The hetero-Friedel-Crafts-Bradsher Cyclizations with Formation of Ring Carbon-Heteroatom (P, S) Bonds, Leading to Organic Functional Materials

The interest in functional materials possessing improved properties led to development of new methods of their synthesis, which allowed to obtain new molecular arrangements with carbon and heteroatom motifs. Two of the classical reactions of versatile use are the Friedel-Crafts and the Bradsher reactions, which in the new heteroatomic versions allow to replace ring carbon atoms by heteroatoms. In the present work, we review methods of synthesis of C–S and C–P bonds utilizing thia- and phospha-Friedel-Crafts-Bradsher cyclizations. Single examples of C–As and lack of C–Se bond formation, involving two of the closest neighbors of P and S in the periodic table, have also been noted. Applications of the obtained π-conjugated molecules, mainly as semiconducting materials, flame retardants, and resins hardeners, designed on the basis of five- and six-membered cyclic molecules containing ring phosphorus and sulfur atoms, are also included. This comprehensive review covers literature up to August 2020.


Introduction
During the last years, π-conjugated molecules containing various ring heteroatoms, such as boron, nitrogen, silicon, sulfur, oxygen, or phosphorus atoms incorporated into polycyclic ring systems gained an increasing importance due to their unique optical and electronic properties which made them useful functional materials, especially in the area of semiconducting materials [1]. Two elements of the fifth and sixth groups of the periodic table, sulfur and phosphorus, occupy a special position in the heteroatom family. Despite the close proximity in main groups and in the third row of the table, the properties of materials containing these two heteroatoms vary considerably due to differences in atomic radii, electronegativities, and a number of free electron pairs available. They are incorporated in five-or six-membered ring systems, mainly thiophene and phosphole derivatives. The latter possesses lower resonance energy compared to the former, originating from differences in configuration of phosphorus (flattened sp 3 ) and sulfur (sp 2 ) atoms. Thus, phosphole has nearly six times weaker aromatic character than thiophene based on aromatic stabilization energies (ASE calc = 3.2 versus 18.57 kcal mol −1 ) [2]. These differences, however, may be an asset, utilized in modulating the material properties based on these molecules. Both phosphorus and sulfur can be present in pendant hetero-organic groups outside the ring [3,4] or can replace one of the ring carbon atoms of the molecular backbones. The latter situation concerns the subject matter of this comprehensive review, which covers literature up to August 2020.
Among various general methods for the synthesis of arenes and heteroarenes, the Bradsher cyclization (1940), which is the intramolecular version of the discovered earlier Friedel-Crafts acylation and alkylation reactions (in 1877), realizes the most common ring closure strategy. From the mechanistic point of view, this reaction is categorized as the electrophilic aromatic substitution S E Ar, in which a carbocation σ complex (arenium ion) is formed as an intermediate. Nearly all organic compounds of electrophilic character may react with (hetero)aromatics in this reaction under suitable activation conditions. It is also known that heteroatom cations generated from p-block-elements including phosphorus and sulfur may also interact with (hetero)arenes to form heteroarenium species and thus enable introduction of ring heteroatoms in place of carbon atoms. This type of modification, which may be referred as a hetero-Friedel-Crafts-Bradsher reaction, is a useful tool for incorporation of heteroatoms into π-conjugated frameworks. Our intention was to summarize, in this review, all synthetic approaches based on mechanistic principles of this reaction leading to five-and six-membered cyclic products via the heteroatom-carbon bond formation. An integral part of this work is a review of properties and applications of the synthesized molecules, which is placed in the end of each subsection. Lack of information means that only synthesis of a new molecule or a group of molecules has been developed. Most of the data, especially in case of thiophene-based materials, concerns opto-electric properties due to the unique structures of the obtained molecules containing considerable unsaturation in addition to phosphorus and sulfur, accompanied by other ring heteroatoms, like oxygen and nitrogen (Scheme 1).
Some selected examples of the hetero-Friedel-Crafts-Bradsher cyclization may be found in earlier literature [1,5].

Cyclisation of Sulfur Derivatives
The first literature report concerning intermolecular Friedel-Crafts sulfinylation of aromatic compounds, starting from diaryl or alkyl aryl sulfoxides, was published in 1926 by Farah and coworkers [6]. After 30 years, Douglas et al. reported the synthesis of methyl phenyl sulfoxide from benzene and methanesulfinyl chloride in the presence of AlCl 3 [7]. Also, Gupta published the synthesis of aromatic N,N-dialkylsulfonamides via the reaction of dialkylsulfamyl chlorides with aromatic hydrocarbons in the presence of AlCl 3 [8]. On the other hand, Yuste and coworkers reported that the intermolecular Friedel-Crafts reaction of alkyl-and arylsulfinates with aromatic systems, activated by electron-donating substituents, provided alkyl aryl and diaryl sulfoxides under mild conditions in moderate to good yields [9].
One of the most efficient key approaches for the synthesis of polycyclic systems containing ring sulfur atom and utilizing intramolecular electrophilic annulation reaction of sulfoxide groups in alkylsulfinylarenes with aromatic rings was introduced by Müllen and coworkers in 1999. The mechanism of this transformation assumed protonation of oxygen atom in the sulfoxide group (1), in the presence of trifluoromethanesulfonic acid (triflic acid, TfOH) with formation of electrophilic sulfonium cation (2). Thus, this acidic activation of sulfoxide resembles activation of carbonyl group in the presence of Brönsted or Lewis acids in S E Ar reactions. In the next step, the sulfonium cation (2) underwent intramolecular, electrophilic substitution reactions followed by elimination of water, to give cyclic methylsulfonium salt (3). In the last step, a base, usually pyridine, promoted demethylation to provide the derivative (4). The above strategy was utilized in syntheses of not only "small molecules" but also polymeric systems (5) starting from polysulfoxides (6) as substrates (Scheme 2). Scheme 2. The reaction mechanism of the thia-Friedel-Crafts-Bradsher annulation leading to the synthesis of polycyclic systems containing a ring sulfur atom.
"small molecules" but also polymeric systems (5) starting from polysulfoxides (6) as substrates (Scheme 2). Scheme 2. The reaction mechanism of the thia-Friedel-Crafts-Bradsher annulation leading to the synthesis of polycyclic systems containing a ring sulfur atom.
Similar synthetic methodology was used by Li and coworkers for the synthesis of thieno[3,2-b;4,5-b']dithiophenes (57). In this approach, 2-bromo-3-methylsulfinylbenzothiophene (58) underwent the Stille coupling reaction with tin derivatives (59) providing teraryls (60), which were next cyclized in the presence of the Eaton's reagent (7.7 wt% P 2 O 5 in CH 3 SO 3 H) and finally aromatized with pyridine to afford the desired products (57) (Scheme 10) [24]. Further investigations showed that compound (57) had suitable HOMO energy levels to be applied in organic transistors as p-channel organic semiconductors. Thin-film transistor characteristics showed that all derivatives displayed a high device reproducibility and nearly no dependence on substrates temperature. Materials 2020, 13, x FOR PEER REVIEW 6 of 24 Scheme 9. The synthesis of new pyrene fused thienoacenes (45-47).

Cyclization of Phosphorus Derivatives
The first example of intermolecular, electrophilic reaction involving a phosphorus precursor with aromatic component under the classical Friedel-Crafts reaction conditions was presented by Maier in 1964 [46]. He found that phosphorus sulfochloride (PSCl 3 ) yielded triphenylphosphine sulfide upon reaction with benzene and excess aluminum chloride. Olah and coworkers developed this method for preparation of triphenylphosphine sulfide in 71% yield from benzene and sulfur, phosphorus trichloride, and aluminum chloride [47].
Desulfurization of (164) with triethylphosphine Et3P afforded the corresponding bis(phosphine) helicene (168) and a selective oxidation of the latter with m-chloroperoxybenzoic acid (MCPBA) delivered the corresponding bisphosphine oxide helicene (169). Due to the non-planarity of the central ring in (164), its aromaticity was reduced but decomposition was not observed even at 600 K under air atmosphere. Scheme 30. The synthesis of bis(phosphine) helicene derivatives (164, 168, 169).
Desulfurization of (164) with triethylphosphine Et 3 P afforded the corresponding bis(phosphine) helicene (168) and a selective oxidation of the latter with m-chloroperoxybenzoic acid (MCPBA) delivered the corresponding bisphosphine oxide helicene (169). Due to the non-planarity of the central ring in (164), its aromaticity was reduced but decomposition was not observed even at 600 K under air atmosphere.
To demonstrate the potential of DOPNA derivatives as OLED materials, the authors fabricated phosphorescent organic light-emitting diodes (PHOLED) using these compounds as hole/exciton blocking layer (HBL) components. The addition of 4-Ph-DOPNA and 6-Ph-DOPNA substantially improved the OLED lifetime.
Usually, intramolecular phospha-Friedel-Crafts-Bradsher cyclization reactions in which P-aryl bonds are formed typically require a strong Lewis acid (for example AlCl 3 ) to activate the P-Cl bond; however, this phospha-cyclization proceeds in THF under relatively mild conditions in the presence of weak Lewis acid (ZnX 2 ).
Most of the obtained benzophosphole derivatives, especially oxides, were fluorescent in solution. High fluorescence quantum yields (0.57-0.94) were obtained in the case of benzophosphole oxides bearing phenyl, amino, and carbazolyl substituents (191). The presence of electron withdrawing substituents on the aryl group at the phosphole phosphorus in the benzophosphole (191a) also had a notable effect. Compounds with 4-fluorophenyl and 4-trifluoromethylphenyl (192) groups exhibited intense blue emission at 420 and 422 nm, respectively. They also revealed high fluorescence quantum yields of 0.86 and 0.93, respectively. The 2-phenyl and 2,3-diphenyl analogues (193) and (194) showed λ abs and λ em red-shifts due to extended conjugation at the 2 and 3 positions.
The same research group reported a similar one-pot approach to the synthesis of benzo[b]phosphole skeleton utilizing, instead of arylzinc and cobalt salt, a combination of arylmagnesium and nickel salt which allowed inversion of regiochemistry of the phospha-cyclization step [56]. Thus, Grignard reagents (195) in the presence of NiCl 2 as a catalyst were added to triple bond of alkynes (196) to form the magnesium intermediates (197) followed by trapping the resulting cis-β-styrylmagnesium species with dichlorophosphine (RPCl 2 ) in the presence of CuCN•2LiCl to afford (198). A weak Lewis acid (MgX 2 ) formed during the reaction, spontaneously catalyzed the phospha-Friedel-Crafts-Bradsher cyclization, leading to the benzo[b]phosphole ring system (199). Oxidation of the latter by hydrogen peroxide afforded the relevant phosphine oxides (200) (Scheme 35).  [57,58].
The presence of a phosphinic acid group (P(O)(OH)) in the triangulene (213) indicated that its complex with copper (213)•Cu 2 (OH) 4 ) could be a highly proton-conducting material. The triangulene was subjected to AC impedance spectroscopy under conditions of controlled humidity. The proton conductivity was found to be 5.9 × 10 −8 S cm −1 at 25 • C and 55% relative humidity (RH). Nyquist plots, under a variety of humidity conditions (from 55% to 95% RH) at 25 • C, showed that conductivity increased with increasing RH.

Conclusions
Introduction of heteroatoms into cyclic, π-conjugated molecules usually delivers new materials with enhanced properties compared to carbon analogs. This was the case with five-and six-membered heteroacenes containing ring phosphorus and sulfur atoms.
These two heteroatoms have been introduced into carbon backbones by harnessing the classical Friedel-Crafts and Bradsher reactions in new heteroatomic versions (thia-and phospha-). The review demonstrates the progress made in both types of reactions, leading to construction of a variety of benzo-and thieno-fused, carbo-and heterocyclic frameworks which gained applications, mainly as semiconducting and light emitting materials in organic diodes, transistors, and photovoltaic devices. Extensive literature and a variety of examples show that this type of reaction has become an important synthetic tool in modern organic chemistry for introduction of ring phosphorus and sulfur into molecular structures. We believe that this review will serve as a useful reference for chemists interested in developing libraries of new thiaand phospha-derivatives and in extending their applications over emerging areas. This review should also stimulate the development of the chemistry of arsenic and selenium, the two heavier neighbors of sulfur and phosphorus in the periodic table, based on electrophilic aromatic substitution reaction.