Axial stereogenicity for designing inherently chiral organic semiconductors.

The topic of my research is focused on the discovery and development of new inherently chiral molecules that, due to their peculiar properties, can be used both as semiconductive material and, when the molecules are deposited as an enantiopure film, as surfaces able to enantiorecognize chiral probes. In the last years, the interest for the organic semiconductors has increased and especially multi-thiophene molecules have attracted considerable attention. Such multi-thiophene materials are obtained by chemical or electrochemical oxidation of a monomer and they are insulator in neutral state but become conductor after p- or n-type doping. Chirality is generally introduced in the polyconjugated semiconductors by attaching chiral pendants to the electroactive backbone but these materials give relevant chirality manifestations only under particular experimental conditions [1]. The idea on which is based this research project is to design a class of compounds that could strictly correlate the conductive polythiophenes backbone to the chirality properties. This requirement is satisfied by the exploitation of the inherent chirality that is based on the concept that the scaffold constituting the stereogenic element responsible for chirality is also the functional group responsible for properties. The peculiarities of the inherently chiral system are that the chirality results from a tailored torsion produced along the conducting oligothiophene backbone, the stereogenic core responsible for chirality is an atropoisomeric bi-thiophene or bi-pyrrole, and the same conjugated system responsible for the electro-optical properties is also responsible for molecular chirality. The first member of this new class, nicknamed BT2T4 (because it consists in a bithianaphthene scaffold leading four thiophenes), showed outstanding properties such as a very high racemization barrier, great chiroptical properties and, deposited as an enantiopure polymeric film on an electrode, it showed amazing enantiorecognition ability [2]. Furthermore, BT2T4 was chemical oxidized by FeCl3 and the mixture of the oligomers was analyzed through HR MALDI spectrometry giving a very surprising result since all the oligomers, namely dimers, trimers and superior oligomers, were found to be cyclic and not open and linear [3]. Prompted by these outstanding results, during the first year of the PhD research we modified the structure of BT2T4 in order to obtain new inherently chiral compounds following two different strategies. The first one is based on the bithiophene tail elongation in order to achieve, after the oxidation, cyclic compounds with bigger cavity. The second strategy, on the other hand, aims to achieve a compound where the bithiophene tails are blocked in a rigid coplanar structure: the rigidity of the system indeed should provide material endowed with better optoelectronic properties. All these compounds were prepared according to the same general procedure starting from the 2,2’-dibromo-3,3’- bithianaphatene that was functionalized with different “pendants” through a Stille reaction. As shown in figure 2 the selected “pendants” were the ter-thiophene (BT2T6), the 3',4'-dibutyl-2,2':5',2''-terthiophene (BT2T6 Bu), the dithienopyrrole-N-octyl (BT2DTP2), the dithienopyrrole-N-methyl-phenyl (BT2DTP2 Ph) and the 4,7-di(thiophen-2-yl)benzo[c][1,2,5]thiadiazole (BT2BTD2). In particular, the introduction of a benzothiadiazole system has a double role: to extend the pendant lenth and, at the same time, to lead to a compound exhibiting optical properties slightly different from the other monomers (i.e. high quantum yields and λ absorption red-shifted). After one year, we reached many promising results: we could confirm that the modification introduced on the BT2 scaffold leads to monomers able to oligomerize through chemical and electrochemical oxidation producing cyclic oligomers with different dimension and shape. We analyzed both monomers and oligomers by different techniques. Futhermore, some of them were separated into enantiomers and their chiroptical properties were investigated. As expected, the compound nicknamed BT2BTD2 has remarkable properties, especially from an optical point of view but unfortunately, we could not exploit it due to its low solubility. For this reason, we planned to modify the structure of the monomer in order to improve the solubility by introducing four EDOT units in place of the four thiophenes. Unfortunately, due to the low solubility of the benzothiadiazole-bis-EDOT (BTDE) it was not possible to obtain the target monomer through the classical synthetic scheme which requires a Pd (0) catalyzed Stille reaction. However, since the bare BTDE appeared an interesting monomer, we investigated its chemical and electrochemical copolymerization in the presence of 3,3’-bithianaphtene. These experiments were carried out in the group of prof. S. Ludwigs of the University of Stuttgart, where I spent my abroad period, exploiting the expertise of the group in the polymer synthesis and electrochemical analysis. Since both chemical and electrochemical oxidation did not give the expected results, we moved our attention to the possibility to achieve a donor-acceptor (D-A) copolymer by copolymerization of the benzothiadiazole-bis-EDOT with the branched terthiophene, nicknamed T3, deeply investigated in that group [4,5]. D-A polymers have recently attracted particular interest since they exhibit a reduced band-gap, due to their in-chain donor-acceptor interaction and for this reason they are used as light-harvesting system in solar cells. Furthermore, besides a long time focused on electrochemical analysis, during the period spent in Germany I synthetized two new compounds. In order to investigate the role of ramification, we prepared a product with the same number of thiophenes as BT2T6 but with a branched structure by functionalizing the atropisomeric scaffold with two T3 units. On the other hand, we synthetized a compound functionalized with four EDOT units, nicknamed BT2E4 which should have provided a material with interesting properties, being EDOT electron-richer than thiophene and ubiquitous in the electroactive materials. During my third year, we focused our attention on a new class of inherently chiral monomer based on the scaffold of the 2,2’-biindole. The design of the new class has two main motivations:  the 2,2’-biindolic core is more electron rich than that of 3,3’-bithianaphtene and the first two oxidations result at an oxidative potential particularly low. This could allowed to discriminate analytes in a different potential window.  the nitrogen atom can be functionalized, tuning solubility and processability of the final material. Especially interesting is the monomer derived from the introduction of a chiral pendant, namely the (R)- or (S)-phenylethyl group, that leads to the formation of two diastereoisomers, theoretically separable through a classical method, avoiding the chiral HPLC. Indeed, the major disadvantage presented by the compounds investigated until now is the fact that their separation into antipodes must be performed through HPLC on a chiral stationary phase. Developing a method that could allow to avoid this tedious step would be an appealing target. In figure 5 are reported two other monomers synthetized according to this strategy: the first is characterized by the presence of two carboxylic groups that could allowed a classical resolution through the formation of diastereoisomeric salts with a chiral base. The second, on the other hand, was obtained as an enantiopure compound through an enantioselective synthesis starting from an enantiopure precursor obtained, in turn, by resolution with camphosulfonic acid. In addition, due to the remarkable properties showed by BT2BTD2, we decided to introduce the benzothiadiazole system on the 2,2’-biindole scaffolds obtaining the first example of a biindole with a pendant different from the bithiophene. The presence of the nitrogen atoms allows the functionalization with two hexylic chains that strongly increase the solubility of the monomer, overcoming the problem found for BT2BTD2. In conclusion, after three years research on inherently chiral electroactive materials new compounds, based on 3,3’-bithianaphtene and 2,2’-biindole core, were synthetized and fully characterized. The new frontier of this kind of inherently chiral monomers results to be the achievement of enantiopure compounds without the use of chiral HPLC and some preliminary interesting results have been obtained. [1] Janssen et al.; J. Molecular Structure, 2000, 521, 285; [2] Sannicolò, F.; Benincori, T. et al.; Angew. Chem., Int Ed., 2014, 53, 2623; [3] Sannicolò, F.; Benincori, T. et al.; Chemistry: an European Journal, 2014, 20, 15261; [4] Link, S.; Ludwigs, S. et al.; Langmuir, 2013, 29, 15463; [5] Goll, M.; Ludwigs, S. et al.; Beilstein J. Org. Chem, 2015, 11, 335; [6] Abbiati, G.; Arcadi, A. el al.; Tetrahedron, 2006, 62, 3033;