Modulation of chiroptical properties in a series of helicene-like

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Modulation of chiroptical properties in a series of helicene-like compounds Laure Guy, Maëlle Mosser, Delphine Pitrat, Jean-Christophe Mulatier, Mercedes Kuku#ka, Monika Srebro-Hooper, Erwann Jeanneau, Amina Bensalah-Ledoux, Bruno Baguenard, and Stephan Guy J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01465 • Publication Date (Web): 09 Aug 2019 Downloaded from pubs.acs.org on August 12, 2019

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The Journal of Organic Chemistry

Modulation of chiroptical properties in a series of helicene-like compounds Laure Guy,∗,† Maëlle Mosser,† Delphine Pitrat,† Jean-Christophe Mulatier,† Mercedes Kukulka,‡ Monika Srebro-Hooper,∗,‡ Erwann Jeanneau,¶ Amina Bensalah-Ledoux,§ Bruno Baguenard,§ and Stéphan Guy§ †Univ. Lyon, ENS Lyon, CNRS, Université Claude Bernard Lyon 1, UMR 5182, Laboratoire de Chimie , F69342, Lyon, France ‡Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland ¶Centre de Diffractométrie Centre de Diffractométrie , Université de Lyon, 5 rue de la doua, 69100 Villeurbanne §Univ. Lyon, Université Claude Bernard Lyon 1, CNRS, UMR 5306, Institut Lumière Matière, F-69622, Lyon, France E-mail: [email protected]; [email protected] Phone: +33 (0)6 1816 4283; +48 (0)12 686 2383

Abstract

group is particularly interested in the development of novel chirowaveguides based on chiral molecules that are transparent in the visible spectral range but demonstrate in this region optical rotation (OR) larger than that for binapthyl derivatives. 6 Based on the promising features of the previously reported helical dibenzo[c]acridine derivative that comprises 8 rings in its structure (molecule 9 in Scheme 1), 7 herein, we present a synthesis and a full characterization of two novel, enantiopure helicenelike systems 5 and 7 exhibiting 11 cycles in their molecular skeleton. They have been obtained on a gram scale from the conglomerate bis-tetralone intermediate 1 8 via a straightforward two-step pathway that involves a cyclization of the axially chiral 10-rings precusors 4 and 6. Photophysical and chiroptical properties of these novel compounds have been studied in solution via OR polarimetry, electronic circular dichroism (ECD) along with non-polarized and circularly polarized luminescence (CPL) spectroscopies, and their strong dependence on a molecular structure has been shown. In particular, high optical activity of the constrained (closed ) derivatives vs. their non-constrained

We describe a large-scale synthesis of a series of helicene-like compounds based on a dibenzo[c]acridine fragment by the Friedlander reaction. The series includes targeted constrained (closed ) derivatives comprising 11 rings that exhibit very intense CPL (glum = 8 × 10−3 ) contrary to their non-constrained (open) 10-rings precursors that are not CPL active. The relationship between structure and chiroptical properties in the series is discussed with the aid of quantum-chemical calculations.

Introduction Helicenes, due to their uncommon molecular structure and physico-chemical properties, arise a large interest in the scientific community. 1,2 Modifications of their regular ortho-fused aromatic rings skeleton give rise to helicene-like compounds that have been playing an important role in the design of new chiroptically active molecules and have opened access for a much wider scope of application. 3–5 Our

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(open) precursors with its enhancement for the systems with larger number of the aromatic rings have been highlighted, revealing the unprecedented helicene-like compounds of very intense CPL (glum = 8 × 10−3 ). The observed relationship between structure and chiroptical properties has been rationalized with a help of first-principles calculations.

nol using iodochloromethane in 65% yield give the desired (±)-, (–)-, or (+)-5. Similarly, 8-aminoquinoline-7-carbaldehyde 3 19 affords 12,12’-dimethoxy-8,8’,9,9’-tetrahydro-13,13’binaphtho[1,2-b][1,10]phenanthroline (–)- and (+)-6 in 72-80% yield, from which enantiopure cyclized derivatives (–)- and (+)-7 are also easily obtained in 60-70% yield.

Results and discussion

Solid-state structure elucidation (±)-4, (±)-6, (+)-5, and (+)-7 gave monocrystals suitable for X-ray analysis by slow evaporation. Table 1 presents ‘face’ and ‘side’ elevations of the molecular geometries of the compounds present in their X-ray crystal structures. The variation in conformations is mainly characterised by a change in the biphenyl torsional angle, θ, which varies from 115◦ to 50◦ along the series 4>6>7>5. The angle ω between the two benzo[h]quinoline or 1,10phenanthroline moieties’ planes, describing helicity of the system, ranges from 62◦ in 4 to 7◦ in 6. The helical pitch (distance between the terminal rings) is mainly affected by the flexibility of backbone allowed by the saturated -CH2 CH2 - (and -O-CH2 -O-) bridges. This is clearly evidenced for 6 that reveals a small distance between two chromophores of 3.6 ˚ A and a small ω ◦ value (7 ) indicating strong intramolecular π-π stacking interactions. Density functional theory (DFT) geometry optimizations performed for isolated molecular structures of 4-7, considering different conformers that varied in the relative orientation of the saturated -CH2 -CH2 bridges (see Figure 1 for 4-5, and Supporting Information for 6-7), confirm strong dependence of θ, ω, and helical pitch parameters for 4-7 on both rigidity of the system, arrangement of the saturated bridges, and intramolecular C– H-π and π-π type interactions between rings.

Synthesis A strategic role of bis-tetralone 1 as a building block in the synthesis of enantiopure dibenzo[c]acridine derivatives has been already proven. 7,8 Helicene-like structures are obtained by extending π-conjugation of the skeleton of 1 thanks to the Friedlaender condensation of aromatic 2-amino-substituted carbonyl compounds with carbonyl derivatives containing non-substituted α-methylene, leading to quinolines. 9 Few limitations for this reaction have been encountered, 10 and a large variety of resulting quinolines containing polyaromatics has been reported. 11–18 As shown in Scheme 1, this reaction allowed a straightforward conversion of 1 into two new helically-shaped (i.e. axially chiral) compounds 5 and 7 composed of 11 rings. Starting from 1 and 1amino-2-naphthaldehyde 2, 19 two simultaneous condensations give 2,2’-dimethoxy-5,5’,6,6’tetrahydro-1,1’-bidibenzo[c,h]acridine, 4. In one step, six new aromatic rings are created with the excellent yield of 91%. Moreover, the conditions (5h at 70 ◦ C under microwave irradiation) are soft enough to maintain the enantiomeric excess of 1. Both enantiomers, (–)-Ra - and (+)-Sa -4, were isolated starting from (+)-Ra - or (–)-Sa -1, respectively. Their absolute configuration was assigned based on our previous results 8 and confirmed here by the comparison of experimental and calculated chiroptical properties. We have proven the large-scale feasibility of this pathway by synthesizing 1.6 g of (–)-4 in one step. Quantitative demethoxylation of (±)-, (–)-, or (+)-4 along with a ring closure at the resulting phe-

Photo-physical properties Absorption, fluorescence, ECD, CPL, and optical rotatory dispersion (ORD) spectra were then studied for molecules 4-7, revealing for ECD, CPL, and ORD a typical mirror-image relationships for (+)- and (–)-enantiomers.


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O

O N

N

1- BBr3 2- CH2ICl

Previous work

O

2

NH2 N

N

O

O

O

N

O O

N

(+)-5 65% (-)-5 63% (+/-)-5 60%

(+)-4 85% (-)-4 95% (+/-)-4 91%

O

O

O N O

O N

(-)-1

N

O

N

O

1- BBr3 2- CH2ICl

N

(+)-8

NH2

3

N O

N

N

(+)-9

N

N

N

O

O

(+)-6 80% (-)-6 72%

(+)-7 72% (-)-7 61% (+/-)-7 64%

Scheme 1: Synthetic pathway for racemic or enantiopure 11-cycles helicene-like compounds 5 and 7 proceeding via 10-cycles precursors 4 and 6. Structures of previously reported, analogous systems (8 and 9) have been recalled for clarity. Table 1: X-ray crystal structures of (±)-4, (+)-5, (±)-6, and (+)-7. Hydrogen atoms are omitted for clarity; O and N atoms are marked red and blue, respectively. θ: biphenyl torsion angle, ω: angle between the two benzo[c]acridine sub-unit planes. 4

5

6

7

Orthorombic, I2/a 115 62

Monoclinic P21 50 31

Orthorombic, P bcn 64 7

Monoclinic P21 52 23

X-ray structures

Space group θ [◦ ] ω [◦ ]

For better readability, only spectra for (+)enantiomers are presented in Figure 2 and Figure 3 (that directly compares ECD spectra of all the systems in the same plot). Complete set of all the spectra is available in Supporting Information. Photophysical data are summarized in Table 2. As can be seen, UV-vis spectra of 4-7 are comparable in terms of the energetic position and spectral intensities of the particular bands, and show no absorption for λ > 380 nm. The corresponding ECD spectra are much more structured and strongly de-

pend on the helical skeleton. Rigidification of the molecular structure in 5 and 7, by introducing the -O-CH2 -O- bridge and consequently ring closure, induces a sign inversion and a profound increase of the intensity of the first ECD band in the low-energy region. Indeed, the lowest-energy ECD band for (+)-4 possesses ∆ε(367nm) = −27 mol−1 ·L·cm−1 , while the bridged compound (+)-5 exhibits a 4 times more intense band ∆ε(373nm) = +104. Similarly, for (+)-6, ∆ε(362nm) = −10 mol−1 ·L·cm−1 compared to (+)-7, ∆ε(369nm) = +100. The


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The Journal of Organic Chemistry Absorbance

Fluorescence

4 5

0.8

0.8

0.4

0.4

0

50.4 (45.7) 120.4 -2939

0.2 (0.2) 116.5 1321

100 (100) 53.2 14649

0 (+)-4 (+)-5

100

Δε (mol-1.l.cm-1)

nB 49.4 (54.1) θ 73.7 [Φ]Dcalc. 10853

Figure 1: Low-energy DFT-optimized (BLYP/TZVP with a continuum solvent model for CH2 Cl2 ) structures of (+)-4 and (+)-5. For structures of the remaining compounds reported here see Supporting Information. Numbers listed are the Boltzmann population values, nB in % (at 298 K, in parenthesis the corresponding values for CH3 CN solvent are provided), biphenyl torsional angle, θ in ◦ , and calculated (LC-PBE0*/SV(P)) molar rotation values [Φ]calc. in 10−1 deg·mol−1 ·cm2 . D

1.2

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ECD

-2

-100 200

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10-3 ΔI (a.u.)

3-III 5-I

-4 250

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λ (nm) ε (105mol-1.l.cm-1)

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0

same trend was observed for the structurally related molecules 8 and 9 that comprise a lower number of aromatic rings in their structure comparing to 4-7 (see Figure 3 and Supporting Information). 7 Time-dependent DFT (TD-DFT) calculations 20,21 overall correctly reproduce these spectral features (see Figure 3). Computational details and a full set of computed data can be found in Supporting Information. An analysis of the simulated spectra shows that this intense low-energy ECD band for 5 and 7 originates from the lowest-energy excitation, dominated by the HOMO-to-LUMO transition of π-to-π* character with π-electron system spread out almost evenly over the whole molecule thanks to rigidity of the molecular structure of these compounds (see Figure 4 and Supporting Information). A noticeable increase in the intensity of this band observed for 5 and 7 compared to 9 along with its red-shift clearly reflects an enlargement of the π-conjugation in the presented here molecules due to introduction of two additional aromatic rings, and resembles a typical behaviour of regular helicenes. 22 An inspection of the orbital energies revealed that the increased π-conjugation in 5 and 7 vs. 9 has a noticeably destabilizing effect on the HOMO level (see Supporting Information), reducing the HOMO-LUMO gap, that

1.2

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0 (+)-6 (+)-7

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-200 -4 200

250

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450

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600

650

λ (nm)

Figure 2: Absorption and fluorescence spectra along with ECD and CPL spectra for (+)-4 and (+)-5 (top), and for (+)-6 and (+)-7 (bottom). Typical concentrations are 10−5 mol·L−1 in CH3 CN / 10−3 mol·L−1 in CH2 Cl2 for ECD / CPL measurements. The scale of CPL was normalized with the same procedure as used for the fluorescence spectra. may rationalize the observed red-shift. The lack of structural constraint in the non-bridged systems 4 and 6 clearly affects their electronic structure (in particular, the degree of π-electron delocalization) as compared to 5 and 7. This can be seen for example in isosurfaces of the corresponding frontier MOs (Figure 4 and Supporting Information), with HOMOs / LUMOs predominantly localized on the π-systems in the central parts / on the terminal aromatic rings of the molecular structures, activating charge-transfer (CT) type electronic transitions in these systems. An analysis of the calculated ECD spectra for the open compounds demonstrates that the experimentally observed significant decrease / sign change of their low-


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4 ,5 (+ )-4 (+ )-6 (+ )-8

2 0 0

E n e rg y / e V 3 ,5

4 ,0

for 8-9 for comparison (see Supporting Information). In line with the differences in the ECD spectra, compounds 5, 7, and 9, helical structure of which is constrained by the methylene bridge, reveal strong optical rotation, while their non-bridged precursors 4, 6, and 8 display between five to ten times lower ORs. As an example, the values of molar OR parameters at sodium D-line wavelength, 589 nm, found for (+)-enantiomers are: [Φ]D (5) ≈ [Φ]D (7) ∼ 14000 > [Φ]D (9) = 8600 10−1 deg·mol−1 ·cm2 while [Φ]D (6) = 5600 > [Φ]D (8) = 4300 > [Φ]D (4) = 1800 10−1 deg·mol−1 ·cm2 (see Table 2). It is noteworthy that the reported here OR values are very large as for organic molecules, exceeding for 5 and 7 those for regular helicenes (e.g. 12000 10−1 deg·mol−1 ·cm2 for P -carbo[6]helicene 2,23 ). As can be seen from Table 2 (see also Supporting Information), the calculations reproduce correctly the enhancement of OR for the closed vs. open systems, and confirm a profound impact of a molecular structure (both geometric via e.g. helical pitch, and electronic via e.g. extension of π-conjugation) on the observed chiroptical properties of these compounds. In particular, as shown for 4 in Figure 1, flexibility of non-constrained compounds seems to lead to a co-existence of various conformers in solution that reveal very different (strongly and weakly positive, and also even negative) OR values, which appears to be directly responsible for the low, on average, OR observed for these systems. The whole family of the dibenzo[c]acridinebased compounds demonstrates a broad blue fluorescence centered between 420 and 492 nm. The normalized spectra for 4-7 are shown in Figure 2 and for 8 and 9 in Supporting Information. The corresponding quantum yields (QY in Table 2) are consistently low in this series (below 2%). In contrast, CPL measurements reach glum = 8 × 10−3 for the closed structures (+)-5 and (+)-7, which is one of the highest values reported for organic molecules. 24,25 Similarly to what was revealed for OR and ECD, CPL is also very sensitive to the molecular structure of the compounds in this series: (+)-4, the open analogue of (+)-5, presents a more regular value of glum = 2.5 × 10−3 , while (+)-6, the open

3 ,0

(+ )-5 (+ )-7 (+ )-9

E x p t. E C D

0 C a lc . E C D L C -P B E 0 * //B L Y P

1 5 0 -1

∆ε / L m o l - 1 c m

-1

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∆ε / L m o l - 1 c m

-1 0 0

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2 5 0

1 0 0 5 0 0

3 0 0

3 5 0

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λ/ n m

-5 0

3 0 0

3 5 0 λ/ n m

4 0 0

4 5 0

Figure 3: Comparison of the experimental ECD spectra of (+)-enantiomers for 4-7. Inset: Corresponding TD-DFT simulated (LCPBE0*/SV(P) with a continuum solvent model for CH3 CN) Boltzmann-averaged spectra in the low-energy region. No spectral shifts were applied. For comparison, ECD spectra for the structurally related systems 8 and 9 have also been presented. energy ECD intensity can be associated with the presence in this spectral region excitations (of partial CT character) that are close in energy and reveal opposite-sign rotatory strength values, and thus cancel each other out, and also with the high flexibility of these systems, leading to various conformers of different ECD spectra contributing to the observed, average one (see Supporting Information). 5

6

7

HOMO

4

(-7.560)

(-7.610)

(-7.549)

(-7.756)

(-0.624)

(-0.825)

(-0.679)

(-0.885)

LUMO

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 4: Isosurfaces (±0.04 au) of the frontier MOs for (+)-enantiomers of 4-7 (conformer I, see Supporting Information for a full set of data). Numbers listed in parenthesis are the corresponding orbital energies, in eV. The ORD spectra were measured between 390 and 550 nm for each enantiomer of 4-7, and


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Table 2: Photophysical data for compounds 4-9 ((+)-enantiomers). ? λ‡ECD gabs λf luo QY glum [α]†D [Φ]†D [Φ]calc. D nm ×10−3 nm % ×10−3 10−1 deg·g−1 ·cm2 10−1 deg·mol−1 ·cm2 10−1 deg·mol−1 ·cm2 4 367 -1.2 437 0.6 2.5 290 1800 3885 5 373 +5 420 1.4 8 2300 13900 14649 6 361 -0.4 492 0.02 0 900 5600 6543 7 371 +5 437 0.2 8 2300 14000 13475 ?? ?? 8 350 -0.8 440 – – 830 4300 3097 9 361 +17 463 1.6 0 1700 8600 9156 ‡ ? † wavelength of the lowest-energy ECD band; calculated at λECD ; measured in CH2 Cl2 solutions; data for 8 and 9 taken from Ref. 7 TD-DFT calculated (LC-PBE0*/SV(P) with a continuum solvent model for CH2 Cl2 ) Boltzmann-averaged values, see Figure 1 and Supporting Information; ?? not determined as (+)-8 seems to undergo chemical transformation upon irradiation (see also Supporting Information).

analogue of (+)-7, demonstrates no CPL. No CPL activity was also observed for both 8 and 9 showing importance of the enlargement of the π-electron system in this series of helicene-like compounds. Although calculated emission properties of 49 noticeably deviate from experimental data (see Supporting Information), the computations enabled us to link stronger CPL activity of 5 and 7 as compared to their precursors 4 and 6 to: (i) more delocalized (π,π*) character of S1 excited states in 5 and 7 due to introducing the -O-CH2 -O- bridge and corresponding rigidification of the molecular structure, and (ii ) pronounced flexibility of 4 and 6 also in their excited state that results in a co-existence of various S1 conformers that due to different electronic character (usually with some CT signature) demonstrate very different numerical characteristics (in particular, opposite-sign rotatory strength values), which may lead to damping of the overall CPL signal for these compounds.

deed, the targeted closed compounds demonstrate opposite-sign and more intense ECD signal in the low-energy region along with strongly enhanced ORs, and more interestingly, very strong CPL activity (glum = 8 × 10−3 ) as compared to their open precursors. The calculations enabled us to link these features with extended π-conjugation and lower conformational flexibility of the compounds upon ring closure. The very high ORs of molecules 5 and 7 together with their intense CPL signals, which are among the highest when considering (small) organic molecules, make them potential candidates for applications, and our group is currently studying their incorporation as chiral material for chirowaveguides-based enantioselective sensors. Additionally, their strong CPL activity can find various applications in enantioselective sensors, 26 chiral optoelectronics and photonics, 27 or spintronics-based devices. 28

Experimental section All experiments were conducted under normal atmospheric conditions. Most of reagents were used as received, without further purification, unless otherwise specified. Experiments under micro-waves were run with a Biotage Initiator 2.5 microwave synthesizer. Analytical thin-layer chromatography was performed on a glass plates coated with 0.25-mm 230-400 mesh silica gel containing a fluorescent indica-

Conclusions In summary, we have efficiently synthesized a series of helically-shaped molecules that exhibit 10 or 11 rings in their skeletons, as pure enantiomers and on a gram scale. The chiroptical properties in the series are fine-tuned with rigidification of the molecular structure. In-


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tor. Column chromatography was performed using silica gel (spherical neutral, particle’s size of 63-210 µm). Bis-tetralone 1 was synthesized and resolved as described, 8 racemic compound (±)-6 was synthesized as published, 29 1amino-naphthaldehyde and 8-aminoquinoline7-carbaldehyde were synthesized as reported. 19 1 H and 13 C NMR spectra were recorded at 500.10352 MHz and 125.76408 MHz, respectively, with a Bruker Avance II 500 spectrometer or at 400.140 MHz and 100.615 MHz, respectively, with a Bruker Avance III 400 MHz spectrometer equiped with a Prodigy broad band probe. Chemical shifts are reported in ppm with reference to Me4 Si standard. Mass spectrometry (HRMS LSIMS) was performed by the Centre de Spectromètrie de Masse, University of Lyon France. For details on UV-vis, ECD as well as non-polarized and circularly polarized luminescence measurements, see Supporting Information.

(Cq), 128.6 (Cq), 127.1 (CH), 126.9 (CH), 126.6 (CH), 125.9 (CH), 125.7 (CH), 124.7 (CH), 124.7 (CH), 124.4 (Cq), 56.6 (CH3 ), 29.2 (CH2 ), 29.0 (CH2 ). HRMS (ESI) m/z: [M + H]+ Calcd for C44 H33 N2 O2 621.2537; Found 621.2511. Synthesis of (–)-4 and (+)-4 The same procedure as described for (±)-4 was used to synthesize pure enantiomers of 4, (–)-4 and (+)-4. In a typical scale experiment, (–)-4 (1.66 g, 95%) was obtained starting from 1.107 g of (+)-1, and (+)-4 (0.300 g, 85%) was obtained starting from 0.393 g of (–)-1. 1 H NMR and 13 C NMR are the same as for (±)-4. Synthesis of methylene bridged bidibenzo [c,h]acridine (±)-5 Demethoxylation: Under argon at 0 ◦ C, to a solution of (±)-4 (0.481 g, 0.775 mmol) in 10 mL of dry CH2 Cl2 was added dropwise a solution of BBr3 1 M in CH2 Cl2 (3.1 mL, 3.1 mmol). The mixture was stirred for 15 h at room temperature, then quenched by dropwise addition of MeOH (5 mL). Half of the solvent was then removed by evaporation and replaced by 50 mL of Et2 O making diol to precipitate as its 2 HBr salt. The brown precipitate was filtered off and washed with 50 mL of Et2 O and not purified further (0.583 g, quantitative). Removal of the methoxy groups was attested by 1 H NMR and HRMS spectroscopies. 1 H NMR (DMSO, 500.10 MHz) δ 8.04 (s, 2H), 7.26 (d, J = 8.13 Hz, 2H), 7.26 (d, J = 8.75 Hz, 2H), 7.71 (m, 2H), 7.68 (d, J = 8.70 Hz, 2H), 7.27 (ddd, J = 8.45 Hz, J = 6.88 Hz, J = 1.08 Hz, 2H), 7.27 (ddd, J = 8.45 Hz, J = 6.88 Hz, J = 1.08 Hz, 2H), 7.09 (d, J = 8.00 Hz, 2H), 6.75 (d, J = 8.00 Hz, 2H), 2.95-2.08 (m , 6H), 2.59 (m, 2H). HRMS (ESI) m/z: [M + H]+ Calcd for C42 H29 N2 O2 593.2224; Found 593.2202. Formation of methylene bridge: (±)Demethoxylated 4 hydrobromide (0.584 g, 0.775 mmol) was placed in a Schlenck flask under argon in 10 mL of dry DMF. Cs2 CO3 (0.505 g, 1.55 mmol) and CH2 ClI (0.058 mL, 0.791 mmol) were added and the mixture was stirred over night at 80 ◦ C. After cooling, DMF

Synthesis of 2,2’-dimethoxy-5,5’,6,6’tetrahydro-1,1’-bidibenzo[c,h]acridine (±)-4 Three microwave tubes were filled each with 1amino-naphthaldehyde 2 (0.725 g, 4.21 mmol), (±)-bis-tetralone 1 (0.369 g, 1.05 mmol), and potassium tert-butoxide (0.472 g, 4.02 mmol) in tetrahydrofuran (THF, 20 mL), and the each mixture was stirred at 70 ◦ C for 5 h under microwave irradiation (average absorption). After cooling, the three mixtures were combined and THF was evaporated. The crude product was diluted with CH2 Cl2 and washed twice with NaClsat . Purification was performed by silica gel column chromatography with CHCl3 as eluent, giving a yellow solid (1.3 g, 91%). mp: 183 ◦ C. 1 H NMR (CDCl3 , 500.10 MHz) δ 7.89 (d, J = 8.2 Hz, 2H), 7.73 (d, J = 7.85 Hz, 2H), 7.60 (d, J = 8.70 Hz, 2H), 7.52 (t, J = 7.5 Hz, 2H), 7.46 (s, 2H), 7.42 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 7.5 Hz, 2H), 7.21 (d, J = 8.25 Hz, 2H), 7.11 (d, J = 8.25 Hz, 2H), 3.71 (s, 6H), 2.71 (s, 2H), 2.62 (m, 2H), 2.47 (m, 2H), 1.77 (m, 2H). 13 C NMR J-MOD (CDCl3 , 125.76 MHz) δ 157.3 (Cq), 152.8 (Cq), 143.9 (Cq), 134.2 (Cq), 133.4 (Cq), 132.8 (Cq), 132.6 (Cq), 132.2 (CH), 131.9


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was removed by evaporation, replaced by 30 mL of CH2 Cl2 , and the organic phase was washed twice by 30 mL of H2 O. After drying over Na2 SO2 , the solution was condensed under reduced pressure to give 0.418 g of crude product purified by chromatography over silica gel, eluted with a gradient of CH2 Cl2 / petroleum ether from 1 / 1 to 4 / 1, giving 0.298 g of a beige solid, which was stirred in 15 mL of CH3 CN overnight to give after filtration a white powder (0.262 g, 60%). mp: decomp. at 250 ◦ C. 1 H NMR (CDCl3 , 500.10 Hz) δ 7.81 (d, J = 8.20 Hz, 2H), 7.79 (d , J = 7.8 Hz, 2H), 7.65 (d , J = 8.64 Hz, 2H), 7.59 (ddd , J = 7.8 Hz, J = 7.8 Hz, J = 6.7 Hz, J = 1.25 Hz, 2H), 7.505 (d, J = 8.0 Hz, 2H), 7.43 (ddd, J = 8.4 Hz, J = 6.9 Hz, J = 1.1 Hz, 2H), 7.38 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 7.19 (s, 2H), 5,78 (2H), 2.42 (td, J = 14.8 Hz, J = 4.8 Hz, 2H), 2.24 (ddd, J = 14.8 Hz, J = 4.8 Hz, J = 1.8 Hz, 2H), 1.94 (ddd, J = 14.8 Hz, J = 4.8 Hz, J = 1.8 Hz, 2H), 0.96 (td, J = 14.8 Hz, J = 4.8 Hz, 2H). 13 C NMR J-MOD (CDCl3 , 125.76 MHz) δ 152.3 (Cq), 151.6 (Cq), 143.5 (Cq), 137.6 (Cq), 134.6 (Cq), 132.8 (Cq), 132.1 (CH), 132.0 (Cq), 131.4 (Cq), 127.9 (CH), 127.5 (CH), 127.0 (CH), 126.9 (CH), 125.4 (CH), 124.63 (CH), 124.61 (CH), 121.3 (CH), 101.7 (CH2 ), 28.5 (CH2 ), 27.2 (CH2 ). HRMS (ESI) m/z: [M + H]+ Calcd for C43 H29 N2 O2 605.2224; Found 605.2204.

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Synthesis of (+)-6 and (–)-6 The same procedure as described for (±)-6 was used to synthesize the pure enantiomers of 6, (–)-6 and (+)-6. In a typical scale experiment, (+)-6 (0.640 g, 80%) was obtained starting from 0.450 g of (–)-1, and (–)-6 (0.768 g, 72%) was obtained starting from 0.6 g of (+)1. 1 H NMR and 13 C NMR are the same as for (±)-6. Synthesis of methylene bridged binaphtho[1,2b][1,10]phenanthroline (±)-7 Demethoxylation: Using the same procedure as for the synthesis of (±)-5, at a typical scale of 0.700 g (1.12 mmol) of (±)-6, a brown precipitate (0.840 g, quantitative) was isolated after the demethoxylation step and not purified further. Removal of the methoxy groups was attested by 1 H NMR and HRMS spectroscopies. 1 H NMR (DMSO, 400.10 MHz) δ 9.06 (bs, 2H), 8.93 (s, 2H), 8.27 (d ,J = 8.21 Hz, 2H), 8.06 (d, J = 8.63 Hz, 2H), 8.01 (bs, 2H), 7.92 (d, J = 9,01 Hz, 2H), 7.40 (dd, J = 8.21 Hz, J = 4.22 Hz, 2H), 7.17 (d, J = 8.05 Hz, 2H), 6.77 (d, J = 8.24 Hz, 2H), 3.56-4.45 (m, 2H), 3.28-3.14 (m, 4H), 3.11-3.00 (m, 2H). HRMS (ESI) m/z: [M + H]+ Calcd for C40 H27 N4 O2 595.2129; Found 595.2099. Formation of methylene bridge: (±)Demethoxylated 6 hydrobromide (0.840 g, 1.12 mmol) was transformed into the bridged derivative following the same procedure as described for (±)-5. The crude was purified by chromatography over silica gel, eluted with CH2 Cl2 / Et3 N, followed by a second chromatography on neutral alumina, eluted with CH2 Cl2 / Et3 N giving a light brown solid (0.435 g, 64%). mp: decomp. at 250 ◦ C. 1 H NMR (CDCl3 , 400.14 Hz) δ 8.86 (dd, J = 4.23 Hz, J = 1.62 Hz, 2H), 8.12 (dd, J = 8.01 Hz, J = 1.25 Hz, 2H), 7.63 (d, J = 8.75 Hz, 2H), 7.50 (m, 4H), 7.43 (d, J = 7.85 Hz, 2H), 7.19 (s, 2H), 7.15 (d, J = 8.05 Hz, 2H), 5.75 (s, 2H), 2.40 (td, J = 14.50 Hz, J = 4.53 Hz, 2H), 2.13 (dd, J = 14.50 Hz, J = 4.53 Hz, 2H), 1.94 (dd, J = 14.50 Hz, J = 4.53 Hz, 2H), 0.71 (td, J = 14.50 Hz, J = 4.60 Hz, 2H). 13 C NMR J-MOD, (CDCl3 , 125.76 MHz) δ 153.3 (Cq), 152.6 (Cq), 149.2

Synthesis of (–)-5 and (+)-5 The same procedure as described for (±)-5 was used to synthesize the pure enantiomers of 5, (–)-5 and (+)-5. In a typical scale experiment, (–)-5 (0.940 g, 63%) was obtained starting from 1.52 g of (–)-4, and (+)-5 (0.760 g, 65%) was obtained starting from 1.2 g of (+)-4. 1 H NMR and 13 C NMR are the same as for (±)-5. Synthesis of dimethoxy binaphtho[1,2b][1,10]phenanthroline (±)-6 The synthesis of (±)-6 was performed as it has been reported elsewhere. 29


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(CH), 146.3 (Cq), 143.5 (Cq), 136.4 (Cq), 134.8 (CH), 134.2 (Cq), 133.2 (Cq), 133.1 (Cq), 131.7 (CH), 127.6 (Cq), 126.9 (CH), 126.7 (Cq), 125.6 (CH), 125.3 (CH), 122.0 (CH), 121.7 (CH), 101.4 (CH2 ), 28.3 (CH2 ), 27.3 (CH2 ). HRMS (ESI) m/z: [M + H]+ Calcd for C41 H27 N4 O2 607.2129; Found 607.211.

emailing data [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

References (1) Shen, Y.; Chen, C.-F. Helicenes: Synthesis and Applications. Chem. Rev. 2012, 112, 1463–1535.

Synthesis of (–)-7 and (+)-7 The same procedure as described for (±)-7 was used to synthesize the pure enantiomers of 7, (–)-7 and (+)-7. In a typical scale experiment, (–)-7 (0.37 g, 61%) was obtained starting from 0.65 g of (–)-6, and (+)-7 (0.373 g, 72%) was obtained starting from 0.53 g of (+)-6. 1 H NMR and 13 C NMR are the same as for (±)-7.

(2) Gingras, M. One Hundred Years of Helicene Chemistry. Part 3: Applications and Properties of Carbohelicenes. Chem. Soc. Rev. 2013, 42, 1051–1095. (3) Verbiest, T.; Elshocht, S. V.; Kauranen, M.; Hellemans, L.; Snauwaert, J.; Nuckolls, C.; Katz, T. J.; Persoons, A. Strong Enhancement of Nonlinear Optical Properties Through Supramolecular Chirality. Science 1998, 282, 913–915.

Acknowledgement We thank the French ANR for funding within the CAPTOR program (ANR-18-CE06-0010-02). M.K. and M.S.-H. acknowledge the PL-Grid Infrastructure and the Academic Computational Center Cyfronet of the University of Science and Technology in Krakow for providing computational resources. We thank Marion Jean and Dr. Nicolas Vanthuyne from the Plateforme de chromatographie chirale (iSm2, Aix Marseille Université) for the enatiomeric excess measurements.

(4) Yang, Y.; da Costa, R. C.; Fuchter, M. J.; Campbell, A. J. Circularly Polarized Light Detection by a Chiral Organic Semiconductor Transistor. Nat. Photonics 2013, 7, 634–638.

Supporting Information Available

(5) Hatakeyama, T.; Hashimoto, S.; Oba, T.; Nakamura, M. Azaboradibenzo[6]helicene: Carrier Inversion Induced by Helical Homochirality. J. Am. Chem. Soc. 2012, 134, 19600–19603. (6) Guy, S.; Baguenard, B.; BensalahLedoux, A.; Hadiouche, D.; Guy, L. Full Polarization Control of Optical Planar Waveguides with Chiral Material. ACS Photonics 2017, 4, 2916–2922.

The Supporting Information is available free of charge on the ACS Publications website at DOI: 1 H NMR and 13 C NMR J-MOD spectra for compounds 4-7; X-ray diffraction data of ??; HPLC conditions and enantiomeric excess measurements for 5 and 7; UV-vis, ECD, CPL, and ORD spectra for each enantiomer of compounds 4-9; computational details; and additional calculated results (PDF) CCDC 1910191, 1910192, 1908083, and 1908084 contain the supplementary crystallographic data for 4, 5, 6, and 7, respectively. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data request/cif , or by

(7) Bensalah-Ledoux, A.; Pitrat, D.; Reynaldo, T.; Srebro-Hooper, M.; Moore, B.; Autschbach, J.; Crassous, J.; Guy, S.; Guy, L. Large-Scale Synthesis of HeliceneLike Molecules for the Design of Enantiopure Thin Films with Strong Chiroptical Activity. Chem. Eur. J. 2016, 22, 3333– 3346.


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(8) Mahieux, J.; Sanselme, M.; Harthong, S.; Melan, C.; Aronica, C.; Guy, L.; Coquerel, G. Preparative Resolution of (±)Bis-tetralone by Means of Autoseeded Preferential Crystallization Induced by Solvent Evaporation (ASPreCISE). Cryst. Growth Des. 2013, 13, 3621–3631.

Page 10 of 12

Effects and Long-Lived Excited States. Inorg. Chem. 2001, 40, 3413–3422. (17) Li, A.-H. et al. A Highly Effective One-Pot Synthesis of Quinolines from o-Nitroarylcarbaldehydes. Org. Biomol. Chem. 2007, 5, 61–64. (18) Rahman, A. F. M. M.; Kwon, Y.; Jahng, Y. Friedländer Reactions of Triacetylmethane - Unusual Distribution of Products. Heterocycles 2005, 65, 2777– 2782.

(9) Cheng, C.-C.; Yan, S.-J. Organic Reactions; American Cancer Society, 2005; Chapter 2, pp 37–201. (10) Li, A.-H. et al. One-Pot Friedländer Quinoline Synthesis: Scope and Limitations. Synthesis 2010, 10, 1678–1686.

(19) Riesgo, E. C.; Jin, X.; Thummel, R. P. Introduction of Benzo[h]quinoline and 1,10Phenanthroline Subunits by Friedländer Methodology. J. Org. Chem. 1996, 61, 3017–3022.

(11) Malinowski, Z.; Fornal, E.; Warpas, A.; Nowak, M. Synthesis of Benzoquinoline Derivatives from Formyl Naphthylamines via Friedländer Annulation Under MetalFree Conditions. Monatsh. Chem. 2018, 149, 1999–2011.

(20) Srebro-Hooper, M.; Autschbach, J. Calculating Natural Optical Activity of Molecules from First Principles. Annu. Rev. Phys. Chem. 2017, 68, 399–420.

(12) Woo-Jin, L.; Jong-Myoung, C.; YurngDong, J. Synthesis of Heteroarylferrocenes by Friedlander Reaction and Their Spectral Properties. Bull. Korean Chem. Soc. 2009, 30, 3061–3065.

(21) Autschbach, J.; Srebro, M. Delocalization Error and ‘Functional Tuning’ in KohnSham Calculations of Molecular Properties. Acc. Chem. Res. 2014, 47, 2592– 2602.

(13) Liang, J. L.; Cha, H.; Jahng, Y. Synthesis and Properties of Annulated 2(Azaar-2-yl)- and 2,2’-Di(azaar-2-yl)-9,9’spirobifluorenes. Molecules 2013, 18, 13680–13690.

(22) Nakai, Y.; Mori, T.; Inoue, Y. Theoretical and Experimental Studies on Circular Dichroism of Carbo[n]helicenes. J. Phys. Chem. A 2012, 116, 7372–7385.

(14) Dennison, G. H.; White, J. M.; Johnston, M. R. Efficient Access to Unsymmetrically 3-Substituted-1,10Phenanthrolines via Microwave Assisted Friedländer Condensation with Aldehydes. ChemistrySelect 2016, 1, 6434–6437.

(23) Moussa, M. E. S.; Srebro, M.; Anger, E.; Vanthuyne, N.; Roussel, C.; Lescop, C.; Autschbach, J.; Crassous, J. Chiroptical Properties of Carbo[6]Helicene Derivatives Bearing Extended π-Conjugated Cyano Substituents. Chirality 2013, 25, 455–465.

(15) Mart´ınez, R.; Ramón, D. J.; Yus, M. Easy α-Alkylation of Ketones with Alcohols Through a Hydrogen Autotransfer Process Catalyzed by RuCl2 (DMSO)4 . Tetrahedron 2006, 62, 8988–9001.

(24) Chen, N.; Yan, B. Recent Theoretical and Experimental Progress in Circularly Polarized Luminescence of Small Organic Molecules. Molecules 2018, 23, No. 3376. (25) Tanaka, H.; Inoue, Y.; Mori, T. Circularly Polarized Luminescence and Circular Dichroisms in Small Organic Molecules:

(16) Riesgo, E. C.; Hu, Y.-Z.; Bouvier, F.; Thummel, R. P.; Scaltrito, D. V.; Meyer, G. J. Crowded Cu(I) Complexes Involving Benzo[h]quinoline: π-Stacking


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Correlation between Excitation and Emission Dissymmetry Factors. ChemPhotoChem 2018, 2, 386–402. (26) Song, F.; Wei, G.; Jiang, X.; Li, F.; Zhu, C.; Cheng, Y. Chiral Sensing for Induced Circularly Polarized Luminescence Using an Eu(III)-Containing Polymer and d- or l-Proline. Chem. Commun. 2013, 49, 5772–5774. (27) Chen, S. H.; Katsis, D.; Schmid, A. W.; Mastrangelo, J. C.; Tsutsui, T.; Blanton, T. N. Circularly Polarized Light Generated by Photoexcitation of Luminophores in Glassy Liquid-Crystal Films. Nature 1999, 397, 506–508. (28) Farshchi, R.; Ramsteiner, M.; Herfort, J.; Tahraoui, A.; Grahn, H. T. Optical Communication of Spin Information Between Light Emitting Diodes. Appl. Phys. Lett. 2011, 98, 162508. (29) Speed, S.; Pointillart, F.; Mulatier, J.-C.; Guy, L.; Golhen, S.; Cador, O.; Le Guennic, B.; Riobé, F.; Maury, O.; Ouahab, L. Photophysical and Magnetic Properties in Complexes Containing 3d/4f Elements and Chiral Phenanthroline-Based Helicate-Like Ligands. Eur. J. Inorg. Chem. 2017, 2100–2111.


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Graphical TOC Entry 11-rings

ECD CPL

10-rings

CPL

glum= 8 10-3

ECD


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Modulation of chiroptical properties in a series of helicene-like

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