Design and synthesis of chiral spirobifluorenes

Article abstract of DOI:10.1002/chir.23186

Chiroptical spectroscopic methods serve as a practical tool for the structural characterization of chiral systems based on the interaction with polarized light. The higher sensitivity of these methods, compared with their achiral counterparts, not only enables the determination of absolute configuration and conformational preferences, but also supramolecular interactions may be monitored. In order to expand the applicability of chiroptical systems, the development of functional materials exhibiting intense chiroptical responses is essential. As a proof of principle, we previously constructed chiroptical interfaces via thioacetate-derivatized allenes. Because of the photoisomerization issues associated with allenes, we have recently proposed their replacement by spirobifluorenes to achieve robust chiroptical systems. Thus, we hereby present the design and synthesis of chiral spirobifluorenes bearing thioacetates suitable for suface functionalization.

Full text of DOI:10.1002/chir.23186

Received: 29 November 2019
DOI: 10.1002/chir.23186
Revised: 27 December 2019
Accepted: 27 January 2020
S P E C I A L I S S U E A R T I C L E
Design and synthesis of chiral spirobifluorenes
1
2
ꢀ
Ani Ozcelik
| María de los Angeles Peña-Gallego
|
1
1
Raquel Pereira-Cameselle
| J. Lorenzo Alonso-Gómez
1
Departamento de Química Orgánica,
Abstract
Universidad de Vigo, Vigo, Spain
2
Chiroptical spectroscopic methods serve as a practical tool for the structural
characterization of chiral systems based on the interaction with polarized light.
The higher sensitivity of these methods, compared with their achiral counter-
parts, not only enables the determination of absolute configuration and confor-
mational preferences, but also supramolecular interactions may be monitored.
In order to expand the applicability of chiroptical systems, the development of
functional materials exhibiting intense chiroptical responses is essential. As a
proof of principle, we previously constructed chiroptical interfaces via
thioacetate-derivatized allenes. Because of the photoisomerization issues asso-
ciated with allenes, we have recently proposed their replacement by
spirobifluorenes to achieve robust chiroptical systems. Thus, we hereby present
the design and synthesis of chiral spirobifluorenes bearing thioacetates suitable
for suface functionalization.
Departamento de Química Física,
Universidad de Vigo, Vigo, Spain
Correspondence
Raquel Pereira-Cameselle and Lorenzo
Alonso-Gómez Departamento de Química
Orgánica, Universidad de Vigo, Campus
Universitario, E-36310 Vigo, Spain.
Email: raquel@uvigo.es; lorenzo@uvigo.
es
Funding information
IBEROS, Grant/Award Number:
0
245_IBEROS_1_E; Xunta de Galicia,
Grant/Award Numbers: GRC2019/24,
ED431F 2016/005
K E Y W O R D S
chiroptical responses, enantiomeric resolution, spriobifluorenes, synthesis
1
| INTRODUCTION
interactions may be monitored as long as any chiral com-
ponent is present.
10,11
Objects are said to be chiral when they do not coincide
with their mirror images. This property is prevalent in
nature where the building blocks of life, ie, amino acids
The advantages of chiroptical responses could be also
beneficial for applications besides structure elucidation.
Nevertheless, suitable chiroptical systems are scarce.
Great effort has been accordingly devoted to the develop-
1,2
or sugars, are chiral.
Particularly, left- and right-
1
2
handed molecules are referred to as enantiomers and
they uniquely respond to another chiral entity. Likewise,
chiroptical responses arise when enantiomeric forms
interact with circularly polarized light that could feature
ment of systems involving purely organic molecules,
13,14
15,16
complexes,
or plasmonic nanostructures
with
remarkable chiroptical properties in solution. In this
17
18
regard, we have achieved oligomeric, cyclic, or cage-
3,4
19
two opposite handedness.
Based on this fact,
shaped molecular geometries through axially chiral
chiroptical spectroscopies such as electronic and vibra-
tional circular dichroism (ECD and VCD) or optical rota-
tory dispersion (ORD) are routinely employed to explore
allenes. From the application point of view, the efficient
integration of chiroptical systems into devices is funda-
mental and hence the state of matter must be carefully
chosen to meet the requirements of a specific application.
Whereas chiroptical solutions are by far the most abun-
dant, little is known regarding the construction of two-
dimensional (2D) chiroptical surfaces that could be
5
chiral systems. Unlike conventional ultraviolet-visible
(UV/Vis) and fluorescence spectroscopies, chiroptical
methods are highly sensitive to predict absolute configu-
6,7
8,9
ration (AC) and conformational preferences. Addi-
tionally, from short to long-range supramolecular
2
0
employed in daily life. Among other strategies, the
Chirality. 2020;1–10.
wileyonlinelibrary.com/journal/chir
© 2020 Wiley Periodicals, Inc.
1

2
OZCELIK ET AL.
inherent chirality of small organic molecules could be
chiroptical responses in solution. Consequently, we
herein report the design, synthesis, and AC assignment
of thioacetate functionalized SBFs CF-3, CF-4, and CF-5
as a milestone towards the development of chiroptical
surfaces (Scheme 1).
21,22
bestowed upon metal surfaces by self-assembly.
To
this end, we employed chiral framework (CF) CF-1 bear-
ing allenes on Ag (111) under vacuum conditions
(Figure 1A). While the molecular chirality was transferred
to 2D nanostructures by the formation of up-standing chi-
ral architectures (UCAs), the poor stability of these first
examples hindered the exploration of chiroptical
2 | MATERIALS AND METHODS
2.1 | General methods
23
responses at room temperature. To tackle this challenge,
we undertook the strategy of self-assembled monolayers
24
(SAMs)
and synthesized both enantiomers of
thioacetate-derivatized CF-2 for the functionalization of
Au surfaces (Figure 1B). Remarkably, the chiroptical
responses of the formed nanoarchitectures were addressed
by means of second harmonic generation CD spectros-
Solvents were dried according to published methods and
32
distilled before use. high-performance liquid chroma-
tography (HPLC)–grade solvents were used for the HPLC
purification. All other reagents were commercial com-
pounds of the highest purity available. Unless otherwise
stated, all reactions were performed under nitrogen
atmosphere. Flash column chromatography (FC) was
carried out using Merck Kieselgel 60 (230-400 mesh)
under pressure. Analytical thin layer chromatography
(TLC) was performed on aluminum plates with silica gel
Macherey-Nagel UV254 and visualized by UV irradiation
(254 nm) or 365 nm or by staining with a solution of pho-
sphomolybdic acid. HPLC was performed using the sepa-
rations module Waters 2695, the photoiode array detector
Waters 996, and the chiral stationary phase Chiralpak IA
(Diacel Chemical Industries Ltd.). UV/Vis and ECD spec-
tra were recorded on a Jasco J-815 spectropolarimeter at
21
copy on a custom-made transparent substrate. However,
8,25
allenes may undergo photoisomerization,
exploitation for everyday applications.
limiting their
For the last two decades, there has been a rapid rise
in the use of spirobifluorenes (SBFs) in the field of
organic electronics due to their high rigidity, solubility,
and peculiar electronic properties provided by the orthog-
onal arrangement of two fluorine units connected by a
26-28
shared quaternary atom.
Furthermore, such com-
pounds may feature axial chirality upon appropriate sub-
stitution. In comparison with different positional
isomers, 2-substituted SBFs are particularly available for
the extension of conjugation, leading to tuning optical
29
ꢀ
1
13
properties in a well-controlled fashion. Seeking for a
25 C employing 1 cm cuvette. H NMR and C NMR
30
ꢀ
more robust chiral axis, we have theoretically and
spectra were recorded in CDCl at 25 C on a Bruker
3
31
experimentally evaluated the reliability of SBFs in the
construction of stable systems presenting remarkable
AMX-400 spectrometer operating at 400.16 MHz and
100.62 MHz with residual protic solvent as the internal
1
references (CDCl , H = 7.26 ppm) for the former and
3
1
3
33
(
C = 77.16 ppm) for the latter. Chemical shifts (δ) are
given in parts per million (ppm), and coupling constants
J) are given in Hertz (Hz). The spectra are reported as
(
follows: δ (multiplicity, coupling constant J, number of
+
protons, and assignment). HRMS (ESI ) were measured
with an APEX3 instrument. All computational calcula-
34
tions were carried out using the Gaussian 09 program
package.
2.2 | General procedure for copper-free
Sonogashira couplings of terminal spiranic
alkyne
Spiranic alkyne (1 eq), aryl or heteroaryl bromide
(
1.2-1.5 eq), Pd (PPh3)4 (0.1 eq), Et N (8.0 eq), and
3
DMF were added to a heat-gun-dried Schlenk tube. The
resulting mixture was thoroughly degassed with three
ꢀ
FIGURE 1 Structures of (A) (M,M)-CF-1 and (B) (M)-CF-2
previously studied for surface functionalization
freeze-thaw cycles and stirred for 20 h at 100 C. After
2
1,23
allowing to cool down to room temperature, the crude

OZCELIK ET AL.
3
SCHEME 1 Synthesis of chiral
frameworks. Reagents and conditions:
(
3 4 3
i) 2-methyl-3-butyn-2-ol Pd (PPh ) , Et N,
ꢀ
DMF, 24 h, 71%; (ii) NaOH, Toluene, 90 C, 8 h
ꢀ
7
8%; (iii) MeSO
2
Cl, Et
3
N, CH
2
Cl
2
, 0-25 C, 20-24
ꢀ
h; (iv) KSAc, DMF, 0-25 C, 3 d, 80% (5), 69% (7),
3 4 3
and 73% (9); (v) Pd (PPh ) , Et N, DMF, 20 h,
4
7% ((±)-CF-3), 66% ((±)-CF-4), and 24% ((±)-
CF-5). For the sake of simplicity, acetyl group is
abbreviated as Ac

4
OZCELIK ET AL.
0
0
was extracted with CH Cl (3×), washed with deionized
water (3×) and brine (3×), and dried over anhydrous
131.7 (2×, C3 and C3 ), 128.5 (2×, C6 and C6 ), 128.2 (2×,
2
2
0
0
C7 and C7 ), 127.5 (2×, C1 and C1 ), 124.3 (2×, C8 and
C8 ), 120.5 (2×, C4 and C4 ), 120.1 (2×, C5 and C5 ), 94.2
0
0
0
Na SO .
2
4
(
2×, ─C≡CC (CH ) OH), 82.0 (2×, ─C≡CC (CH ) OH),
3
2
3 2
6
5.7 (2×, ─C (CH ) OH), 65.6 (C9), 31.5 (4×, ─C
3 2
2
.3 | General procedure for preparation
(CH ) OH) ppm. ESI-MS: m/z Calcd. for C H NaO
3 2 35 28 2
[(M + Na)] 503.19815; found, 503.19816.
+
of thioacetates
Into a heat-gun-dried round-bottom flask, alcohol (1.0
ꢀ
eq) was dissolved in CH Cl and cooled to 0 C. Subse-
2.4 | (± ±-2-(3-methyl-3-hydroxy-1-butyn-
1-yl±-2 -ethynyl-9ꢀ9 -spirobi[fluorene]((± ±-3±
2
2
0
0
quently, Et N (1.5 eq) and MeSO Cl (2.0 eq) were added
3
2
dropwise. After 10 minutes, the ice bath was removed
and the resulting mixture was stirred for 18 to 24 hours
at 25 C. Once the reaction was completed, an aqueous
(±)-2 (0.47 mmol, 227 mg), anhydrous NaOH (70.5 mmol,
2834 mg), and dry toluene (94 mL) were added to the
heat-gun-dried two-necked round-bottom flask. The mix-
ꢀ
solution of saturated NaHCO was added. The reaction
3
ꢀ
mixture was extracted with CH Cl (3×), washed with
ture was stirred for 8 hours at 90 C. After cooling to room
2
2
deionized water (2×) and brine (1×), and dried over
temperature, deionized water was added and the aqueous
layer was extracted with EtOAc (3×). The organic layer
was washed with deionized water (2×) and brine (1×)
and dried over anhydrous Na SO . Purification via flash
anhydrous Na SO . The resulting oil was dissolved in
2
4
ꢀ
DMF and cooled to 0 C. After addition of KSAc (1.5 eq),
the ice bath was removed and the mixture was stirred for
2
4
ꢀ
3
days at 25 C. The crude was poured to deionized water
column chromatography (SiO , gradient from 25% to 30%
2
and extracted with CH Cl (3×). The organic layer was
EtOAc/n-hexane) gave (±)-3 as pale yellow solid (155.0
2
2
washed with deionized water (4×) and brine (2×) and
mg, 78%). Spectroscopic data matched to that of previ-
31 1
dried over anhydrous Na SO . Finally, the solvent was
ously reported. H NMR (400.16 MHz, CDCl , δ): 7.9 –
2
4
3
evaporated under vacuum to give the corresponding
thioacetate of sufficient purity.
7.8 (m, 4H), 7.53 (dd, J = 7.9, 1.4 Hz, 1H), 7.45 (dd, J =
7.9, 1.4 Hz, 1 H), 7.39 (td, J = 7.5, 1.0 Hz, 1H), 7.38 (td,
J = 7.5, 1.0 Hz, 1H), 7.14 (td, J = 7.5, 1.0 Hz, 1H), 7.13 (td,
J = 7.5, 1.1 Hz, 1H), 6.84 (dd, J = 1.3, 0.5, 1H), 6.77 (dd,
J = 1.4, 0.5, 1H), 6.73 (d, J = 7.6 Hz, 1H), 6.72 (d, J = 7.6
0
2
1
.3.1 | (± ±-2ꢀ2 -bis(3-methyl-3-hydroxy-
0
-butyn-1-yl±-9ꢀ9 SBF((± ±-2±
Hz, 1H), 2.97 (s, 1H, C≡C─H), 1.52 (s, 6H, 2×CH ) ppm.
3
0
Into a heat-gun-dried Schlenk tube, (±)-2,2 -dibromo-
0
9
(
1
,9 -SBF ((±)-1) (1.05 mmol, 500 mg) and Pd (PPh )
2.4.1 | 5-bromo-2-(acetylthiomethyl±
pyridine (5±
3
4
0.21 mmol, 243 mg) were added and purged for
0 minutes. Afterwards, Et N (5.3 mL) and DMF (15.7
3
mL) were added. The resulting mixture was purged for
additional 30 minutes. Finally, 2-methyl-3-butyn-2-ol
Following the general procedure for the preparation of
thioacetates, alcohol 4 (1.06 mmol, 200 mg) was dissolved
in CH Cl (2.9 mL) and treated with Et N (1.6 mmol,
(
5.27 mmol, 0.52 mL) was added and the mixture stirred
2
2
3
ꢀ
for 24 hours at 105 C. After cooling down, the deionized
water was added. The aqueous layer was extracted with
CH Cl (3×) and the organic layer washed with deionized
0.22 mL) and MeSO Cl (2.20 mmol, 0.12 mL) for 18 hours.
2
After work-up, the crude was dissolved in DMF (5.3 mL)
and stirred for 48 hours with KSAc (1.60 mmol, 182 mg)
to give 5 as a pale brown oil (195 mg, 80%). The spectro-
2
2
water (4×) and brine (2×) and dried over anhydrous
2
1 1
Na SO . Purification via flash column chromatography
scopic data was identical that of previously reported.
H
2
4
(
SiO , 30% EtOAc/n-hexane) yielded (±)-2 as pale brown
NMR (400.16 MHz, CDCl , δ): 8.58 (d, J = 1.9 Hz, 1H,
C6), 7.74 (d, J = 8.3 Hz, 1H, Py), 7.26 (d, J = 8.3, 1H, Py),
2
3
1
solid (362.3 mg, 71%). H NMR (400.16 MHz, CDCl , δ):
7
Hz, 2H, H4 and H4 ), 7.44 (dd, J = 7.9, 1.5, 2H, H3 and
H3 ), 7.38 (td, J = 7.5, 1.1 Hz, 2H, H6 and H6 ), 7.13 (td,
J = 7.5, 1.1 Hz, 2H, H7 and H7 ), 6.77 (dd, J = 1.5, 0.7 Hz,
2
1
CDCl , δ): 148.6 (2×, C8b, and C8b ), 148.4 (2×, C8a, and
C8a ), 142 (2×, C4a and C4a ), 141.2 (2×, C4b and C4b ),
3
0
.83 (d, J = 7.5 Hz, 2H, H5 and H5 ), 7.78 (dd, J = 7.9, 0.7
4.19 (s, 2H, PyCH S), 2.36 (s, 3H, SCOCH ) ppm.
2
3
0
0
0
0
2.4.2 | 6-bromo-2-(acetylthiomethyl±
pyridine (7±
0
0
H, H1 and H1 ), 6.72 (d, J = 7.6 Hz, 2H, H8 and H8 ),
13
.51 (s, 12H, 2×(CH ) ) ppm. C NMR (100.63 MHz,
3
2
0
Following the general procedure for the preparation of
thioacetates, alcohol 6 (1.06 mmol, 200 mg) was dissolved
3
0
0
0

OZCELIK ET AL.
5
0
in CH Cl (2.9 mL) and treated with Et N (1.6 mmol,
J = 7.9, 1.3 Hz, 1H, H3 ), 7.42 (td, J = 7.5, 1.5 Hz, 1H,
2
2
3
0
0
.22 mL) and MeSO Cl (2.20 mmol, 0.12 mL) for 24 hours.
H6), 7.41 (td, J = 7.5, 1.5 Hz, 1H, H6 ), 7.30 (d, J = 7.8
2
0
0
After work-up, the crude was dissolved in DMF (6 mL)
and stirred for 72 hours with KSAc (1.60 mmol, 182 mg)
Hz, 1H, H3 ), 7.17 (td, J = 7.6, 1.1 Hz, 1H, H7), 7.16 (td,
0
J = 7.6, 1.1 Hz, 1H, H7 ), 6.91 (d, J = 1.0 Hz, 1H, H1),
1
0
to give 7 as a pale brown oil (181 mg, 69%). H NMR
6.81 (d, J = 1.0 Hz, 1H, H1 ),6.76 (d, J = 7.5 Hz, 1H, H8),
6.75 (d, J = 7.5 Hz, 1H, H8 ), 4.24 (s, 2H, PyCH S), 2.37
0
(
400.16 MHz, CDCl , δ): 7.48 (t, J = 7.6 Hz, 1H), 7.35 (d,
3
2
3
1
J = 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H), 4.20 (s, 2H,
(s, 3H, SCOCH ), 1.53 (s, 6H, C (CH3) ) ppm. C NMR
3 2
13
00
(100.63 MHz, CDCl , δ): 194.9(─C═O), 156.4 (C2 , Py),
3
PyCH S), 2.35 (s, 2H, SCOCH ) ppm. C NMR (100.62
2
3
00
151.7 (C6 , Py), 148.7, 148.6, 148.4, 148.2, 142.5, 141.9,
MHz, CDCl , δ): 194.5 (─C═O), 158.8 (C2, Py), 141.3 (C6,
3
00 0
141.1, 141.0, 139.1 (C4 , Py), 131.8 (C3), 131.7 (C3 ), 128.6
Py), 139.0 (C4, Py), 126.5 (C5, Py), 122.0 (C3, Py), 34.7
0
0
(
PyCH S), 30.2 (SCOCH ) ppm. ESI-MS: m/z Calcd. for
(C7), 128.5 (C7 ), 128.2 (2×, C6 + C6 ), 127.4 (2×, C1 +
2
9
3
81
7
0
0
0
0
C H BrNOS and C H9 BrNOS [(M + H)]+, 245.95827
C1 ), 124.3 (C8), 124.2 (C8 ), 122.8 (C3 , Py), 122.1 (C2),
8
9
8
0 00
121.7 (C2 ), 120.6, 120.5, 120.2, 120.1, 118.9 (C5 , Py),
and 247.95662; found, 245.95866 and 247.95662.
9
(
4.4 (─C≡CC (CH ) OH), 93.1 (─C≡CC (CH ) OH), 86.3
─C≡CPy), 82.3 (─C≡CPy), 65.6 (2×, C9 and C
3
2
3 2
2
.4.3 | 4-bromo-1-(acetylthiomethyl±
(CH ) OH), 35.3 (PyCH S), 31.5 (2×C (CH ) OH), 30.3
3 2 2 3 2
benzene (9±
(─COCH ) ppm. HRMS-ESI: m/z Calcd. for C H NO S
3 40 30 2
+
[
(M + H)] , 588.19918; found, 588.19843.
Following the general procedure for the preparation of
thioacetates, alcohol 8 (2.67 mmol, 500 mg) was dissolved
in CH Cl (7.4 mL) and treated with Et N (4.00 mmol,
0
2.4.5 | (± ±-2 -[(6-[(acetylthio±methyl]
2
2
3
0
.56 mL) and MeSO Cl (5.35 mmol, 0.31 mL) for 22 hours.
pyridin-2-yl±ethynyl]-2-(3-hydroxy-
3-methylbut-1-yn-1-yl±-9ꢀ9 -
spirobi[fluorene] ((± ±-CF-4±
2
0
After work-up, the crude was dissolved in DMF (9.9 mL)
and stirred with KSAc (4.00 mmol, 457 mg) to give 9 as a
1
dark brown oil (475 mg, 73%). H NMR (400.16 MHz,
CDCl , δ): 7.41 (d, J = 8.5, 2H, H3 and H5), 7.16 (d, J =
Following the general procedure described for copper-
free Sonogashira cross-coupling, (±)-3 (0.14, 60 mg),
heteroaryl bromide 7 (0.17 mmol, 41.3 mg), Pd (PPh3)4
3
8
.5, 2H, H2 and H6), 4.05 (s, 2H, PhCH S), 2.34 (s, 3H,
2
13
SCOCH ) ppm. C NMR (100.63 MHz, CDCl , δ): 194.9
3
3
(
─C═O), 136.9 (C), 131.8 (2×, C3 and C5, Ph), 130.6 (2×,
(0.014 mmol,16.4 mg), Et N (1.2 mmol, 0.16 mL), and
3
C2 and C6, Ph), 121.3 (C), 32.9 (PhCH S), 30.4 (SCOCH )
DMF (1.5 mL) were added to a heat-gun-dried Schlenk
tube. After stirring the mixture up for 20 hours and
work-up, purification of the crude through flash column
2
3
79
ppm. ESI-MS: m/z Calcd. for C H BrOS and
9
10
81
10
+
C H BrOS [(M + H)] , 244.9630 and 246.9609; found,
9
2
44.9639 and 246.9620.
chromatography (SiO , 35% EtOAc/n-hexane) yielded
2
1
(±)-CF-4 as pale yellow solid (54.5 mg, 66%). H NMR
(
400.16 MHz, CDCl , δ): 7.9 – 7.8 (m, 3H, H5, H4 and
3
0
0
0
2
.4.4 | (± ±-2 -[(5-[(acetylthio±methyl]
H5 ), 7.78 (d, J = 7.9 Hz, 1H, H4 ), 7.62 (dd, J = 7.9, 1.5
Hz, 1H, H3), 7.53 (t, J = 7.8 Hz, 1H and H4 ), 7.44 (dd,
J = 7.9, 1.5 Hz, 1H, H3 ), 7.40 (td, J = 7.5, 1.5 Hz, 1H and
H6), 7.38 (td, J = 7.5, 1.5 Hz, 1H, H6 ), 7.26 (d, J = 7.5
Hz, 1H, H5 ), 7.23 (d, J = 7.5 Hz, 1H, H3 ), 7.15 (td, J =
7.6, 1.1 Hz, 1H, H7), 7.13 (td, J = 7.6, 1.1 Hz, 1H, H7 ),
6.96 (d, J = 1.2 Hz, 1H, H1), 6.82 (d, J = 1.1 Hz, 1H, H1 ),
6.75 (d, J = 7.8 Hz, 1H, H8), 6.73 (d, J = 7.8 Hz, 1H, H8 ),
4.25 (s, 2H, PyCH S), 2.33 (s, 3H, C OCH )0.1.51 (s, 6H,
2×C(CH ) ) ppm. C NMR (100.63 MHz, CDCl , δ):
3 2 3
195.1 (─C═O), 158.2 (C2 , Py), 148.6, 148.5, 148.4, 148.2,
142.9 (C6 , Py), 142.6, 141.9, 141.1, 141.0, 137.0 (C4 , Py),
131.9 (C3), 131.7 (C3 ), 128.7 (C7), 128.5 (C7 ), 128.2 (2×,
C6 and C6 ), 128.1 (C1), 127.4 (C1 ), 125.7 (C5 , Py),
124.3 (C8), 124.2(C8 ), 122.5 (C3 , Py), 122.1 (C2 ), 121.3
(C2), 120.6, 120.5, 120.2, 120.1, 94.3 (C≡CC (CH ) OH),
0
0
pyridin-2-yl±ethynyl]-2-(3-hydroxy-
-methylbut-1-yn-1-yl±-9ꢀ9 -
spirobi[fluorene] ((± ±-CF-3±
0
0
3
0
0
0
00
0
0
0
Following the general procedure described for copper-
free Sonogashira cross-coupling, spiranic alkyne (±)-3
0.14, 60 mg), aryl bromide 5 (0.20 mmol, 48.2 mg), Pd
PPh ) (0.014 mmol,16.4 mg), Et N (1.12 mmol, 0.16
mL), and DMF (1.5 mL) were added to a heat-gun-dried
Schlenk tube. After stirring the mixture up for 20 hours
and work-up, purification of the crude through flash col-
umn chromatography (SiO , gradient from 25% to 40%
EtOAc/n-hexane) yielded (±)-CF-3 (38.8 mg, 47%) as pale
yellow solid. H NMR (400.16 MHz, CDCl , δ): 8.57 (dd,
J = 2.1, 0.9 Hz, 1H, H6 ), 7.9 – 7.8 (m, 3H, H5, H5 and
H4), 7.80 (d, J = 7.9 Hz, 1H, H4 ), 7.63 (dd, J = 8.1, 2.1
Hz, 1H, H4 ), 7.58 (dd, J = 7.9, 1.3 Hz, 1H, H3), 7.47 (dd,
(
(
3
4
3
2
3
13
0
0
0
0
00
0
0
2
0
0
0
0
1
0
00
0
3
00
0
3
2
0
89.7 (C≡CC (CH ) OH), 89.0 (─C≡CPy), 82.4 (─C≡CPy),
65.6 (2×, C9 and C (CH ) OH), 35.4 (PyCH S), 31.5 (2×,
3 2 2
3
2
0
0

6
OZCELIK ET AL.
─
C (CH ) OH), 30.3 (─COCH ) ppm. HRMS-ESI: m/z
Among the other coinage metals, Au strongly interacts
with S and presents several advantages for instance not
having stable oxides at ambient conditions. Therefore,
the proposed CFs CF-3, CF-4, and CF-5 (Scheme 1,
Figure 2) are composed of a chiral moiety, an aromatic
spacer, and a head group (Figure 2).
3
2
3
+
Calcd. for C H NNaO S [(M + Na)] , 610.18112; found,
40
29
2
6
10.18085.
0
2
.4.6 | (± ±-2 -[(5-[(acetylthio±methyl]
benzene-2-yl±ethynyl]-2-(3-hydroxy-
Whereas the chirality of CFs is introduced by the
photostable SBF, an acetyl protection is undertaken for
the anchoring group in order to avoid by-products
encountered with thiols (ie, formation of disulfides,
Scheme 1). Starting off with CF-3, this first member is
0
3
-methylbut-1-yn-1-yl±-9ꢀ9 -
spirobi[fluorene] ((± ±-CF-5±
Following the general procedure described for copper-
free Sonogashira cross-coupling, (±)-3 (0.11, 45 mg), aryl
2
1
the spiro analogue of the previously studied CF-2.
bromide
9
(0.15 mmol, 36.5 mg), Pd (PPh3)4
Referring to our earlier studies, the interaction between
molecules and the surface by the pyridine ring is
expected to favor up-right orientation. To further unveil
the influence of the aromatic spacer on the properties of
the resulting functionalized surfaces, spiro compounds
CF-4 and CF-5 feature different substitution pattern and
aromatic spacer, respectively.
(0.011 mmol,12.7 mg), Et N (0.99 mmol, 0.12 mL), and
3
DMF (1.5 mL) were added to a heat-gun-dried Schlenk
tube. After stirring the mixture up for 20 hours and
work-up, purification of the crude through flash column
chromatography (SiO , gradient from 25% to 30% EtOAc/
n-hexane) led to (±)-CF-5 as pale pale yellow solid (15.5
2
mg, 24%).
0
(
400.16 MHz, CDCl , δ): 7.9 – 7.8 (m, 3H, H5, H5 and
3
0
H4), 7.78 (dd, J = 7.9, 0.5 Hz, 1H, H4 ), 7.55 (J = 7.9, 1.5
Hz, 1H, H3 ), 7.44 (J = 7.9, 1.5 Hz, 1H, H3), 7.39 (td, J =
3.2 | Synthesis
0
0
00
7
.4, 1.0 Hz, 2H, H6 and H6 ), 7.33 (d, J = 8.3 Hz, 2H, H3
CF-3, CF-4, and CF-5 were synthesized through a non-
enantioselective pathway (Scheme 1), followed by enan-
tiomeric resolution (more details are given in the next
section).
0
0
00
00
and H5 ), 7.20 (d, J = 8.3 Hz, 2H, H2 and H6 ), 7.14 (td,
0
J = 7.4, 1.0 Hz, 2H, H7 and H7 ), 6.88 (dd, J = 1.5, 0.5 Hz,
0
1
H, H1 ), 6.80 (dd, J = 1.5, 0.5 Hz, 1H, H1), 6.75 (d, J =
0
7
.4 Hz, 1H, H8 or H8 ), 6.73 (d, J = 7.4 Hz, 1H, H8 or
Sonogashira cross coupling of (±)-1 with a large
excess of 2-methyl-3-butyn-2-ol gave disubstiuted (±)-2
(71%). The reaction was also performed through CuI/Pd
(PPh ) Cl catalytic system and the yield decreased by
20% since Cu(I) salts could induce the dimerization of
acetylene through Glaser-type oxidative homocoupling.
To investigate the effect of the solvent, toluene was
0
H8 ), 4.08 (s, 2H, PhCH S), 2.34 (s, 3H, SC OCH ), 1.51
2
3
1
3
(s, 6H, 2×C(CH ) ) ppm. C NMR (100.63 MHz, CDCl ,
3 2 3
δ): 195.1 (─C═O), 148.7, 148.6, 148.5, 148.4, 142.1, 142.0,
3
2
2
00
00
00
1
1
41.2 (2×), 137.9 (C1 , Ph), 131.8 (C3 and C5 , Ph),
0
00
00
31.7 (C3 and C3 ), 128.9 (C2 and C6 ,Ph), 128.5 (2×, C7
0
0
0
and C7 ), 128.2 (2×, C6 and C6 ), 127.5 (C1 ), 127.4 (C1),
0
00
1
24.3 (2×, C8 and C8 ), 122.6 (C), 122.3 (C4 , Ph), 122.1,
0
0
1
20.5 (2×, C5 and C5 ), 120.2 (C4), 120.1 (C4 ), 94.2
(
C≡CC (CH ) OH) , 90.0 (─C≡CPh), 89.7 (─C≡CPh),
3
2
8
2.5 (C≡CC (CH ) OH), 65.7 (2×, C9, and C (CH ) OH),
3
2
3 2
3
3.4 (PhCH S), 31.5 (2×, ─C (CH ) OH), 30.5 (─COCH )
2
3 2
3
ppm. HRMS-ESI: m/z Calcd. for C H NaO S [(M +
41
30
2
+
Na)] , 609.18587; found, 609.18748.
3
3
| RESULTS AND DISCUSSION
.1 | Design
The stability of a chiral molecule-substrate pair plays a
crucial role towards the development of robust
chiroptical surfaces. Taking into account the strategy of
SAMs, surface properties could be tailored in a well-
controlled fashioned through the adsorption of organic
thiols on Au surfaces either from liquid or gas phase.
FIGURE 2 Representation of chiral frameworks

OZCELIK ET AL.
7
employed and no traces of product was observed. Subse-
quently, the selective deprotection was achieved by pre-
cisely controlling the reaction time as well as
temperature leading to (±)-3 in 78% yield. On the other
hand, commercially available alcohols 4, 6, and 8 were
transformed to the corresponding thioacetates by two
stiution of each mesylate by SAc in DMF, yielding
5 (80%), 7 (69%) and 9 (73%) of sufficient purity to be
used without further purification. It is important to note
that the described procedure for the preparation of each
thioacetate was more efficient than Appel-type reaction
conditions with CBr4 and PPh . Finally, copper-free
3
consecutive S 2 reactions. While the former involved the
Sonogashira reaction between thioacetates 5, 7, and
9 with (±)-3 afforded the desired CFs (±)-CF-3 (47%),
(±)-CF-4 (66%), and (±)-CF-5 (24%), respectively.
Regarding the final step, the same conditions were
employed to understand the reactivity of each aromatic
halide. The higher yields for pyridine-containing CFs
could be attributed to the inductive effect of the nitrogen
atom, which is not present in thioacetate 9.
N
treatment of each alcohol with an excess of MeSO Cl and
2
Et N in CH Cl , the latter was the nucleophilic sub-
3
2
2
TABLE 1 Thermal stability of CF-3, CF-4, and CF-5
ꢀ
Compound
Temperature ( C±
CF-3
CF-4
CF-5
172.3
254.5
214.2
The thermal bahavior of the racemic mixtures of CF-
3, CF-4, and CF-5 were examined by means of ther-
mogravimetric analysis under air atmosphere. We note
from Table 1 that overall the compounds presented high
thermal stability, which may be affected by the substitu-
tion pattern as well as aromatic moiety. Once exceeding
the presented temperature values, each compound was
decomposed.
TABLE 2 Enantiomeric resolution data of CF-3, CF-4, and
CF-5
Retention
Flow
Time
Compound Solvent System
(min/mL± (min±
a
b
b
b
CF-3
CF-4
CF-5
i-PrOH/CH
n-Hex
2
Cl
2
/
2.0
2.0
2.0
17.3 ; 24.6
3.3 | Enantiomeric Resolution
(2/20/78±
a
i-PrOH/CH
n-Hex
2
Cl
2
/
35.0 ; 39.5
The enantiomers of CF-3, CF-4, and CF-5 were resolved
through semi-preparative HPLC using the chiral station-
ary phase Chiralpak IA (CSP, Diacel Chemical Industries
Ltd.). As summarized in Table 2, the conditions were
slightly modified due to the different polarity of each
compound (for chromtograms, see Supporting
Information).
(
1/15/84±
Chloroform/
n-Hex (30/70±
a
23.2 ; 24.8
Abbreviation: HPLC, high-performance liquid chromatography.
a
Retention times for fraction A obtained from HPLC.
b
Retention times for fraction B obtained from HPLC.
FIGURE 3 Simplified structures (P)-10,
(
P)-11, and (P)-12 used for density functional
theory (DFT) studies from CF-3, CF-4, and CF-
, respectively
5

8
OZCELIK ET AL.
3
.4 | Absolute Configuration Assignment
state properties, the obtained geometries were further
optimized and their vibrational frequencies were calcu-
lated at cam-B3LYP/6-31G(d,p) level including the sol-
vent effect through the polarizable continuum model
(PCM). ECD and UV/Vis spectra were subsequently sim-
ulated solving 20 states at the same level of theory. Typi-
cally, the chiral signatures of possible minima contribute
in chiroptical responses as a function of their predicted
Ab initio methods have been widely employed for shed-
35
ding light on chiroptical responses. Since our synthetic
methodology was non-enantioselective, density func-
tional theory (DFT) studies were carried out to
unambigously assign the AC of each fraction obtained
from the enantiomeric resolution.
The CFs were simplified by removing thioacetate and
dimethyl alcohol moieties (Figure 3) due to the fact that
their influence on the AC determination was found to be
insignificant (for more details see Figures S1–S9 and S13–
S15 in the Supporting Information). To perform confor-
mational anaylses of simplified structures (P)-10, (P)-11,
and (P)-12, the potential energy surfaces were initially
scanned through varying dihedral angles in redundant
coordinates at B3LYP/6-31G(d,p) (Figure 4). Unlike in
the case of (P)-12, anti and syn conformations of similar
energies were determined for pyridine bearing (P)-10 and
5
Gibbs free energies according to Boltzmann distribution.
Therefore, ECD spectra of (P)-11 and (P)-12 were derived
from the equal contribution of anti and syn
conformations.
The experimental UV/Vis and ECD spectra were
recorded for the resolved enantiomers of CF-3, CF-4, and
CF-5 in CH Cl at different concentrations (from 2 ×
2
2
(
P)-11 as the N atom could be either in the vicinity or far
from the spiranic C atom (Figure 4). Considering the
experimental conditions and describing well the excited-
FIGURE 5 Comparison of the experimental circular
dichroism (CD) spectra of the enantiomers of CF-3 (solid grey and
black lines for fractions A and B, respectively) with that of
simulated of simplified structure (P)-10 (dash dot line). The
2 2
experimental spectra were measured in CH Cl at a concentration
of 2 × 10− M. For the sake of clarity, the simulated spectrum was
5
shifted by 0.20 eV
FIGURE 6 Comparison of the experimental circular
dichroism (CD) spectra of the enantiomers of CF-4 (solid grey and
black lines for fractions A and B, respectively) with that of
simulated of simplified structure (P)-11 (dash dot line). The
FIGURE 4 Conformational analyses of simplified structures
(
top) (P)-10 and (bottom) (P)-11 by potential energy surface
2 2
experimental spectra were measured in CH Cl at a concentration
mapping at B3LYP/6-31G(d,p) level. The dihedral angle is
represented by a-b-c-d. The two minimum structures, anti- and syn-
conformations, have similar energies
of 4 × 10− M. For the sake of clarity, the simulated spectrum was
5
shifted by 0.19 eV

OZCELIK ET AL.
9
functionalization of Au surfaces, but also it may lead to
rationalizing the effect of substitution pattern as well as
aromatic spacers on the chiroptical responses of the
formed nanoarchitectures.
ACKNOWLEDGEMENTS
This work was funded by Xunta de Galicia
(
(
ED431F 2016/005 and GRC2019/24) and IBEROS
0245_IBEROS_1_E). A.O. thanks Xunta de Galicia for
predoctoral fellowship. J.L.A.-G. thanks the Spanish
Ministerio de Economía y Competividad for a “Ramón
y Cajal” research contract. All authors gratefully
acknowledge CACTI de Vigo. The authors also would
like to thank A. Acuña Couña (CACTI de Vigo) for his
support in the enantiomeric resolution and TGA
analysis.
FIGURE 7 Comparison of the experimental circular
dichroism (CD) spectra of the enantiomers of CF-5 (solid grey and
black lines for fractions A and B, respectively) with that of
simulated of simplified structure (P)-12 (grey solid line). The
2 2
experimental spectra were measured in CH Cl at a concentration
of 4 × 10−5 M. For the sake of clarity, the simulated spectrum was
shifted by 0.20 eV
ORCID
Ani Ozcelik https://orcid.org/0000-0002-3475-6928
ꢀ
María de los Angeles Peña-Gallego https://orcid.org/
0
0− M to 4 × 10−5 M). The prepared solutions were mea-
5
1
000-0002-6898-8305
Raquel Pereira-Cameselle https://orcid.org/0000-0003-
634-9799
J. Lorenzo Alonso-Gómez https://orcid.org/0000-0002-
107-0120
sured for 3 weeks under daylight irridiation. The charac-
teristic shapes and intensities of the UV and ECD bands
remained unchanged, demonstrating the photostability
of the developed CFs (please refer to Figures S10–S12 in
the Supporting Information for the spectra).
2
6
The experimental spectra feature vibronic couplings
apart from the pure electronic transitions; however, they
are broadly in a good agreement with the simulated ECD
spectra of simplified structures (P)-10, (P)-11, and (P)-12
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