Sulfoxide-directed metal-free cross-couplings in the expedient synthesis of benzothiophene-based components of materials

A metal-free approach combining sulfoxide-directed metal-free C–H cross-couplings with tuneable heterocyclizations and dimerizations allows expedient access to important organic materials.


Introduction
The selective formation of carbon-carbon bonds to aromatic rings is a critical goal in science. 1 Although the use of rst row metals is an important and growing eld (e.g. Fe, Co, Ni, Cu), modern cross-coupling technology still typically involves the use of platinum group metals (e.g. Pd, Ru, Rh, Pt), 2 and the development of cross-coupling reactions that do not involve the use of an expensive and/or supply-risk metal is highly desirable. 3 Such processes have additional benets as trace metal contamination in products arising from metal-catalyzed processes is a concern in industry, particularly the pharmaceutical and organic electronic sectors. 4 In the latter eld, even 'undetectable' levels of palladium contaminant can have a detrimental effect on the electrical properties of materials and thin lm device performance. 4d Here we describe an expedient metal-free approach to important benzothiophene-based architectures, including motifs that are crucial components in valuable organic small molecule and polymeric materials (Scheme 1A). 5 Organic materials are increasingly prepared using C-H activation methods mediated by platinum group metals 6 in addition to cross-couplings using classical Pd-catalyzed methods. 7 Benzodithiophenes (BDTs) 8 and napthodithiophenes (NDTs), 9 in particular, have been exploited in high-performance smallmolecule/oligomeric semi-conducting materials (e.g. 1-4), polymeric semiconductors, 8,9 and in co-polymers for solar cells 8,9 (e.g. 5 and 6) (Scheme 1B).
The crucial benzothiophene-based motifs are typically prepared using Pd-catalyzed cross-coupling processes in one or more key steps. Our approach utilizes sulfoxide-directed metalfree C-H cross-coupling processes, 10 allowing established Pd-catalyzed couplings and associated metal-contamination to be avoided, and new diversity-introducing hetero-and Scheme 1 (A) Short metal-free approach to privileged benzothiophenes. (B) Benzothiophene-based organic materials. NDT ¼ napthodithiophene; BDT ¼ benzodithiophene; m ¼ electron mobility; PCE ¼ Power Conversion Efficiency.
carbocyclizations mediated by electrophiles. The novel approach has been used in the metal-free synthesis of a range of benzothiophenes including components of materials, and both validated organic materials and previously unknown organic materials for evaluation.

Results and discussion
A two-directional, metal-free route to NDT materials We began by exploring the conversion of the products of our sulfoxide-directed, metal-free, propargylative C-H crosscoupling 10 to benzothiophenes. Pleasingly, straight-forward variation of iodine or acid-mediated conditions (A-C) allowed access to a wide range of decorated benzothiophene motifs bearing different levels of oxidation at the carbon adjacent to the benzothiophene ring (Scheme 2). 11 In addition, a wide range of substituents on the aromatic ring are tolerated thus allowing the electronic properties of target materials to be tuned (vide infra).
A proposed mechanism for the formation of benzothiophenes under iodine-mediated conditions A-C is set out in Scheme 3. Upon treatment with iodine, cyclization gives sulfonium salts I that undergo demethylation and tautomerization to form common iodide intermediates II. Upon heating, homolysis gives radicals III that either undergo quenching with O 2 (conditions A) to give ketone products, possibly via alkylhydroperoxide intermediates IV, or with 1,4-cyclohexadiene (conditions B) to give alkyl substituted benzothiophene products. Under conditions C, elimination of iodides II gives alkenyl benzothiophene products. Acid-mediated cyclization (alternative conditions B) gives alkyl substituted benzothiophene products directly aer demethylation of sulfonium salt intermediates.
Further diversity can be introduced by tuning the conditions of the subsequent two-directional heterocyclization. For example, while acid-mediated cyclization of 9 and 10b (variant Scheme 2 Tuneable electrophile-mediated, heterocyclization to give decorated benzothiophenes (isolated yields after purification).
Scheme 3 Proposed mechanism for the tuneable iodine-mediated, heterocyclization to give decorated benzothiophenes.
Scheme 4 Two-directional, sulfoxide-directed, metal-free crosscouplings involving substrates derived from dihydroxynaphthalenes; R ¼ n-C 6 H 13 (isolated yields after purification). of conditions B; the use of NaI facilitates demethylation of sulfur in an intermediate sulfonium salt; Schemes 2 and 3) delivers alkyl-substituted materials 11 and 12, respectively, iodine-mediated cyclization delivers acyl-substituted materials 13 and 14 (all 2 steps from sulfoxide). Furthermore, iodinemediated cyclization of 9 and 10b under eliminative conditions gave alkenylated products 15 and 16 (Scheme 5). NDT products 11-16 are potential small molecule organic materials in their own right (vide infra) 9d,g and 11-14 were characterized by X-ray crystallographic analysis (Fig. 1). 13 Thus, sulfoxide-directed cross-couplings allow palladium-mediated couplings to be avoided in the four-step synthesis of validated (11 and 12) and unexplored (13-16) types of organic material.
A metal-free route to BDT materials Attractively, the sulfoxide moiety in our approach can be viewed as a 'safety-catch' directing group: only upon oxidation to the sulfoxide is the substrate receptive to cross-coupling. Furthermore, the directing group is reduced during the coupling, the directing effect is 'switched-off', and over-alkylation is impossible. 10b Selective coupling in bis-sulde substrates bearing latent directing groups is therefore possible provided selective oxidation can be achieved. For example, symmetrical bis-sulde starter unit 17 and intermediate 19 can be selectively activated and thus undergo selective metal-free cross-coupling. This allows the controlled metal-free construction of unsymmetrical targets such as BDT 21 using iterative sulfoxide-directed crosscoupling (Scheme 6). The ability to prepare unsymmetrical small-molecule materials is crucial for several applications including the immobilization of materials on surfaces in the exploitation of self-assembled monolayers (SAM) in organic electronic devices. 14 We next addressed the challenge of developing a short, metalfree synthesis of extended BDT motifs. Such motifs are typically prepared by Pd-catalyzed Sonogashira, Suzuki, or Negishi couplings. 8 Tuning the heterocyclization of the products from metal-free cross-coupling delivers benzothiophenes bearing conjugated alkenes (Scheme 2, conditions C). Subsequent, unprecedented iodine-mediated, carbocyclative dimerization conveniently delivers novel, substituted benzodithiophenes 22-28 in moderate to excellent yield (3 steps overall from sulfoxide). The structure of 22 was conrmed by X-ray crystallography. 13 Crucially, the alkyl substituents on the central benzene ring, and the electronic properties of the anking benzene rings, can be readily varied through judicial choice of propargylsilane and sulfoxide coupling partners in the metal-free approach (Scheme 7A). A proposed mechanism for the novel dimerization is shown in Scheme 7B: homocoupling of the activated alkene 29 followed by acid-mediated cyclization gives intermediate 30 en route to dimers 22-28.
We have carried out preliminary evaluation of the materials prepared. Cyclic voltammetry and UV/Vis spectroscopy were Scheme 5 'Tuneable' 2-directional heterocyclizations for the metalfree synthesis of NDT materials (isolated yields after purification). Scheme 6 'Safety-catch' sulfoxide directing groups in metal-free cross-couplings: potential for the selective synthesis of unsymmetrical benzothiophene-based components.
used to determine the HOMO/LUMO levels and energy gaps for compounds 11-16 and 22-28. In particular, compounds 11-14 showed a low lying HOMO of <À5.5 eV and energy band gap greater than 3 eV, consistent with previous reports suggesting the orientation of the thiophene ring has little effect on the electronic structure of the core. 9h As expected, a lowering of the HOMO/LUMO was observed for the acyl-substituted derivatives.
Thin lms of compounds 11-14 were characterised using Xray diffraction and atomic force microscopy, and organic eld effect transistors (OFETs) were prepared and analysed using the conventional thin lm transistor techniques. 15 Consistent with previous observations, 9d,g,h novel materials 11 and 13 formed smooth thin lms and demonstrated p-type (hole transporting) behaviour in a eld effect transistor. In particular, compound 11 demonstrated a mobility of 0.2 cm 2 V À1 s À1 , high current on/ off ratio of 10 7 and a threshold voltage of À22 V over an average of 9 devices. This performance is consistent with those reported for fused benzothiophene semiconductors. 9h

Conclusions
In conclusion, a metal-free approach allows expedient access to benzothiophene-based systems that are components of important materials or are proven organic materials in their own right. The approach combines sulfoxide-directed metalfree C-H cross-couplings with novel tuneable electrophilemediated heterocyclizations and carbocyclative dimerizations. As benzothiophene-based materials are typically prepared using Pd-catalyzed cross-coupling processes, our approach allows potential issues of metal cost and supply, and the metal-contamination of products, to be avoided.