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Review

Chiral Polythiophenes: Part I: Syntheses of Monomeric Precursors

by
Dorota Krasowska
1,*,
Rafał Karpowicz
2,* and
Józef Drabowicz
1,3,*
1
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland
2
Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland
3
Institute of Chemistry, Jan Dlugosz University in Czestochowa, Armii Krajowej Ave. 13/15, 42-200 Czestochowa, Poland
*
Authors to whom correspondence should be addressed.
Molecules 2021, 26(14), 4205; https://doi.org/10.3390/molecules26144205
Submission received: 31 May 2021 / Revised: 26 June 2021 / Accepted: 7 July 2021 / Published: 10 July 2021
(This article belongs to the Special Issue Conducting Polymers)
Browse Figures
Versions Notes

Abstract

:
The purpose of this mini-review is to comprehensively present the synthetic approaches used for the preparation of non-racemic mono- and multi-substituted thiophenes, which, in turn, can be applied as precursors for the synthesis of chiral polythiophenes isolated as a single chemical entity or having supramolecular thin-layer architectures.

1. Introduction

The phenomenon of chirality plays a key role not only in plant and animal life, but also in the biological activity of drugs, food additives and agrochemicals [1,2,3,4,5]. In consequence, chiral structures are used very often as active components in pharmaceutical [6,7,8,9], agrochemical [10,11] and food formulations [12]. The last two decades have witnessed a growing demand for such derivatives as essential component of new materials including nonfunctionalized and functionalized polythiophenes (PTs). Interest in this group of synthetic polymeric materials comes from the hope that they may mimic the behavior of natural polymers and find application, for example, as chiral sensors, chiral catalysts and chiral chromatographic supports. When considering chiral PTs, the most readily available group should be derivatives of general formula 2 (Scheme 1) containing at least one substituent with a stereogenic center at the three-position (or at the four-position or both positions). They can be prepared by the chemical or electrochemical oxidation of the corresponding monomers of general formula 1 (unsubstituted or suitably functionalized in the two and/or five positions).
The synthetic non-regioselective routes to 2,5-coupled, 3-substituted polythiophenes provides the polythiophenes with a lower degree of HT (head-to-tail) type coupling in the main polymeric chain. They contain more regiochemical defects, which results in a distortion of the conjugated chain and a lower effective conjugation. Among these methods are chemical oxidative coupling using the Sugimoto protocol [13] and dehalogenative polycondensation using Ni(COD)2 [14]. The growing demand for the highly conductive materials applicable in electronic devices (i.e., field effect transistors, organic light-emitting diodes, photovoltaic cells, or sensors) induces the rapid developments in the regiospecific routes to regioregular PTs since the regioregular structure affects the improvement of their physico-chemical properties and their self-organization. Most of the synthetic approaches are based on the transition metal-catalyzed coupling reactions [15,16,17]. The first synthesis of regioregular head-to-tail coupled poly(3-alkylthiophenes) (PATs) was reported by McCullough and Lowe [18]. In this approach, the starting material is 2-bromo-3-substituted thiophene, which is selectively metalated with lithium diisopropylamide (LDA) and then treated with magnesium bromide, which led to the formation of the corresponding Grignard reagents. Their coupling reaction is catalyzed by Ni(dppp)Cl2. The modification of this method, developed by McCollough, is the GRIM metathesis procedure, which requires the use of a 2,5-dibromo-substituted thiophene derivative. The substrate reacts with the Grignard reagent, forming the corresponding thienyl magnesium halides, which then undergo a Ni-catalyzed coupling reaction. The polymerization proceeds via a living chain growth polycondensation mechanism that was independently discovered by Yokozawa and McCullough in 2004 [19,20]. Another regiospecific polymerization route that provides head-to-tail (HT) coupling products is the so-called Rieke method. It involves Ni-catalyzed coupling of organozinc halides generated in situ from 2,5-dihalogented thiophene derivatives by reactive forms of zinc [21]. The exception is when the palladium catalyst [Pd(PPh3)4] is utilized in this reaction of organozinc species, leading to a regiorandom type of coupling.
All the above-mentioned regiospecific polymerizations giving access to a wide range of 3-substituted polythiophenes with enhanced chiroptical properties require the use of a Ni-based catalyst and are based on the initial generation of organozinc or organomagnesium halides.
In turn, the Pd-catalyzed HT-coupling based polymerizations were also developed. These pathways demonstrate the good efficiency in Suzuki or Stille coupling reactions using boro- or organotin compounds generated from the starting 2-monohalo-thiophene derivatives. The Pd-catalyzed Stille or Suzuki polymerizations have already been found to proceed via step-growth polymerization and by a non-controlled mechanism providing the polymers with the lower polydispersity [15,22]. It should be noted that the organotin or organoboronic derivatives should be prepared under cryogenic conditions and they should be isolated prior to the next step.
Advances in the development of the efficient polymerization techniques leading to well-ordered conjugated polymers are based on some modifications, mostly in the Kumada-based polycondensation, which uses the internal initiator/catalyst and as well the recently applied external initiator species [23,24]. Kumada catalyst transfer condensative polymerization, being a modified GRIM method, is a controlled chain-growth polymerization that requires the use of a Ni-based chain initiator/catalyst.
The pool of controlled chain grow polymerizations complements a Pd-RuPhos protocol that is Pd-catalyzed Negishi coupling polymerization between organozinc compounds [25].
Dehydrohalogenative polycondensation is the other example of Ni-catalyzed [Ni(dppp)Cl2] polymerization, which requires the use of a mono-halogenated thiophene substrate and a Knochel–Hauser base to proceed at room temperature with high regioregular couplings [26,27,28].
The other strategy to synthesize regioregular polythiophenes, apart from the selection of a methodology distinguished by the type of metal catalyst, the reaction conditions and the control over the polymerization of monomeric units, relies on designing the symmetrical units. In this way, regiochemically defined polythiophenes could be obtained from the units that contain the spacer block between 3-substituted thiophenes. Similarly, HH-TT coupled PATs and TT-HH PATs are accessible from regiochemically defined bithiophenes, i.e., the HH-dimer of substituted thiophene or TT dimers and synthesized via one of the non-regiospecific methods ( i.e. FeCl3-mediated chemical polymerization).
These studies were summarized less or more briefly, occasionally, as part of reviews on chiral conductive polymers [29,30,31,32,33]. It is obvious that in all the studies devoted to the synthetic and structural aspects in the chemistry of chiral PTs, the preparation of the appropriately designed monomeric substrate constitutes an indispensable opening stage. Reading the original chemical literature gives the impression that the topic is treated quite briefly and without taking into account sufficient experimental details, the knowledge of which should be more or less helpful for all researchers in this field, especially for beginners entering this fascinating and rapidly developing topic. Therefore, the main focus of this mini-review is to extensively discuss the applied synthetic approaches extracted from the original publications that have been published since the first article on this topic in 1988 [34]. Taking into accounts the analysis of the substrate requirements of the mentioned polymerization methods, we propose the organization of the manuscript based on the type of substitution in monomeric precursors. Below, one by one, we will present protocols leading to optically active (or in some cases to racemic) thiophene derivatives of general structure 1:
(a)
monothiophenes substituted at the three-position of the ring with a group containing a stereogenic center or stereogenic axis;
(b)
monothiophenes substituted at the three-position of the ring with a group containing a stereogenic center and at once functionalized at the two and/or five positions;
(c)
monothiophenes substituted at the three and four positions with a group(s) containing a stereogenic center and nonfunctionalized or functionalized at the two and/or five positions;
(d)
β-(mono or di) substituted bithiophenes functionalized with a substituent containing a stereogenic carbon atom or a stereogenic heteroatom;
(e)
other (oligo)thiophenes functionalized with a substituent containing a stereogenic carbon atom or a stereogenic heteroatom.

2. Syntheses of 3-Substituted Monothiophenes Functionalized with a Substituent Containing a Stereogenic Center or a Stereogenic Axis

2.1. Syntheses of 3-Substituted Monothiophenes Nonfunctionalized in the Two and Five Positions

Due to the growing interest in the design of conducting polythiophenes with improved electrical and optical properties, mechanical, chemical and thermal stability, the research devoted to the synthesis of novel, diversely substituted monomeric units, for example those with the chiral 2-methylbutyl group. These functions are introduced into the structures while designing chiral nematic liquid crystals.
With a view to combining the liquid crystalline structure with a conductive polythiophene backbone, 3-(S)-2-methylbutylthiophene monomer 7 was synthesized [35] by reacting the generated from (S)-(+)-1-bromo-2-methylbutane 4 Grignard reagent 5 with 3 -bromothiophene 6 (Scheme 2) following the literature report devoted to a general method for the alkylation and arylation of haloheterocyclic compounds, which occurs in the presence of a catalytic quantity of [NiCl2(dppp)] (where dppp stands for Ph2 P(CH2)3PPh2) [36]. Later on, this procedure, carried out with commercially available 1-bromo-2-methylbutane (Aldrich) having [α]D = +4.5, c 5, CHCl3, was found to give thiophene 7, purified by distillation, with [α]D = +7.37 (neat) in 58% yield [37]. There are also two other reports on the use of this protocol [38,39] but without giving any details of yield and specific rotation.
The monomer 7 (0.25 M solution) was oxidatively electropolymerized with an applied potential of 5 V, in a two-electrode cell consisting of a glassy-carbon working electrode (0.26 cm2), a platinum wire counter electrode, in a dry MeCN and the Et4NBF4 (0.25 M) solution [35].
The chiral ordering in an aggregated conjugated poly{3-(S)-[2-methylbutyl]thiophene} was examined too after producing the polymeric materials using the ferric chloride oxidative method [37]. The doping effect prior to aggregation along with the doping level was explored to find the factors contributing to control chiral arrangement in conjugated polymer aggregates.
Moreover, the studies on the polymerization also comprised their regioregular polymeric analogues. First, the synthesis of HT regioregular 2,5 coupled poly-3-(S)-2-methylbutylthiophene was reported by Langeveld-Voss et al. [40]. Then, the regioregular polymer was prepared with a Ni(dppp)Cl2 catalyst using the Grignard metathesis developed by McCullough ][38,41] However, this procedure requires the preparation of 2,5 di brominated precursor; therefore, this synthetic procedure will be mentioned below in the subsequent chapter.
A recent China patent [42] lists among the product of cross-coupling of organozinc reagents and heterocyclic (pseudo)halides, racemic 3-(1-ethyl)butylthiophene 9 formed by the reaction of 3–bromothiophene 6 with hexan-3-ylzinc chloride 8 (Scheme 3).
Earlier, an EU patent owned by Nippon Telegraph and Telephone Corporation [43] reported the preparation 3-(S)-2-methyoctylthiophene monomer 12 achieved by coupling, generated from (S)-(+)-1-bromo-2-methyloctyl 10 Grignard reagent 11 with 3-bromothiophene 6 in the presence of a catalytic quantity of [NiCl2(dppp)] (Scheme 3). A similar approach was reported for the preparation of 3-(S)-3,7-dimethyoctylthiophene monomer 15 conducted by reacting the Grignard reagent 14 obtained from (S)-(+)-1-bromo-3,7-dimethyloctyl 13 with 3-bromothiophene 6. Unfortunately, specific rotation data are not available (Scheme 3) [44].
The direct introduction of the substituent into the three position of the thiophene ring can be implemented by the Suzuki cross-coupling reaction, as illustrated in the synthesis of optically active (R)-3-(4-(4-ethyl-2-oxazolin-2-yl)phenyl)thiophene (EOPT) 18 [45].
The reaction occurred between 3-thiopheneboronic acid 17 and the oxazoline derivative 16 (prepared independently starting from ethyl 4-iodobenzoate and (R)-2-amino-1-butanol via an optically active hydroxy amide derivative [46]). The reaction carried out in the presence of K3PO4 in toluene using Pd(PPh3)4 as a catalyst gave 18 (EOPT) in 85% yield (Scheme 4) [47]. The enantiomeric excess of 18 was estimated to be greater than 99% using europium tris[3 -(trifluoromethylhydroxymethylene)-(+)-camphorate] (Eu(tfc)3) as a chiral shift reagent (1H NMR spectrum measured in CDCl3).
The regioregular polythiophene derived from monomeric thiophene 18 was synthesized according to a modified McCullough’s procedure when monobrominated thiophene derivative was used as a starting material. Dehalogenative polycondensation according to a Yamamoto protocol was used as well, successfully starting from the dibrominated analogue of the monomer 18. It provided, however, the regiorandom polymer. The purpose of synthesizing the two polymers that differ in the regioregularity was to compare their chiroptical properties and to examine the influence of the regioregularity of the main chain on the induction of a chiral supramolecular aggregate in the chiral polythiophenes [47].
Among the optically active 3-alkylthiophene monomers, the most numerous groups are the compounds in which the alkyl group is functionalized at the terminal carbon atom by attaching a moiety containing a stereogenic center. The list of such compounds opens 3-[3-[(S)-2-phenylbutoxy)]propyl]thiophene 21a and its enantiomer 21b prepared by the reaction of the 3-(3′-thienyl)propyl toluene-p-sulfonate 19 with the enantiomers of 2-phenylbutanol 20a,b (Scheme 5) [34,48]. The monomers were next electropolymerized, applying a current density of 2 mA cm−2 in a one-compartment three-electrode cell containing the monomer and NBu4PF6 in nitrobenzene. Chiral polythiophenes, poly-21a and poly-21b, feature a high conductivity and were able to stereoselectively recognize the chiral anions used as doping agents during voltammetric cycles [34].
The preparation of 3-[2-((S)-2-methylbutoxy)ethyl]thiophene 24 was, for the first time, mentioned as early as 1994 in a paper coming from the Meijer’s group [49]. They isolated it in 83% yield by reacting 2-(3-thienyl)ethanol 23 (obtained in 89% yield by a reduction of 3-thiopheneacetic acid with LiAIH4) with a tosylate 22 of the commercially available optically pure (S)-(−)-2-methyl-l-butanol 3. This protocol was later referenced, without specifying characterization details, in three other publications by this team [40,50,51]. On the other hand, the paper by Ochiai et al. [52] contains the full experimental details of the protocol presented in Scheme 6. This protocol is given below. The monomer, after its conversion into the 2,5-dibromosubstituted derivative, was used to obtain an optically active regioregular 2,5-coupled analogue, poly(3-[2-((S)-2-methylbutoxy)ethyl]thiophene), containing a 93% HT head-to-tail linkage, according to the modified Rieke method [52]. The corresponding regiorandom poly-(S)-24 was obtained by the FeCl3-oxidative polymerization of 24 [49].
Another example of the condensation reaction aimed at appending a chiral moiety into the side chain of a 3-substituted thiophene derivative is the synthesis of the dextrorotatory enantiomer of thiophene containing an amino acid residue (+)-R- 25a. The transformation begins with the conversion of 3-thienylethanol 23 to the corresponding tosylate and follows by the reaction with a protected unnatural amino acid, N-t-Boc-d-Ser (Scheme 7) [53]. A similar sequence of reactions using N-t-Boc-l-Ser gave the opposite enantiomer of ethoxythiophene (−)-S-25b. Their further transformations into the corresponding methyl esters of serine-substituted monothiophenes (+)-R-26a. or (−)-S-26b involve estrifications using Ag2O and MeI (Scheme 7) [54].
The tert-butoxycarbonyl group was removed (using a TFA/DCM solution) prior to polymerization. The free amino acid substituted thiophene monomer (R)-25a and its methyl ester analogue 26a or its enantiomer 26b were polymerized using a method reported by Sugimoto et al. using chemical oxidation with FeCl3 in chloroform. The water-soluble polymers, converted into the ammonium chloride salts, were precipitated by adding acetone [53,54].
Synthesis of the monomers (R)-(−)-2-(3-thienyl)ethyl N-(3′,5′-dinitrobenzoyl)- α-phenylglycinate 29a and (S)-(+)-2-(3-thienyl)ethyl N-(3′,5′-dinitrobenzoyl)- α-phenylglycinate 29b involves a similar approach based on the condensation of (R)-(−) or (S)-(+)-N-(3,5-dinitrobenzoyl)- α-phenylglycine 27a or 27b with 3-(2-iodoethyl)thiophene 28a carried out in a basic medium (Scheme 8) [55]. Their enantiomeric excesses were supported by 1H NMR spectra measured in the presence of Eu(tfc)3. They are commonly used as chiral selectors in Pirkle’s stationary phases [56,57], applied in HPLC enantioselective analysis [58].
Once the monomers were isolated in good yields, namely, 51% for (R)-29a and 49% for (S)-29b, respectively, they were polymerized by oxidative coupling with FeCl3 in CHCl3 (Scheme 8). The optical activity of the polythiophenes was maintained as evidenced by the specific optical rotation values of [α]D28 = −29.0 (2.5, THF) for poly-(−)-(R)-29a and [α]D28 = +28.4 (2.5, THF) for poly-(+)-(S)-29b.
Several 3-substituted thiophenes (32a,b, 33a,b, 34b), wherein thiophene rings are linked directly or via an alkyl spacer to a chiral acetal ring such as a 1,3-dioxalane having two stereogenic carbon atoms, were prepared using optically active diethyl tartrate 31 and 3-thiophenecarboxaldehyde 30a or 3-thiophenepropanal 30b as starting materials. Their synthesis is shown in Scheme 9 [59].
The compounds 32a,b and 33a,b were subjected to an anodic polymerization. It was reported that poly-(33b) was stable toward oxidative cycling. For poly-(33), the progressive electrochemical growth was observed in CH2Cl2 with 0.1M Bu4NBF4 as an inert electrolyte, while no polymerization occurred using CH3CN.
Recently, a few racemic and optically active 2-(3′-thienyl)ethyl alkyl (aryl) sulfoxides 39a–c were prepared by reacting racemic or diasteromerically pure O-alkyl arene(alkyl) sulfinates 37a–f (prepared in turn from arene(alkane)sulfinyl chlorides 35a–c and an appropriate racemic or optically active alcohol 36) with 2-(3′-thienyl)ethylmagnesium bromide 38 (Scheme 10). [60]. Moreover, sulfoxides 39a and 42 were also obtained as racemates via the oxidation of the corresponding sulfides: 2- (3′-thienyl)ethyl p-tolyl 41 or 3-thienylmethyl p-tolyl 40 using a 30 wt% solution of hydrogen peroxide as an oxidizing reagent (Scheme 11) [60].
The subsequent transformations led to the N-unprotected, optically active 2-(3′-thienyl)ethyl (p-toluene/n-hexadecyl) sulfoximines (R)-(−)-45 and (R)-(−)-46. The imination of sulfoxides (R)-(+)-39a or (R)-(−)-39c using O-(mesitylsulfonyl)hydroxylamine (MSH) 43, following the procedure developed by Tamura in 1972 [61] and Johnson in 1974 [62] (Scheme 12), proceeded in an enantioselective manner, and took place with the retention of the configuration at the stereogenic sulfur atom. It is interesting to note that this sulfoximine, having 97% ee, showed only a very weak, almost an imperceptible cotton effect in the circular dichroism spectrum recorded in methylene chloride. The racemic n-hexadecyl sulfoximine 46 was also obtained following this procedure.
The N functionalization of racemic n-hexadecyl-2-(3′-thienyl)ethyl sulfoximine 45 was based on its reaction with 5-bromo-5′-hexyl-2,2′-bithiophene 47 in the presence of potassium carbonate and catalytic amounts of copper (I) iodide and N,N′-dimethylethane-1,2-diamine (DMEDA) (Scheme 13) [60]. This protocol, leading to N-bithiophene derivative 48 constitutes a modification of the procedure described by Bolm in 2005 [63], by which this coupling reaction was carried out with cesium carbonate as a base.
The monothiophenes 49–51 containing a sulfonate function attached to the thiophene ring at the three-position through an ethylene linker were also prepared with the aim of their usage to obtain new chiral high molecular weight analogues. The condensation of the corresponding alkanesulfinyl chlorides 35b and 35d,e with 2-(3′-thienyl)ethanol 23 carried out in the presence of triethylamine in an ether solution gave the sulfonic esters in 50–87% yields (Scheme 14) [60].
Another class of monomers designed to synthesize new chiral polythiophenes in order to evaluate their properties are monothiophenes containing the substituent with a stereogenic phosphorus atom at the three-position of the ring. For this purpose, the phosphine oxide based monothiophene (−)-(S)-53a was synthesized first.
Upon alkylation of the metalated tert-butylphenylphosphine oxide 52b with 2-(3′ thienyl)ethyl bromide 28b (or chloride 28c), the optically active (S)-tert-butylphenyl-2-(3′-thiophene)ethylphosphine oxide 53a could be isolated. The reaction proceeds with the retention of the configuration at a phosphinyl phosphorus atom and without detectable racemization (Scheme 15) [64]. This procedure was simultaneously patented [65,66] and applied for the preparation of racemic phosphine oxide rac-53.
Following the procedure of the reaction of sodium 2-(3′-thienyl)ethoxide 23b with tert-butylphenylposhinyl chloride 52c, the representative of the phosphonates, namely, racemic O-2-(3′-thienyl)ethyl tert-butylphenylphosphinate 54, was prepared in 93% yield (Scheme 16) [64].
The above monomers, sulfoxides 39a–c, sulfoximines (R)-(−)-45 and (R)-(−)-46, alkanesulfonates 49–51, phosphine oxides (−)-(S)-53a and phosphonates rac-54 were converted into the polythiophene analogues, in most cases by chemical oxidative polymerization according to a Sugimoto et al. protocol, or, in the case of the phosphorus based derivatives, via both the FeCl3-promoted method and electropolymerization [64]. Iron (III) chloride was the optimal oxidizing coupling agent, except for the polymerizations of optically active sulfoxides. Its use for polymerizing the enantiomerically pure sulfoxides failed in terms of isolating the optically active polymeric products. This was due to the release of gaseous HCl during polymerization, which led to racemization. The optical properties of the polythiophenes with different types of substitution were examined using UV–VIS and fluorescent spectroscopy, and the circular dichroism and polarimetric measurements were conducted to examine their chirality. The fluorescence quantum efficiency in the solutions of the regioirregularly 2,5-coupled polythiophenes reaches 24%.
The synthesis of the 3-substituted monothiophenes containing an alkyl side chain attached to the thiophene ring through a heteroatom was developed, as the presence of the heteroatom directly attached to the heterocyclic ring affects the properties of the monomers as well the products of their polymerizations.
One of the representatives is alkoxy substituted thiophene with an electro-donating substituent, optically active (+)-3-[(S)-(2-methylbutoxy)]thiophene (TOR*) 57, which was prepared in 67% yield by the acid catalyzed reaction of 3-methoxythiophene 55 with (S)-(−)-2-methyl-1-butanol 3 refluxed in a toluene solution for 24 h in the presence of a catalytic amounts of p-toluenesulfonic acid monohydrate (Scheme 17) [67].
The monomer (S)-57 was used to prepare novel, optically active oligothiophenes using synthetic methods suitable for obtaining regioregular head-to-tail and head-to-head/tail-to-tail derivatives (if starting from the bithiophene monomers). The chiral (S)-(2-methyl)butyl moiety was introduced into the three-position of the thiophene ring through heteroatoms, such as O as well S (present in the compound 58) to prepare oligomeric regioregular HT-coupled oligomers being suitable models for the evaluation of the effect of the heteroatom presence in the side chain on the macromolecular aggregation and, consequently, on the chiroptical properties of the material in the solid state. The GRIM (Grignard metathesis) procedure, via a magnesium/bromine exchange, was adopted for the polymerization under a high regio control.
In turn, the sulfur analogue of 57, optically active (+)- 3-[(S)-2-methylbutylsulfanyl]thiophene 59, was obtained by the alkylation of potassium 3-mercaptothiophenate 58b, prepared in situ by treating the parent 3-thiophenethiol 58a with potassium tert-butylate in ethanol, with the 1-bromo-2-methylbutane enantiomer, (+)-(S)-4 (Scheme 18) [68]. The monomer was, similar to its oxygen analogue, polymerized using the GRIM method.
A similar approach was used for the preparation of optically active (+)-3- [(S)-3,7-dimethyloctylsulfanyl]thiophene 61 and a racemic 3-[2-butyloctyl] thioeter 62. This synthetic route, reported originally by Barbarella and co-workers [69] begins with a lithium−halogen exchange reaction of 3-bromothiophene 6 followed by quenching with sulfur to give 3-thiophenethiol 58a, which, after its conversion into the corresponding potassium thiolate 58b, reacted with bromoalkanes [(+)-(S)-13 or 60] to provide facile access to the target 3-(alkylthio)thiophenes 61,62 (Scheme 19) [70].
In the case of sulfides 61 and 62, the dehydrohalogenative polycondensation method was used for their polymerization The monobrominated products were the starting materials for a Kumada polymerization procedure that produces highly regioregular HT polythiophenes in high yields In this procedure Knochel’s base [28,71] was used to deprotonate the monomer, and 0.5 mol % NiCl2(dppe) was applied as the catalyst. Poly-61 and poly-62 exhibited electrochemical behavior with reversible p-doping and dedoping processes. The helicity of chiral polymers was examined using the CD measurements taken in the solution and in the solid states. The CD measurements in solution showed strong bisignate cotton effects for the π–π* transitions in poly-(S)--61, whereas no cotton effect was observed for poly-62. The addition of MeOH, a poor solvent, to the polymers resulted in an increased CD signal corresponding to the formation of an ordered helical aggregation.

2.2. Syntheses of 3-Substituted Monothiophenes Functionalized in the Two Position

In this sub-class of monothiophenes substituted in the three-position with a substituent containing a stereogenic carbon atom or a stereogenic heteroatom and additionally functionalized in the two -position, the most abundant group are those with halogen substituents in the two- -position. Additionally, in turn, among them, 2-bromo derivatives were the most often obtained. They are typically prepared by the bromination of the parent 3-substituted monothiophenes mentioned above with N-bromosuccinimide (NBS) under selected conditions, as summarized in Scheme 20.
As an example, 3-[(−) 3-(S)-3,7-dimethyoctyl]thiophene 15 was converted to (−) 2–bromo-3-(S)-(3,7-dimethyoctyl)thiophene 63 [72,73,74]; (+)-3-[2-((S)-2- methylbutoxy)ethyl]thiophene 24 to (+)-2-bromo-3-[2-((S)-2- methylbutoxy)ethyl]thiophene 64[50] [50,51,75]; (+)- 3-[(S) -2-methylbutylsulfanyl]thiophene 59 to the corresponding 2-bromo derivative 65 [67,68,70]; (+)-3- [(S)-3,7-dimethyloctylsulfanyl]thiophene 61 to 2-bromo derivative 66 [70] and (R)-3-(4-(4-ethyl-2-oxazolin-2-yl)phenyl)thiophene (EOPT) 18 to EOPT-Br 67 (Scheme 20) [47].
An interesting synthesis of (S)-(1)-2-bromo-3-[2-[4-[N-methyl-N-(3,7-dimethyloctyl)amino]phenyl]ethenyl]thiophene 70 was achieved by the coupling of the aldehyde 68 with 2-bromothiophenephosphonate 69 under a Wittig–Horner reaction (Scheme 21). 1H NMR spectroscopy confirmed that trans-70 is formed exclusively [76]. The regioregular polythiophene poly-70 was prepared by the polycondensation of 70 via a Stille coupling with Pd(PPh3)4 as a catalyst. Their physicochemical measurements indicated that the sidechain influences on the spectroscopic (absorption, emission) and electrochemical behavior and that the sidechain chirally stacks in conditions in which the polymer backbone aggregates. This indicates the ability of inducing a (chiral) lamellar organization of conjugated moieties, present in their sidechain.
The selective iodination of optically active thiophenes 7 and 24 was elaborated while synthesizing (S)-(+)-2-iodo-3-(2-methylbutyl)thiophene 71 [39] and (S)-2-iodo- 3-[2-methylbutoxy)ethyl]thiophene 72 [49]. The iodination of the optically active 3-[(S)-(+)-2-methylbutyl]thiophene 7 followed the method of Suzuki [77] (Scheme 22). The monoiodo-substituted thiophene (S)-71 was used to prepare the terthiophene derivative, which served as a monomeric unit in the formation of the copolymer poly-71 via the FeCl3-mediated oxidative coupling.
2-((S)-2-Methylbutoxy)ethyl]thiophene 24 was iodinated at the two-position using I2, in HNO3, to give (S)- 2-iodo- 3-[2-methylbutoxy)ethyl]thiophene 72 in 47% yield after distillation (Scheme 23). The latter was transformed into the polymeric analogue poly-(S)-72 using McCullough’s method. The corresponding regiorandom isomer of poly-72 was also obtained by the FeCl3-mediated oxidative polymerization of 24 at −20 °C.

2.3. Syntheses of 3-Substituted Monothiophenes Functionalized in the Two and Five Positions

In this sub-class of monothiophenes substituted in the three-position with a substituent containing a stereogenic carbon atom or a stereogenic heteroatom, the halogen-functionalized compounds in the two- and five-positions of the thiophene ring constitute the most abundant group. Additionally, in turn, among them, dibromo derivatives were most often prepared. They are prepared most easily by the dibromination of the parent 3-substituted using N-bromosuccinimide (NBS) or bromine. In this manner, 3-[(−) 3-(S)-3,7-dimethyoctyl]thiophene 15 was converted to -(−) 2,5 –dibromo-3-(S)-(3,7-dimethyoctyl)thiophene 73 (Scheme 24, Entry 1) [44]. Unfortunately, specific rotation data are not available.
Similarly, (+)-3-[2-((S)-2- methylbutoxy)ethyl]thiophene 24 was converted to (+)-2,5-dibromo-3-[2-((S)-2- methylbutoxy)ethyl]thiophene 74 (Scheme 24, Entry 2) [50,52].
An analogous reaction of optically active 3-[2-(1- methyloctyloxy)ethyl]thiophene 75 afforded either the monobromothiophene 75 or dibromothiophene 77, dependent on the amount of NBS used (Scheme 24, Entry 3) [78]. Fully regioselective dibromination was again observed for 3-[2-methylbutylsulfanyl]thiophene 59, giving the corresponding 2.5-dibromo derivative 78 (Scheme 24, Entry 4) [67,68,70,79]; (+)-3- [(S)-3,7-dimethyloctylsulfanyl]thiophene 61, leading to 2,5-dibromo derivative 79 (Scheme 24, Entry 5) [80] and (+)-3-[(S) -2-methylbutoxyl]thiophene 57, giving the corresponding 2.5-dibromo derivative 80 (Scheme 24, Entry 6) [67].
The sequential halogenation of the 3-substituted monothiophenes was also conducted. Thus, 2,5-dibromo-(R)-3-(4-(4-ethyl-2-oxazolin-2-yl)phenyl)thiophene (EOPT-Br2) 81 was obtained by the subsequent bromination of (R)-67 (EOPT-Br) at the five-position of the thiophene ring (Scheme 25) under similar conditions [47,61,81]. In turn, (+)-2-bromo-5-iodo-3-((S)-3,7- dimethyloctyl)thiophene (S)-82 was prepared by the iodination of 2-bromo-3-((S)-3,7-dimethyloctyl)thiophene (S)-63 with iodine in the presence of iodobenzene diacetate. (Scheme 25) [22,73,82,83,84].
The other synthetic modifications concern the functionalization of the terminal reactive groups attached to the side chains in the three positions of the thiophene ring. This strategy is exemplified by the reaction of 2,3,5-trisubstituted monothiophenes having a functional group in the three-position permitting a coupling reaction with a chiral moiety, as illustrated in Scheme 26. The coupling reaction of 2,5-dibromothiophene-3-carboxylic acid 83 or 2,5-dibromothiophene-3-acetic acid 84 with 10-(4-(4′-(4′′-(2-fluorooctyloxy)phenylcarbonyloxy))-biphenoxy)decylol 85 occurred in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethyloaminopyridine (DMAP). The debrominative polycondensation of the resulting monomers 86, 87 using the Ni zerovalent catalyst and the bis-chelating bipyridine ligand was applied for the preparation of the polymers, containing liquid crystalline side chains, poly-86 and poly-87 [85].
A similar esterification reaction of 2,5-dibromothiophene-3-carboxylic acid 83 and (S)-1,1,1-trifluoro-undecan-2-ol 98 was found to afford the chiral ester 89, while the Mitsunobu reaction of 2,5-dibromothiophene-3- carboxylic acid 83 and (S)- 2-octanol 90 gave the corresponding ester 91, as shown in Scheme 27 [86]. The stereogenic center in (S)-2-octanol 90 was converted into (R)-configuration in the ester 91, having [α]D = −15.49, without racemization, since this reaction occurs with the SN2-type Walden inversion (Scheme 27) [87].
The monomer 89 was used for copolymerization with 2,5-bistannylated thiophene or 2′,5′’-distanyllated bithiophene via a Pd-catalyzed Stille polycondensation reaction. The chiral aggregation for the obtained polymers, poly-89a and poly-89b, was investigated using CD spectroscopy measurements.
2,5-Dibromo-3-(6-bromohexyl)thiophene 92 reacted with permetylated 6-O-monohydroxy-α-cyclodextrin 93 in the presence of sodium hydride to give the bulky permethyl-α-cyclodextrin 94 in which the thiophene ring is attached through a hexamethylene linker (Scheme 28) [88].

3. Syntheses of 3,4-Disubstituted Monothiophenes

The first dialkyl-substituted chiral polythiophene, PDMOT: poly-{3,4-bis[(S)-2-methyloctyl]thiophene}, poly-96 was synthesized in 2002 [89]. The synthesis of its precursor, the monomer 96: 3,4-bis[(S)-2-methyloctyl]thiophene, was thereby developed and reported therein. It comprised the Kumada type coupling of 3,4-dibromothiophene 95 with (S)-2-methyloctylmagnesium bromide catalyzed by a Ni(II) catalyst to provide the product in 21% yield (Scheme 29). The precursor 96 was polymerized according to the Sugimoto protocol via the oxidative method. Interestingly, the UV–vis spectrum of PDMOT showed the absorption band at a shorter wavelength (λmax), 318 nm in chloroform, compared to monoalkyl-substituted polythiophenes. It was suggested that it could be due to the electronic effects of the electron donating alkyl side chains or due to their steric demands. It was assumed that the steric effects of the two branched chiral alkyl side chains in the polythiophene are responsible for an unusual CD spectrum and the significant thermo- and solvato-driven effects observed in the CD spectra.
While exploring the EDOT (ethylenedioxythiophene) derivatives, it was shown that the Mitsunobu reaction was an efficient route for the synthesis of mono- and disubstituted EDOTs and 3,4-propylenedioxythiophenes (ProDOTs) [90,91]. However, the one drawback it suffered from was a moderate yield, which prevailed in the case of the Mitsunobu reaction for synthesizing disubstituted EDOTs.
Later, the same research group demonstrated the high yielding alternative for the synthesis of the EDOT monomers achieved by transetherification of 3,4-dimethoxythiophene 103 with (chiral) glycols 104 [92]. The chiral 3,4-ethylenedioxythiophenes EDOTs, having two substituents at the ethylene bridge, containing two stereogenic centers in their units, were designed to ensure high regioregularity in the subsequent polymerization to produce chiral PEDOTs. In fact, it was also demonstrated that the stereochemistry of the monomers affected the electronic properties of the corresponding chiral PEDOT derivatives.
The general synthetic protocol comprises the reactions of 3,4-dimethoxythiophene 97 with glycol derivatives 98a–d catalyzed by p-toluenesulfonic acid (Scheme 30).
The reaction yield was lowered (20%) when (meso)-2,3-butanediol 98a was used in preparing EDOT 99a, (entry 1, Table 1). The stereochemistry of the starting 1,2-diols did not affect the yields in forming the resulting EDOTs in which the configurations are fully retained (entries 2–4: 73–82%; entries 5–9: 52–68%). All novel disubstituted EDOT derivatives 98a,d were polymerized to PEDOTs using potentiodynamic electrooxidation.
A similar method, based on the transetherification of diols with 3,4-dimethoxythiophene 97, was also applied for the synthesis of monomers 102a,b, enantiomerically pure disubstituted 3,4-propylenedioxythiophenes containing (2S)-methylbutyl and (2S)-ethylhexyl sidechains [93].
The procedure used for the synthesis of monomeric 3,4-propylenedioxythiophenes was modified in respect to a protocol for the racemic analogues described earlier [94]. The chiral alcohols, (2S)-methylbutanol 100a and (2S)-ethylhexanol 100b, were converted into the corresponding tosylates. The resulting products reacted with diethyl malonate anion to give malonic acid esters. Upon reduction with LiAlH4, the corresponding diols 101a,b were obtained. Transetherification of the latter with 3,4-dimethoxythiophene 97 afforded oxidatively polymerizable ProDOT-((2S)-methylbutyl)2 (102a) and ProDOT-((2S)-ethylhexyl)2 (102b) (Scheme 31). To obtain the corresponding polymers with enantiomerically pure sidechains, bromination with NBS preceded a nickel-catalyzed Grignard metathesis polymerization. The optical properties of the polymer poly-102b were studied using UV–vis absorption, fluorescence and CD spectroscopy, and compared to the chiral methylbutyl derivative poly-102a. The aggregation process was followed by CD spectroscopy, which indicated that the two polymer forms chiral helical aggregates were similar to other chiral alkyl polythiophenes. Notably, the polymer poly-102b was recognized to have a fluorescence with a high quantum yield of 0.43 in xylene solution, while in the xylene/DMFmixture, along with a small decrease in the fluorescence quantum yield down to 0.28, a red-shift of the absorbance in the UV–vis spectrum was observed. Upon the addition of the poor solvent, a red-shift of the absorption spectrum and the vibronic features suggested more ordered, planar chains.
Among the class of π-conjugated polymers, polythiophenes with two alkylsulfanyl substituents in the β positions were also subject to detailed research. This class of polymers are expected to act as sensors for palladium or ruthenium by the quenching of their fluorescence to a greater extent than the quenching observed for nonthio functionalized polythiophenes.
The representative for the studies was 3,4-bis(3,7- dimethyloctylthio)thiophene, 104, with a structure designed to possess well solubilizing chains attached to sulfur atoms, which was first synthesized and was then polymerized by oxidative coupling with iron(III) chloride, to give polythiophene derivative poly-104 (Scheme 32) [95].
In the further studies, chiral bis-alkyloxo-substituted 111 and bis-alkylthio polythienylethynylene 112 derivatives have been synthesized to examine their affinity to coordinate transition metals and the influence of aggregation on the quenching of fluorescence upon coordination to metals [95]. The synthetic pathway started with the iodination of 105 and 106 at the two- and five-position by N-iodosuccinimide (NIS). The iodinated products, 107 and 108, were acetylated by a reaction with trimethylsilylacetylene catalyzed by tetrakis(triphenylphosphine)palladium(0) and copper(I) iodide. The TMS-protected intermediate was treated with tetrabutylammonium fluoride to remove the silyl group to give 109 and 110.
These monomers, 109 and 110, and iodinated monothiophene monomers 107 and 108 were subjected to Pd-catalyzed polycondensation to give the corresponding polymers 111 and 112 (Scheme 33).

4. Syntheses of β-Substituted Bithiophenes Functionalized with a Substituent Containing a Stereogenic Carbon Atom or a Stereogenic Heteroatom

The polyfluorene–thiophene copolymers have attracted much attention due to their optical and electrical properties. One of the components in the π-conjugated co-polymer, a polyfluorene derivative, is responsible for high photoluminescence quantum yields, good solubility and an interesting thermotropic liquid crystalline nature. The second component, polythiophene derivative, provides good processability and unique properties that are tunable by various side chains. The polyfluorene–thiophene copolymers, such as: poly[9,9-dihexylfluorenealt-(3-{2-[(S)-(+)-1-methyloctyloxy]ethyl}thiophene)] (113) and poly[9,9-dihexylfluorene-alt-(3-{2-[(S)-(+)-1-methyloctyloxy]ethyl}-2,2′-bithiophene)] (114) (Figure 1) [78], having chiral side chains located, in each of the model compound, in a different distance from the fluorene units, were obtained and screened for their optical properties. The synthesis of 113 and 114 was achieved via the Pd catalyzed Suzuki coupling method by reacting dibromides 77 and 124, respectively, with 9,9-dihexylfluorene-2,7-bis(trimethylene boronate) (Scheme 34). Both copolymers exhibited a solvatochromism that was related to the strong self-organization of the copolymers. In the circular dichroism spectra, strong bisignate Cotton effects were observed in the methanol/chloroform mixed solutions.
The monomers for 113 and 114, 2,5-dibromo--3-{2-[(S)-(+)-1-methyloctyloxy]ethyl}thiophene 77 and 2,5-dibromo-3-{2-[(S)-(+)-1-methyloctyloxy]ethyl}2,2′-bithiophene 117, respectively, were synthesized as shown in Scheme 34 [78,96].
The β,β’-Disubstituted bithiophene with two (S)-2-methylbutylsulfanyl substituents was prepared and applied as a monomer for chemical (FeCl3) or electrochemical polymerization, leading to a regioregular head-to-head/tail-to-tail poly(β,β’-disubstituted bithiophene) [97].
The synthesis of (+)-4,4′-bis[(S)-2-methylbutylsulfanyl]-2,2′-bithiophene 120 (Scheme 35) comprised the bromine–lithium exchange when 4,4′-dibromo-2,2′-bithiophene 118 [98] was treated with butyl lithium, followed by a reaction with (+)-bis[(S)-2-methylbutyl]disulfide 119.
The synthesis of the modified bithiophenes, bearing one-alkylsulfanyl substituent in the β-position and one other substituent in the β’-position, was further developed [68]. The purpose of these studies was to gain a better insight into the reactivity of β-alkylsulfanyl-substituted bithiophenes as they were converted into the octithiophene derivatives via one-pot oxidative coupling with FeCl3.
Among the designed structures of chiral unsymmetrical β-alkylsulfanyl bithiophenes are 4-bromo-4′-[(S)-2-methylbutylsulfanyl]-2,2′-bithiophene 124 and 4-iodo-4′-[(S)-2-methylbutylsulfanyl]-2,2′-bithiophene 125, which were synthesized as shown in Scheme 36. The Stille-type coupling between a tin- (122) and a halo-derivative (121) was applied to obtain the intermediate bithiophenes 123. Tert-butylammonium fluoride was used for the desilylation to form compound 124, while 58% hydroiodic acid was the desilylating agent and allowed the bromide to be replaced with iodide at once to give compound 125.

5. Syntheses of Other Thiophenes Functionalized with a Substituent Containing a Stereogenic Carbon Atom or a Stereogenic Heteroatom

The transformations of the chiral monothiophene 7 into 2-iodo-3-[(S)-(+)-2-methylbutyl]thiophene (+)-(S)-71 followed by the coupling with 2,5-dihalogenated thiophene provided 3,3′′-di[(S)-(+)-2-methylbutyl]-2,2′:5′,2′′-terthiophene, which served as a precursor to a new regioregular optically active polymer synthesized by FeCl3 oxidative coupling polymerization (Scheme 37) [39].
The synthesis of chiral (R)- and (S)-copolymers consisting of poly(p-terphenylene)s and poly(bithienylene-phenylene)s has been developed [99]. The polymers were distinguished by valuable fluorescent and photo responsive properties. Upon irradiation of ultraviolet and visible light, the polymers showed reversible quenching and emitting behaviors as a result of the photo-chemical isomerization of the dithienylethene fragments. The precursor of these polymers is the monomer (R)-129, the synthetic route of which is shown in Scheme 38.
The chiral fragment was delivered by a 2-methyloctyl chain appended to the hydroxyl of the 4-hydroxybenzoic acid. For its introduction, ethyl ester of the 4-hydroxybenzoic acid was coupled with (S)-2-nonanol under the Mitsunobu reaction conditions to obtain (R)-126.
The hydrolysis of ethyl-4-[(R)-1-methyloctoxy]benzoate (R)-126 gave a free carboxylic function. The benzoic acid derivative (R)-127 thus formed, reacted with the dithienylethene derivative 128 via coupling between the hydroxy group and the carboxyl group of (R)-127, which was carried out in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP), leading to the formation of the monomer (R)-129. The copolymerizations occurred through a Suzuki coupling reaction between (R)-136 and 4,4′-biphenyldiboronic acid bis(propyl glycol)cyclic ester in the presence of Pd(PPh3)4 or through a Stille coupling between (R)-129 and 5,5′-bis-trimethylstannyl-2,2′-bithiophene, catalyzed by Pd2(dba)3 (2-furyl)3P, to give poly-129a or poly-129b, respectively.
The axial stereogenicity was introduced into the skeleton of a π-conjugated copolymer by a new molecular building block with versatile synthetic handles, a tetrasubstituted adamantane derivative 130, synthesized from achiral 2,6-adamantanedione and 4-bromocatechol. Thus, the formed racemic bromide 130 was further converted into the electroactive monomers 131 and 132 after adopting the Suzuki coupling methodology (Scheme 39). The structures of the two monomers differed in terminal thienyl units, the first of those contained the monothiophenes at the ends of the core, while the second contained the terminal bithiophene units. The racemic electroactive polymers built from axially stereogenic adamantyl segments, were synthesized by electropolymerization of the monomers 131 and 132, respectively [100].

6. Conclusions

In summary, this mini-review discusses the synthetic routes to mono- or bithiophene derivatives containing substituent(s) with a chiral element (stereogenic center or chiral axis) that can then serve as substrates in the polymerization reaction. We hope that the protocols for the synthesis of chiral monomeric thiophenes presented in this article will help practitioners of organic chemistry to design an appropriate pathway to obtain new valuable thiophene derivatives as chiral precursors of conjugated (co)polymers. The review covers the synthetic routes to derivatives that are functionalized at the β (β’) positions of the thiophene rings and those that are functionalized at one or both of the α positions. This division is due to the fact that, depending on the polymerization method under consideration, differently substituted mono- or bithiophenes are needed. The intended second part of the review will discuss various polymerization methods, the choice of which depends on the ease of access to the optically active monomeric substrate and the laboratory conditions allowing the selected polymerization technique to be used from among the following: McCullough’s approach, the Grignard metathesis (GRIM) reaction, the Rieke zinc coupling reaction, the Yamamoto condensation, the dehydrohalogenative polycondensation, the Kumada catalyst transfer condensation polymerization (KCTCP), the FeCl3-mediated polymerization (chemical oxidative polymerization), other transition metal catalyzed methods based on the Stille, Suzuki cross-coupling reactions or electropolymerization.

Author Contributions

All the authors, D.K., R.K. and J.D., contributed equally to the preparation of this review paper and should be considered as corresponding authors. All authors have read and agreed to the published version of the manuscript.

Funding

Financial support from the Polish National Science Centre (UMO-2014/15/ST5/05329 and 2017/01/X/ST5/01991) is gratefully acknowledged.

Conflicts of Interest

The authors declare no conflict of interest.

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Molecules 26 04205 sch001 550
Scheme 1. The general approach to conductive polymers 2 from the monomeric units 1.
Scheme 1. The general approach to conductive polymers 2 from the monomeric units 1.
Molecules 26 04205 sch001
Molecules 26 04205 sch002 550
Scheme 2. Synthesis of 3-[(S)-2-methylbutyl]thiophene 7 by the cross-coupling reaction of (S)-(2-methylbutyl)magnesium bromide 5 with 3-bromothiophene 6 and the subsequent electro- [35] and chemical polymerizations [37].
Scheme 2. Synthesis of 3-[(S)-2-methylbutyl]thiophene 7 by the cross-coupling reaction of (S)-(2-methylbutyl)magnesium bromide 5 with 3-bromothiophene 6 and the subsequent electro- [35] and chemical polymerizations [37].
Molecules 26 04205 sch002
Molecules 26 04205 sch003 550
Scheme 3. Synthesis of 3-[(1-ethyl)butyl]thiophene 9, 3-[(S)-2-methyloctyl]thiophene 12 and 3-[(S)-3,7-dimethyloctyl]thiophene 15 by the cross-coupling reaction of 3-bromothiophene 6 with the corresponding alkylmagnesium or alkylzinc halides.
Scheme 3. Synthesis of 3-[(1-ethyl)butyl]thiophene 9, 3-[(S)-2-methyloctyl]thiophene 12 and 3-[(S)-3,7-dimethyloctyl]thiophene 15 by the cross-coupling reaction of 3-bromothiophene 6 with the corresponding alkylmagnesium or alkylzinc halides.
Molecules 26 04205 sch003
Molecules 26 04205 sch004 550
Scheme 4. The cross-coupling of oxazoline 16 with 3-thiopheneboronic acid 17. Syntheses of the regioregular and regiorandom poly-18.
Scheme 4. The cross-coupling of oxazoline 16 with 3-thiopheneboronic acid 17. Syntheses of the regioregular and regiorandom poly-18.
Molecules 26 04205 sch004
Molecules 26 04205 sch005 550
Scheme 5. Synthesis of 3-[3-[(S)-2-phenylbutoxy)]propyl]thiophene 21a and its enantiomer 21b.
Scheme 5. Synthesis of 3-[3-[(S)-2-phenylbutoxy)]propyl]thiophene 21a and its enantiomer 21b.
Molecules 26 04205 sch005
Molecules 26 04205 sch006 550
Scheme 6. Synthesis of 3-[2-((S)-(1)-2-methylbutoxy)ethyl]thiophene 24 and its polymerizations.
Scheme 6. Synthesis of 3-[2-((S)-(1)-2-methylbutoxy)ethyl]thiophene 24 and its polymerizations.
Molecules 26 04205 sch006
Molecules 26 04205 sch007 550
Scheme 7. Synthesis of 2-tert-Butoxycarbonylamino-3-(2-thiophen-3-yl-ethoxy)-propionic acid (25), its conversion to methyl ester analogue (26) and the polymerizations using FeCl3-mediated oxidative method.
Scheme 7. Synthesis of 2-tert-Butoxycarbonylamino-3-(2-thiophen-3-yl-ethoxy)-propionic acid (25), its conversion to methyl ester analogue (26) and the polymerizations using FeCl3-mediated oxidative method.
Molecules 26 04205 sch007
Molecules 26 04205 sch008 550
Scheme 8. Synthesis of the monomers of thienyl phenylglycinate 29a and 29b and their polymerization.
Scheme 8. Synthesis of the monomers of thienyl phenylglycinate 29a and 29b and their polymerization.
Molecules 26 04205 sch008
Molecules 26 04205 sch009 550
Scheme 9. Synthesis of selected 3-substituted (poly)thiophenes with a chiral 1,3-dioxalane moiety.
Scheme 9. Synthesis of selected 3-substituted (poly)thiophenes with a chiral 1,3-dioxalane moiety.
Molecules 26 04205 sch009
Molecules 26 04205 sch010 550
Scheme 10. Synthesis of 2-(3′-thienyl)ethyl alkyl (aryl) sulfoxides 39a–c by reacting sulfinates 37a–f with 2-(3′-thienyl)ethylmagnesium bromide 38.
Scheme 10. Synthesis of 2-(3′-thienyl)ethyl alkyl (aryl) sulfoxides 39a–c by reacting sulfinates 37a–f with 2-(3′-thienyl)ethylmagnesium bromide 38.
Molecules 26 04205 sch010
Molecules 26 04205 sch011 550
Scheme 11. Oxidations of the 2- (3′-thienyl)alkyl p-tolyl sulfides 40 and 41 using a 30 wt% solution of hydrogen peroxide.
Scheme 11. Oxidations of the 2- (3′-thienyl)alkyl p-tolyl sulfides 40 and 41 using a 30 wt% solution of hydrogen peroxide.
Molecules 26 04205 sch011
Molecules 26 04205 sch012 550
Scheme 12. The preparation of 2- (3′-thienyl)ethyl p-tolyl(n-hexadecyl) sulfoximines by an imination with MSH and the subsequent polymerization.
Scheme 12. The preparation of 2- (3′-thienyl)ethyl p-tolyl(n-hexadecyl) sulfoximines by an imination with MSH and the subsequent polymerization.
Molecules 26 04205 sch012
Molecules 26 04205 sch013 550
Scheme 13. N-Bithienylation of racemic sulfoximine 45 catalyzed by Cu(I) DMEDA complex.
Scheme 13. N-Bithienylation of racemic sulfoximine 45 catalyzed by Cu(I) DMEDA complex.
Molecules 26 04205 sch013
Molecules 26 04205 sch014 550
Scheme 14. Condensation of alkanesulfinyl chlorides 35b and 35d,e with 2-(3′-thienyl)ethanol 20.
Scheme 14. Condensation of alkanesulfinyl chlorides 35b and 35d,e with 2-(3′-thienyl)ethanol 20.
Molecules 26 04205 sch014
Molecules 26 04205 sch015 550
Scheme 15. Alkylation of the metalated tert-butylphenylphosphine oxide 52b with 2-(3′ thienyl)ethyl bromide 23b.
Scheme 15. Alkylation of the metalated tert-butylphenylphosphine oxide 52b with 2-(3′ thienyl)ethyl bromide 23b.
Molecules 26 04205 sch015
Molecules 26 04205 sch016 550
Scheme 16. Reaction of tert-butylphenylphosphinyl chloride 52c with sodium 2-(3′ thienyl)ethoxide 23b.
Scheme 16. Reaction of tert-butylphenylphosphinyl chloride 52c with sodium 2-(3′ thienyl)ethoxide 23b.
Molecules 26 04205 sch016
Molecules 26 04205 sch017 550
Scheme 17. Acid–catalyzed reaction of 3-methoxythiophene 55 with (S)-(−)-2-methyl-1-butanol 3.
Scheme 17. Acid–catalyzed reaction of 3-methoxythiophene 55 with (S)-(−)-2-methyl-1-butanol 3.
Molecules 26 04205 sch017
Molecules 26 04205 sch018 550
Scheme 18. Alkylation of potassium 3-mercaptothiophenate 58b by 1-bromo-2-methylbutane (S)-(+)-4.
Scheme 18. Alkylation of potassium 3-mercaptothiophenate 58b by 1-bromo-2-methylbutane (S)-(+)-4.
Molecules 26 04205 sch018
Molecules 26 04205 sch019 550
Scheme 19. Alkylation of potassium 3-mercaptothiophenate 58b by chiral bromo-alkanes (13) or (60) in the preparation of alkylsulfanylthiophenes and the route to their polymerization.
Scheme 19. Alkylation of potassium 3-mercaptothiophenate 58b by chiral bromo-alkanes (13) or (60) in the preparation of alkylsulfanylthiophenes and the route to their polymerization.
Molecules 26 04205 sch019
Molecules 26 04205 sch020 550
Scheme 20. Selective brominations of thiophenes functionalized with a chiral alkyl group.
Scheme 20. Selective brominations of thiophenes functionalized with a chiral alkyl group.
Molecules 26 04205 sch020
Molecules 26 04205 sch021 550
Scheme 21. A Wittig–Horner reaction of the aldehyde 68 with 2-bromothiophenephosphonate 69.
Scheme 21. A Wittig–Horner reaction of the aldehyde 68 with 2-bromothiophenephosphonate 69.
Molecules 26 04205 sch021
Molecules 26 04205 sch022 550
Scheme 22. Iodination of 3-[(S)-(+)-2-methylbutyl]thiophene 7.
Scheme 22. Iodination of 3-[(S)-(+)-2-methylbutyl]thiophene 7.
Molecules 26 04205 sch022
Molecules 26 04205 sch023 550
Scheme 23. Iodination of 2-((S)-2-methylbutoxy)ethyl]thiophene 24.
Scheme 23. Iodination of 2-((S)-2-methylbutoxy)ethyl]thiophene 24.
Molecules 26 04205 sch023
Molecules 26 04205 sch024 550
Scheme 24. Double bromination of optically active thiophene derivatives with NBS or Br2.
Scheme 24. Double bromination of optically active thiophene derivatives with NBS or Br2.
Molecules 26 04205 sch024
Molecules 26 04205 sch025 550
Scheme 25. Bromination of optically active bromothiophene 67 with NBS and iodination of bromothiophene 63.
Scheme 25. Bromination of optically active bromothiophene 67 with NBS and iodination of bromothiophene 63.
Molecules 26 04205 sch025
Molecules 26 04205 sch026 550
Scheme 26. Coupling reaction of thiophenecarboxylic acids 83 and 84 with chiral alcohol 85.
Scheme 26. Coupling reaction of thiophenecarboxylic acids 83 and 84 with chiral alcohol 85.
Molecules 26 04205 sch026
Molecules 26 04205 sch027 550
Scheme 27. Esterification of 2,5-dibromothiophene-3-carboxylic acid 83 with optically active alcohols 88 and 90. Copolymerization reaction via Stille coupling method.
Scheme 27. Esterification of 2,5-dibromothiophene-3-carboxylic acid 83 with optically active alcohols 88 and 90. Copolymerization reaction via Stille coupling method.
Molecules 26 04205 sch027
Molecules 26 04205 sch028 550
Scheme 28. Synthesis of the permethyl-α-cyclodextrin 94 modified with a 2,5 dibromothiophene ring.
Scheme 28. Synthesis of the permethyl-α-cyclodextrin 94 modified with a 2,5 dibromothiophene ring.
Molecules 26 04205 sch028
Molecules 26 04205 sch029 550
Scheme 29. The approach to (poly)3,4-bis[(S)-2-methyloctyl]thiophene.
Scheme 29. The approach to (poly)3,4-bis[(S)-2-methyloctyl]thiophene.
Molecules 26 04205 sch029
Molecules 26 04205 sch030 550
Scheme 30. Novel EDOTs 99b–d synthesis via the acid-catalyzed transetherification reaction and their use to obtain the corresponding PEDOTs.
Scheme 30. Novel EDOTs 99b–d synthesis via the acid-catalyzed transetherification reaction and their use to obtain the corresponding PEDOTs.
Molecules 26 04205 sch030
Molecules 26 04205 sch031 550
Scheme 31. Synthesis of chiral 3,4-propylenedioxythiophenes ProDOTs 102a,b from enantiomerically pure (2S)-methylbutanol 100a and (2S)-ethylhexanol 100b.
Scheme 31. Synthesis of chiral 3,4-propylenedioxythiophenes ProDOTs 102a,b from enantiomerically pure (2S)-methylbutanol 100a and (2S)-ethylhexanol 100b.
Molecules 26 04205 sch031
Molecules 26 04205 sch032 550
Scheme 32. Synthesis of monomer 3,4-bis(3,7- dimethyloctylthio)thiophene 104 and its high molecular weight analogue poly-104.
Scheme 32. Synthesis of monomer 3,4-bis(3,7- dimethyloctylthio)thiophene 104 and its high molecular weight analogue poly-104.
Molecules 26 04205 sch032
Molecules 26 04205 sch033 550
Scheme 33. Synthesis of monomers: 3,4-bis(3(S),7-dimethyloctyloxy)-2,5-diiodothiophene 107, 3,4-bis(3(S),7-dimethyloctylthio)-2,5-diiodothiophene 108, 3,4-bis(3(S),7-dimethyloctyloxy)-2,5-diethynylthiophene 109, 3,4-bis(3(S),7-dimethyloctylthio)-2,5-diethynylthiophene 110 and the products of their copolymerization 111 and 112.
Scheme 33. Synthesis of monomers: 3,4-bis(3(S),7-dimethyloctyloxy)-2,5-diiodothiophene 107, 3,4-bis(3(S),7-dimethyloctylthio)-2,5-diiodothiophene 108, 3,4-bis(3(S),7-dimethyloctyloxy)-2,5-diethynylthiophene 109, 3,4-bis(3(S),7-dimethyloctylthio)-2,5-diethynylthiophene 110 and the products of their copolymerization 111 and 112.
Molecules 26 04205 sch033
Molecules 26 04205 g001 550
Figure 1. Structures of copolymers with the chiral side chains.
Figure 1. Structures of copolymers with the chiral side chains.
Molecules 26 04205 g001
Molecules 26 04205 sch034 550
Scheme 34. Synthesis of 2,5-dibromo-3-{2-[(S)-(+)-1-methyloctyloxy]ethyl}-2,2′-bithiophene (117) as a precursor for copolymerization with 9,9-dihexylfluorene-2,7-bis(trimethylene boronate).
Scheme 34. Synthesis of 2,5-dibromo-3-{2-[(S)-(+)-1-methyloctyloxy]ethyl}-2,2′-bithiophene (117) as a precursor for copolymerization with 9,9-dihexylfluorene-2,7-bis(trimethylene boronate).
Molecules 26 04205 sch034
Molecules 26 04205 sch035 550
Scheme 35. Synthesis of monomer 120 and its conversion to poly[4,4′-bis[(S)-2-methylbutylsulfanyl]-2,2′-bithiophene poly-120.
Scheme 35. Synthesis of monomer 120 and its conversion to poly[4,4′-bis[(S)-2-methylbutylsulfanyl]-2,2′-bithiophene poly-120.
Molecules 26 04205 sch035
Molecules 26 04205 sch036 550
Scheme 36. Synthesis of chiral unsymmetrically substituted bithiophenes serving as monomers for octithiophene analogues poly-124 and poly-125.
Scheme 36. Synthesis of chiral unsymmetrically substituted bithiophenes serving as monomers for octithiophene analogues poly-124 and poly-125.
Molecules 26 04205 sch036
Molecules 26 04205 sch037 550
Scheme 37. Synthesis of terthiophene derivative and its oxidative polymerization [39] following the general method of Sugimoto et al. using CCl4 as a solvent.
Scheme 37. Synthesis of terthiophene derivative and its oxidative polymerization [39] following the general method of Sugimoto et al. using CCl4 as a solvent.
Molecules 26 04205 sch037
Molecules 26 04205 sch038 550
Scheme 38. Synthesis of monomer (R)-129 and the routes to the copolymerizations via the Suzuki or Stille coupling methods.
Scheme 38. Synthesis of monomer (R)-129 and the routes to the copolymerizations via the Suzuki or Stille coupling methods.
Molecules 26 04205 sch038
Molecules 26 04205 sch039 550
Scheme 39. Synthesis of thienyl-based monomers 131 and 132 containing axially chiral adamantyl segments as their core.
Scheme 39. Synthesis of thienyl-based monomers 131 and 132 containing axially chiral adamantyl segments as their core.
Molecules 26 04205 sch039
Table
Table 1. Transetherification reaction of 3,4-dimethoxythiophene 97 and (chiral) diols 98a–d to (enantiomerically pure) disubstituted EDOTs 99a–d.
Table 1. Transetherification reaction of 3,4-dimethoxythiophene 97 and (chiral) diols 98a–d to (enantiomerically pure) disubstituted EDOTs 99a–d.
Glycol Deriv.EDOT Deriv.Yield [%]
1 Molecules 26 04205 i00199a-meso20
2 Molecules 26 04205 i00299b-trans79
3 Molecules 26 04205 i00399b-(R,R)73
4 Molecules 26 04205 i00499b-meso82
5 Molecules 26 04205 i00599c-cis/trans63
6 Molecules 26 04205 i00699c-trans65
7 Molecules 26 04205 i00799c-(R,R)68
8 Molecules 26 04205 i00899c-(S,S)66
9 Molecules 26 04205 i00999c-cis52
10 Molecules 26 04205 i01099d-trans47
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Krasowska, D.; Karpowicz, R.; Drabowicz, J. Chiral Polythiophenes: Part I: Syntheses of Monomeric Precursors. Molecules 2021, 26, 4205. https://doi.org/10.3390/molecules26144205

AMA Style

Krasowska D, Karpowicz R, Drabowicz J. Chiral Polythiophenes: Part I: Syntheses of Monomeric Precursors. Molecules. 2021; 26(14):4205. https://doi.org/10.3390/molecules26144205

Chicago/Turabian Style

Krasowska, Dorota, Rafał Karpowicz, and Józef Drabowicz. 2021. "Chiral Polythiophenes: Part I: Syntheses of Monomeric Precursors" Molecules 26, no. 14: 4205. https://doi.org/10.3390/molecules26144205

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