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Project titleNew synthetic chemistry of 4-(het)aryl-3-oxobutanoic acid derivatives for development of functional photochromic molecules

Research area 03 - CHEMISTRY AND MATERIAL SCIENCES, 03-101 - Synthesis, structure and reactivity of organic compounds

KeywordsPhotochromism, diarylethene, photoswitching, organic synthesis, cyclization, thiophene, azoles, ketoester, cyclopentenone, cyclohexenone, photomodulation

Annotation
During the last decades, chemists all over the world yearned for remote and reversible control of materials, devices, and processes with light. We can say that those studies are guided by scientific maxim “irradiate et impera”. Realization of these dreams will undoubtedly open new exciting opportunities for science, industry, and medicine. Thus, a new area photopharmacology has been just emerged in medicine. The phenomenon “photochromism” is usually the basis for a desired photocontrol. Among a number of organic photochromes, diarylethenes with heterocyclic moieties occupy a special place. This proposal is devoted to solving two problems: the development of a new class of photochromic diarylethenes with photocontrolled acidity and a new class of diarylethenes-precursors. Compounds whose pKa values can be reversibly changed by the action of light have been actively investigated in recent years (starting from the pioneering work of J.-M. Lehn in 1999).The field of their potential application is wide - from the control of reactivity and catalytic activity to the control of bioavailability of drugs. The project proposes a new concept of photo-controlled acidity, consisting in reversible keto-enol tautomerization, which becomes possible during the photocyclization of diarylethene bearing a phenol bridge. It is expected that the proposed photochromes will exceed in the key parameters known literary examples (first of all, the change of the dissociation constant ΔpKa). One of the optimal ways to investigate structure property correlations and the synthesis of diarylethenes with desired properties or functions is the use of a photochromic compound precursor, which could be used for the synthesis of a wide range of diarylethene derivatives by chemical modiﬁcations. The most successful diarylethenes precursors (developed by M. Irie and B. Feringa) feature easily modifiable hetaryl substituents. In this project, it is planned to develop a new class of accessible and easily modifiable diarylethenes based on the 4-hydroxy-4-methylcyclopent-2-enone bridge. From a synthetic point of view, the novelty of the project is justified by the investigation of the transformations of a new class of synthones - esters and amides of 4-(het) aryl-3-oxobutanoic acid, the first of which was developed in our laboratory only in 2011. To solve the first problem, the condensation of 4-(het)aryl-3-oxo-butanoates with 1,4-di(het) arylbut-2-ene-1,4-diones by the Robinson type reaction will be investigated (only one example in J. Org. Chem. 2004, 69, 2591). To solve the second problem, a detailed study of the unique reaction, the aerobic dimerization of ethyl 4-(het)aryl-3-oxobutanoates with the formation of a cyclopentenone ring (an example is described on a single substrate, see A.G. Lvov et al., Org. Lett. 2017, 19, 4395) will be provided. Based on the results of the project, it is planned to publish 3 articles in the high-ranking journals of the first quartile (Q1), including one review.

Expected results
1) New synthetic method for cyclohexenones by condensation of esters and amides of 4-(het)aryl-3-oxobutanoic acid with 1,4-di(het)arylbut-2-ene-1,4-diones. Scope and limitations. Development of oxidation of these cyclohexenones to the corresponding phenols. 2) Development of new class of photochromes with a controlled value of pKa. 3) New synthetic method for the substituted cyclopentenones by the aerobic dimerization of 4-(het)aryl-3-oxobutanoic acid derivatives.

Annotation of the results obtained in 2019
The keto-enol tautomerism of photochromic derivatives of ethyl 2-oxocyclohex-3-encarboxylate was studied. For the first time, the process of photocontrollable keto-enol tautomerism of β-ketoester was realized using the diarylethene with thiophene moieties. This process is based on the reversible cyclization / cycloreversion of the hexatriene system. In the case of the initial form of diarylethene, the keto-enol equilibrium is almost completely shifted towards ketone. Photocyclization of the diarylethene leads to a new equilibrium containing a significant fraction of the enol tautomer. Stabilization of the enol occurs due to a system of conjugated double bonds and an intramolecular hydrogen bond. Irradiation with visible light leads to the formation of the initial diarylethene in the form of a ketone. This phenomenon is observed both in polar and non-polar solvents. A related diarylethene containing a 2-(imidazol-2-yl)pyridine derivative as a moiety at the central double bond can act as a ligand with two coordinating sites, while the β-ketoester fragment as an enolate acts as one of the sites. The cyclic iron(II) complexes were obtained and their magnetic properties were studied.

Publications

1. Dashitsyrenova D. D., Lvov A. G., Frolova L. A., Kulikov A. V., Dremova N. N., Shirinian V. Z., Aldoshin S. M., Krayushkin M. M., Troshin P. A. Molecular structure–electrical performance relationship for OFET-based memory elements comprising unsymmetrical photochromic diarylethenes Journal of Materials Chemistry C, J. Mater. Chem. C, 2019, 7, 6889--6894 (year - 2019) https://doi.org/10.1039/C9TC01273G

2. Lvov A.G., Mörtel M., Yadykov A.V., Heinemann F.W., Shirinian V.Z., Khusniyarov M.M. Photochromic diarylethene ligands featuring 2-(imidazol-2- yl)pyridine coordination site and their iron(II) complexes Beilstein Journal of Organic Chemistry, Beilstein J. Org. Chem. 2019, 15, 2428–2437 (year - 2019) https://doi.org/10.3762/bjoc.15.235

3. Lvov A.G., Yadykov A.V., Lyssenko K.A., Heinemann F.W., Shirinian V.Z., Khusniyarov M.M. Reversible shifting of a chemical equilibrium by light: The case of keto−enol tautomerism of a β‑ketoester Organic Letters, Org. Lett. 2020, 22, 604−609 (year - 2020) https://doi.org/10.1021/acs.orglett.9b04376

4. Lvov A. G., Yokoyama Y., Shirinian V. Z. Post-modification of the ethene bridge in the rational design of photochromic diarylethenes The Chemical Record, Chem. Rec. 2020, 20, 51–63 (year - 2020) https://doi.org/10.1002/tcr.201900015

5. - Российские ученые выяснили характеристики элементов памяти в органической электронике ТАСС, - (year - )

Annotation of the results obtained in 2018
The analysis of synthetic methods towards photochromic diarylethene precursors with modifiable ethene bridges and their application in the development of photochromes with desired characteristics was performed (collaboration with Prof. Yasushi Yokoyama, Yokohama National University). We have demonstrated a great potential of these molecules in rational design of photochromes, for example, with quantum yields and fatigue resistance. Robinson-type condensation of ethyl 4-hetaryl-3-oxobutanoates with 1,4-di(hat)arylbut-2-ene-1,4-diones and chalkones was studied. A range of previously unknown photochromic diarylethenes with cyclohexenone bridge was synthesized. The oxidation of these compounds to corresponding phenols was studied. Previously elaborated methods using copper(II) bromide or iodine allowed obtaining of phenols bearing aromatic groups at 5 position, while keto-group in this position prevents oxidation. Photochemistry of these dihetarylphenoles was studied. Photochromic performance of diarylethenes with cyclohexenone bridge bearing the fragment of ethyl acetoacetate (ethyl 4,5-bis(2,5-dimethylthiophen-3-yl)-3-oxo-1,2,3,6-tetrahydro-[1,1'-biphenyl]-2-carboxylate) was investigated. Photocyclization of this diarylethene with subsequent enolization was proved by combination of experimental methods (electronic spectroscopy, 1H NMR spectroscopy, X-ray analysis). Only one molecule with similar properties was described up to date (Nat. Chem. 2018, 10, 1031; Nat. Catal. 2018, 1, 516). However, for this molecule an enol (in the form of phenol moiety) serves as initial stable form. Currently, such molecular systems are of great fundamental interest (for review, see: M. Kathan, S. Hecht, Photoswitchable molecules as key ingredients to drive systems away from global thermodynamic minimum, Chem. Soc. Rev. 2017, 46, 5536). The possibility of enolization of related systems was demonstrated in the case of bis(pyrazolyl)borate complexes of iron(II). It was demonstrated, that aerobic base-induced dimerization of ethyl 4-phenyl-3-oxobutanoates results in two isomeric 4-hydroxycyclopentenones. The structures of these products were proved by X-ray analysis and 2D NMR spectroscopy. It was found, that phenylacetone unable to dimerize under reaction conditions towards the corresponding cyclopentenones. A series of methoxy-substituted 4-hydroxycyclopentenones has been synthesized.

Publications

1. D. D. Dashitsyrenova, A. G. Lvov, L. A. Frolova, A. V. Kulikov, N. N. Dremova, V. Z. Shirinian, S. M. Aldoshin, M. M. Krayushkin, P. A. Troshin Molecular structure–electrical performance relationship for OFET-based memory elements comprising unsymmetrical photochromic diarylethenes Journal of Materials Chemistry C, - (year - 2019)

2. Andrey G. Lvov, Yasushi Yokoyama, Valerii Z. Shirinian Post‐modification of the Ethene Bridge in the Rational Design of Photochromic Diarylethenes THE CHEMICAL RECORD, - (year - 2019) https://doi.org/10.1002/tcr.201900015