Synchronous enantiomeric enrichment of both reactant and product by absolute asymmetric synthesis using circularly polarized light. Part 1. Theoretical and experimental verification of the asymmetric photoisomerization of methyl norbornadiene-2-carboxylate to methyl quadricyclane-1-carboxylate

Article abstract of DOI:10.1039/b100751n

We propose a new absolute asymmetric synthesis (NAAS), in which the irradiation with left- or right-handed circularly polarized light (CPL) of a racemic reactant leads to the synchronous enantiomeric enrichment of both reactant and product. NAAS has two subcategories: (a) reversible NAAS (CPL excites both the reactant and the product), (b) irreversible NAAS (only the reactant is excited by CPL). Here in the first paper of this series of papers we consider irreversible NAAS. We have deduced the theoretical equations that determine the relationship between the enantiomeric excesses (ee's) of both reactant and product and the progress of the CPL-induced photoreaction. Using the clear and reversible photoisomerization of chiral methyl norbornadiene-2-carboxylate (I) to chiral methyl quadricyclane-1-carboxylate (II) by CPL-irradiation in acetonitrile, we experimentally verified the equations. The ee's of both reactant and product are remarkably dependent on the anisotropy factor (g = Δε/ε) of the reactant. The ee of the reactant increases to 100% if the irradiation is continued to the stage that nearly all of the reactant is consumed. Conversely, the ee of the product gradually decreases from g/2 during the initial stages to zero at the final stage of the irradiation. This is the first time that the relationship between the ee of product and the progress of the photoreaction is experimentally examined based upon theoretical considerations.

Full text of DOI:10.1039/b100751n

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Synchronous enantiomeric enrichment of both reactant and
product by absolute asymmetric synthesis using circularly polarized
1
light. Part 1. Theoretical and experimental verification of the
asymmetric photoisomerization of methyl norbornadiene-2-
carboxylate to methyl quadricyclane-1-carboxylate†
2
Hideo Nishino, Asao Nakamura and Yoshihisa Inoue*
Inoue Photochirogenesis Project, ERATO, JST, 4-6-3 Kamishinden, Toyonaka, 560-0085, Japan
Received (in Cambridge, UK) 22nd January 2001, Accepted 21st June 2001
First published as an Advance Article on the web 14th August 2001
We propose a new absolute asymmetric synthesis (NAAS), in which the irradiation with left- or right-handed
circularly polarized light (CPL) of a racemic reactant leads to the synchronous enantiomeric enrichment of both
reactant and product. NAAS has two subcategories: (a) reversible NAAS (CPL excites both the reactant and the
product), (b) irreversible NAAS (only the reactant is excited by CPL). Here in the first paper of this series of papers
we consider irreversible NAAS. We have deduced the theoretical equations that determine the relationship between
the enantiomeric excesses (ee’s) of both reactant and product and the progress of the CPL-induced photoreaction.
Using the clear and reversible photoisomerization of chiral methyl norbornadiene-2-carboxylate (I) to chiral methyl
quadricyclane-1-carboxylate (II) by CPL-irradiation in acetonitrile, we experimentally verified the equations. The ee’s
of both reactant and product are remarkably dependent on the anisotropy factor (g = ∆ε/ε) of the reactant. The ee of
the reactant increases to 100% if the irradiation is continued to the stage that nearly all of the reactant is consumed.
Conversely, the ee of the product gradually decreases from g/2 during the initial stages to zero at the final stage of the
irradiation. This is the first time that the relationship between the ee of product and the progress of the photoreaction
is experimentally examined based upon theoretical considerations.
The asymmetric synthesis of chiral compounds has become
important in modern chemistry, as optically pure compounds
are among other things, biologically active, playing vital roles in
pharmacological and agrochemical processes. Many attempts
have been made to obtain optically active materials using cir-
2
3
cularly polarized light since le Bel and van’t Hoff recognized
the potential usefulness of left- and right-handed circularly
polarized light (l- and r-CPL) in the late 19th century. Using
CPL to obtain optically active materials is a type of “absolute
asymmetric synthesis,” wherein asymmetric induction is brought
about through preferential excitation of one of the enantiomers
in a racemic mixture using l- or r-CPL irradiation. The degree
of preferential excitation is determined by the anisotropy
Scheme 1 Asymmetric photodestruction.
which is less able to absorb the l- or r-CPL undergoes lower
photodestuction, thus increasing the ee of this reactant, as
the antipode is preferentially destroyed to achiral product(s).
In this type of AAS, the photochemical process is irreversible,
and the enantiomers do not interconvert. There have been
4,5
factor, also known as the g factor, which was defined by Kuhn
7
as the normalized difference in molar extinction coefficients
between optical isomers toward l- or r-CPL at a given
wavelength, eqn. (1), where ε and ε are the molar extinction
many reports concerning asymmetric photodestruction, typ-
ical examples being the photodestructions of camphor and
11
R
S
trans-bicyclo[4.3.0]nonan-8-one.
Kagan provides us with a theoretical examination of the
evolution of the ee by photodestruction of a racemic sample
g = |ε Ϫ ε |/ε
(1)
R
S
6,12
using l- or r-CPL.
If the photodestruction product is also
coefficients of each enantiomer towards l- or r-CPL,
chiral, the evolution of the optical purity of both the reactant
and the decomposition product is expected to proceed simul-
taneously. However, a theoretical and experimental study of
4–9
ε = (ε ϩ ε )/2 and 0 ≤ g < 2.
R
S
Absolute asymmetric syntheses (AAS) have been classified
into three categories according to the manner of enantio-
differentiation, these being (a) asymmetric photodestruction,
6,12
this scenario has not been performed.
In photochemical deracemization processes,
7–9,12
by defin-
(
b) photochemical deracemization, and (c) photochemical
ition the combined enantiomer concentration does not change
during the photoreaction and the process is photochemically
reversible. The shift of the photochemical equilibrium between
the enantiomers occurs through CPL-induced enantioselective
excitation, as shown in Scheme 2. This is a photoresolution
process, and does not produce a new product. There are some
reports concerning photochemical deracemization processes
7–10
asymmetric fixation.
In asymmetric photodestruction, each
enantiomer in a racemic reactant is destroyed photochemically
according to the degree of preferential excitation by l- and
r-CPL at a given wavelength, Scheme 1. Here the enantiomer
†
Electronic supplementary information (ESI) available: the UV spec-
trum of MCP in acetonitrile. See http://www.rsc.org/suppdata/p2/b1/
13,14
of, for example, transition metal complexes,
and to the
b100751n/
best of our knowledge there are only a few descriptions of
DOI: 10.1039/b100751n
J. Chem. Soc., Perkin Trans. 2, 2001, 1693–1700
This journal is © The Royal Society of Chemistry 2001
1693

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A closer inspection reveals that there are two subcategories
of NAAS, as follows; in class (a) a photochemical equilibrium
between the reactant and the product(s) is established, because
the reaction mixture is irradiated with CPL which is able to
excite both of the components of the reaction (see Scheme 4b).
In class (b), the reactant is excited by the CPL, but the product
is not, thus as it cannot absorb the incident light it is rendered
an irreversible process.
Scheme 2 Asymmetric photoderacemization.
Burnham and Schuster have proposed in a recent paper a
new AAS using the reversible photodestruction of 1,1Ј-
binaphthylpyran.‡ The crucial difference between this AAS
and the AAS proposed in this paper is whether or not the
enantiomers racemize photochemically. In Schuster’s AAS
the enantiomers of the reactant racemize photochemically,
but in our case the enantiomers do not racemize either
photochemically or thermally at ambient temperature. The
theoretical equations reported in the present paper are not
applicable to Schuster’s AAS.
organic compounds which undergo exclusive photoderacemiz-
10,15–17
21
ation.
Indeed, the enantiomeric isomerization of many
18
organic compounds is often accompanied by side reactions.
The photochemical process of asymmetric fixation is very
similar to asymmetric destruction as shown in Scheme 3. Here, a
Norbornadienes and quadricyclanes have been widely
investigated, because the photoisomerization of norbornadiene
to quadricyclane has a potential application as a solar energy
22–25
storage system.
Quadricyclane is a highly strained
cyclopropane–cyclobutane-fused compound, which can be
prepared photochemically via an intramolecular [2 ϩ 2]
cycloaddition of excited norbornadiene. The reverse reaction is
also possible with photolysis or thermolysis of quadricyclane
Scheme 3 Photochemical asymmetric fixation.
thermal racemization of the reactants occurs, and an enantio-
selective photoreaction, induced by l- or r-CPL, then leads to
22,26–28
7
leading to the recovery of norbornadiene.
The inter-
optically active products. When the thermal racemization of
conversions of some norbornadiene and quadricyclane deriv-
atives are reported not to be accompanied by side reactions, and
the reactant is absent, this becomes an asymmetric photo-
destruction process. The R/S ratio of the product is equal to
the ratio of the molar extinction coefficients, ε /ε . There are
22,27
quadricyclanes are thermally stable at ambient temperature.
R
S
The asymmetric introduction of substituents renders the
norbornadiene–quadricyclane system chiral, and thus, photo-
isomerization between chiral norbornadiene and quadricyclane
using CPL irradiation should behave as an example of our
proposed NAAS.
a few examples of photochemical asymmetric fixation, with
the oxidative photocyclization of 1-(2-benzo[c]phenanthryl)-
2
-phenylethylene to hexahelicene, via dihydrohexahelicene,
and the photocyclization/hydrogen migration of N-methyl-N-
arylenamines to N-methyldihydroindoles in this category of
19,20
Curiously it has rarely been recognised that norbornadienes
and quadricyclanes will have chiral properties when appro-
priately substituted, and the chiroptical properties of only a few
AAS.
In this paper, we propose a new absolute asymmetric syn-
thesis (NAAS) induced by CPL as shown in Scheme 4, in which
29,30
chiral norbornadiene derivatives have been reported.
To the
best of our knowledge, no optical resolution of chiral quadri-
cyclane derivatives has to-date been reported. Moreover, no
systematic investigations have been performed on the photo-
chemical conversion between such chiral norbornadienes and
quadricyclanes, and thus, the stereochemical consequences of
such a photocyclization are not yet known.
In this study, the theoretical equations are formulated for the
relationship between the reactant and product ee’s and the
conversion in the class (b) NASS, i.e. the one-way photo-
isomerization of a norbornadiene derivative to the correspond-
ing quadricyclane. Thus, the chiroptical properties of methyl
norbornadiene-2-carboxylate (I) and methyl quadricyclane-1-
carboxylate (II) are reported, as are the stereochemical con-
sequences of the photocylization of I to II. This is followed by
details of the CPL induced isomerization of I to II (Scheme 5),
Scheme 4 Reversible (a) and irreversible (b) new absolute asymmetric
synthesis (NAAS), where both reactant and product are chiral.
Scheme 5 Photoisomerization of I to II.
and discussion concerning the relationship between the ee of
I and the conversion, and as well as the relationship between the
ee of II and the conversion. This is the first report in which the
focus is on the theoretical formulation of the relationship
between the ee of the product and the conversion.
the reactant is chiral and the product is also chiral. The reactant
and the product are photochemically interconvertible, and the
enantiomers do not racemize either photochemically or ther-
mally at ambient temperature. The product is not the stereo-
isomer of the reactant. This renders the NAAS different from
all previously described absolute asymmetric syntheses. It is
predicted that enantiomeric enrichment will occur in both the
reactant and the product.
‡
The IUPAC name for 1,1-binaphthylpyran is 4H-benzo[f]naphtho-
[2,1-c]chromene.
1
694
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Results and discussion
Theoretical treatment
The relationship between the ee of the reactant and the conver-
sion. The relationship between the ee of the remaining reactant,
y, and the extent of the reaction, x, is described by the following
equations [eqn. (2)–eqn. (4)], which were originally introduced
(
2)
(
(
3)
4)
6,12
by Kagan et al. for asymmetric destruction,
where cR and
cS are the concentrations of (R)- and (S)- isomers of the react-
ant, respectively, cR0 and cS0 are the initial concentrations of
the reactant isomers, and g is the anisotropic factor of the
remaining reactant defined by eqn. (1).
The sign of g is naturally dependent on the helical sense of
the CPL employed for excitation. Eqn. (2) is described for the
excitation by r-CPL. If one uses l-CPL for excitation, g should
be replaced by Ϫg.
Fig. 1 (a) Simulated relationship between the ee of the remaining
Eqn. (2) is based on the assumption that the consumption
rate for each enantiomer of the reactant is proportional to ε
for the CPL excitation. This assumption can be justified, if the
absorbance of the solution is so low that the % absorption for
the solution is nearly proportional to the concentration. (See
Appendix 1 for details.)
Fig. 1a shows the dependence of the ee of the reactant on
the conversion x upon CPL irradiation. The ee curves were
calculated for reactants with various g factors using eqn. (3). In
all cases, the ee of the reactant approaches 100% during the
final stages of the reaction. Thus, I irradiated with l- or r-CPL
at 290 nm, should ultimately obtain 100% ee of (ϩ)- and (Ϫ)-I,
respectively.
reactant and the conversion according to the reactant’s g factor at the
CPL irradiation wavelength. (b) Simulated relationship between the ee
of the product and the conversion according to the reactant g factor at
the CPL irradiation wavelength.
verified by the limiting value of yЈ as x→0 [eqn. (7)]. (See
Appendix 2 for details.)
(7)
Kagan et al. expected that the ee of the product should be g/2
6
during the initial stages of the CPL induced photodestruction.
Relationship between the ee of product and the conversion. The
ee for the product, yЈ, is expressed in terms of y and x in eqns.
However, the dependence of yЈ on x has not been described in
the literature.
(
5) and (6), if the photocyclization is not accompanied by
Fig. 1b also shows that, when the g factor is larger, the ee of
the product falls sharply at the 50% conversion point, whereas a
smaller g factor results in a decrease in ee only at the very final
stage of the reaction, albeit that the initial ee is lower for smaller
g factors.
Experimental verification
(
(
5)
6)
Chiroptical properties of I and II. The chiroptical properties
of I and II, i.e. the CD and UV spectra and the g factor derived
from these spectra, are shown in Fig. 2. All of the UV and CD
2
0
spectra were measured in acetonitrile. Specific rotations ([α]
D
)
were also measured: (Ϫ)-I, Ϫ41.55 (c 0.0624 in acetonitrile),
(
ϩ)-II, 322 (c 0.00375 in acetonitrile).§
Fig. 2a shows two absorption maxima at 229.5 nm and
around 265 nm in the UV spectrum of (±)-I, although norbor-
nadiene and methyl acrylate, which may be regarded as model
racemization or side reactions, where the notation RЈ and SЈ is
used for the products of R and S in terms of reactant.
compounds for I, do not have any absorption bands beyond
Fig. 1b shows the dependence of the product’s ee on the
conversion upon irradiation. The ee values were calculated
for various reactants with differing g factors, putting them
into eqn. (6), using the values of x and y which were calculated
with eqn. (2). This simulation demonstrates that the ee of
the product is g/2 during the initial stages of the reaction,
ultimately approaching zero over the final stages. This is also
31,32
2
2
50 nm.
(ϩ)-I and (Ϫ)-I show bisigned CD spectra over the
00–340 nm region (Fig. 2c). The g factors for (ϩ)-I and (Ϫ)-I
also exhibit two extrema in this region (Fig. 2e), indicating that
the broad absorption in this region is composed of two bands.
Ϫ1
2
Ϫ1
§ [α]D Values are given in units of 10 deg cm g
.
J. Chem. Soc., Perkin Trans. 2, 2001, 1693–1700
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Fig. 4 UV spectral changes of the acetonitrile solution of racemic I
0.261 mM) irradiated with l-CPL for 0 min (solid line), 60 min (broken
line), 90 min (short and long broken line), 105 min (short broken line),
00 min (short and dot line), 340 min (dot line) at 290 nm.
(
2
Fig. 2 Chiroptical properties of (ϩ)- and (Ϫ)-I and (ϩ)- and (Ϫ)-II in
acetonitrile. These CD data are corrected to 100% enantiomeric excess
using the results from chiral HPLC analysis.
Fig. 5 Relationship between the % conversion and the irradiation time
upon irradiation of the solutions of racemic I with l-CPL (᭺), r-CPL
(
᭹) and LPL (ꢀ) at 290 nm.
The stereochemical consequence of photocyclization. The
stereochemical consequences of photocyclization of I to II
were examined for (Ϫ)-I using UV and CD spectroscopy, by
irradiating with LPL at 290 nm, a wavelength at which II does
not absorb.
Fig. 3a shows the evolution of the UV spectrum of an
acetonitrile solution of (Ϫ)-I upon irradiation at 290 nm. The
absorption bands for (Ϫ)-I at 228 and 256 nm slowly disappear
and a new band appears at 215 nm, which is similar in shape to
the UV spectrum of II. Two isosbestic points were observed at
2
09 and 218 nm during this irradiation.
Changes in the CD spectra of (Ϫ)-I upon irradiation at
90 nm are shown in Fig. 3b. Here, the CD extrema of (Ϫ)-I at
29 and 271.5 nm gradually diminished and a new extreme
2
2
appeared at 215 nm, accompanied by an isosbestic point at
2
07 nm.
Fig. 3 Stereochemical consequences of photocyclization from (Ϫ)-I to
The changes in the CD and UV spectra are consistent with
(
ϩ)-II in acetonitrile. (a) Changes in the UV spectra when (Ϫ)-I (0.102
the complete photocyclization of (Ϫ)-I to (ϩ)-II carried out at
a wavelength where the product does not absorb the exciting
light.
mM) was irradiated with LPL for 0 min (solid line), 3 min (broken line),
8 min (short and long broken line), 146 min (short broken line) at 290
6
nm. (b) Changes in the CD spectra when (Ϫ)-I (0.0236 mM) was
irradiated with LPL for 0 min (solid line), 70 min (broken line), 105 min
(
short and long broken line), 165 min (short broken line) at 290 nm.
The bold solid lines represent the UV and CD spectra of enantiopure
ϩ)-II.
Asymmetric photoisomerization of racemic I with CPL. As
demonstrated in Fig. 3a, a NAAS was carried out when (±)-I
was irradiated at 290 nm with l-CPL (Fig. 4). The absorption
band at 260 nm weakened in intensity, and two isosbestic points
were observed in the UV spectra at 209 and 218 nm. Similar
changes in the UV spectra were also observed when (±)-I
was irradiated with r-CPL or linearly polarised light (LPL) at
290 nm.
Fig. 5 shows the relationship between the conversion and the
irradiation time for (±)-I, irradiated with l- or r-CPL or LPL at
290 nm. The conversions were determined by the intensities of
the UV absorption at 280 nm where only I absorbs light.
Because all of the points fall on the same time–conversion
(
In contrast, the UV spectrum of (±)-II exhibits only one
absorption maximum at 220 nm, which tails off until 270 nm.
These spectral features are consistent with those of methyl
cyclopropanecarboxylate (MCP), which do not show absorp-
tions above 270 nm. The CD spectra of (ϩ)-II and (Ϫ)-II also
show a maximum at 217.5 nm, as shown in Fig. 1d, and it
appears that the UV and CD absorptions are composed of a
single band. Hence, the anisotropy factor shows an almost flat
profile over the wavelength region.
1
696
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Fig. 6 (a) Typical CD spectral changes upon irradiation at 290 nm of
the acetonitrile solutions of racemic I with l- and r-CPL. (b) The
ultimate CD spectrum obtained upon r-CPL irradiation for 290 min
was simulated by the sum (bold line) of the CD spectra of (ϩ)-I (dashed
line) and (ϩ)-II (solid line).
Fig. 7 Development of the circular dichroism at (a) 280 nm and (b)
45 nm upon irradiation at 290 nm of racemic I in acetonitrile with
l-CPL (᭺), r-CPL (᭹) and LPL (ꢀ).
2
throughout the irradiation, as shown in Fig. 4. Therefore, we
have to use the ee instead of the ellipticity for evaluating the
development of the enantiomeric enrichment.
Here, we define the ee of the reactant I and the product II
when the enantiomeric enrichment occurs by CPL irradiation.
We have to do this because absolute configuration of the enan-
tiomers of I and II has not yet been determined. We correlate
(Ϫ)-I with (R)-I, (ϩ)-I with (S)-I, (ϩ)-II with (R)-II, (Ϫ)-II
with (S)-II. Therefore we define the ee of I and II as given in
eqns. (8) and (9), respectively.
curve, it is likely that the intensities of the incident CPL and
LPL were essentially identical.
The changes in the CD spectrum that arose when I was
irradiated with l- and r-CPL at 290 nm are shown in Fig. 6a. The
two peaks observed at 215 and 270 nm became more intense
during the course of the irradiation. A simulated CD spectrum
for the irradiation of (±)-I is given in Fig. 6b. It is predicted that
(
Ϫ)-I is preferentially excited with r-CPL at 290 nm, resulting
in enrichment of (ϩ)-I.
After measuring the CD spectra, the reaction mixtures were
analyzed by GC, using a biphenyl added as an internal stand-
ard. The UV spectra and GC analysis showed that the total
concentration of I and II was conserved after CPL irradiation,
and no byproduct was detected, thus the photoisomerization of
I to II in acetonitrile proceeds without any side reactions. The
presence of isosbestic points in the UV spectra also supports a
quantitative conversion.
(
8)
(9)
The ee’s of I and II were calculated using the values of
the ellipticity and absorbance obtained from CD and UV
measurements. The concentration of I was obtained by using
the value of the absorbance at 280 nm, where II has no absorb-
ance. The concentration of II was obtained by assuming no side
It is well known that the photocyclization is a unimolecular
33
reaction, and thus the decrease in the concentration of I is
always equal to the increase in the concentration of II. When a
solution of I is irradiated with r-CPL at 290 nm, the CD spectra
should be mixture of the CD spectrum of (ϩ)-I and the CD
spectrum of (ϩ)-II at a ratio of 1 : 1. The spectra shown in Fig.
reactions for the isomerization, eqn. (10), where [I] is the initial
0
concentration of I.
6
b, which were generated based on this assumption, perfectly
(
10)
coincide with the experimentally obtained spectra (Fig. 6a).
The CD band at 280 nm, which is shown in Fig. 6a, reflects
the enantiomeric enrichment of I when I is irradiated with CPL
at 290 nm, where ∆ε of (ϩ)- and (Ϫ)-II is zero, and the band
at 220 nm reflects the simultaneous enantiomeric enrichment
of II when I is irradiated with CPL at 290 nm. However, the
enantiomeric enrichment of II was estimated from the CD
extinction at 245 nm because the magnitude of the ∆ε of
The optical purities (op’s) are obtained using eqns. (11) and
12), where θ’s are the ellipticity (mdeg) of the solution.
(
(11)
(12)
Throughout this study, the ee is assumed to be equal to the op.
For the ee of I the values of the ellipticity at 280 nm were used,
because ∆ε of (ϩ)- and (Ϫ)-II is zero at this wavelength. For
the ee of II the value of θ at 245 nm was used, because ∆ε of
(
ϩ)- and (Ϫ)-I is zero at this wavelength.
Fig. 7 shows the relationship between the ellipticity at 280 nm
and the irradiation time. The ellipticity at 280 nm first increases,
and then levels out. However, the concentration of I changes
during the irradiation. The concentration of I decreases
(
ϩ)- and (Ϫ)-I is zero at this wavelength.
J. Chem. Soc., Perkin Trans. 2, 2001, 1693–1700
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reactants to achiral products, has also been shown to be valid
for the photoisomerization of racemic mixtures. Our study has
also provided a method which can be used for the analysis of
the product ee, and eqns. (2) and (6) derived from Kagan’s
equation are also useful for making this analysis.
The chiroptical properties of I and II were examined in
acetonitrile. (Ϫ)-I isomerizes to (ϩ)-II when it is irradiated with
LPL at a non-absorbing wavelength of II (290 nm), and (ϩ)-I
isomerizes to (Ϫ)-II under the same conditions. The photo-
isomerization proceeds without any side reactions. When I is
irradiated with r-CPL at 290 nm, the enantiomeric enrichment
of (ϩ)-I and (ϩ)-II occurs, and the reverse relationship is
observed for irradiation with l-CPL at 290 nm. This reaction
obeys eqn. (2), and thus the enantiomeric enrichment of the
reactant I by CPL irradiation will increase to 100% ee at nearly
1
00% conversion. Conversely, the enantiomeric enrichment of
the product II gradually decreases and approaches zero at the
final stage. The relationship between the ee of the product and
the conversion is remarkably dependent on the g factor of the
reactant. The initial ee of the product is g/2 (here: 0.6%) in
agreement with eqn. (7). These results suggest that we can
obtain a reactant and product ee of around 40% at a conversion
of 50% if starting material with a g factor of unity is used.
Fig. 8 Theoretical (solid and broken lines) and experimental (plots)
relationship between the % ee of (a) reactant (I) and (b) product (II)
and the conversion.
Experimental
General
1
H-NMR spectra were recorded on a 400 MHz NMR spectro-
The ee for I was plotted against the conversion in Fig. 8a,
which shows that the ee of I increases with the conversion.
The ee for II was plotted against the conversion in Fig. 8b.
Upon CPL irradiation, as shown in Fig. 7b, the ellipticity at
meter (JEOL EX-400). All chemical shifts (δ) are reported in
ppm from a TMS internal standard (0.00 ppm) and coupling
constant (J) values are reported in Hz. UV spectra were meas-
ured with a JASCO V-560 spectrometer. CD spectra were
measured with a JASCO J-720WI or a JASCO J-725 spectro-
meter. The optical rotations were measured with a Perkin Elmer
341 polarimeter with a thermostated 10 cm cell. Molar circular
2
45 nm first increased and then remained constant, and as
shown in Fig. 4, the concentration of II increases during this
period. This means that the enantiomeric enrichment of II
decreases according to the CPL irradiation as shown in Fig. 8b.
The solid and dashed lines in Fig. 8a are calculated by
putting the observed g value at 290 nm (g = 0.012) into eqn. 2,
and the curve shows good agreement with experimental data.
Thus, (±)-I irradiated with l- and r-CPL at 290 nm results in the
enrichment of (ϩ)- and (Ϫ)-I, respectively, and the behavior of
the ee at 280 nm obeys eqn. (2).
2
0
dichroism (∆ε) and specific rotation ([α] §) of each enantiomer
D
of I and II reported were corrected for the enantiomeric
excesses (ee’s) of the isolated enantiomers following chiral
HPLC analysis. In the present paper, the notations of (ϩ) or
(Ϫ) refer to the sign of the optical rotations that were measured
at the sodium D-line (589.3 nm).
Photolyses were carried out in UV spectroscopic grade
acetonitrile (Merck) without any further purification. The
photolyzed solutions were analyzed with CD and UV spectro-
meters, as well as gas chromatography (Shimadzu, GC14-A)
over a CBP-1 column (Shimadzu).
Upon deriving eqn. (2), Kagan assumed that the rate con-
stants of the asymmetric photoreaction (photodestruction) are
proportional to the molar extinction coefficients, ε and εS,
R
6,12,34
respectively.
This can be justified if the concentration of
the solution is so low that the % absorption is approximately
proportional to the concentration. So, in our experiment,
absorbance of solutions at 290 nm was always kept less than
Materials
Methyl norbornadiene-2-carboxylate (I, methyl bicyclo[2.2.1]-
hepta-2,5-diene-2-carboxylate). I was synthesized according to
the procedure of Fienemann and Hoffmann. Anhydrous
aluminum trichloride (22.4 g, 0.17 mol) was added to a 300 mL
round-bottomed flask fitted with a reflux condenser and a
thermometer, and then 200 mL of dry benzene was added to
the vessel suspended in an ice bath. Methyl prop-2-ynoate
0
.1.
The solid and dashed lines in Fig. 8b depict eqn. (6), and also
35
show a good agreement with experimental data. The ee of
product II, gradually decreases, approaching zero at the final
stage of the photoisomerization. The theoretical curve in
Fig. 8b also shows that the ee of the product (II) is initially g/2,
i.e. 0.6%, and this is also verified by experiment. The ee of the
product can be predicted accurately with eqns. (2) and (6).
Therefore, our work presents the first report which demon-
strates, with experimental evidence, that a class (b) NAAS actu-
ally exists, and that the ee of the chiral product is initially g/2,
further explaining in detail the relationship between the ee of
product and the progress of the photoreaction.
(
28.0 g, 0.33 mol) was then added, resulting in a yellow color-
ation. Finally, cyclopentadiene (22.1g, 0.33 mol) was added in a
dropwise fashion within 30 min with stirring, and the reaction
mixture was stirred for additional 1 h. Then, the solution was
poured into aqueous sodium hydrogen carbonate solution.
Ether (200 mL) was then added to the mixture, and the mix-
ture was washed several times with water (300 mL). The ether
solution was dried over magnesium sulfate. After the ether was
evaporated from the solution, the crude product was purified by
chromatography on a column of silica gel eluted with toluene:
yield 40.8 g (82.3%), bp 43.5–44.0 ЊC/1 Torr (Found: C, 71.96;
H, 6.72. Calc. for C H O : C, 71.98; H, 6.71%); δ (400 MHz;
Conclusions
In this study, we have described an NAAS, the photoisomeriz-
ation of racemic reactant (I) into the chiral product (II).
Kagan’s equation for the ee of the reactant, which was orig-
inally formulated to describe the photodestruction of racemic
9
10
2
H
CDCl ; Me Si) 7.65 (1 H, d, J = 2.9 Hz, 3-H), 6.91 (1 H, dd,
3
4
J = 4.4, 3.4 Hz, 6-H), 6.73 (1 H, dd, J = 4.4, 3.4 Hz, 5-H), 3.90
1
698
J. Chem. Soc., Perkin Trans. 2, 2001, 1693–1700

View Online
(
(
1 H, br s, 1-H), 3.73 (3 H, s, COMe), 3.71 (1 H, br s, 4-H), 2.15
1 H, d, J = 6.4 Hz, 7-H), 2.12 (1 H, d, J = 6.4 Hz, 7-H).
(
(
13)
Methyl quadricyclane-1-carboxylate (II, methyl tetracyclo-
2,7 4,6
[
3.2.0.0 .0 ]heptane-1-carboxylate). II was synthesized accord-
36
ing to the procedure of Kaupp and Prinzbach. I (3.00 g, 0.020
mol) in acetonitrile (160 mL) was photolyzed through a Pyrex
filter under a nitrogen atmosphere. The product was purified by
column chromatography (toluene) on silica gel, and was dis-
tilled under vacuum: yield 2.43 g (81%), bp 40–41 ЊC/2 Torr
14)
(
Found: C, 71.92; H, 6.75. Calc. for C H O : C, 71.98; H,
9 10 2
6
.71%); δ (400 MHz; CDCl ; Me Si) 3.67 (3 H, s, COMe), 2.42
H 3 4
2
of the incident light beam (cm ), V is the volume of the solution
(
1 H, ddd, J = 2.4, 1.5, 1.5 Hz, 5-H), 2.27 (1 H, dd, J = 4.8, 1.5
3
(
dm ), A is the absorbance of the reaction mixture in the reac-
Hz, 2-H), 2.17 (1 H, ddd, J = 11.7, 1.5, 1.5 Hz, 3-H), 2.09 (1 H,
ddd, J = 11.7, 1.5, 1.5 Hz, 3-H), 2.00 (1 H, ddd, J = 2.4, 2.4, 1.5
Hz, 4-H), 1.67 (1 H, ddd, J = 5.8, 4.8, 2.4 Hz, 7-H), 1.58 (1 H,
ddd, J = 5.8, 2.4, 2.4 Hz, 6-H).
r
R
r
S
tion cuvette, ε
and ε
represent the molar extinction coefficients
when (R)- and (S)-isomers are excited by the irradiation of
r-CPL, respectively, l is the path length of the reaction cuvette,
r
R
r
S
Φ is the quantum yield of the reaction, k
and k
represent the
rate constants when (R)- and (S)-isomers are excited by the
irradiation of r-CPL respectively and t is the reaction time. If
the incident light beam covers all the surface of the cuvette, the
value of the term, Sl/V, becomes 1000.
Thus the rate constants for the reaction become proportional
Methyl cyclopropanecarboxylate (MCP). MCP was distilled
at atmospheric pressure (bp 118–119 ЊC).
37
Optical resolution
Each enantiomer was isolated using HPLC (Japan Analytical
Industry, LC-908) with the following chiral columns: I was
resolved using a Chiracel OD column (Daicel, 20.0 × 250 mm)
eluted with propan-2-ol–hexane (1 : 100) as eluent; II was
resolved using a Chiralpack AS column (Daicel, 4.6 × 250 mm)
with propan-2-ol–hexane (1 : 200) as eluent.
to the molar extinction coefficients.
Appendix 2
In eqn. (7) the limit value of yЈ was given as in eqn. (15).
The % ee’s of the resolved enantiomers were estimated by
using HPLC (JASCO, Gulliver PU-980, 860-CO, UV-970) with
the following conditions; for (ϩ)- and (Ϫ)-I, Chiracel OD
(
Daicel, 4.6 × 250 mm) with propan-2-ol–hexane (1 : 200) as
eluent, and for (ϩ)- and (Ϫ)-II, Chiralpack AS (Daicel,
.6 × 250 mm) with propan-2-ol–hexane (1 : 200) as eluent
% ee: (Ϫ)-I, 99.4%; (ϩ)-I, 97.6%; (Ϫ)-II, 97.3%; (ϩ)-II,
8.9%).
4
(
9
(15)
Photolysis
Eqn. (4) can be reduced into the form shown in eqn. (16), by
differentiating this equation we obtain eqn. (17). Finally dy/dx
can be expressed as in eqn. (18). If x reaches 0, y reaches 0 to
give eqn. (19).
A solution of I (0.26 mM) was put in a rectangular cell
(
10 × 10 × 40 mm) made of Suprasil quartz, and the cell was
sealed under an argon atmosphere. The solutions were irradi-
ated at 290 nm with l- and r-CPL generated with a CPL source
made in-house in collaboration with JASCO. A 500 W xenon
arc lamp (Ushio) was used as the light source, which was placed
in front of an elliptical mirror. After the light beam was made
parallel by two mirrors, it was made monochromatic with a
grating monochromator (JASCO, CT-10) and then collimated
with a fused silica lens. The light beam was linearly polarized
with a polarizer (Melles Griot, 03PTA403), and was circularly
polarized with a Soleil-Babinet’s compensator (Shimadzu, 691-
(
16)
(
(
17)
18)
0
2013-02). The degree of circular polarization was estimated to
be 92%, using a combination of an analyzer (Melles Griot,
3PTA403) and a silicon photodiode (Hamamatsu Photonics,
0
S1336-8BQ). The full width at half-maximum (FWHM) of
CPL and LPL was 15 nm at 290 nm. The sample cell was
located in the cell holder.
(
19)
Appendix 1
If the concentration of the solution is so low that the % absorp-
tion for the solution is approximately proportional to the
concentration, the rates of the decrease of the enantiomers of
the reactant via the irradiation of r-CPL are as given in eqns.
Acknowledgements
We would like to thank Mr Takashi Takakuwa (JASCO Co.
Ltd.) for useful suggestions concerning the measurement of
CD spectra, and Dr Simon Everitt (Inoue Photochirogenesis
Project) for discussions and insights, as well as corrections
and improvements arising from preliminary reading of this
manuscript.
37
(
(
13) and (14), where c and c are the concentrations of the
R S
R)- and (S)-isomers respectively, I is the incident photon flux
ex
Ϫ2 Ϫ1
expressed as einstein cm s ,¶ S is the area of the cross section
2
3
¶
1 einstein = 1 mole of light (6.023 × 10 quanta).
J. Chem. Soc., Perkin Trans. 2, 2001, 1693–1700
1699

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