snap)-2 in
S
2
ph/Rph, respectively. The synthesis of 9-membered (Snap)-
started with the conversion of commercially available
nap)-6 to (Snap)-7 (Scheme 1). Transformation of (Snap)-
into urea (Snap)-9 resulted in low yield (up to 13%), and
CDCl exhibited a sharp IR absorption band associated
3
-1
with a negative VCD signal at 2099 cm (Figure 2c). The
entire VCD pattern observed in the N=C=N stretching re-
gion as well as below 1600 cm closely resembled that
(S
7
-1
subsequent dehydration of (Snap)-9 by TsCl and base was
also inefficient (0-13%). Optimization of the reaction
conditions from (Snap)-7 to (Snap)-2 led to a synthetic path-
way through thiourea (Snap)-8. Treatment of (Snap)-7 with
predicted for (Snap)-(SNCN)-2, with no discernible features
of (Snap)-(RNCN)-2. These results bolstered the predicted
strong bias in the carbodiimide axial chirality. Thus, we
consider 2 as the first carbodiimide whose axial chirality
is virtually one-handed (>100:1). Similar conclusions
were reached when using different levels of theory such
as B3LYP/TZVP, wB97DX/6-311++G(d,p), and
B3LYP/6-311++G(d,p)/PCM (chloroform) (Figure S3).
CS
2
, pyridine, and I and the following removal of hydro-
2
gen sulfide using MsCl afforded (Snap)-2 in a moderate
yield. As (Snap)-2 readily decomposed during reaction and
work-up, it was crucial to quench the reaction immedi-
ately after checking the disappearance of (Snap)-8 on TLC
and purify the product using neutral silica-gel column
chromatography. Starting from (Snap)-1,1′-bi-2-naphthol,
Meanwhile, little preference for carbodiimide chirality
was computationally predicted for (Snap)-3 and (Snap)-4
1
6
(SNCN : RNCN = 3:2 for (Snap)-3, and 1:1 for (Snap)-4). In
1
3-membered (Snap)-3 and 19-membered (Snap)-4 were
14
line with these predictions, a weaker VCD signal was ob-
also synthesized. Enantiomeric (Rnap)-2 and (Rnap)-3
were prepared to validate the VCD results.14
served for (Snap)-3 and no VCD signal was recognized for
-1
(S
nap)-4 at around 2100 cm in CDCl despite the strong
3
Next, DFT calculations and VCD measurement of the
carbodiimides 2-4 were carried out to study the biases in
their axial chirality. DFT optimizations of (Snap)-2 with
varying C11-N1••N1′-C11′ dihedral angle at the
B3LYP/6-311++G(d,p) level found two energy minima
corresponding to (Snap)-(SNCN)-2 (+69.2°) and (Snap)-
IR absorption (Figure 2d and 2e). We concluded that the
flexible linkers in (Snap)-3 and (Snap)-4 reduced stereo-
chemical influences by the chiral binaphthyl on the car-
bodiimide moiety and that the carbodiimide chirality of
(Snap)-2 is effectively regulated by conformational re-
straints.
(RNCN)-2 (−54.5°) geometries (Figure 2a). Both dihedral
Scheme 1. Synthesis of (Snap)-2, (Snap)-3, and (Snap)-4
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tions), and was 7.4 kcal/mol less stable than the most sta-
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ble SNCN state (Figure 2a). This barrier height is compara-
ble with that calculated for dimethylcarbodiimide (Figure
S2) and those previously estimated for acyclic and cyclic
6a,7,8,10
carbodiimides.
Thus, we concluded that the confor-
mational restraints of (Snap)-2 excluded inversion and
trans-rotation mechanisms but did not elevate the barrier.
These results also suggested that the experimentally de-
tected single-handedness of the carbodiimide unit of
(
S
nap)-2 is thermodynamically but not kinetically regu-
lated.
Interestingly, (Snap)-4 in DMSO and DMF exhibited a
moderately strong VCD signal with little changes in the
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corresponding IR absorption at 2132 cm (Figure 2e).
Meanwhile, rigid (Snap)-2 in DMSO showed only minor
-1
changes in the VCD band at 2099 cm (Figure S4). These
results pointed out that the solvent-induced VCD signal
of (Snap)-4 was due to the changes in the equilibrium be-
1
8
tween SNCN and RNCN states. To our knowledge, this is
the first example where the axial chirality of a car-
bodiimide is altered by external stimuli. With more elab-
orate molecular design, N=C=N group should find vari-
19
ous usages such as a mobile unit for molecular machines
and a chiroptical ON/OFF switch.
1
3e,20
Intrigued to construct a carbodiimide with one-handed
axial chirality from achiral building blocks instead of chi-
ral ones, we then studied structurally-related 5. Simpler
structure of 5 should also be useful for future studies cor-
relating the reactivity and structure of carbodiimides.
Synthesis of 5 has been described in only one report,
which performed neither stereostructural analysis nor en-
2
1
antioseparation. We synthesized 5 from achiral 10 using
a similar procedure to that for (Snap)-2 (Figure 3a). Grati-
fyingly, chiral HPLC (Chiralpak IC column, Daicel) us-
Figure 2. (a) Calculated energies and geometries for (Snap)-
NCN)-2, (Snap)-(RNCN)-2, and the transition state (TS). The
dihedral angle θ is defined as C11-N1••N1′-C11′. The Boltz-
mann populations (P) were calculated at 298 K. The VCD
(
S
ing hexane/EtOAc/Et N eluent resulted in baseline sepa-
3
ration of the first-eluted (R )-5 and second-eluted (S )-5
ph
ph
(Figure S7). No racemization of the biphenyl unit was ob-
served after heating at 70 °C for 1 hour (see Figure S8)
and after storing at rt in EtOAc for 3 months. DFT calcu-
lations and VCD spectroscopy of (Sph)-5 found its stereo-
chemical properties to be comparable to those of (Snap)-2.
Namely, (Sph)-(SNCN)-5 was predicted to be more stable
(
top) and IR (bottom) spectra of (b) calculated (Snap)-(SNCN)-
(red) and (Snap)-(RNCN)-2 (black), (c) observed (Snap)-2, (d)
observed (Snap)-3, and (e) observed (Snap)-4. The spectra of
2
-
1
(
1
S
nap)-4 in DMSO-h
6
(2200-1900 cm ), DMSO-d
6
(below
-1
-1
900 cm ), and in DMF-h
shown. The calculated VCD spectra below 1600 cm are
magnified for clarity. Calculation conditions:
DFT/B3LYP/6-311++G(d,p). Measurement conditions: c =
7
(2200-1900 cm ) are also
-1
‡
than (Sph)-(RNCN)-5 (∆G 4.3 kcal/mol and ∆G 7.6
1
5
kcal/mol; Figure 3b). The calculated preference for the
SNCN chirality of (Sph)-5 was corroborated by agreement
0
.1 M; l = 50 µm.
between the VCD spectrum observed for (Sph)-5 and the
The isomerization barrier of (Snap)-2 was studied
one simulated for (S )-(SNCN)-5 (Figure 3c and 3d). The
ph
through transition state calculations and intrinsic reaction
coordinate analysis. Three isomerization mechanisms
have been proposed for carbodiimides: cis-rotation, in-
version, and trans-rotation.8 Exploration of each transi-
tion state found cis-rotation to be the only possible isom-
erization pathway for (Snap)-2.17 The identified cis-rota-
tion transition state possessed the C11-N1••N1′-C11′ di-
hedral angle close to zero (−5.9° by B3LYP/6-
(S )-(RNCN)-5 species, on the other hand, was not de-
ph
tected experimentally. Therefore, this study showcased
the utility of a conformationally-restrained structure to
create carbodiimides with highly biased, virtually one-
handed axial chirality from chiral as well as achiral com-
ponents.
,10
Our attempts to crystallize (Snap)-2, (Snap)-3, (Snap)-4,
and (Sph)-5 were not successful. Fortunately, racemic (±)-
311++G(d,p); see Figures S3 for other calculation condi-
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5
formed needle-like crystals from a hexane/EtOAc solu-
Figure 3. (a) Synthesis and enantioseparation of 5. (b) Cal-
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tion. X-ray diffraction analysis revealed its solid-state
structure as a mixture of (Sph)-(SNCN)-5 and (Rph)-(RNCN)-
5
the solution state (Figure 3e). The C7-N1••N1′-C7′ dihe-
dral angle for (Sph)-5 in the crystal (+77.5°) was slightly
different from the DFT-optimized structure (Table S1). Of
note, although the N=C=N angles of various car-
bodiimides are known as nonlinear (~170°),
the crystalline 5 is almost linear (179.6°). This finding
proposed the usefulness of conformational restraints for
regulating not only the carbodiimide chirality but also the
N=C=N angle.
culated energies and geometries for (Sph)-(SNCN)-5, (Sph)-
(RNCN)-5, and the transition state (TS). The dihedral angle θ
is defined as C7-N1••N1′-C7′. The Boltzmann populations
, in line with the stability of SNCN chirality of (Sph)-5 in
(
P) were calculated at 298 K. The VCD spectra of (c) calcu-
lated (Sph)-(SNCN)-5 (red) and (Sph)-(RNCN)-5 (black) and (d)
observed for (Sph)-5 in CDCl . The entire strong peak at ca.
3
-1
2100 cm calculated for (Sph)-(RNCN)-5 is shown in the inset.
Calculation conditions: DFT/B3LYP/6-311++G(d,p). Meas-
urement conditions: c = 0.1 M; l = 50 µm. (e) Molecular
structure of (Sph)-5 in the solid state determined by X-ray
crystallography of (±)-5. Thermal ellipsoids are drawn at the
50% probability level.
6,22
that for
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The existence of a carbodiimide with one-handed axial
chirality has been elusive for more than 85 years. Here,
we present a strategy to obtain such carbodiimides using
conformationally-restrained systems, and have demon-
strated the preparation of (Snap)-2 and (Sph)-5, whose bi-
ases in the carbodiimide chirality are higher than 100:1.
Furthermore, this study observed that the chiral properties
of carbodiimides were modified by external stimuli. The
insight obtained in this work should lead to the prepara-
tion of various carbodiimides such as ones useful for
asymmetric reactions and molecular machines. Just as the
emergence of chiral allenes developed various scientific
fields, we hope this work to ultimately open new research
areas of chiral carbodiimides.
ASSOCIATED CONTENT
Supporting Information. The Supporting Information is
available free of charge on the ACS Publications website.
Procedures for experiment and calculation, synthesis, and
characterization; supporting figures and table; coordinates of
selected calculated geometries (PDF)
Crystallographic data for 5 (CIF)
AUTHOR INFORMATION
Corresponding Author
*
E-mail: ttaniguchi@sci.hokudai.ac.jp
* E-mail: kmonde@sci.hokudai.ac.jp
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Low-temperature NMR measurements were performed at
High-Resolution NMR Laboratory, Faculty of Science, Hok-
kaido University. This work was supported by JSPS
KAKENHI Grant Nos. JP26702034, JP15H03111 and
JP18H02093.
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(
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(
(
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(
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Isomerization Mechanism of Diazacumulenes. J. Am. Chem.
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Theoret. Chim. Acta 1971, 23, 195-202.
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(14) See Supporting Information.
(15) The energy differences between SNCN and RNCN diastereomers
are virtually unchanged when ∆E, not ∆G, is used (4.1 kcal/mol
(
(
for (Snap)-2 and 4.6 kcal/mol for (S )-5).
ph
(16) Unexpectedly, both (Snap)-(SNCN)-3 and (Snap)-(RNCN)-3 were
predicted to show a negative induced VCD signal at around 2100
-1
cm , which hampered the analysis of its S
NCN
: RNCN ratio
through VCD spectroscopy (Figure S5).
1
317.
(17) Due to the conformational restraints by the binaphthyl unit and
the small ring size, no geometries amenable to DFT structural
optimization were obtained for trans-rotation (θ close to 180°)
and for inversion transition states.
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(
11) (a) Schlögl, K.; Mechter, M. An Optically Active
Carbodiimide. Angew. Chem. Int. Ed. 1966, 5, 596. (b) Červinka,
O.; Dudek, V.; Senft, V. Optically active (R,S,aS)-(+)-N,N′-
bis(α-phenylethyl)carbodiimide. Collect. Czech. Chem.
Commun. 1978, 43, 1087-1090. (c) Červinka, O.; Dudek, V.;
(18) In accordance with the low racemization barrier of car-
bodiimide, no meaningful signal broadening informative for
1
Štíhel,
heptamethylenecarbodiimide. Collect. Czech. Chem. Commun.
979, 44, 2843-2845.
Z.;
Zikmund,
J.
Optically
active
S
NCN : RNCN ratio was observed by the low-temperature H NMR
3
measurement of (Snap)-4 in CDCl above its freezing point (Fig-
ure S6).
1
(
12) (a) He, Y.; Wang, B.; Dukor, R. K.; Nafie, L. A. Determination
of Absolute Configuration of Chiral Molecules Using
Vibrational Optical Activity: A Review. Appl. Spectrosc. 2011,
(19) (a) Kaseem, S.; van Leeuwen, T.; Lubbe, A. S.; Wilson, M. R.;
Feringa, B. L.; Leigh, D. A. Artificial molecular motors. Chem.
Soc. Rev. 2017, 46, 2592-2621. (b) Leigh, D. A.; Marcos, V.;
Nalbantoglu, T.; Vitorica-Yrezabal, I. J.; Yasar, F. T.; Zhu, X.
Pyridyl-Acyl Hydrazone Rotaxanes and Molecular Shuttles. J.
Am. Chem. Soc. 2017, 139, 7104-7109.
(20) (a) Anger, E.; Srebro, M.; Vanthuyne, N.; Toupet, L.; Rigaut,
S.; Roussel, C.; Autschbach, J.; Crassous, J.; Reau, R. Ruthe-
nium-Vinylhelicenes: Remote Metal-Based Enhancement and
Redox Switching of the Chiroptical Properties of a Helicene
Core. J. Am. Chem. Soc. 2012, 134, 15628-15631. (b) Nishi-
kawa, T.; Nagata, Y.; Suginome, M. Poly(quinoxaline-2,3-diyl)
as a Multifunctional Chiral Scaffold for Circularly Polarized Lu-
minescent Materials: Color Tuning, Energy Transfer, and
Switching of the CPL Handedness. ACS Macro Lett. 2017, 6,
431-435.
6
5, 699-723. (b) Nafie, L. A. Vibrational Optical Activity:
Principles and Applications; Wiley: Chichester, 2011. (c)
Stephens, P. J.; Devlin, F. J.; Cheeseman, J. R. VCD
Spectroscopy for Organic Chemists; CRC Press: Boca Raton,
2012. (d) Taniguchi, T. Analysis of Molecular Configuration and
Conformation by Electronic and Vibrational Circular Dichroism:
Theoretical Calculation and Exciton Chirality Method. Bull.
Chem. Soc. Jpn. 2017, 90, 1005-1016. (e) Taniguchi, T.; Monde,
K. Exciton Chirality Method in Vibrational Circular Dichroism.
J. Am. Chem. Soc. 2012, 134, 3695-3698. (f) Taniguchi, T.;
Nakano, K.; Baba, R.; Monde, K. Analysis of Configuration and
Conformation of Furanose Ring in Carbohydrate and Nucleoside
by Vibrational Circular Dichroism. Org. Lett. 2017, 19, 404-407.
13) Binaphthalenes have been utilized to control the axial chirality
of an attached moiety such as biphenyl and bipyridyl units. See:
(a) Becker, J. J.; White, P. S.; Gagné, M. R. Asymmetric Catal-
ysis with the Normally Unresolvable, Conformationally Dy-
namic 2,2′-Bis(diphenylphosphino)-1,1′-biphenyl (Biphep). J.
Am. Chem. Soc. 2001, 123, 9478-9479. (b) Shimada, T.; Kina,
A.; Hayashi, T. A New Synthetic Route to Enantiomerically Pure
Axially Chiral 2,2′-Bipyridine N,N′-Dioxides. Highly Efficient
Catalysts for Asymmetric Allylation of Aldehydes with Allyl(tri-
chloro)silanes. J. Org. Chem. 2003, 68, 6329-6337. (c) Mikami,
K.; Kataoka, S.; Yusa, Y.; Aikawa, K. Racemic but Tropos (Chi-
rally Flexible) BIPHEP Ligands for Rh(I)-Complexes:ꢀ Highly
Enantioselective Ene-Type Cyclization of 1,6-Enynes. Org. Lett.
2004, 6, 3699-3701. (d) Takaishi, K.; Suzuki, J.; Yabe, T.; As-
ano, H.; Nishikawa, M.; Hashizume, D.; Muranaka, A.;
Uchiyama, M.; Yokoyama, A. Conformational and Optical
Characteristics of Unidirectionally Twisted Binaphthyl-Bi-
(
(21) Hiatt, R. R.; Shaio, M.-J.; Georges, F. Synthesis of an Unusual
Carbodiimide. J. Org. Chem. 1979, 44, 3265-3266.
(22) (a) Molina, P.; Alajarín, M.; Sánchez-Andrada, P. Synthesis
and Nuclear Magnetic Resonance Study of 1,3-Diazacyclonona-
l,2-diene: An Unusual Carbodiimide. J. Org. Chem. 1996, 61,
4289-4299. (b) Schmittel, M.; Steffen, J.-P.; Rodríguez, D.;
2
6
Engelen, B.; Neumann, E.; Cinar, M. E. Thermal C -C Cycliza-
tion of Enyne-Carbodiimides:ꢀ Experimental Evidence Contra-
dicts a Diradical and Suggests a Carbene Intermediate. J. Org.
Chem. 2008, 73, 3005-3016. (c) Kulikov, O. V.; Siriwardane, D.
A.; McCandless, G. T.; Barnes, C.; Sevryugina, Y. V.; DeSousa,
J. D.; Wu, J.; Sommer, R.; Novak, B. M. Self-Assembly of n-
Alkyl- and Aryl-Side Chain Ureas and Their Derivatives as Evi-
denced by SEM and X-ray Analysis. Eur. J. Org. Chem. 2015,
7511-7518.
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Figure 1. Studies on the axial chirality of carbodiimides. Both (A) acyclic carbodiimides and (B) cyclic
carbodiimides exist as inseparable racemic mixture. (C) Acyclic carbodiimides with chiral substituents were
studied in our preliminary study. See the Supporting Information for details. (D) Carbodiimides with
conformational restraint.
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Figure 2. (a) Calculated energies and geometries for (Snap)-(SNCN)-2, (Snap)-(RNCN)-2, and the transition
state (TS). The dihedral angle θ is defined as C11-N1••N1′-C11′. The Boltzmann populations (P) were
calculated at 298 K. The VCD (top) and IR (bottom) spectra of (b) calculated (Snap)-(SNCN)-2 (red) and
(Snap)-(RNCN)-2 (black), (c) observed (Snap)-2, (d) observed (Snap)-3, and (e) observed (Snap)-4. The
spectra of (Snap)-4 in DMSO-h6 (2200-1900 cm-1), DMSO-d6 (below 1900 cm-1), and in DMF-h7 (2200-1900
cm-1) are also shown. The calculated VCD spectra below 1600 cm-1 are magnified for clarity. Calculation
conditions: DFT/B3LYP/6-311++G(d,p). Measurement conditions: c = 0.1 M; l = 50 μm.
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Figure 3. (a) Synthesis and enantioseparation of 5. (b) Calculated energies and geometries for (Sph)-
SNCN)-5, (Sph)-(RNCN)-5, and the transition state (TS). The dihedral angle θ is defined as C7-N1••N1′-C7′.
(
The Boltzmann populations (P) were calculated at 298 K. The VCD spectra of (c) calculated (Sph)-(SNCN)-5
(
red) and (Sph)-(RNCN)-5 (black) and (d) observed for (Sph)-5 in CDCl . The entire strong peak at ca. 2100
3
cm-1 calculated for (Sph)-(RNCN)-5 is shown in the inset. Calculation conditions: DFT/B3LYP/6-311++G(d,p).
Measurement conditions: c = 0.1 M; l = 50 μm. (e) Molecular structure of (Sph)-5 in the solid state
determined by X-ray crystallography of (±)-5. Thermal ellipsoids are drawn at the 50% probability level.
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Synthesis of (Snap)-2, (Snap)-3, and (Snap)-4
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