Photochemically Induced Ring Opening of Spirocyclopropyl Oxindoles: Evidence for a Triplet 1,3-Diradical Intermediate and Deracemization by a Chiral Sensitizer

Article abstract of DOI:10.1002/anie.202008384

The photochemical deracemization of spiro[cyclopropane-1,3′-indolin]-2′-ones (spirocyclopropyl oxindoles) was studied. The corresponding 2,2-dichloro compound is configurationally labile upon direct irradiation at λ=350 nm and upon irradiation at λ=405 nm

Full text of DOI:10.1002/anie.202008384

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Accepted Article
Title: Photochemically Induced Ring Opening of Spirocyclopropyl
Oxindoles: Evidence for a Triplet 1,3-Diradical Intermediate and
Deracemization by a Chiral Sensitizer
Authors: Xinyao Li, Roger J. Kutta, Christian Jandl, Andreas Bauer,
Patrick Nuernberger, and Thorsten Bach
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10.1002/anie.202008384
Angewandte Chemie International Edition
RESEARCH ARTICLE
Photochemically Induced Ring Opening of Spirocyclopropyl
Oxindoles: Evidence for a Triplet 1,3-Diradical Intermediate and
Deracemization by a Chiral Sensitizer
Xinyao Li,[a] Roger J. Kutta,[b] Christian Jandl,[a] Andreas Bauer,[a] Patrick Nuernberger,[b] and Thorsten
Bach[a]*
[a]
Dr. X. Li, Dr. C. Jandl, Dr. A. Bauer, Prof. Dr. T. Bach
Department Chemie and Catalysis Research Center (CRC)
Technische Universität München
Lichtenbergstraße 4, D-85747 Garching
Fax: +49 (0)89 289 13315
E-mail: thorsten.bach@ch.tum.de
Hompage: http://www.oc1.ch.tum.de/home_en/
Dr. R. J. Kutta, Prof. Dr. P. Nuernberger
Institut für Physikalische und Theoretische Chemie,
Universität Regensburg
[b]
Universitätsstr. 31, D-93053 Regensburg
Supporting information for this article is given via a link at the end of the document.
Abstract: The photochemical deracemization of spiro[cyclopropane-
1,3'-indolin]-2'-ones (spirocyclopropyl oxindoles) was studied. For the
corresponding 2,2-dichloro compound it was found that it is
configurationally labile upon direct irradiation at = 350 nm and upon
irradiation at  = 405 nm in the presence of achiral thioxanthen-9-one
as the sensitizer. The triplet 1,3-diradical intermediate generated in
the latter reaction was detected by transient absorption spectroscopy
and its lifetime was determined ( = 22 s). Using a chiral thio-
xanthone or xanthone both with a lactam hydrogen bonding site as a
photosensitizer allowed the deracemization of differently substituted
chiral spirocyclopropyl oxindoles with yields of 65-98% and in 50-85%
ee (17 examples). Three mechanistic contributions were identified to
co-act favourably for high enantioselectivity. First, the binding
constants to the chiral thioxanthone differ by a factor of 3 for the minor
and the major enantiomers. Second, the molecular distance is smaller
by ≈ 100 pm in the complex of the minor enantiomer, presumably
promoting a more efficient energy transfer. Third, the lifetime of the
intermediate 1,3-diradical exceeds the one of the complex, facilitating
a racemic deactivation back to the ground state.
chiral compound via a transient achiral intermediate which decays
to either one of the two enantiomers. The achiral intermediate
does not accumulate but serves only to racemize the compound.
An achiral catalyst thus enables in combination with light a
conversion of an enantiopure compound to a racemic product
mixture (Scheme 1). This entropically favored process has ample
precedents in thermal chemistry and is frequently a nuisance but
rarely synthetically desirable.
Scheme 1. Photochemical deracemization of a racemate by a chiral catalyst vs.
racemization of an enantiopure compound by an achiral catalyst.
The reverse process, i.e. a photochemical deracemization,[6]
however, is synthetically very useful. Indeed, a large number of
chiral compounds are prepared in racemic form and need to be
Introduction
Photochemistry offers access to reaction pathways which are not
viable in the electronic ground state (thermal reactions).[1] In the
context of enantioselective catalysis[2] it has been recognized that
photoexcited chiral compounds can transfer their chirality to
prochiral substrates and enable a selective isomerization. In
particular, cyclic alkenes such as (Z)-cycloheptene and (Z)-
cyclooctene have been frequently studied in the isomerization to
their chiral (E)-diastereoisomers.[3] Likewise, achiral cis-1,2-
diphenylcyclopropane has been employed as a precursor to chiral
trans-1,2-diphenylcyclopropane.[4] While the latter method has
never led to useful enantioselectivities, the isomerization of
cycloalkenes has provided access to enantiomerically enriched
products in up to 87% ee.[3f] However, the reaction suffers from
the fact that significant amounts of the achiral (Z)-isomer remain
unconverted. A conceptually different approach which avoids
stable achiral intermediates aims at the deracemization[5] of a
separated at a later stage by sophisticated methods.[7]
A
deracemization enables a complete conversion of the racemate
to a single enantiomer. A key element of the pathway shown
above is to find a chiral catalyst which processes only one
enantiomer of a given substrate to provide the putative achiral
intermediate. Since the achiral intermediate decays to both
enantiomers[8] enrichment of the other enantiomer is ensured by
repetitive racemization cycles. Although photochemical derace-
mization methods have been suggested for some time,[2h] it was
not until very recently that the first highly enantioselective method
was reported. Based on the use of chiral thioxanthone 1[9] it was
found that 3-(1’-alkenylidene)-piperidin-2-ones (3) could be dera-
cemized almost quantitatively and with high enantiomeric excess
(ee).[10] In subsequent studies, the thioxanthone was used in both
enantiomeric forms (1 and ent-1) as was the related compound
1
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10.1002/anie.202008384
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RESEARCH ARTICLE
2[11] and its enantiomer ent-2. Work with cyclopropanes 4[12] was
performed employing mainly catalyst ent-1 and chiral sulfoxides
5[13] were deracemized with catalyst ent-2. Allenes have remained
so far the best suited substrate class and 3-(1’-alkenylidene)-
pyrrolidin-2-ones (6) have recently been employed in the context
of synthetic work which aimed at a subsequent conversion of axial
into point chirality.[14] In the same study, catalyst 1 was also found
to successfully deracemize azepan-2-one 7 albeit in lower ee.
might undergo ring opening upon triplet sensitization and form
1,3-diradical II as an achiral intermediate. If so, a deracemization
as generally described in Scheme 1 was conceivable for this
substrate class. Although the ring opening of cyclopropanes upon
triplet sensitization has some precedents,[19] there is also
evidence that the compounds can undergo ring opening by a
single electron transfer process.[20] Both reductive and oxidative
quenching of a photoexcited chromophore are possible and a
racemization/deracemization could also occur for example via
putative radical cation III.
Scheme 2. Putative formation of 1,3-diradical II from spirocyclopropyl oxindoles
I
as a possible sensitized (energy transfer) pathway for racemiza-
tion/deracemization and structure of an alternative intermediate III accessible
via electron transfer.
Figure 1. Structure of deracemization catalysts 1, 2 and of products 3-7
obtained enantioselectively by a photochemical deracemization.
The synthesis of racemic spirocyclopropyl oxindoles was readily
achieved from the 3-diazo-indolin-2-ones which served as
precursors for a carbene addition to the respective olefin.[21] The
studies commenced with the dichlorosubstituted substrate rac-8a
which was available from 1,1-dichloroethene (Figure 2). The two
enantiomers 8a and ent-8a were separable by chiral HPLC which
enabled us to assess the integrity of the stereogenic C3 carbon
center upon irradiation. The first electronic absorption band
ranges from ca. 335 nm to 275 nm peaking at  = 295 nm (MeCN,
 = 1690 M1 cm1). The triplet energy of the oxindole 8a was
determined as ET = 298 kJ mol1 from its phosphorescence
spectrum (77 K, EtOH). Upon extended irradiation at  = 405 nm
(Figure 2, left; for spectral data of all light sources, see the SI)
enantiopure oxindole 8a remained configurationally stable.
Surprisingly, achiral TX induced a rapid racemization despite the
fact that its triplet energy is significantly lower (E ≈ 30 kJ mol1)
than the triplet energy of compound 8a.
In all cases depicted in Figure 1, it had been postulated that the
achiral intermediates involved in the photochemical processes
are triplet intermediates.[15] Indeed, a typical workflow for the dis-
covery of a sensitized deracemization reaction aims to find
suitable conditions for a racemization of enantiopure compounds
induced by an achiral triplet sensitizer, e.g. by the parent
compounds thioxanthen-9-one (TX) with a reported ET = 268 kJ
mol1 (77 K, EtOH)[16] or by xanthene-9-one [ET = 308 kJ mol1, 77
K, ethanol-ether-isopentane (EPA)].[17] Once it is confirmed that
the catalyst is – in concert with light – solely responsible for the
racemization, the deracemization with chiral catalysts can be
studied and optimized. Although some circumstantial evidence
was collected to support the hypothesis of triplet sensitization as
the operating mechanistic pathway in the above-mentioned
deracemization reactions, the postulated radical intermediate has
not yet been detected spectroscopically.
In the present study, we have investigated the deracemization of
biologically and synthetically relevant[18] spirocyclopropyl
oxindoles (spiro[cyclopropane-1,3'-indolin]-2'-ones) in the
presence of catalysts 1 and 2. Our results demonstrate an
efficient deracemization for this compound class to be possible.
Furthermore, we investigated the mechanism of the process by
transient absorption spectroscopy and computational studies and
identified the diradical intermediate previously proposed. The
results are discussed in the context of different selectivity
parameters generally relevant for deracemization reactions.
100
80
60
40
20
0
100
80
60
40
20
0
0
2
4
6
t (h)
8 10 12 14
0
2
4
6
t (h)
8
10
Results and Discussion
Figure 2. Racemization (■) of compound 8a to rac-8a in MeCN as the solvent:
Time profile (c = 1.5 mM) for exc = 405 nm in the absence (●) and in the
presence (■) of 0.15 mM thioxanthen-9-one (left); time profile for exc = 350 nm
in the absence (■) and in the presence of piperylene (right, 15 mM: ●; 30 mM:
▲).
Racemization and Detection of the 1,3-Diradical Intermediate.
Spirocyclopropyl oxindoles with the general structure I (Scheme
2) exhibit a lactam motif which enables hydrogen bonding to
sensitizers 1 and 2. It was hypothesized that the compounds
2
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10.1002/anie.202008384
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RESEARCH ARTICLE
The racemization experiment was also performed at low
temperature (25 °C, see the SI) under otherwise identical
conditions. After 10 hours of irradiation, compound 1a retained its
configuration (90% ee) indicating that the energy transfer (ET)
requires a thermal activation to be successful, either because it is
endergonic (as likely the case here) or a steric hindrance has to
be overcome. Irradiation with light of shorter wavelength ( = 350
nm) led to a racemization which was complete after 14 hours
(Figure 2, right). The racemization was notably decelerated by
addition of piperylene. Since piperylene is an established triplet
quencher[22] the latter result suggested that the racemization
occurs via a triplet intermediate. The former result indicated that
sensitizer 1 might be a suitable deracemization catalyst because
The red DADS in Figure 3a was rescaled accordingly by a factor
of 1/ET in order to emphasize the good agreement between
experiment and theory for both involved triplet species.
Considering the concentration of rac-8a, the bimolecular ET rate
is (3.2±0.2)108 M1 s1 and thus the reaction is rather efficient but
still slower than theoretically expected for a fully diffusion limited
reaction (1.861010 M1 s1, see the SI for further details). The cal-
culations further show that the geometrically optimized structure
of 38a is a 1,3-diradical resulting from opening of the cyclopropane
ring (see inset of Figure 3b). The TA experiments support the
mechanism depicted in Scheme 2 for the sensitized reaction and
allowed us to determine the lifetime of the 1,3-diradical as  =
22 µs in non-degassed MeCN at room temperature.[25]
its triplet energy is similar (ET
=
263 kJ mol1, 77 K,
trifluorotoluene)[10] to that of TX. Further, it was of importance to
choose an irradiation wavelength which results only in sensitized
excitation via the chiral catalyst and avoids any direct excitation
of the substrate.
In the next step, we investigated the mechanism of the racemi-
zation reaction by transient absorption (TA) spectroscopy using
an advanced set-up[23] allowing for simultaneous recording of
temporal and spectral information on the reaction dynamics (see
the SI for a detailed description of the used setup and data
analysis). To this end, the triplet sensitizer TX which is achiral and
lacks a binding site was employed. The dynamics of TX in various
solvents are well studied. Intersystem crossing (ISC) occurs
within a few ps[24] and leads to the formation of a characteristic
triplet-triplet (TnT1) absorption band that decays with a lifetime
of 45 µs in argon-saturated MeCN at room temperature.[16] In our
TA experiments with TX in MeCN under ambient conditions, the
data showed two temporal components (Figure 3a).
The faster component was limited by the duration of the excitation
pulse (ca. 10 ns) and comprised the characteristic spontaneous
1
emission from TX around 410 nm, as evidenced by the gray
decay-associated difference spectrum (DADS) in Figure 3a. The
slower component with a decay time of 104 ns (= kTX-1 = (kbisc + kq
[O2])-1, light blue DADS) represents the TnT1 signal and ground-
state bleach, in full agreement with the literature[16,24a] and
corroborated by a quantum chemical calculation using the
extended multi-configuration quasi-degenerate perturbation
theory (XMCQDPT) on top of the complete active space self-
consistent field (CASSCF) method (Figure 3b, blue line). No
transient signals remained on longer timescales, indicating that
3TX decays entirely back to the ground state, with the reduced
lifetime due to quenching by 3O2. In the presence of 12.3 mM
rac-8a, the 3TX decay time was reduced to 74 ns (dark blue DADS
Figure 3. (a) DADS of TA studies with TX in the absence (gray and light blue)
and presence (black, dark blue, red) of rac-8a (12.3 mM) in MeCN, excited at
exc = 355 nm. (b) Electronic transitions (sticks) for 3TX and 1,3-diradical 38a
convoluted with gaussians (the peak widths are taken from a fit of the
corresponding experimental absorption bands, see SI) calculated at the RHF-
CPCM(MeCN)-TD-DFT-B3LYP//DEF2-TZVP level of theory (see the SI for
details). The inset shows geometrically optimized structures.
3
in Figure 3a), and again TX completely returned to the ground
state. However, the DADS describing the triplet decay showed a
lower amplitude in the spectral region between 400 and 500 nm
than without a quencher (compare light and dark blue DADS,
respectively), because the decay of 3TX was accompanied by the
formation of a new transient component (red DADS). The latter
spectrum revealed two distinct absorption bands peaking at ca.
350 nm and 450 nm. The new species, thus, had a rise time of
74 ns and decayed with a time constant of 22 µs.
Since the reduced radical anion TX of TX was reported to also
exhibit an absorption between 400-500 nm,[26] we recorded its
absorption spectrum upon electron transfer from N,N-diisopropyl-
3
ethylamine to TX. The lifetime and its spectrum (see the SI for
further details) were completely different from the lifetime and
spectrum of the intermediate observed for the reaction between
3TX with rac-8a (Figure 3a). Furthermore, the kinetics of TX− are
accompanied by the persistence of the TX ground-state bleach
A comparison of the spectral position and shape of the spectrum
3
with the calculated triplet absorption spectrum of 8a (red line in
3
Figure 3b) corroborates a successful ET from 3TX to rac-8a. The
quantum yield for ET from the triplet can be determined from
the corresponding decay rates to ET = 1  kTX/kTX rac 8a = (29±2)%.
signal, in contrast to the case of the 1,3-diradical 8a. A single
electron transfer as predominant pathway can consequently be
ruled out.
+
-
3
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10.1002/anie.202008384
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Photochemical Deracemization. An initial screening of the
reaction conditions for the desired deracemization (rac-8a → 8a)
was performed with fluorescent lamps emitting at  = 420 nm
(Table 1). This set-up had been previously used for reactions
catalyzed by thioxanthone 1 and its enantiomer ent-1.[10,12] Based
on the racemization data and supported by time-dependent
measurement of the enantiomeric excess (ee) an irradiation time
of eight hours was considered sufficient to reach the photo-
stationary state and was selected to evaluate possible solvents
for the reaction. Benzene and trifluorotoluene gave the best
results (entries 3 and 4) while dichloromethane was slightly (entry
1) and toluene (entry 2) significantly inferior, at least in terms of
enantioselectivity. It was gratifying to note, though, that even at
this stage the ee was higher than the ee achieved with quinolone-
derived cyclopropanes 4 (Figure 1).[12] The originally chosen con-
centration of c = 2.5 mM was based on precedent from previous
work[10,12] and it was found that in the present case a further
decrease of the concentration led to an increased enantio-
selectivity (entry 5). An increase in the catalyst concentration led
to a slight ee improvement (entry 6). Further variations did not
lead to better results under the chosen irradiation conditions (for
further optimization attempts, see the SI).
narrower emission spectrum was consequently chosen. The
photostationary state was reached under these conditions already
after four hours and the use of the LED resulted indeed in an
improved selectivity (entry 7). It was confirmed that trifluoro-
toluene remained the preferred solvent under these conditions
when compared to acetonitrile and dichloromethane (entries 8
and 9) and it was also confirmed that
a low substrate
concentration remains preferable (entry 10). Lowering the catalyst
loading led to a decrease in enantioselectivity (entry 11).
Exemplarily, entries 12 and 13 depict additional changes which
were tried (lower reaction temperature, different light source) but
did not further improve the selectivity. The ideal conditions for
achieving a high enantioselectivity for the deracemization rac-8a
 8a (Scheme 3) included an excitation at 420 nm, a substrate
concentration of 1.5 mM in trifluorotoluene, and a catalyst loading
of 10 mol%. The yield of isolated product was high (85%)
confirming the stability of the compound under the reaction
conditions. Despite the optimization the enantioselectivity was not
fully consistent (80-85% ee) due to minimal variations in the
content of water and air. In the specific case of product 8a, the
routinely performed analogous reaction at 25°C did not improve
the enantioselectivity. In some other cases (products 8b and 8e)
a minimal improvement was detected at lower temperature. In
general, the degree of enantioselectivity for substituted spiro-
cyclopropyl oxindoles 8b-8h was slightly lower as compared to
the parent compound 8a but it should also be noted that the
conditions (concentration, solvent, light source) were not
individually adapted to each substrate. The extensive functional
group tolerance of sensitizer 1 had been demonstrated in pre-
vious studies.[9,10,12] The absolute configuration of compound 8a
was determined by anomalous X-ray diffraction and the assign-
ment for the other cyclopropanes was based on analogy.[27]
Table 1: Reaction optimization of the photochemical deracemization rac-8a →
8a catalyzed by chiral thioxanthone 1.
c
1
light
source[a]
t[b]
[h]
ee[c]
[%]
entry[a]
solvent
[mM]
[mol%]
1
2
2.5
2.5
2.5
2.5
1.25
2.5
1.5
1.5
1.5
3.0
1.5
1.5
1.5
CH2Cl2
PhMe
PhH
10
10
10
10
10
15
10
10
10
10
5
FL
FL
8
8
8
8
8
8
4
4
4
4
4
4
5
55
31
60
59
65
62
85
35
22
80
55
64
70
3
FL
4
PhCF3
PhCF3
PhCF3
PhCF3
MeCN
CH2Cl2
PhCF3
PhCF3
PhCF3
PhCF3
FL
5
FL
6
FL
7
LED
LED
LED
LED
LED
LED
LED
8
9
10
11
12[d]
13[e]
10
10
[a]
Reactions were carried out in the given solvent at room temperature.
Irradiation was performed at λexc = 420 nm either with a fluorescent lamp (FL)
or with a light-emitting diode (LED). Spectral data of the light sources are
provided in the SI. [b] irradiation time. [c] The enantiomeric excess was calculated
from the enantiomeric ratio (8a/ent-8a) as determined by chiral HPLC analysis.
[d] The reaction was performed at 0 °C. [e] The reaction was performed at exc
405 nm (LED).
=
Scheme 3. Deracemization of 2,2-dichlorospiro[cyclopropane-1,3’-indoline]-2’-
ones (rac-8) catalyzed by chiral thioxanthone 1.
Since the fluorescent lamps show a broad emission band that
stretches into the UV region, we speculated that the intrinsic non-
catalyzed racemization (Figure 2) might deteriorate the outcome
of the reaction (vide supra). A light-emitting diode (LED) with a
The second substrate class which we investigated carried a
dialkyl-substituted carbon atom in the cyclopropane ring and
optimization was performed with 2,2-diethyl-spiro[cyclopropane-
4
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RESEARCH ARTICLE
1,3’-indoline]-2’-one (rac-9a). Although compound 9a has a
similar triplet energy (ET = 298 kJ mol1, 77 K, EtOH) as 8a, an
attempted deracemization with thioxanthone 1 failed. It was found
that xanthone 2 with a higher triplet energy facilitates the desired
reaction when the irradiation was performed at exc= 366 nm. In
a control experiment, we secured that irradiation with the chosen
light source in the absence of a sensitizer does not lead to a
racemization. The subsequently optimized reaction conditions (for
details see the SI) could be transferred to several other substrates
rac-9 (Scheme 4) and the desired enantioenriched products were
isolated in 82-98% yield with 65-82% ee. The high yield of the
photochemical deracemization is notable given the high triplet
energy of the sensitizer and its notorious tendency for C-H
abstraction in the excited state.[11,28] Xanthone 2 was shown to be
compatible with chloro, alkoxy and protected amino groups. From
prior work,[13] the compatibility of the catalyst with bromo, sulfoxy,
and cyano groups had been established.
Indeed, DFT studies (see the SI) support the notion that the
distance d between the two chromophores in 1∙ent-8a and 1∙8a is
significantly different with d in the range of ca. 100 pm.
According to the theory of energy transfer,[30,31] the rate difference
correlates to the distance by ed with the critical parameter 
representing the sensitivity of the electron transfer to the distance
of separation. Although there are no data available for the energy
transfer from 1 to a given substrate, typical values for  are in the
order of 102 pm1.[1b,30c,d] Very crudely, the increased distance
between the energy donor and the energy acceptor in complex
1∙8a should consequently lead to a decrease of the rate for
electron transfer by at least 1/e, i.e. by ca. 0.37, relative to 1∙ent-
8a. If one takes into account the above-mentioned preference for
the formation of 1∙ent-8a vs. 1∙8a, the two factors co-act towards
the observed enantioselectivity.
Scheme 5. Binding constants (Ka) of complexes 1∙ent-8a and 1∙8a as
determined by 1H NMR titration at 25 °C in [D6]-benzene. Distances between
the marked carbon atoms were calculated by DFT methods (see the SI for
further details).
For a mechanistic understanding, a third important contribution for
the deracemization process has now been obtained for 8a, i.e. the
lifetime of the triplet intermediate 38a. Given that typical lifetimes
for complexes between sensitizers such as 1 and 2 and hydrogen
bonding substrates are below 1 s,[28] it can be safely assumed
that the cyclization will not occur within complex 1∙38a, as
substantiated by the 22 s lifetime determined for 38a (equilibrium
in Scheme 6). Since the steric bias exerted by the thioxanthone
skeleton would in this case favor a cyclization to ent-8a (bottom
left reaction in light gray in Scheme 6), a cyclization in the
absence of any steric bias is desirable leading to a racemic
mixture of 8a and ent-8a (reaction on the right in Scheme 6).
Support for this assumption stems from the enantioselective
cyclization of 1,4- and 1,5-diradicals mediated by a chiral template
closely related to compound 1.[32]
Scheme 4. Deracemization of 2,2-dialkyl-substituted spiro[cyclopropane-1,3’-
indoline]-2’-ones (rac-9) catalyzed by chiral xanthone 2.
Mechanistic Analysis and Discussion. Among the critical
parameters that have been identified for the deracemization to be
successful,[10,12-14] the most obvious parameter is the association
of the two oxindole enantiomers I and ent-I to the sensitizer. In
an ideal scenario, the major enantiomer I does not bind to the
sensitizer while enantiomer ent-I shows efficient binding. We
determined the specific binding constants for the two enantiomers
ent-8a and 8a to sensitizer 1 by NMR titration[29] and identified a
better binding of the former enantiomer (Scheme 5). However, the
values were unexpectedly low and indicated only a minor binding
preference for ent-8a. Based on these data alone the degree of
deracemization and the observed enantioselectivity cannot be
accounted for.
Scheme 6. Dissociation of triplet 1,3-diradical 38a from sensitizer 1 and its
decay to spirocyclopropyl oxindoles 8a and ent-8a.
A second parameter which influences the enantioselectivity is the
rate of sensitization within the complexes. We have previously
proposed[10] that the known distance dependence of energy
transfer[30] plays a major role in the deracemization process.
Based on the above-mentioned data a preliminary kinetic scheme
can be drawn (Scheme 7) for the sensitized deracemization of
spirocyclopropyl oxindoles I which helps to visualize the key data.
The pathway on the right (in black) is preferred over the pathway
5
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10.1002/anie.202008384
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RESEARCH ARTICLE
on the left (in gray). Both the higher association constant of ent-I
[Ka (ent-I) > Ka (I)] to the sensitizer (Sens) and the more rapid
sensitization followed by ring opening to the 1,3-diradical (k’1 > k1)
guarantee that the minor enantiomer is processed more rapidly.
However, it is also crucial that the dissociation of the intermediate
II is rapid because the cyclization within the complex would favor
the production of ent-I (k’2 > k2). Cyclization of the free 1,3-
diradical II leads to the racemic mixture with a rate constant kII
the upper limit of which can be determined by its lifetime .
Acknowledgements
Financial support by the Deutsche Forschungsgemeinschaft (Ba
1372/24-1) is gratefully acknowledged. XL thanks the Alexander
von Humboldt foundation for a research fellowship. O. Ackermann,
F. Pecho, and J. Kudermann (all TU München) are acknowledged
for their help with HPLC and GLC analyses. We are grateful to J.
Großkopf (TU München) for his assistance in recording the
luminescence spectra. Dr. G. Storch (TU München) is
acknowledged for discussions regarding the DFT calculation.
Keywords: enantioselectivity · hydrogen bonds ·
photochemistry · sensitizers · time-resolved spectroscopy
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Scheme 7. General scheme for the deracemization of spirocyclopropyl
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Entry for the Table of Contents
The good ones go into the pot, the bad ones go into your crop: A chiral thioxanthone- or xanthone-based sensitizer allows for the
differentiation of cyclopropane enantiomers and for a photochemical deracemization (17 examples, up to 85% ee). The key intermediate
of this entropically disfavored process was identified by transient absorption spectroscopy to be a 1,3-diradical with a lifetime of  = 22
s.
8
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