Synthesis, chiroptical and SHG properties of polarizable push – pull dyes built on p -extended binaphthyls †

We report on new enantiopure binaphthyl derivatives in which electron-donating and electron-withdrawing substituents are placed in direct conjugation, to create active push – pull dyes for NLO applications. The dyes, unprecedentedly, extend their p -bridge from the 3,3 0 positions of the binaphthyl units, and incorporate as acceptors pyridine units, possessing a coordinating nitrogen atom useful for further supramolecular polarization of the chiral dyes. The p -bridge is constructed by the sequential attachment of phenylenevinylene units to the enantiopure binaphthyl derivatives through Horner – Wadsworth – Emmons ole ﬁ nation, which proceed with high stereoselectivity, a ﬀ ording stereode ﬁ ned chiral dyes. The polarization of the terminal pyridine units by means of labile complexation with Pd 2+ ions has been demonstrated using both optical and chiroptical methods. The polarization by protonation can be made reversible in solution and solid state by exposure to ammonia vapors, as shown by absorption and emission spectroscopies. NLO properties, as determined by EFISH generation measurements in solution, are signi ﬁ cant for the bisprotonated species when compared to previously reported binaphthyl substrates. TDDFT calculations show that the hyperpolarizability tensor contribution is responsible for enhancing SHG values upon protonation up to one order of magnitude, highlighting the potential of such ortho related, axially-chiral push – pull dyes for functional NLO applications.


Introduction
Conjugated organic materials are currently used or being developed for a number of technological applications.Amongst these, well-dened p-extended organic oligomers have been the subject of increasing attention in the last few decades, either in solution or in bulk.Their utility as model structures for the understanding of the solution and bulk scale properties of conjugated polymers should also be stressed. 1One of the most prominent examples of the application of conjugated organic molecules is in the eld of second harmonic generation (SHG), 2 a nonlinear optical property which is at the foundation for advanced technologies in materials science and biological imaging.SHG is forbidden in the presence of a centrosymmetric material; chiral organic molecules, by denition noncentrosymmetric, have thus been widely studied as materials capable of SHG. 2 Chirality can play a fundamental role in tuning the properties of nanoscale structures, and of matter in general; in addition, nanostructuring via self-assembly of the chiral organic dyes has been shown to have pronounced effects and amplications of their SHG response. 3Amongst known atropoisomeric chiral compounds, binaphthyls play a preeminent role, but applications of these compounds in the eld of nanosciences are recent, and not yet fully explored. 4Typical efficient organic p-conjugated chromophores for SHG are "push-pull" in nature, bearing both electron-withdrawing and electron-donating organic functionalities in direct conjugation with each other, by means of an extended conjugated bridge with delocalized p-electrons.
Binaphthyl compounds have been exploited for the realization of second-order nonlinear optical (NLO) materials, having the combined advantages of being chromophores, and carrying the required element of chirality for bulk anisotropy. 5n fact, several organic molecular modules have been reported in which electron donating substituents in the 2,2 0 positions of the binaphthyl skeleton (dialkoxy substituents, such as in compound 1 (ref.6) in Fig. 1, or dialkylamino substituents, such as in compound 2 (ref.7) in Fig. 1) have their counterpart in the electron-withdrawing substituents placed at the most electrophilic 6,6 0 position (Fig. 1, top).Pyridines, being electron-poor heterocycles, can be ideal "pull" end moieties, when in direct p-conjugation with other "push" functionalities, for the preparation of efficient SHG chromophores: in fact, as an additional feature, they can be coordinated to their nitrogen atom, and their "pull" electronic character is in this case further enhanced. 8This coordination can be either irreversible (covalent functionalization, as in compound 2) or reversible, by means of weak coordination with a metal cation, protonation, supramolecular complexation through halogen bonding. 9The reversible protonation of the pyridinic moiety has recently resulted in interesting switchable emissive and non linear optical (NLO) materials. 10In addition to compound 2, several other pyridine-binaphthyl p-conjugated systems have been reported, branching out from the 3,3 0 or 6,6 0 -positions of the binaphthyl skeleton, for elegant applications in the eld of metal-organic frameworks, or metallamacrocycles. 11he substitution pattern can be amongst the various factors, which include weak intramolecular interactions, buttressing effects by sterically hindered substituents in vicinal positions, and at the supramolecular level, packing effects in crystals, which can have a profound effect on the dihedral angle between the naphthyl units of the binaphthyl moiety.Given our previous synthetic work with binaphthyl compounds derivatized at the 3,3 0 positions, 12 and our recent realization of crescent, pushpull, PPV-like chromophores, 13 we present here the synthesis of novel enantiopure binaphthyls, in which pyridyl substituents branch out from the 3,3 0 positions of the binaphthyl skeleton (Fig. 1, bottom).Here we discuss on the chiroptical properties associated with complexation of the pyridine nitrogen atoms to Pd 2+ ions and on the modulation of the optical behavior using acidic vapor as an external trigger.

Synthesis of the molecular modules
In our design strategy (Fig. 1, bottom), the electron-donating -OR substitutents are in an ortho relationship with respect to the growing p-bridge in the 3,3 0 position, achieving efficient conjugation with the p-bridge and charge transfer with the electron-withdrawing unit since resonance delocalization of p-electrons is feasible.The synthetic approach makes use of a convergent approach for the instalment of pyridine endcapping functionalities, and of Horner-Wadsworth-Emmons (HWE) olenation reactions for the efficient and highly stereoselective formation of conjugated double bonds within the p-bridge.13a Amongst the two possible retrosynthetic approaches for the construction of the envisaged molecules, we used a difunctional phosphonate binaphthyl derivative (compound 3 in Scheme 1), in combination with p-extended pyridylaldehydes in HWE ole-nation reactions.In fact, previous work in our laboratories on similar substrates had revealed that the complementary approach, that is, the use of dialdehyde 4 in combination with a p-extended benzyl pyridyl phosphonate is not viable, since decomposition occurs in the presence of the strong bases required for HWE reactions, when carbon-carbon double bonds are present in the p-extended structures.
The synthesis of the key compounds is shown in Scheme 2. Enantiopure starting materials for this work were obtained via multistep syntheses starting from the commercially available, enantiopure (R)-BINOL, and they were chemically transformed under nonracemizing conditions. 14Diphosphonate (R)-3 was obtained from known enantiopure dibromide (R)-5 via the Arbuzov reaction, and isolated in pure form by column chromatography.Reaction of (R)-3 with commercially-available 4-pyridylaldehyde 6 gave compound (R)-7 using standard HWE conditions (THF, t-ButOK).The compound was obtained as a mixture of diastereoisomers, with ca.15% of the cis stereoisomer present, which we were not able to purify further by standard chromatography.The obtainment of a nontrivial quantity of the more sterically congested cis stereoisomer might be rationalized by the fact that the electron-withdrawing pyridine moiety, can stack, in this conguration, over the p-rich binaphthyl unit.Elongation of the p-bridge was carried out making use of the acetal-protected phosphonate 8, which gave the extended pyridyl sinthon 9 by HWE with 4-pyridylaldehyde 6.Small amount of cis stereoisomer could in this case be easily separated by standard chromatography.Aer deprotection under mild acidic conditions, elongated aldehyde 10 was obtained and used without further purications.Finally, double HWE olenation between 3 and 10 gave stereopure compound (R)-11 in excellent yields.It was fully characterized by 1 H, 13 C and 2D NMR spectroscopies and mass spectrometry.
The 1 H NMR spectrum of compound (R)-11 is shown in Fig. 2  (top).The NMR analysis demonstrated that the double substitution occurred efficiently and conrmed that, within the limit of detection of the NMR technique, both newly formed carboncarbon double bonds in compound (R)-11 are in the trans conguration exclusively (with 3 J HH coupling constants of ca.16 Hz).
The attribution of the signals related to the vinyl protons was made possible especially by evaluation of the HETCOR 2D NMR experiment, allowing us to assign the peaks and calculate the values of the coupling constants, which are essential to discriminate between cis and trans disubstituted carboncarbon double bonds (Fig. S1 †).
The lowest energy conformation (Fig. 2, bottom) for molecule (R)-11, obtained by molecular modelling calculations (see below), display an almost perfectly C 2 symmetrical structure, with a dihedral angle between the two naphthyl least-squares planes of 85.6 .Interestingly, the conjugated fragments (pydirine-double bond-phenylene-double bond) extending from the 3,3 0 positions are fully coplanar, but such planar system is signicantly out of the plane of the naphthyl unit to which it is bonded (dihedral angle equal to 31.0 ), owing to the steric effects of the neighbouring OCH 3 groups in the 2,2 0 positions of the binaphthyl skeleton.
The NMR signal at 8.6 ppm (Fig. 2 top), related to the a-pyridyl protons, and, to a lesser extent, the signal at 7.4 ppm, related to the b-pyridyl protons, are broad, indicating that one or more dynamic processes are in place, becoming slow on the NMR timescale at this temperature and for this instrument operational frequency (300 MHz). 15The processes must exchange the positions of the internal and external a-pyridyl protons, so that they are not anymore equivalent by symmetry.These processes can be in principle due to either: (a) the libration of the pyridine fragments around their own main aryl axis, or (b) the rotation of the entire conjugated fragments (pyridine-double bond-phenylene-double bond) around the neighbouring OCH 3 groups, that is, from top to bottom with respect to the naphthyl plane. 16,17tical and chiroptical characterization of the supramolecular polarization using Pd 2+ The coordination of the difunctional ligand (R)-11 with Pd 2+ was monitored by means of a full titration of the compound with Pd(MeCN) 2 Cl 2 .This Pd 2+ salt has been previously reported for the formation of complexes in which two pyridine functionalities displace the labile nitrile ligands to form trans-tetracoordinate, square-planar complexes. 18It is fully soluble in polar organic solvents (MeCN, DMF).The UV-vis titration in MeCN is shown in Fig. 3 (top).The shi of the l max of the ligand (365 nm), attributed to the p-p* transition, towards longer wavelengths (381 nm), is in agreement with a coordination of the transition metal cation to the pyridine nitrogen atoms, and  thus a further polarization of the "push-pull" system.The observed stoichiometry at saturation (1 : 1 ligand vs. Pd 2+ ) matches with the complete incorporation of the pyridine moieties (two per ligand) into the Pd 2+ complexes.The behaviour of the binding prole (inset in Fig. 3, top) is sigmoidal, which is not only indicative of multiple equilibria, but also generally associated with positive cooperativity. 19It is likely that the multiple equilibria in play involve the formation of both oligomeric and cyclic species (see below, NMR titration).
A titration experiment in DMF essentially conrmed the behavior observed in MeCN, and differences were found only in the relative intensities of the p-p* band of the free and complexed ligands.
The titration was also monitored by CD spectroscopy (Fig. 3, bottom): an intense exciton couplet signal, classical signature of binaphthyl compounds and due to the two naphthyl chromophores oriented essentially perpendicular to each other, could be observed, with the inversion point corresponding to the l max of the ligand.The exciton couplet shi towards longer wavelengths upon complexation, and the signal change saturates at ca. 1 eq., in close parallel to the UV-vis titration.The symmetry of the couplet, in terms of intensities of the lowest and highest energy branches, is maintained throughout the titration, pointing to the dominant presence of either uncomplexed or symmetrically dicomplexed species at every stage of the titration, supporting that a highly cooperative binding behaviour is in play.
In order to examine the coordination behavior further, and to conrm the formation of a linear coordination polymer rather than dimeric or oligomeric cyclic species, a 1 H NMR titration was performed.The titration could not be made in CD 3 CN, since using this solvent an insoluble aggregate was formed at the concentrations needed for 1 H NMR measurements (at least 10 À3 M, two orders of magnitude higher than the UV titrations).Upon addition of Pd 2+ (R)-11 in DMF, instead, the aggregate species was completely soluble.The NMR spectra for the titration in d 7 -DMF are reported in Fig. S2; † general broadening of the signals is observed, with no further changes observed aer the addition of 1 eq. of Pd 2+ , in agreement with the proposed formation of a coordination polymer via pyridine trans coordination to the Pd 2+ center.The formation of small quantities of cyclic species, however, cannot be completely ruled out.

Linear and nonlinear optical switching behavior by protonation-deprotonation reaction
The UV-vis absorption spectrum of compound (R)-11 in CHCl 3 , displays one major band at 367 nm.This band is essentially unshied in a polar solvent such as CH 3 CN.By comparison, l max for 6,6 0 -disubstituted binaphthyls such as compounds 1 and 2, bearing irreversibly alkylated pyridine nitrogen, is red shied to a substantial extent (Table 1).
The possibility of switching the optical properties of (R)-11 via protonation/deprotonation is clearly illustrated in Fig. 4. Upon exposure of the CHCl 3 solution of (R)-11 to HCl vapors, the absorption maximum is shied to 414 nm, a red-shi that can be attributed to protonation of the pyridine moiety with formation of (R)-11$2HCl, in agreement with the red shi observed for the (R)-11$PdCl 2 complex.The shi is however considerably larger for the protonated system (47 vs. 16 nm).
The reverse transformation can be induced by treatment of the solution with NH 3 vapors, as conrmed by absorption  spectroscopy.Interestingly, the protonation-deprotonation process is accompanied by a macroscopic variation in the emissive behaviour.In fact, (R)-11 in CHCl 3 displays an intense emission centred at 444 nm which is shied to 534 nm upon exposure to HCl and restored aer treatment with NH 3 vapors.A similar interconversion process can be induced by exposure of solid (R)-11 to HCl and ammonia vapors.The initial 560 nm emission of (R)-11 powder is, in fact, shied to 600 nm aer exposure to HCl vapors and restored by treatment with ammonia vapors (Fig. S3 †).
The observation of a 50 nm red-shi of the absorption band upon exposure of the CHCl 3 solution to HCl vapors prompted us to monitor the second-order NLO properties during the (R)-11/ (R)-11$2HCl interconversion.Hyperpolarizabilities of compounds (R)-11 and (R)-11$2HCl in CHCl 3 were measured at 1907 nm by electric eld-induced second harmonic generation (EFISH) 20 and the values are summarized in Table 2.
A higher second-order NLO response of (R)-11$2HCl with respect to (R)-11 has been obtained in agreement with the observed absorption red-shi.According to DFT and TDDFT calculations on the doubly protonated form of (R)-11 (see below, Computational studies), the modest variation of the dipole moment from the ground to the excited state of (R)-11$2HCl is not responsible for its observed high second order NLO response compared to (R)-11, which should be instead attributed to both the red shi of the absorption band and the increased oscillator strength.The solid-state interconversion between (R)-11 and (R)-11$2HCl was also monitored by means of the Kurtz-Perry powder method 21 at the non-resonant wavelength of 1907 nm.Powdered batches of (R)-11 and (R)-11$2HCl showed SHG efficiency respectively equal and 0.7 times that of standard urea.Low SHG signals for powders, with concomitant high SHG values observed in solution, have been recorded for other binaphthyl residues 6 and must be associated with an unfavourable antiparallel or close to antiparallel dipole orientation in the solid state, which is presumably enhanced upon bisprotonation.

Computational studies
DFT and TDDFT calculations on (R)-11 in CHCl 3 provided two p / p* excitations at 359 and 357 nm, presenting very high oscillator strengths (f ¼ 2.8 and 1.6, respectively).The former peak is associated principally with HOMOÀ1 / LUMO and HOMO / LUMO+1 transitions, and the latter to HOMO / LUMO and HOMOÀ1 / LUMO+1 transitions (see ESI † for a plot of the frontier orbitals).Both pairs of HOMOs and LUMOs are characterized by similar energies but different localization schemes, with HOMOÀ1 and LUMO+1 more localized on one naphthyl moiety of the molecule, and HOMO and LUMO more localized on the other moiety.As a result, owing to almost symmetrical charge transfers involved in the transitions from one naphthyl moiety to the other one, both absorption peaks are globally characterized by a small charge transfer, as evidenced by a modest increase of the dipole moment from the ground state (m g ¼ 5.33 D) to the excited states (m e ¼ 6.56 and 7.03 D for the rst and second peak, respectively).
The absorption band of (R)-11$2HCl was well reproduced by DFT and TDDFT calculations on the doubly protonated form of (R)-11 in CHCl 3 , with two p / p* excitations at 412 and 409 nm (f ¼ 3.0 and 1.4, respectively), very similar in character to those obtained for the neutral compound although characterized by individual transitions with much larger charge transfer (see ESI †).The almost symmetrical charge transfers involved in the transitions from one naphthyl moiety to the other one determine a very small variation of the dipole moment from the ground state (m g ¼ 38.47 D) to the excited states (m e ¼ 34.18 and 34.34 D for the rst and second peak, respectively).
CPKS calculations in CHCl 3 reproduced well the hyperpolarizability tensor b trend of the neutral and the doubly protonated forms of (R)-11.The vector components along the respective dipole directions were b ¼ 106 and 880 Â 10 À30 esu, respectively.It is interesting to compare the computed hyperpolarizability of (R)-11 with that of the hypothetical 6,6 0 -disubstituted compound, analogous to 1 and 2 but functionalized in the same way as (R)-11.CPKS calculations in CHCl 3 provided signicantly increased hyperpolarizability values (b ¼ 328 and 1540 Â 10 À30 esu for the neutral and the doubly protonated forms, respectively).Such enhancement should be ascribed to the increased extension of the p-electron delocalized system.In fact, while the dihedral angle between the two naphthyl least-squares planes of this hypothetical compound, 81.5 , was quite similar to that of (R)-11, the conjugated fragment (pydirine-double bondphenylene-double bond) bonded to the 6,6 0 position was essentially coplanar to the naphthyl unit (dihedral angle equal to 5.1 ).

Conclusions
We have reported on push-pull binaphthyls of novel conception, in which the p-bridge, bearing at its "pull" end a pyridine  unit, extends from the 3,3 0 -binaphthyl skeleton, bearing alkoxy "push" unit in the 2,2 0 positions.These innovative dyes are chiral, securing NLO response, and polarizable through protonation or a coordination event.The HWE olenation methodology has been an efficient tool for the construction of extended, enantiopure binaphthyl derivatives with high isolated yields.The presence of the terminal pyridine units gives the possibility of further polarizing the system, either by weak coordination with a transition metal, or by reversible protonation.In both cases, the observed shi towards lower energies of the absorption major band indicates that the degree of additional polarization achieved is signicant.CD spectroscopy helped to elucidate this very highly active CD chromophore, whose characteristic CD couplet shis in intensity but not in symmetry, as to indicate complete saturation of the coordinating nitrogen atoms of the pyridine ligands.The EFISH values for the system are remarkable, when compared with those obtained for similar systems reported in the literature.

General experimental
All available compounds were purchased from commercial sources and used as received.Compounds (R)-5 (ref.22) and 8 (ref.23) were prepared as previously described.THF (Na, benzophenone), Et 2 O (Na, benzophenone) and CH 2 Cl 2 (CaH 2 ) were dried and distilled before use. 1 H and 13 C NMR spectra were recorded from solutions in CDCl 3 on Bruker 200 or AMX300 with the solvent residual proton signal as a standard.Analytical thin layer chromatography was performed on silica gel, chromophore loaded, commercially available plates.Flash chromatography was carried out using silica gel (pore size 60 A, 230-400 mesh). 1 H and 13 C NMR spectra were recorded from solutions in CDCl 3 on 200-300 MHz or 500 MHz spectrometer with the solvent residual proton signal or tetramethylsilane as a standard.The UV-vis spectroscopic studies were recorded using commercially-available spectrophotometers.Mass spectra were recorded using an electrospray ionization instrument (ESI).Optical rotations were measured on a polarimeter in a 10 cm cell with a sodium lamp (l ¼ 589 nm) and are reported as follows: [a] rt D (c ¼ mg (mL) À1 , solvent).CD spectra were recorded at 25 C at a scanning speed of 50 nm min À1 and were background corrected.Each spectrum is the instrument average of four consecutive scans.Mass spectra were recorded using an electrospray ionization instrument.

Procedure for NMR, UV and CD titrations
The titration experiments were conducted as follows: to a stock solution of chromophore (R)-11 (solution A) were added several aliquots of the Pd 2+ salt (solution B).Solution B is formed by the Pd 2+ salt (at higher concentration) dissolved in solution A, in order to maintain one species always at the same, constant concentration.

Absorption and emission spectroscopy
Electronic absorption spectra were obtained using a Jasco V-530 spectrophotometer.Photoluminescence (PL) measurements were obtained with a SPEX 270 M monochromator equipped with a N 2 cooled charge-coupled device exciting either with a monochromated Xe lamp or an Ar + laser.The spectra were corrected for the instrument response.

NLO measurements
EFISH measurements were carried out in CHCl 3 and DMF solutions at the concentrations specied in Table 2, at a nonresonant fundamental wavelength of 1907 nm using a Q-switched, mode-locked Nd 3+ :YAG laser.The 1064 nm initial wavelength was shied to 1907 nm by a Raman shier with a high-pressure H 2 cell.

Computational details
The molecular structures of (R)-11, its bisprotonated form and the analogous 6,6 0 -disubstituted compounds have been optimized in CHCl 3 within the DFT approach, using the PBE0 functional 27,28 which has previously been judged well suited for describing the electronic features of a series of organic dyes. 29he 6-311G** basis set was chosen for all atoms.Solvent effects have been taken into account using the conductor-like polarizable continuum model, CPCM. 30Using the PBE0/6-311G** optimized geometries, standard vertical Time Dependent DFT (TDDFT) calculations [31][32][33] have been carried out at the TD-uB97X/6-311++G** level using the so-called nonequilibrium approach, to determine the absorption wavelengths.The uB97X 34 functional was found to provide the better agreement with the experimental results with respect to other tested functionals (PBE0 and M062X), which gave too high excitation energies in particular for the bisprotonated form.Hyperpolarizabilities have been computed at the same frequency as used in the experiment, using the Coupled Perturbed Kohn Sham (CPKS) approach with the CAM-B3LYP functional, 35 which was recently recommended for hyperpolarizability calculations of midsize organic chromophores. 36he reported hyperpolarizability values include the 1/2 factor to be compared with the experimental results.All calculations have been performed with the Gaussian suite of programs. 37

Scheme 2
Scheme 2 Synthesis of the molecular modules.

Table 1
a Data taken from ref. 6. b Data taken from ref. 7.

Table 2
Nonlinear optical properties of 11 and 11$2HCl in solution