Control of the helical chirality of enantiopure sulfinyl (Z)-azobenzene-based photoswitches

Article abstract of DOI:10.1002/chem.201203243

A new class of enantiopure ortho,ortho-disubstituted azobenzene photoswitches has been synthesized from (S)-2-(p-tolylsulfinyl)benzoquinone and arylhydrazines. The sulfoxide acts as a unidirectional controller of the helical chirality that arises in the Z isomer after photoisomerization. Highly congested E-azobenzenes 5 c showed two atropisomeric diastereoconformers in the solid state that converged upon irradiation into a unique Z isomer with defined helicity (M), as evident in the X-ray structure. The chiroptical properties of this three-state enantiopure switch can be externally tuned both photochemically and/or thermally. Theoretical CD spectra calculated by using time-dependent DFT methods support the existence of two atropoisomeric E isomers and only one Z isomer with (M) helicity. Complementary to the classical azobenzene-based switches, the photoswiching event is promoted under green/blue light and do not occur under UV irradiation. Switch hitter: ortho,ortho-Disubstituted azobenzene phothoswitches were synthesized from (S)-2-(p-tolylsulfinyl)-p-benzoquinone and arylhydrazines. The sulfoxide unidirectionally controlled helical chirality in the Z isomer. The (E)-azobenzenes showed two diastereoconformers that converged upon irradiation to a Z isomer with defined helicity (M). The chiroptical properties of this switch were tuned photochemically and/or thermally (see figure). Copyright

Full text of DOI:10.1002/chem.201203243

FULL PAPER
DOI: 10.1002/chem.201203243
Control of the Helical Chirality of Enantiopure Sulfinyl (Z)-Azobenzene-
Based Photoswitches
Irene NfflÇez,[a] Estíbaliz Merino,[a] Mercedes Lecea,[a] Silvia Pieraccini,[b]
Gian Piero Spada,[b] Carlo Rosini,[c] Giuseppe Mazzeo,[c] María Ribagorda,*[a] and
M. Carmen CarreÇo*[a]
In memory of Christian G. Claessens
Abstract: A new class of enantiopure
ortho,ortho-disubstituted azobenzene
photoswitches has been synthesized
verged upon irradiation into a unique
Z isomer with defined helicity (M), as
evident in the X-ray structure. The chi-
roptical properties of this three-state
enantiopure switch can be externally
tuned both photochemically and/or
thermally. Theoretical CD spectra cal-
culated by using time-dependent DFT
methods support the existence of two
atropoisomeric E isomers and only one
Z isomer with (M) helicity. Comple-
mentary to the classical azobenzene-
based switches, the photoswiching
event is promoted under green/blue
light and do not occur under UV ir-
from
(S)-2-(p-tolylsulfinyl)benzoqui-
none and arylhydrazines. The sulfoxide
acts as a unidirectional controller of
the helical chirality that arises in the
Z isomer after photoisomerization.
Highly congested E-azobenzenes 5c
showed two atropisomeric diastereo-
conformers in the solid state that con-
Keywords: azobenzenes
· circular
dichroism · helical structures · mo-
lecular switches · quinones
AHCTUNGTRENNGrUN adiation.
Introduction
easy to control. The induction of a defined configuration of
the photoemergent Z helicity (P or M) represents a chal-
lenge in the design of new chiroptical devices in which the
local configuration of the chromophore can be directed by
irradiation. Despite the numerous chiral azobenzenes that
have been reported so far, only a few studies have investi-
gated the stereoselective formation of (P)- or (M)-helical Z-
azobenzenes. Controlled photoisomerization has been ach-
ieved by using a chiral imidazole cyclopeptide linked to an
azo system[6] or an axially chiral binaphthyl-substituted azo-
benzene inserted into a macrocycle.[7] In both cases, the
The isomerization of azobenzenes[1] induces a geometrical
change between the almost-planar E isomers and the bent
Z isomers, in which both aryl groups adopt an edge-to-face
orientation. Such reversible changes, which are typically in-
duced by irradiation with UV light, are associated to signifi-
cant differences in the properties of the isomers and have
been used to develop numerous molecular switches.[2,3] With
appropriate substitution patterns, azobenzenes can photo-
ACHTUNGTRENNUNGisomerize under green/blue-light irradiation, which is highly
attractive for biological applications.[4] The bent Z systems[5]
homoACTHNGUTERNcUNG hiral units, which are bonded as a clamp to both aro-
adopt a chiral helical structure whose configuration is not
matic azo groups through aliphatic fragments (Figure 1),
successfully control the Z helical chirality, thereby resulting
in the photoisomerization of azobenzenes. However, the
[a] I. NfflÇez, Dr. E. Merino, Dr. M. Lecea, Dr. M. Ribagorda,
Prof. Dr. M. C. CarreÇo
Departamento de Química Orgµnica (Módulo-01)
Universidad Autónoma de Madrid
Cantoblanco, 28049-Madrid (Spain)
E-mail: maria.ribagorda@uam.es
carmen.carrenno@uam.es
[b] Dr. S. Pieraccini, Prof. Dr. G. P. Spada
Dipartimento di Chimica Organica “A. Mangini”
Alma Mater Studiorum, Università di Bologna
Via San Giacomo 11, 40126 Bologna (Italy)
[c] Prof. Dr. C. Rosini,+ Dr. G. Mazzeo
Dipartimento di Chimica “A. Tamburro”
Università della Basilicata, 85100 Potenza (Italy)
[+] Deceased 2010.
Supporting information for this article is available on the WWW
1
under http://dx.doi.org/10.1002/chem.201203243, including the H and
Figure 1. Photoswitching process of enantiopure clamp-like cyclic-type
azobenzenes and sulfinyl azobenzenes.
13C NMR spectra and X-ray crystallography data.
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control of such chirality in the absence of cyclic elements re-
mains a significant challenge.
In 2007,[8a] we uncovered the ability of an enantiopure
sulfoxide that is directly linked to the azobenzene system to
fix a rigid conformation in both E and Z isomers. Herein,
we report the synthesis of enantiopure ortho,ortho-disubsti-
tuted (SS)-p-tolylsulfinyl azobenzenes and show that the
sulfoxide is able to transfer the chirality onto the azo
system, whose photoisomerization leads to a unique Z-azo-
benzene with fixed (M) helical chirality, as shown by X-ray
diffraction and CD spectroscopy. The (SS)-sulfoxide, which
is surrounded by two substituents, generates an unexpected
chiral axis in the E-azobenzene isomers and, consequently, a
three-state azo switch, based on two different E isomers and
one Z isomer, is afforded. This switching event can be pro-
moted thermal and photochemically, without using UV
light, by irradiation with green (546 nm, E-to-Z) or blue
light (436 nm, Z-to-E).
Results and Discussion
The most frequently used methods to synthesize azo-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Au-catalyzed oxidation of anilines, and the Pd-catalyzed N-
arylation of tert-butoxycarbonyl (Boc)-protected hydrazines,
followed by oxidative deprotection.[9] In spite of these meth-
ods, sterically hindered asymmetrically substituted systems,
such as ortho,ortho-disubstituted azobenzenes, are still diffi-
cult to access, mainly owing to steric effects throughout the
coupling processes. We have recently reported the prepara-
Scheme 1. Synthesis of 2-(p-tolylsulfinyl)azobenzenes (3) and the X-ray
crystal structure of (E)-3c.
tion of azobenzenes through (NH4)2[Ce
N
carbonyl group of the quinone.[9c,11] In our case, the presence
of the sulfoxide in the benzoquinone framework drastically
changed the regioselectivity of the reaction. The configura-
tional integrity of the sulfinylazobenzenes (3, up to 99% ee)
was confirmed by HPLC (see the Supporting Information).
The structures of azo compounds 3b and 3c were confirmed
by X-ray diffraction.[12] These solid-state structures displayed
the characteristic almost-planar rod-like shape of E-azoben-
zenes. Two intramolecular hydrogen bonds, between the OH
groups at the C3 and C6 positions and the sulfinyl oxygen
atom and the adjacent azo nitrogen atom, respectively, fixed
a rigid E-azo conformation in the structure (Scheme 1).
However, attempts to photoisomerize the azo derivatives
(3) failed, probably owing to the presence of intramolecular-
ly associated OH groups. Thus, we transformed the hydroxy
groups into their methyl-ether derivatives to obtain suitable
photochemical switches. After employing various condi-
tions,[13] enantiopure azobenzenes (SS)-5 (>99% ee, see the
Supporting Information) could be obtained by the treatment
of compounds 3 with trimethylsilyldiazomethane (Table 1).
lyzed reactions of commercially available arylhydrazines
with p-benzoquinone dimethyl bis-ketals.[8c] These mild re-
ACHTUNGTRENNUNGaction conditions allowed us to synthesize enantiopure
ortho- or metha-sulfinyl-substituted azobenzenes from (S)-p-
tolylsulfinyl-functionalized p-quinone bis-ketals in a highly
regioselective manner.[8] Based on our previously reported
synthesis, we wanted to study the reactions of (SS)-2-(p-tol-
ylsulfinyl)benzoquinone (1) with arylhydrazines (2;
Scheme 1). This reaction successfully occurred at room tem-
perature in a highly regioselective manner, thus leading ex-
clusively to 2-(p-tolylsulfinyl)azobenzene products (3) in
moderate to good yields. These products could be formed in
a two-step, one-pot process that was initiated by the 1,4-ad-
dition of the aryhydrazines (2) onto the more electrophilic
C3 position of compound (1), that is, vicinal to the electron-
withdrawing sulfoxide group, which was key to the synthesis
of such overcrowded azo compounds. Enolization of the re-
sulting Michael-type intermediate (I) afforded a hydroqui-
none hydrazine (II), which was oxidized in situ into the de-
sired azo compound (3) by an excess of quinone.[10]
Notably, the reactions between arylhydrazines and benzo-
quinone derivatives typically afford 4-azophenols from an
initial 1,2-nucleophilic attack of the nitrogen atom on the
Photoisomerization studies: The quantitative isomeric com-
positions (E/Z ratios) of azobenzenes 5a–5c were deter-
mined by HPLC; their specific optical rotations were meas-
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Helical Chirality of Sulfinyl Z-Azobenzene-Based Photoswitches
FULL PAPER
Table 1. Synthesis and photoisomerization of 1,4-dimethoxy-2-(p-tolylsulfinyl) azoben-
zenes 5a–5d, E/Z ratios,[a] and [a]D20 values.[b]
PSScis to stand for 20 days. In the case of com-
pounds 5a and 5c, the ECD spectrum of the result-
ing PSScis (Figure 2a and c, dashed lines) showed a
red-shifted positive band at about 430 nm, which
was more intense than that at about 390 nm in the
initial-state PSStrans (Figure 2a and c, solid lines).
Moreover, the intensity of the negative band in the
initial state at about 510 nm decreased in com-
pounds 5a and 5c and almost disappeared in the
PSScis of compound 5c. In the case of pentafluoro-
substituted azobenzene 5b, the positive and nega-
tive bands that corresponded to the PSScis at
>300 nm (Figure 2b, dashed line) were notably less
intense compared to the initial state (Figure 2b,
solid line). All of these spectroscopic changes con-
firmed that the E!Z isomerization of the azo
moiety had a notable influence on the overall ge-
ometry and chirality of compounds 5. The presence
of the intense CD bands at l>300 nm must be a
consequence of a transfer of chirality from the sulf-
oxide to the azo system in both the Z and E isom-
ers. Upon irradiation at 436 nm, reverse CD and
UV/Vis spectroscopic changes occurred within 20–
30 min to reach a PSStrans that was identical to the initial
states of compounds 5.
Crystallization of compound 5c (EtOAc/n-hexane) afford-
ed two different crystals that were resolved independently
as the azo (Z)-5c (Figure 3) and (E)-5c isomers
(Figure 4).[17] The X-ray crystal structure of the Z isomer
showed the characteristic bent shape of Z-azobenzene and,
more interestingly, the exclusive formation of a chiral M-
helicene-like structure (Figure 3). The aryl group (I) was ori-
ented towards the edge-face of the aryl ring (II), thus allevi-
ating the steric congestion by placing the ortho-CF3 substitu-
ent distant from the influence of the methoxy group of the
ring (I). The sulfoxide adopted a fixed conformation to re-
lease the polar repulsion between the sulfinyl oxygen atom
and the vicinal OMe group. In such a disposition, the p-tolyl
group is oriented almost perpendicular (97.88) to the aryl
ring (I). Thus, the positive Cotton effect in the ECD spec-
trum of the PSScis state of compound 5c (Figure 2c, dashed
line, about 430 nm) could be associated with the M-helical
twist[18] that is observed for compound (Z)-5c in the solid
state. In PSScis, only one set of NMR signals was evident,
which corresponded to the presence of only one Z isomer.
In accordance with the X-ray structure, an M configuration
was assigned to the structure (SS,M,Z)-5c.
Initial (PSStrans)
E/Z
[a]2D0
PSScis
D (808C)
E/Z
Entry
5
E/Z
[a]2D0
[a]2D0
D[a]2D0
1
2
3
4
5a
5b
5c
5d
78:22
65:35
85:15
ꢀ948
48:52
30:70
63:37
–
ꢀ228
ꢀ596
ꢀ144
–
92:8
80:20
98:2
–
ꢀ1288
ꢀ1628
ꢀ860
–
1060
1032
716
–
ꢀ1032
ꢀ760
ꢀ700
100:1:0
[a] E/Z ratios were determined by HPLC (Chiralpack AD column, n-hexane/iPrOH,
85:15, 0.9 mLminꢀ1); [b] iPrOH, c=0.025 gdLꢀ1
.
ured at the same time as the HPLC analysis, thus ensuring
an accurate relationship between the E/Z ratios and [a]D20
values. The samples were carefully prepared to avoid E-to-Z
isomerization. Although we tried to minimize exposure to
white light, HPLC analysis revealed that, in the initial state,
azobenzenes 5a–5c already had a non-negligible amount of
the Z isomers (15 to 35%), presumably owing to exposition
to daylight during the synthetic process, whereas compound
5d did not show the presence of its Z iso
mer.[14] Initial E/Z
ACHTUNGTRENNUNG
ratios and [a]2D0 values are listed in Table 1.
The UV/Vis spectra of the initially obtained compounds 5
were very similar and were dominated by the sulfoxide ab-
sorption at l=250 nm and characteristic p!p* and n!p*
transition bands of the aromatic azo chromophore at 380
and 490 nm, respectively (Figure 2, solid line).[15] The elec-
tronic circular dichroism (ECD) spectra of initial states 5a–
5c (Figure 2, solid line) showed a sequence of oppositely
signed bands: a positive absorption at l=268 nm, which cor-
responded to the (SS)-sulfoxide, a negative band at about
320–330 nm followed by an intense positive band at about
390 nm, and a second negative band at about 510 nm. The
Cotton effects in the region 300–560 nm can be ascribed to
the transitions of the azo group and reflect a transfer of chi-
ACHTUNGTRENNUNGrality from the chirogenic sulfoxide to the azo system. Irra-
diation of initial states 5a–5c with UV light (l=365 nm) did
not trigger any photoisomerization. Pleasingly, irradiation
with green light (l=546 nm) successfully prompted E-to-Z
isomerization.[14]
The maximum populations of the Z isomers (PSScis,
Table 1) were reached after irradiation for 60 min [(Z)-5a
52%, (Z)-5b 70%, and (Z)-5c 37%].[16] Thermal Z!E re-
laxation at room temperature was much slower than the
To our surprise, the unit cell of compound (E)-5c consist-
ed of two different structures (Figure 4, A and B), which, in
sharp contrast with the customary almost-planar structure of
E-azobenzenes, showed an exceptionally twisted disposi-
tion.[19] X-ray diffraction indicate that structures (SS)-A and
(SS)-B had a different orientation of the aryl group (I) with
ꢀ
respect to the N=N aryl moiety (II), as can be seen from
ꢀ
ꢀ
their opposite N=N C1 C2 dihedral angles (FA =ꢀ78.208,
FB =+58.998). The methoxy groups and the sulfoxide at the
C2 position of ring (I) force the N=N double bond up (A)
photoinduced isom
ACHTUNGTRENNUNGerization. For example, for compound 5c,
the initial state was regained after allowing a solution of
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M. Ribagorda, M. C. CarreÇo et al.
or down (B) with respect to the
aryl plane (I). Notably, in such
a disposition, the p systems of
the N=N group can only be de-
localized through aryl ring (II).
Therefore, dipole repulsion be-
[20]
ꢀ
tween the S O bond and the
ꢀ
vicinal C OMe bond of the
methyl ether, in combination
with the polarized N=N double
bond, might be responsible for
the conformational preference
of structures A and B. Thus, ro-
ꢀ
tation around the C1 N1 bond
of azo A would afford a less-fa-
vored conformer (B’), in which
dipolar repulsion between the
N=N group and the SO bond
can be minimized by rotation of
ꢀ
the C S single bond, thereby
leading to structure B. The X-
ray structures of compound
(E)-5c showed the presence of
a
chiral axis with opposite
handedness for A and B and,
consequently, they could be
considered as atropoisomeric
structures.[21] In contrast to the
solid-state structures, atropo-
AHCTUNGERTGiNNUN somers A and B could not be
detected by either 1H NMR
spectroscopy[22] or by chiral
HPLC in solution,[23] which
only showed one E isomer
peak.[24]
Low-temperature
19F NMR spectroscopy (158 K)
in [D8]THF allowed us to detect
the presence of two sets of sig-
nals that could be assigned to
both atropoisomers (A and B,
see the Supporting Informa-
tion). Presumably, the substitu-
tion pattern around the atom
nitrogen (N1) was not bulky
Figure 2. CD (left) and UV/Vis spectra (right) of compounds: a) (SS)-5a (0.96 mm), b) (SS)-5b (0.934 mm), and
c) (SS)-5c (0.98 mm) in CDCl3. Solid lines represent the original spectra of the E isomers (initial state) and PSS
after irradiation at 436 nm (excess E isomers); dashed lines represent PSS after irradiation at 546 nm (excess
Z isomers); e is given in mꢀ1 cmꢀ1
.
ꢀ
enough to fully restrict rotation around the C N single
bond in solution at room temperature and, therefore, A and
B can be considered as atropoconformers.
To gather more experimental evidence for the presence of
the E atropoconformers, we carefully examined the ECD
spectra of an enriched sample of compound (E)-5c. Thus, a
solution of initial azo-5c (E/Z, 85:15) was heated at 808C to
promote the Z-to-E thermal isomerization[25] and, after
10 min, an E-enriched-5c sample (E/Z, 98:2) was obtained
(Table 1, entry 3) with a higher [a]2D0 value than the initial
azo-5c (ꢀ860 and ꢀ760, respectively). The ECD spectrum
of compound azo-5c at 808C (Figure 5a, pink line) showed
a broad positive band at about 400 nm, which was slightly
Figure 3. M-helical diastereoisomer and X-ray crystal structure of com-
pound (Z)-5c.
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Helical Chirality of Sulfinyl Z-Azobenzene-Based Photoswitches
FULL PAPER
five times without alteration of
the ECD and UV/Vis spectra
of each three states of the azo-
benzene switch. Finally, initial-
state 5c was recovered when a
solution of the E-enriched
sample was left at room tem-
perature in the sunlight (Fig-
ure 5a, dark-blue line).
Changes in specific optical
rotation between the PSScis
and E-enriched states were
measured
for
azo-5a–5c
(Table 1): D[a]2D0 =1060 (5a),
1032 (5b), and 716 (5c). All of
these values reflected a signifi-
cant influence of the isomeriza-
tion process on the chirality of
these azo compounds. In the
same way, several thermal
cycles of E-enriched isomer 5c
(heating up to 808C and cooling
to room temperature in the
dark) were also repeated and
showed similar ECD curves
(Figure 5b).
Computational Studies
To gain further support for all
of these observations, we calcu-
lated the corresponding CD
spectra for atropoconformers A
and B, as well as the theoretical
spectra of the M- an P-helical
Z isomers of compound 5c.
Analysis of the ECD spectra by
using ab initio techniques led to
Figure 4. X-ray projection of the chiral axis and conformational equilibrium of atropoconformers A and B of
(E)-5c.
blue-shifted and less intense (De=+2.66) than the corre-
sponding band of initial-state 5c (dark-blue line, about
420 nm, De=+6.81). The second negative band at about 490
was also shifted (20 nm) with respect to the initial state
(about 510 nm) but had a similar intensity (De=ꢀ1.61). To
our surprise, after cooling the E-enriched sample to room
temperature in the dark, a different ECD spectrum was re-
corded. The most-significant change was the intensity of the
negative band at about 480 nm, which increased significantly
from De=ꢀ1.61 to ꢀ4.16 (Figure 5a, green line). Because
the E/Z ratio of the E-enriched azo-5c state at RT was 98:2,
only a conformational change of the E-azobenzene between
atropoconformers A and B could explain these thermal var-
iations. Moreover, from this E-enriched azo-5c state (RT),
irradiation at l=546 nm gave the PSScis state (Figure 5a,
light-blue line) and, on heating the PSScis sample, E-en-
riched azo-5c (808C, Figure 5a, pink line) was regained.
This sequential heating/irradiation sequence was repeated
safe structural determination, thereby allowing an assign-
ment of absolute configuration.[26,27] The experimental ECD
spectra of atropoACTHNUTRGNEUNGisomeric conformers (aS,Ss,E)-5c (A) and
(aR,Ss,E)-5c (B), as well as structures (M,Z)-5c and (P,Z)-
5c, were simulated on the basis of time-dependent density
functional theory (TDDFT) by using the long-range-correct-
ed CAM-B3LYP functional[28] and the TZVP basis set;[29,30]
the theoretical spectra are shown in Figure 6. The ECD
spectra of compounds (aS,Ss)-5c (A) and (aR,Ss)-5c (B) are
almost a mirror image in the region 320–620 nm (Figure 6,
black and pink lines). A broad positive band (De=+16) at
about 450 nm is observed for (aR,E)-5c (B; Figure 6, pink
line) and a similar negative band (De=ꢀ28) is present at
about 490 nm in the spectrum of (aS,E)-5c (A; Figure 6,
black line).
This band, largely owing to a HOMO–LUMO excitation,
occurred with negligible oscillatory strength and could be
ꢀ
assigned to an n p* transition of the azobenzene chromo-
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M. Ribagorda, M. C. CarreÇo et al.
phore, taking into account its energy position. Moreover,
the ECD spectrum of (E)-atropoconformer A not only dif-
fers in the sign of the dominant Cotton effect but also in the
fact that this band in (aR,E)-5c (B) is blue-shifted with re-
spect to the same band in the (aS,E)-5c (A) atropisomer (by
about 40 nm). The experimental thermal ECD study of com-
pound (E)-5c showed that, at higher temperatures, the
broad positive band centered at about 405 nm had a higher
intensity (absolute value) than the negative band at about
487 nm (Figure 5a, pink line), whilst, at RT, the negative
band was significantly more intense (Figure 5a, green line).
All of this evidence, together with the theoretical ECD
spectra of both atropoconformers, suggested that (aR,E)-5c
(B), with an intense positive band at 450 nm in the theoreti-
cal ECD, must be the major atropoconformer at 808C,
whereas, at RT, a 50:50 mixture of (aR)-B and (aS)-A E-azo
species must exist. ECD calculation of M,Z and P,Z struc-
tures[30] (Figure 6, red and blue lines, respectively) provided
positive bands that were allied to HOMO–LUMO excita-
tion (De=+25 at 470 nm for M,Z and De=+7 at 480 nm for
P,Z). The theoretical ECD spectrum of the M,Z structure
possessed a negative band (De=ꢀ12) at 312 nm and a posi-
tive band at 260 nm (De=+32). A weak positive band (De=
+1) at 310 nm and a negative band (De=ꢀ14) at 260 nm oc-
curred in the calculated ECD spectrum of the P,Z structure,
thus showing a quite opposite trend with respect to the M-
helical isomer in the range 380–200 nm. According to the
experimental ECD spectrum (Figure 5a, light-blue line), the
calculated ECD spectrum of the M,Z structure appears to
be the best-fitting one.
We also attempted to simulate the ECD spectra of initial-
state 5c before and after irradiation (PSStrans and PSScis).
As a consequence of the frequency difference at the maxi-
mum of the two atropoconformers of compound (E)-5c, the
conformationally averaged simulated ECD spectrum of pure
(E)-5c (A/B, 50:50; Figure 7a, solid line) showed a sulfoxide
band (250 nm) and a sequence of oppositely signed bands
(the negative band at lower energy and the positive band at
higher energy) in the range 400–600 nm, as observed experi-
mentally. The theoretical ECD spectrum of PSScis-5c
(which simulated the experimentally observed E/Z:M 60:40
mixture, Figure 7b) exhibited a positive band in the region
600–400 nm. The qualitative agreement with the experimen-
tal ECD curves was very good (Figure 7, dashed line).
Figure 5. a) ECD spectra of compound 5c (”10ꢀ3 in DMF). Dark-blue
line: initial state and PSStrans; pink line: enriched E isomers at 808C;
green line: enriched E isomers at room temperature; light-blue line:
PSScis. b) ECD thermal changes of compound 5c (E/Z, 98:2). Isodichroic
point: l=422 nm (black circle).
We calculated the relative stability of atropoconformers
(aS,Ss,E)-5c (A) and (aR,Ss,E)-5c (B), as well as both heli-
mers (M,Z)-5c and (P,Z)-5c, to deduce a Bolzmann’s distri-
bution of their relative populations at the same B3LYP/
TZVP level (see the Supporting Information). As expected,
the E isomers are more stable than both Z isomers (by more
than 8 kcalmolꢀ1; Table 2). Structure (aS,E)-A was slightly
more stable than atropoconformer (aR,E)-B. The calculated
energy content of both M and P Z isomers also supports the
absence of the P-helical Z isomer after the photoisomeriza-
tion process, because the difference in the energy content of
both isomers (DG=8.3 kcalmolꢀ1) justifies the presence of
the M-helical Z product as the sole diastereomer.
Figure 6. Theoretical ECD spectra of (aS,Ss,E)-5c (A; black line),
(aR,Ss,E)-5c (B; pink line), (M,Z)-5c (red line), and (P,Z)-5c (blue line).
3402
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 3397 – 3406

Helical Chirality of Sulfinyl Z-Azobenzene-Based Photoswitches
FULL PAPER
green light (l=546 nm). Structural congestion and polar re-
pulsion are at the heart of the two-state conformational
equilibrium in the Z isomer between atropoconformers A
and B. The M helical configuration that was induced in the
Z isomer after irradiation was controlled by the SS sulfoxide,
which adopted a fixed disposition to minimize dipolar repul-
sion. The trans/cis photostationary states (PSS) can be
reached by irradiation with green and blue light (at 546 nm
or 436 nm, respectively), whereas the thermal back-isomeri-
zation into 98% (E)-5c, which has a preferred (aR,E)-B
conformation, can be performed by heating at 808C. Upon
cooling to room temperature, a new equimolecular mixture
of the aR/aS atropoconformers of (E)-5c resulted. The ex-
change between both atropoconformers and the Z isomer
can be monitored by using ECD spectroscopy. Theoretical
calculations supported all of the experimental data.
Experimental Section
General: All of the reagents were purchased from Aldrich Chemical Co.
and used without further purification. MeCN, Et2O, and DMF were dried
over activated 4 Š molecular sieves. Analytical TLC was performed on
precoated sheets of silica gel 60 and flash column chromatography was
performed on silica gel 60 (230–400 mesh, Merck). The eluents employed
for flash chromatography are reported as v/v percentages. (S)-2-(p-Tolyl-
sulfinyl)benzoquinone (1) was prepared according to a literature proce-
dure.[31] 1H NMR, 19F NMR, and 13C NMR spectra were acquired on a
AV-300 Bruker spectrometer in CDCl3 at 300, 282.4, and 75 MHz, respec-
tively; a DRX-500 Bruker spectrometer was used also in specific cases
(500, 470.6, and 125 MHz, respectively). Chemical shifts (d) are reported
in part per million (ppm) and are calibrated with respect to residual sol-
vent peaks (1H: d=7.26 ppm, 13C: d=77.0 ppm). MS and HRMS were
acquired at the Servicio Interdepartamental de Investigación (SIdI), Uni-
versidad Autónoma de Madrid, on a VG Auto Spec mass spectrometer.
UV/Vis spectra were recorded on a JASCO-Type U-best 560 Hewlett
Packard 8453 spectrometer. Chiral HPLC was performed at RT on a
Chiralpack AD column on an Agilent 1100 Series HPLC that was equip-
ped with a variable-wavelength UV/Vis spectrometer. Absorption and
circular dichroism (CD) spectroscopy were performed on a Jasco Model
J-710 spectropolarimeter. Optical rotations were measured on a Perkin–
Elmer 241C polarimeter with a sodium D line (589 nm) at the tempera-
ture, solvent, and concentration indicated. Melting points were obtained
in open capillary tubes.
Figure 7. Calculated ECD spectra (velocity formalism) of: a) pure (E)-5c
(aR/aS, 50:50; solid line), and b) PSScis (solid line). Experimental spectra
are provided for comparison (dashed lines).
Table 2. Relative free energies and populations (P) of all of the isomers
of (E)-5c and (Z)-5c.
[a]
Isomer DG [kcalmolꢀ1
]
P (all isomers) [%][b] P (Z isomers) [%][c]
aS,E
aR,E
M,Z
P,Z
0.0
0.5
8.3
69.7
30.3
0.0
0.0
100
0
16.6
[a] Relative free energies; [b,c] population percentages, based on DG
values that were calculated at the DFT/B3LYP/TZVP level of theory of
all isomers [b] and Z isomers [c].
Conclusion
Photoisomerization studies: CD and UV/Vis experiments were per-
formed at 208C by irradiating the solutions of the azobenzenes in a
0.1 cm thermostatic quartz cell with the Xe lamp of the dichrograph
(150 W). A high-pressure Hg lamp (400 W) was used for the chiral
HPLC and optical-rotation measurements and interference filters (Oriel)
were used to select the wavelengths. Photostationary states were ensured
by monitoring composition changes over time by taking UV spectra at
different intervals until no changes were observed. Ratios of the E/Z iso-
mers (by HPLC) were determined by monitoring at the isosbestic point
at 210 nm.
We have reported the regioselective synthesis of a new class
of enantiopure ortho,ortho-disubstituted azobenzenes from
2-p-tolylsulfinyl-p-benzoquinone and arylhydrazines. The
thermal and photoisomerization processes, as studied by
UV/Vis and CD spectroscopy and chiral HPLC, showed
that the sulfoxides acted as a conformational and configura-
tional controller of the azobenzene-type switches (5). Strong
differences were observed in the specific optical rotations of
the Z and E isomers, as a consequence of the presence of
different chiral units in these azo compounds. In particular,
(SS)-sulfinyl azo compound 5c can be considered as a new
three-state enantiopure switch, owing to its two (E)-atropo-
Synthesis of 3,5-dihydroxy-2-p-tolylsulfinylazobenzenes (3)
(SS)-2’,5’-Difluoro-3,6 dihydroxy-2-p-tolylsulfinylazobenzene (3a): To a
solution of 2,5-difluorophenylhydrazine (2a, 55 mg, 0.38 mmol, 1 equiv)
in anhydrous MeCN (1.9 mL, 0.2m) was added a solution of (SS)-2-p-tol-
ylsulfinylbenzoquinone (1, 187 mg, 0.76 mmol, 2 equiv) in MeCN (11 mL,
0.07m) over 24 h at RT by using a syringe pump (rate: 7.5 mLminꢀ1).
Upon completion of the reaction, water (10 mL) was added and the mix-
ture was extracted with EtOAc (3”5 mL). The combined organic layers
were dried (MgSO4) and concentrated under reduce pressure. Column
chromatography on silica gel (EtOAc/n-hexane, 1:10) afforded compound
ACHTUNGTRENNUNGisomers, namely A and B, whose relative ratio can be exter-
nally modulated by changing the temperature, and a third
(M,Z)-isomer state that can be obtained by irradiation with
Chem. Eur. J. 2013, 19, 3397 – 3406
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3403

M. Ribagorda, M. C. CarreÇo et al.
3a (23 mg, 37% yield) as a red solid. M.p. 161–1628C; [a]2D0 =+267 (c=
0.0019 in CHCl3); 1H NMR (300 MHz, CDCl3): d=12.55 (s, 1H), 11.43
(s, 1H), 7.68–7.65 (AA’, 2H, Tol), 7.38 (ddd, J=8.7, 5.7, and 3.0 Hz, 1H),
7.28–7.26 (BB’, 2H, Tol), 7.25–7.14 (m, 2H), 7.08 and 7.04 (AB, J=
9.3 Hz, 2H), 2.36 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=159.1 (dd,
J=246.5 and 2.2 Hz), 155.2 (dd, J=255.3 and 2.8 Hz), 154.3, 147.8, 142.6,
141.0, 138.5 (dd, J=8.8 and 6.6 Hz), 132.6, 130.4 (2C), 128.5, 125.9 (2C),
123.8, 119.8, 119.3 (dd, J=25.3 and 8.3 Hz), 118.2 (dd, J=22.0 and
8.3 Hz), 103.8 (d, J=26.0 Hz), 21.4 ppm; 19F NMR (282.4 MHz, CDCl3):
d=ꢀ115.4 (d), ꢀ128.4 ppm (d); MS (EI): m/z (%): 388 (13) [M]+, 372
(41), 279 (27), 250 (45), 219 (16), 183 (7), 159 (14), 141 (37), 113 (79), 91
(76); HRMS (EI): m/z calcd for C19H14N2O3F2S: 388.0693 [M]+; found:
388.0680.
8.5, 7.3 and 1.3 Hz, 1H), 7.29–7.27 (BB’, 2H, Tol), 7.08 and 6.90 (AB, J=
9.8 Hz, 2H), 2.36 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=164.1,
156.0, 155.7, 142.9, 142.0, 140.7, 140.5, 135.0, 134.3, 130.5 (2C), 128.2,
127.4, 126.0, 125.9 (2C), 117.7, 115.1, 21.4 ppm; MS (EI): m/z (%): 91
(84), 111 (35), 139 (92), 181 (10), 227 (24), 259 (62), 278 (12), 349 (13),
381 (11), 397 (8); HRMS (EI): m/z calcd for C19H15N3O5S: 397.0732
[M]+; found: 397.0718.
Synthesis of 3,6-dimethoxy-2-p-tolylsulfinylazobenzenes (5)
(SS)-2’,5’-Difluoro-3,6-dimethoxy-2-p-tolylsulfinyl-azobenzene (5a): To a
solution of compound (SS)-3a (35.5 mg, 0.09 mmol, 1.0 equiv) in 2m dry
Et2O and 4m dry EtOH was added (diazomethyl)trimethylsilane (6–
10 equiv) at RT. Upon completion of the reaction (TLC, about 7 days),
the mixture was concentrated under reduce pressure. Column chromatog-
raphy on silica gel (EtOAc/n-hexane, 1:1) afforded compound 5a
(18.6 mg, 50% yield, 99% ee) as an orange oil. [a]2D0 =ꢀ948 (c=0.025,
(SS)-2’,3’,4’,5’,6’-Pentafluoro-3,6-dihydroxy-2-p-tolylsulfinylazobenzene
(3b): To a solution of 2,3,4,5,6-pentafluorophenylhydrazine (2b, 46 mg,
0.23 mmol, 1 equiv) in anhydrous MeCN (1.9 mL, 0.2m) was added a so-
1
iPrOH); H NMR (500 MHz, CDCl3): d=7.67–7.65 (AA’, 2H, Tol), 7.48–
ACHTUNGTRENNUNGluACHTUNGTRENNUNGtion of (SS)-2-p-tolylsulfinylbenzoquinone (1, 114 mg, 0.46 mmol,
7.45 (m, 1H), 7.24–7.22 (BBꢁ, 2H, Tol), 7.20–7.18 (m, 2H), 7.12 and 6.94
(AB, J=9.1 Hz, 2H), 3.92 (s, 3H), 3.70 (s, 3H), 2.37 ppm (s, 3H);
13C NMR (125 MHz, CDCl3): d=158.8 (dd, J=246.1 and 2.3 Hz), 156.9
(dd, J=255.7 and 2.3 Hz), 153.3, 147.8, 144.3, 141.1, 140.7 (dd, J=35.7
and 9.6 Hz), 139.6, 129.4, 128.9 (2C), 125.3 (2C), 119.9 (dd, J=25.2 and
8.2 Hz), 118.0 (dd, J=22.5 and 8.7 Hz), 116.2, 116.2, 114.9, 104.8 (d, J=
25.2 Hz), 57.3, 56.9, 21.3 ppm; 19F NMR (470.6 MHz): d=ꢀ117.1,
ꢀ127.6 ppm; MS (EI): m/z (%): 416 (26) [M]+, 400 (33), 309 (100), 287
(59), 244 (20), 229 (30), 201 (11), 185 (8), 129 (26), 113 (47), 91 (37);
HRMS (EI): m/z calcd for C21H18N2O3F2S: 416.1006 [M]+; found:
416.1001. HPLC: Daicel Chiralpack AD, n-hexane/iPrOH, 85:15,
0.9 mLminꢀ1, 210 nm, t(S)=27 min, T=258C.
2 equiv) in MeCN (10 mL, 0.07m) over 24 h at RT with a syringe pump
(rate: 5 mLminꢀ1). Upon completion of the reaction, water (10 mL) was
added and the mixture was extracted with EtOAc (3”5 mL). The com-
bined organic layers were dried (MgSO4) and concentrated under reduce
pressure. Column chromatography on silica gel (EtOAc/n-hexane, 1:6) af-
forded compound 3b (67 mg, 75% yield) as a red solid. M.p. 161–1628C;
[a]2D0 = + 125 (c=0.0064 in CHCl3, 99% ee); 1H NMR (300 MHz,
CDCl3): d=11.89 (s, 1H), 11.54 (s, 1H), 7.68–7.65 (AA’, 2H, Tol), 7.28–
7.26 (BBꢁ, 2H, Tol), 7.10 and 7.07 (AB, J=9.4 Hz, 2H), 2.36 ppm (s,
3H); 13C NMR (75 MHz, CDCl3): d=154.5, 146.3, 142.6, 142.1 (dtt, J=
261, 13.2 and 3.8 Hz), 141.5 (dddd, J=255, 12.6, 8.2 and 4.4 Hz, 2C),
140.8, 138.2 (dtt, J=246, 13.7 and 4.4 Hz, 2C), 133.6, 130.3 (2C), 129.4,
126.0 (2C), 125.4 (td, J=7.7 and 4.9 Hz), 123.5, 120.3, 21.4 ppm;
19F NMR (282.4 MHz, CDCl3): d=ꢀ147.8 and ꢀ148.0 (m, 2F), ꢀ149.3
and ꢀ149.4 (m), ꢀ160.5 and ꢀ160.7 ppm (m, 2F); MS (EI): m/z (%): 442
(24), 426 (20), 334 (5), 304 (29), 272 (9), 211 (16), 183 (21), 139 (27), 109
(41), 91 (56); HRMS (EI): m/z calcd for C19H11N2O3F5S: 442.0411 [M]+;
found: 442.0403. HPLC: Daicel Chiralpack IA, n-hexane/iPrOH, 90:10,
0.5 mLminꢀ1, 210 nm, t(S)=14 min T=258C.
(SS)-2’-Trifluoromethyl-3,6-dihydroxy-2-p-tolylsulfinylazobenzene (3c):[31]
To a solution of (SS)-2-p-tolylsulfinylbenzoquinone (1, 50 mg, 0.2 mmol,
1 equiv) in MeCN (0.2 mL) was added 2-(trifluoromethyl)phenylhydra-
zine (2c, 37 mg,0.21 mmol, 1 equiv) neat at RT opposite addition to 2a
and 2b. After 5 min, water (5 mL) was added and the mixture was ex-
tracted with EtOAc (3”5 mL). The combined organic layers were dried
(MgSO4) and concentrated under reduce pressure. Column chromatogra-
phy on silica gel (EtOAc/n-hexane, 1:3) afforded compound 3c (31 mg,
36% yield) as a red solid. M.p. 124–1268C; [a]2D0 =+179 (c=0.0034 in
CHCl3); 1H NMR (300 MHz, CDCl3): d=12.18 (s, 1H), 11.38 (s, 1H),
7.83 (d, J=7.2 Hz, 1H), 7.81 (d, J=6.6 Hz, 1H), 7.72 (t, J=7.4 Hz, 1H),
7.67–7.64 (AA’, 2H, Tol), 7.61 (t, J=7.6 Hz, 1H), 7.26–7.24 (BB’, 2H,
Tol), 7.08 and 7.04 (AB, J=9.4 Hz, 2H), 2.35 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=154.1, 147.2, 146.4, 142.5, 141.0, 133.1, 132.6, 131.2,
130.4 (2C), 128.3, 127.3 (q, J=31.4 Hz), 127.0 (q, J=5.5 Hz), 126.5 (q,
J=274.0 Hz), 126.3 (q, J=5.5 Hz), 125.8 (2C), 123.5, 116.8, 21.4 ppm;
MS (EI): m/z (%): 420 (35) [M]+, 402 (38), 311 (18), 282 (50), 257 (32),
229 (19), 201 (13), 173 (17), 145 (88), 109 (66), 91 (58); HRMS (EI): m/z
calcd for C20H15N2O3F3S: 420.0755 [M]+; found: 420.0747.
(SS)-2’,3’,4’,5’,6’-Pentafluoro-3,6-dimethoxy-2-p-tolylsulfinylazobenzene-
AHCTUNGRTEG(NNNU 5b): To a solution of compound (SS)-3b (30 mg, 0.07 mmol, 1.0 equiv) in
2m dry Et2O and 4m dry EtOH was added (diazomethyl)trimethylsilane
(6–10 equiv) at RT. Upon completion of the reaction (TLC, about
3 days) the mixture was concentrated under reduce pressure. Column
chromatography on silica gel (EtOAc/n-hexane, 1:1) afforded compound
5b (30 mg, 0.06 mmol, 90% yield) as an orange oil. [a]2D0 =ꢀ1032 (c=
0.025, iPrOH); 1H NMR (300 MHz, CDCl3): d=7.60–7.57 (AA’, 2H,
Tol), 7.25–7.22 (BB’, 2H, Tol), 7.14 and 7.00 (AB, J=9.1 Hz, 2H), 3.94 (s,
3H), 3.70 (s, 3H), 2.37 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=
153.3, 148.1, 144.0–143.6 y 140.7–140.4 (dm, J=251.2 Hz), 143.2–143.0
and 139.8–139.4 (dm, J=268.2 Hz, 2C), 139.8–139.4 y 136.5–136.0 (dm,
J=260.0 Hz, 2C), 139.8, 129.2, 129.0 (2C), 127.8–127.4 (m), 125.2 (2C),
125.0, 116.7, 116.3, 116.2, 57.3, 57.0, 21.2 ppm; 19F NMR (282.4 MHz,
CDCl3): d=ꢀ148.8 and ꢀ149.0 (m, 2F), ꢀ150.4 and ꢀ150.6 (m), ꢀ161.5
and ꢀ161.6 ppm (m, 2F); MS (EI): m/z (%): 470 (100) [M]+, 454 (16),
407 (32), 363 (45), 333 (14), 287 (31), 243 (24), 198 (27), 167 (29), 139
(39), 91 (36); HRMS (EI): m/z calcd for C21H15N2O3F5S: 470.0724 [M]+;
found: 470.0712; HPLC: Daicel Chiralpack IA, n-hexane/iPrOH, 85:15,
0.9 mLminꢀ1, 210 nm, t(S)=144 min, T=258C.
(SS)-2’-Trifluoro-3,6-dimethoxy-2-p-tolylsulfinylme-thylazobenzene (5c):
To a solution of compound (SS)-3c (79 mg, 0.19 mmol, 1.0 equiv) in 2m
dry Et2O and 4m dry EtOH was added (diazomethyl)trimethylsilane (6–
10 equiv) at RT. Upon completion of the reaction (TLC, about 7 days),
the mixture was concentrated under reduce pressure. Column chromatog-
raphy on silica gel (EtOAc/n-hexane, 1:1) afforded compound 5c (51 mg,
0.11 mmol, 60% yield, 99% ee) as an orange solid. M.p. 168–1698C;
[a]2D0 =ꢀ760 (c=0.025, iPrOH); 1H NMR (300 MHz, CDCl3): d=7.81–
7.78 (dm, J=7.0 Hz, 1H), 7.67 (dt, J=8.5 and 2.5 Hz, 1H), 7.64 (dt, J=
7.9 and 1.3 Hz, 1H), 7.58 (ddd, J=7.6, 1.9 and 0.8 Hz, 1H), 7.55–7.52
(AAꢁ, 2H, Tol), 7.20–7.17 (BBꢁ, 2H, Tol),7.12 and 6.90 (AB, J=9.1 Hz,
2H), 3.84 (s, 3H), 3.65 (s, 3H), 2.35 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3): d=152.1, 149.7, 146.1, 144.5, 140.9, 139.6, 132.7, 130.8, 128.9
(2C), 128.0 (q, J=31.7 Hz), 126.3 (q, J=5.3 Hz, 2C), 125.0 (2C), 123.7
(q, J=274.1 Hz), 117.8, 116.8, 114.1, 57.2, 56.8, 21.2 ppm; 19F NMR
(282.4 MHz, CDCl3): d=ꢀ57.6 ppm (m, 3F, CF3); MS (EI): m/z (%): 448
(100) [M]+, 385 (34), 341 (42), 287 (16), 243 (35), 145 (76), 91 (25);
HRMS (EI): m/z calcd for C22H19N2O3F3S: 448.1068 [M]+; found:
448.1060; HPLC: Daicel Chiralpack IA, n-hexane/iPrOH 85:15,
0.9 mLminꢀ1, 210 nm, t(S)=62 min, T=258C.
(SS)-3,6-Dihydroxy-2’-nitrophenyl-2-p-tolylsulfinylazobenzene (3d): To a
solution of 2-nitrophenylhydrazine (2d, 52 mg, 0.33 mmol, 1 equiv) in an-
hydrous MeCN (1.6 mL, 0.2m) was added a solution of (SS)-2-p-tolylsulfi-
nylbenzoquinone (1, 164 mg, 0.67 mmol, 2 equiv) in MeCN (10 mL,
0.07m) over 24 h at RT by using a syringe pump (rate: 7 mLminꢀ1). Upon
completion of the reaction, water (10 mL) was added and the mixture
was extracted with EtOAc (3”5 mL). The combined organic layers were
dried (MgSO4) and concentrated under reduce pressure. Column chroma-
tography on silica gel (EtOAc/n-hexane, 1:6) afforded compound 3d
(98 mg, 75% yield) as a red solid. M.p.: 173–1748C; [a]2D0 =- 424 (c=
0.0021 in CHCl3); 1H NMR(300 MHz, CDCl3): d=14.6 (s, 1H), 11.9 (s,
1H), 8.21 (dd, J=8.5 and 1.4 Hz, 1H), 7.93 (dd, J=8.3 and 1.1 Hz, 1H),
7.75 (dd, J=7.3 and 1.2 Hz, 1H), 7.71–7.68 (AA’, 2H, Tol), 7.43 (ddd, J=
3404
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 3397 – 3406

Helical Chirality of Sulfinyl Z-Azobenzene-Based Photoswitches
FULL PAPER
(SS)-3,6-Dimethoxy-2’-nitro-2-p-tolyl-sulfinylazo-benzene (5d): To a solu-
tion of compound (SS)-3d (12 mg, 0.033 mmol) in dry Et2O (0.5 mL) was
added a solution of diazomethane (0.55 mL, 0.33 mmol, 0.6m in Et2O).
Upon completion of the reaction (TLC, about 7 days), the mixture was
concentrated under reduce pressure. HPTLC chromatography (EtOAc/n-
hexane 1:1) afforded compound 5d (10 mg, 0.023 mmol, 90% yield) as
an orange oil. [a]2D0 =ꢀ700 (c=0.020 in CHCl3); 1H NMR (500 MHz,
[D7]DMF): d=8.20 (dd, J=8.2 and 1.3 Hz, 2H), 7.98 (td, J=7.7 and
1.3 Hz, 1H), 7.91 (td, J=7.7 and 1.3 Hz, 1H), 7.8 (dd, J=8.2 and 1.3 Hz,
2H), 7.58–7.56 (AAꢁ, 2H, Tol), 7.34–7.32 (BB’, 2H, Tol), 7.48 and 7.31
(AB, J=9.2 Hz, 2H), 4.09 (s, 3H), 4.08 (s, 3H), 2.37 ppm (s, 3H);
13C NMR (125 MHz, [D7]DMF): d=152.3, 146.1, 144.3, 142.1, 133.8,
133.4, 132.4, 130.5, 129.3 (2C), 124.8 (2C), 124.2 (2C),119.2, 117.5, 115.0,
79.2, 56.8, 56.6, 20.5 ppm; HRMS (FAB): m/z calcd for C21H19N3O5S:
426.1124 [M+H]+; found: 426.1045.
Fernµndez Mudarra, E. Merino, M. Ribagorda, J. Org. Chem. 2004,
69, 3413–3416.
[9] a) E. Merino, Chem. Soc. Rev. 2011, 40, 3835–3853; b) I. Szele, H.
Zollinger, Top. Curr. Chem. 1983, 112, 1; c) A. Grirrane, A. Corma,
H. Garcia, Science 2008, 322, 1661–1664; d) Y.-K. Lim, K.-S. Lee,
C.-G. Cho, Org. Lett. 2003, 5, 979–982; e) E. Merino, M. Ribagorda,
Beilstein J. Org. Chem. 2012, 8, 1071–1090.
[10] Under these reaction conditions, the starting 2-(p-tolylsulfinyl)ben-
zoquinone (4) may undergo a rapid redox reaction (quinone/hydro-
quinone) prior to reaction with the arylhydrazine (3). To avoid this
redox reaction, a highly diluted solution of 2-(p-tolylsulfinyl)benzo-
quinone (0.07m in MeCN) was slowly added (by syringe pump) to
the solution of the arylhydrazine (see the Experimental Section).
[11] a) K. Naemura, T. Wakebe, K. Hirose, Y. Tobe, Tetrahedron: Asym-
metry 1997, 8, 2585–2595; b) T. Kaneda, Y. Ishizaki, S. Misumi, J.
Am. Chem. Soc. 1988, 110, 2970–2972.
[12] CCCD-856594 ((E)-3b) and CCCD-856635 ((E)-3c) contain the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Crystal data
for (E)-3b: C19H11F5N2O3S1; a=11.504(2), b=6.2895(15), c=
12.486(2) Š; b=102.432(14)8; space group P21. Crystal data for (E)-
Acknowledgements
3c:
21.7513(18) Š; space group P212121.OK
[13] Under the typical basic methylation conditions, low and/or ir-
reproducible yields and partial racemization of the sulfoxide (70%
C22H19F3N2O3S1;
a=6.2269(5),
b=13.4295(11),
c=
The contribution of Prof. Carlo Rosini (1948–2010) to the planning of
this work and to the early stages of this study was fundamental in the
preparation of this article. This work was supported by the Ministerio de
Ciencia e Innovación (CTQ2008-04691/BQU and CTQ2011-24783), the
Comunidad de Madrid and European Social Fund (SOLGEMAC-S2009/
ENE-1617), and the MIUR (Italy) through the National Interest Re-
search Program (PRIN 2009, 2009N5JH4F 002). I.N. and E.M. thank the
MEC for fellowships.
AHCTUNGTRENNUNG
ee) were observed by chiral HPLC.
[14] The absorption spectra of nitro-substituted derivative 5d remained
unchanged upon irradiation at different wavelengths and in different
solvents. For examples of substituent effects on azobenzene isomeri-
zation, see: a) J. Dokicì, M. Gothe, J. Wirth, M. V. Peters, J.
Schwarz, S. Hecht, P. Saalfrank, J. Phys. Chem. A 2009, 113, 6763–
6773; b) H. M. D. Bandara, S. C. Burdette, Chem. Soc. Rev. 2012, 41,
1809–1825.
[15] H. Suzuki, Electronic Absorption Spectra and Geometry of Organic
Molecules, Academic Press, New York, 1967, p. 503.
[16] Samples were irradiated until their rotatory power remained con-
stant. The quantitative isomeric compositions (E/Z ratio) of the pho-
tostationary states (PSS) were analyzed by HPLC with simultaneous
measurement of the optical rotation.
[17] CCCD-856391 ((E)-5c) and CCCD-856392 ((Z)-5c) contain the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif. Crystal data for
(E)-5c: C22H19F3N2O3S1; a=28.2593(15), b=7.6733(5), c=
19.5138(9) Š; b 94.958(3)8, space group C-2. Crystal data for (Z)-5c:
a=8.0062(8), b=12.8888(12), c=21.118(2) Š; space group
P212121.OK
[18] N. Berova, L. D. Bari, G. Pescitelli, Chem. Soc. Rev. 2007, 36, 914–
931.
[19] Increasing the size of the ortho substituents on the E-azobenzenes
can lead to a slight rotation of the aryl group that locates it outside
of the plane; see: H. Rau, Yu-S. Quan, J. Photochem. Photobiol. A
1988, 42, 321–327.
[1] a) H. Suginome, CRC Handbook of Organic Photochemistry and
Photobiology (Eds.:W. M. Horspool, P. S. Song), CRC, Boca Raton,
1995, pp. 824–840; b) J. Henzl, M. Mehlhorn, H. Gawronski, K.-H.
Rieder, K. Morgenstern, Angew. Chem. 2006, 118, 617–621; c) B.-Y.
Choi, S.-J. Kahng, S. Kim, H. Kim, H. W. Kim, Phys. Rev. Lett. 2006,
96, 156106.
[2] a) Molecular Switches (Ed.: B. L. Feringa), Wiley-VCH, Weinheim,
2001; b) M. M. Russew, S. Hecht, Adv. Mater. 2010, 22, 3348–3360;
c) T. Hugel, N. B. Holland, A. Cattani, L. Moroder, M. Seitz, H. E.
Gaub, Science 2002, 296, 1103–1106; d) V. Balzani, A. Credi, B.
Ferrer, S. S. M. Venturi, Top. Curr. Chem. 2005, 262, 1–27; e) E. R.
Kay, D. A. Leigh, F. Zerbetto, Angew. Chem. 2007, 119, 72–196;
Angew. Chem. Int. Ed. 2007, 46, 72–191; f) C. Dugave, L. Demange,
Chem. Rev. 2003, 103, 2475–2532; g) R. H. El Halabieh, O. Mermut,
C. J. Barrett, Pure Appl. Chem. 2004, 76, 1445–1465; h) K. Murao-
ka, T. Kinbara, T. Aida, Nature 2006, 440, 512–515; i) M. Yamada,
M. Kondo, J. Mamiya, Y. Yu, M. Kinoshita, C. J. Barret, T. Ikeda,
Angew. Chem. 2008, 120, 5064–5066; Angew. Chem. Int. Ed. 2008,
47, 4986–4988; j) K. Ichimura, S.-K. Oh, M. Nakagawa, Science
2000, 288, 1624–1626.
[3] a) A. A. Beharry, G. A. Woolley, Chem. Soc. Rev. 2011, 40, 4422–
4437; b) C. Renner, L. Moroder, ChemBioChem 2006, 7, 868–878.
[4] a) A. A. Beharry, O. Sadovski, G. A. Woolley, J. Am. Chem. Soc.
2011, 133, 19684–19687; b) W. Wu, L. Yao, T. Yang, R. Yin, F. Li, Y.
Yu, J. Am. Chem. Soc. 2011, 133, 15810–15813.
[5] O. Weingart, Z. Lan, A. Koslowski, W. Thiel, J. Phys. Chem. Lett.
2011, 2, 1506–1509.
[6] G. Haberhauer, C. Kallweit, Angew. Chem. 2010, 122, 2468–2471;
Angew. Chem. Int. Ed. 2010, 49, 2418–2421.
ꢀ
[20] The dipole interactions that are associated with the S O bond of
the sulfoxides have been shown to control the orientation of differ-
ent functional groups; for example, see: a) M. S. Betson, J. Clayden,
M. Helliwell, D. Mitjans, Org. Biomol. Chem. 2005, 3, 3898–3904;
b) J. Clayden, J. Senior, M. Helliwell, Angew. Chem. 2009, 121,
6388–6391; Angew. Chem. Int. Ed. 2009, 48, 6270–6273; c) J. Clay-
den, S. P. Fletcher, S. J. M. Rowbottom, M. Helliwell, Org. Lett.
2009, 11, 2313–2316.
[7] a) K. Takaishi, M. Kawamoto, K. Tsubaki, T. Furuyama, A. Murana-
ka, M. Uchiyama, Chem. Eur. J. 2011, 17, 1778–1782; b) K. Ta-
kaishi, A. Muranaka, M. Kawamoto, M. Uchiyama, J. Org. Chem.
2011, 76, 7623–7628.
[8] a) M. C. CarreÇo, I. García, I. NfflÇez, E. Merino, M. Ribagorda, S.
Pieraccini, G. P. Spada, J. Am. Chem. Soc. 2007, 129, 7089–7100;
b) M. C. CarreÇo, I. García, M. Ribagorda, E. Merino, S. Pieraccini,
G. P. Spada, Org. Lett. 2005, 7, 2869–2872; c) M. C. CarreÇo, G.
[21] a) Stereochemistry of Organic Compounds, E. L. Eliel, S. H. Wilen,
L. N. Mander, Wiley, New York, 1994; b) G. P. Moss, Pure Appl.
Chem. 1996, 68, 2193–2222.
[22] The 1H NMR spectra of compound 5c in various solvents (CHCl3,
C6D6, [D6]acetone, [D4]MeOH, [D8]THF, [D5]DMF, and
[D6]DMSO) and at different temperatures (ꢀ100 to 508C; for de-
tails, see the Supporting Information) displayed a single sharp set of
Chem. Eur. J. 2013, 19, 3397 – 3406
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3405

M. Ribagorda, M. C. CarreÇo et al.
signals, thus indicating that the atropoisomers that were observed in
the solid state were interconvertible in the solution state.
[23] HPLC chiral columns tested: Chiralpack IC, IA, IB, OD, and AS.
[24] A second peak was also observed in the HPLC traces, which corre-
sponded to 15% of the Z isomer.
[25] All of the E-enriched isomers were obtained by heating the corre-
sponding solutions at 808C; then, the samples, covered with foil,
were left to cool to room temperature before HPLC and [a]2D0 meas-
urements. In the case of azo-5b, 20% of the Z isomer was detected
after this process.
[26] A. Koslowski, N. Sreerama, R. W. Woody, in Circular Dichroism:
Principles and Applications (Eds.: K. Nakanishi, N. Berova, R. W.
Woody), Wiley-VCH, Weinheim, 2000, p.55.
[27] For a general discussion of the ab initio calculations of the chiropti-
cal properties, see: a) J. Autschbach, Chirality 2009, 21, E116–E152;
b) J. Autschbach, L. Nitsch-Velasquez, M. Rudolph, Top. Curr.
Chem. 2010, 298, 1–98.
C. F. Chabalowski, M. J. Frisch, J. Phys. Chem. 1994, 98, 11623; d) T.
Yanai, D. P. Tew, N. C. Handy, Chem. Phys. Lett. 2004, 393, 51–57.
[29] The calculations were performed by using the GAUSSIAN09 pack-
age.
[30] Theoretical ECD spectra were obtained for both the length and ve-
locity representations by using the lowest 30 states from the excita-
tion energies and rotational strengths as a sum of the Gaussian func-
tions that were centered at the wavelength of each transition, with a
parameter (s, width of the band at 1/e height) of 0.4 eV. As input ge-
ometries, atomic coordinates from the DFT/B3LYP/TZVP-opti-
mized structures of compounds (Z)-5c, (aR,E)-5c (B), and (aS,E)-
5c (A) from the X-ray analysis of compound 5c have been em-
ployed. The ECD input geometry of compound (P,Z)-5c was built
by changing the dihedral angle (X) in compound (M,Z)-5c and opti-
mizing this new input structure at the DFT/B3LYP/TZVP level.
[31] M. C. CarreÇo, J. L. García Ruano, A. Urbano, Synthesis 1992, 651–
653.
[28] a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648; b) C. Lee, W. Yang,
R. G. Parr, Phys. Rev. B 1988, 37, 785; c) P. J. Stephens, F. J. Devlin,
Received: September 11, 2012
Published online: January 25, 2013
3406
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ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 3397 – 3406