Skip to main content
NCBI home page
ACS AuthorChoice logoLink to ACS AuthorChoice
. 2024 Apr 22;89(9):6138–6148. doi: 10.1021/acs.joc.4c00122

Derivatization of 2,1,3-Benzothiadiazole via Regioselective C–H Functionalization and Aryne Reactivity

Susanna Kunz †, Fredrik Barnå †, Mauricio Posada Urrutia †, Fredric J L Ingner †, Andrea Martínez-Topete †, Andreas Orthaber ‡, Paul J Gates §, Lukasz T Pilarski †,*, Christine Dyrager †,*
PMCID: PMC11077497  PMID: 38648018

Abstract

graphic file with name jo4c00122_0007.jpg

Despite growing interest in 2,1,3-benzothiadiazole (BTD) as an integral component of many functional molecules, methods for the functionalization of its benzenoid ring have remained limited, and many even simply decorated BTDs have required de novo synthesis. We show that regioselective Ir-catalyzed C–H borylation allows access to versatile 5-boryl or 4,6-diboryl BTD building blocks, which undergo functionalization at the C4, C5, C6, and C7 positions. The optimization and regioselectivity of C–H borylation are discussed. A broad reaction scope is presented, encompassing ipso substitution at the C–B bond, the first examples of ortho-directed C–H functionalization of BTD, ring closing reactions to generate fused ring systems, as well as the generation and capture reactions of novel BTD-based heteroarynes. The regioselectivity of the latter is discussed with reference to the Aryne Distortion Model.

Introduction

2,1,3-Benzothiadiazole (BTD, 1, Figure 1) is a privileged electron acceptor unit1 found at the core of numerous fluorescent probes2 and phototheranostics3 as well as covalent organic frameworks,4 and optoelectronic devices5 (including in polymers,6 OLEDs,7 solar cells,8 and transistors9). BTD has also recently found new roles in catalytic hydrogen production.10 The growing interest in BTD derivatives makes user-friendly approaches to functionalization a highly attractive prospect. Despite this, options for derivatizing BTD directly have remained remarkably few. Foremost among these are: (i) electrophilic aromatic substitution (to 2a), which typically requires harsh conditions due to BTD’s electron-poor nature, and which can deliver mixtures of C4- and C7-substituted products,11 and (ii) tactics based on stoichiometric metalation (to 2b).12 The C5–H or C6–H positions have remained essentially unaddressed. In practice, C5- and/or C6-substituted BTDs almost invariably require de novo assembly of the thiadiazoloid ring, usually from toxic SOCl2 and substituted aryl-1,2-diamines,13 which can themselves be tedious to prepare. This has restricted access to many potentially valuable BTD-based scaffolds and the exploration of their properties and of the contexts in which these can be exploited.

Figure 1.

Figure 1

Open in a new tab

Functionalizing BTD: established approaches versus the C–H functionalization approach explored in this study.

Recent years have seen C–H functionalization14 emerge as a transformative technology for expediting synthesis through previously impossible reactions and increasingly sustainable protocols.15 However, reports on the catalytic C–H functionalization of BTD have been sparse and overwhelmingly focused on Pd-catalyzed C4/C7 arylation,16 where CMD-type processes most easily take effect.17

Our teams’ interest in C–H functionalization18 and the use of BTD derivatives for bioimaging11b,19 led us to envisage Ir-catalyzed C–H borylation20 as a route to C5-boryl building block 3a, in which the versatility of the C–B bond could be leveraged for decorating C5 directly and, importantly, for manipulating the neighboring C4 and C6 positions. Here, we describe the application of this strategy as an entry point to numerous novel BTD-based structures via C4–, C5–, and C6–H activation and even via unprecedented BTD-based heteroarynes.21

Results and Discussion

Boryl BTD via C–H Borylation

At the outset, we explored the Ir-catalyzed C–H borylation of 1 using B2(pin)2 and [Ir(OMe)COD]2 as the precatalyst. Two sets of optimized conditions are shown in Scheme 1a (see Table S1 for more details). Conditions A gave borylated derivatives 3 in 86% yield, with a strong preference for the desired building block 3a (64%), with 4-boryl (3b, 6%), 4,6-diboryl (3c, 8%), and 4,7-diboryl (3d, 8%) congeners forming in minor amounts. For heteroarenes lacking sterically hindering substituents, Ir-catalyzed C–H borylation is often selective for the most acidic position,20b but suppressing multiple borylations can be challenging. In BTD, C4–H is the most acidic proton;12 the high C5–H regioselectivity observed here is probably accounted for by the inhibitory effect of the N3 lone pair, by analogy with pyridines and quinolines.22 In situ instability of C4-boryl species 3b–d is unlikely to explain the high levels of C5H borylation observed. Subjecting 3b to conditions A resulted in a mixture of the diboryl products (3c/3d = 1:1), with no loss of B(pin) from the C4 position—i.e., 3b is stable under the borylation conditions. Additionally, compounds 3a–d proved indefinitely bench stable under air.

Scheme 1. Generation of BTD-Based Boronates.

Scheme 1

Open in a new tab

Yield determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. Scale: 0.5 mmol BTD.

1 g scale reaction: 3a formed in 56% spectroscopic yield (see the Supporting Information for more details).

For boronate interconversions: DEA = diethanolamine; MTBE = methyl-tert-butylether; and MIDA = methyliminodiacetic acid.

More forcing conditions (conditions B), involving higher catalyst, ligand and B2(pin)2 loadings, as well as a higher temperature, gave exclusively the diborylated products with a strong preference for 4,6-diboryl BTD derivative 3c, which can arise from a second borylation of either 3a at C7–H or 3b at C6–H. We anticipate that this very direct route to 3c will help challenge the conspicuous paucity of unsymmetrically substituted BTDs in the research literature, the properties of which are poorly explored.

More generally, we tentatively ascribe the need for elevated temperatures (only traces of borylated products formed at temperatures <40 °C) to the coordination by the sulfur atom in 1 to the catalyst’s Ir center, as has been invoked for thiophene substrates.22a Throughout, the ligand Me4phen gave higher yields and regioselectivity than did other commonly used ligands for C–H borylation (dtbpy, dmbpy, dMeObpy, and SiO2-SMAP23).

As the reactivity profile of organoboron reagents may be honed or modulated for different applications through the substituents at boron,24 we also examined the conversion of 3a to its relatives 3e–g (Scheme 1b). Deprotection of 3a to the corresponding boronic acid 3e using diethanolamine (DEA) and acid hydrolysis18h,25 occurred in very good yield (85%), as did conversion to the trifluoroborate salt 3f (90%) under the mild conditions developed by the group of Lloyd-Jones.26

The MIDA-protecting group can act as a valuable stabilizer of otherwise labile C–B bonds,27 and B(MIDA) boronates themselves have earned prominence as valuable building blocks in iterative24d,24j,28 and even automated29 synthesis.30 We obtained novel BTD-based B(MIDA) boronate 3g in 65% yield through ligation of the B center in 3e with methyliminodiacetic acid and concomitant water abstraction.24i

Ipso Substitutions

As an initial foray into leveraging the versatility of the C–B bond in building blocks 3, we explored a range of ipso substitutions, beginning with extending BTD’s π-system via Suzuki-Miyaura cross-coupling of 3a (Scheme 2a).31 Simple Pd(OAc)2/XPhos or PdCl2(dppf)-based systems gave biaryls 4a–h in good-to-excellent yields from a range of electronically diverse (hetero)aryl bromides. Notably few 5-aryl BTD derivatives have been reported to date, and the influence of (hetero)aryl substituents at C5, e.g., on the photophysical properties of BTD-based compounds, has been explored only very sparingly, usually as one-off examples.2d,32 The pyrimidyl group of 4g was installed as a directing group to enable extensions of the π-system through subsequent C4–H and C6–H functionalizations (see Scheme 4).

Scheme 2. Ipso Substitutions of the C–B Bond in Boronates 3.

Scheme 2

Open in a new tab

GAM = glyoxylic acid monohydrate; HMPO = anti-1,2,2,3,4,4-Hexamethylphosphetane 1-oxide.

Scheme 4. Directed C–H Functionalization Reactions.

Scheme 4

Open in a new tab

4-Bromoacetophenone (1.0 equiv.) added in two portions (16 h, then 25 h).

Ratio of C4/C6 arylation. Major regioisomer shown.

rt to 60 °C.

Scale: 0.5 mmol BTD.

Next, we expanded the reaction scope using Cu-catalyzed33 and mediated34ipso halogenation, which provided the corresponding 5-chloro (5a), -bromo (5b), and -iodo (5c) analogues (Scheme 2b). The novel iodonium salt356 could be accessed via transfer of the BTD moiety from 3f to the IIII center of diacetoxy(mesityl)-λ3-iodane, MesI(OAc)2, prior to anion exchange with NaOTs (Scheme 2b). To the best of our knowledge, only a single example of a BTD-based iodonium salt has been reported previously, which Zhang and Liang used to effect nucleophilic substitutions.16k As described below, 6 gave new options for derivatizing the BTD benzenoid ring by acting as a precursor to the corresponding 4,5-benzothiadiazolyne (see Scheme 5). Scheme 2c shows four further functionalizations of 3a and 3e. Oxidation of 3a using Oxone gave phenolic derivative 7 in near-quantitative yield, which we expect to serve as a convenient basis for generating new BTD-based push–pull systems. Boronic ester 3a also underwent oxidative Pd-catalyzed homocoupling36 to the heterobiaryl system 8, which has been of interest recently as a component of electrochromic polymers.37 The synthesis of 8 previously proceeded by condensation of SOCl2 and 3,3′,4,4′-tetraaminobiphenyl. Boronic acid 3e was amenable to organocatalytic formylation recently reported by Mariano, Xie, and Wang,38 furnishing aldehyde 9. Existing syntheses of 9 have relied on oxidation of the corresponding alcohol, in turn, obtained from the benzylic bromide, which is derived from a methyl group. Our route to 9 thus shortcuts a tedious multistep sequence.39 Finally, diaryl amines 10a and 10b were generated via a phosphacycle-catalyzed intermolecular reductive amination using nitroarenes as coupling partners.40 The high yields of these reactions are particularly pleasing, as efforts to generate 5-aryl BTDs via Chan-Lam41 or Buchwald-Hartwig32f,42 aminations (from 5-Br-BTD) gave only low-to-moderate yields (see the Supporting Information for details).32d,43

Scheme 5. Generation, Distortion, and Trapping of 2,1,3-Benzothiadiazol-4,5-yne.

Scheme 5

Open in a new tab

MTBE = Methyl tert-butylether.

Fused BTD Motifs

Fused carbazoles are key components of innumerable organic solar cells and other optoelectronic devices.8a,44 Tetracycles 11a and 11b (Scheme 3) specifically represent a class of fused thiadiazolocarbazoles that have shown promise as electron transporters in electroluminescent materials.45 We obtained 11a from 10b via intramolecular Pd-catalyzed C4–H arylation46 (Conditions K) with complete regioselectivity, which is accounted for by the greater ease with which C4–H activates under base-assisted palladation.16,17 To the best of our knowledge, this marks the first example of direct C–H arylation as a route to fused BTD-based systems.

Scheme 3. Access to Tetracyclic and Hexacyclic Thiadiazolocarbazoles via Derivatization of 5-Boryl or 4,6-Diboryl BTDs.

Scheme 3

Open in a new tab

Modifications: Pd(OAc)2 (4 mol %), XPhos (4 mol %), bromoarene (2.4 equiv.), K3PO4 (3.0 equiv.), 80 °C, 21 h.

The regioisomer 11b could be accessed directly by reductive cyclization of nitroarene 4e (Scheme 3) in 81% yield via the Cadogan reaction35b,47 (Conditions L). The cyclization occurred with exclusive regioselectivity, which is especially rare for Cadogan reactions of substrates with multiple sterically unhindered sites. In the case of 11b, we attribute this to a significant difference in nucleophilicity between the C4 and C6 positions of the BTD unit. This difference notwithstanding, the novel hexacyclic system 11c was also accessible via the Cadogan reaction of dinitro arene 4i (obtained from diboronate 3c), which demonstrates that both aromatic positions of the BTD framework may be addressed this way. By contrast, efforts to cyclize the aniline 4d to 11b using an oxidative Ir-catalyzed C–H amination48 gave a much lower yield of 25%, possibly due to inhibitive coordination to Ir and/or the Cu oxidant by the nitrogen or sulfur lone pairs.

Directed C–H Functionalizations

The use of catalytic C–H functionalization as a tactic to extend the BTD π-system is in its infancy. To complement the range of reactions reported to date,16 as well as to explore the prospects of addressing both C4–H and C6–H positions from a common directing group, we initially examined carboxylate-assisted17 Ru-catalyzed arylations and Rh-catalyzed alkenylation using 4g as a substrate (Conditions M and N, respectively, Scheme 4). With one equivalent of bromoarene, the Ru system gave C4–H-arylated product 12a with very high regioselectivity (15:1 rr), underscoring the greater preference of carboxylate-assisted C–H activation for the C4 position. However, this could be readily adapted to yield the 4,5,6-triaryl BTD system 12b by using 3 equiv of bromoarene. Otherwise, sequential arylations under Conditions M could be used to introduce two electronically differentiated aromatic units (12c). The identities of these regioisomers were verified by using 1D-NOESY NMR spectroscopy, which showed no undirected arylation at C7–H, underscoring the complementarity between directed and undirected C–H arylation approaches. Similarly, the room-temperature Rh-catalyzed C–H alkenylation (Conditions N) was C4–H selective (13a,b) but could be used to address C6–H in 12a to give the 4,5,6-trisubstituted BTD system 13c in good yield. The C4–H position of 4g was also amenable to directed Rh-catalyzed oxidative C–H/C–H coupling with 2-methylthiophene (product 14, Scheme 4c),49 which complements the undirected Ru system described by Singh.16h Access to structures such as 4f and 14 should prove valuable as many BTD-based functional molecules comprise thiophenyl groups.

Subjecting 4h to Conditions M did not result in any C–H functionalization, confirming the importance of the ortho-directing group effect.

Finally, to expand the set of Pd-catalyzed approaches to BTD C–H functionalization, we examined the prospect of generating 4,5,6-trifunctionalized BTD via the Catellani reaction, in which Ar–H bonds ortho with respect to an iodide are substituted via catalytic Pd/norbornene cooperation (Scheme 4d).50 Iodide 5c thus underwent C4,C6-dialkylation, prior to a C5–H alkenylation with methyl acrylate to give 15. The dibutylation of the BTD backbone is significant as the solubility and photophysical properties of BTD-based polymers can be enhanced through the inclusion of alkyl side chains.51 However, the paucity of available synthetic methods for modifying the BTD system itself has meant that alkyl groups have been typically attached to pendant rings, such as thiophenes.51,52 We anticipate that the Catellani approach described here will offer valuable new options in this context.

To the best of our knowledge, the reactions described here are the first demonstrations that Ir-, Ru-, Pd-, and Rh-catalyzed C–H functionalization is a viable approach for addressing C5 and C6 positions of BTD. As many directing groups are compatible with transition-metal functionalizations of this kind and because of the modularity with which the incoming substituents can be introduced, we anticipate the C–H functionalization approach exemplified here will open valuable new opportunities to incorporate variously modified BTDs into functional molecules. For example, one rare report from Shaoming and co-workers53 describes that polymers based on 4,6- rather than 4,7-substituted BTDs exhibit markedly greater solubility, enabling the synthesis of polymer chains with higher molecular weights. Investigations of the photophysical properties arising from novel BTD substitution patterns are ongoing in our laboratory.

2,1,3-Benzothiadiazol-4,5-yne

Arynes are remarkably versatile electrophiles able to accept a huge variety of functional groups to two neighboring aromatic carbons in a single procedure.54 Accordingly, arynes have secured roles as key intermediates in the syntheses of natural products,55 biaryl systems,56 polycyclic aromatic hydrocarbons,57 and beyond.58 A variety of methods for the generation of arynes has been reported,59 including deprotonation ortho to the I(III) center of diaryliodonium salts,59b,60 which is mild and operationally simple. This ejects an iodoarene as the nucleophile and creates a strained triple bond in the aromatic ring, which is trapped by an arynophile. For unsymmetrical (hetero)arynes, the regioselectivity of the trapping step can be rationalized using the Garg and Houk’s Aryne Distortion Model,61 which holds that initial nucleophilic attack by an arynophile will occur at the more linear of the two distorted triple bond carbon atoms. The extent of distortion at these positions can be calculated with relative ease for ground-state aryne intermediates, and the difference between the two internal bond angles, Δθ, correlates with expected regioselectivity. Values of Δθ > 4° can be considered as predicting “synthetically useful” levels of regioselectivity;62 in practice Δθ > 8° typically results in complete or near-complete selectivity for the “flatter” carbon atom.

Unfortunately, very few heteroaryne building block molecules have been developed, especially those that can be activated under mild conditions. Even simple heteroaryne precursors can be challenging or tedious to synthesize. To the best of our knowledge, indolynes and pyridynes are the only heteroarynes with commercially available mild-to-activate precursors.

We anticipated that the strongly electronegative N atoms, especially N3, would induce considerable distortion,63 in the novel 2,1,3-benzothiadiazol-4,5-yne (16, Scheme 5), and that this intermediate could be accessed by regioselective C4–H deprotonation of iodonium salt 6.64 DFT calculations at the B3LYP/6–311++G(d,p) level predicted significant distortion [Δθ = 132.1° (C5) – 122.2° (C4) = 9.9°] of the triple bond in 16 in favor of C5-selective nucleophilic attack. To test this prediction and the viability of exploiting BTD-based arynes in synthesis, we subjected 6 to KOtBu in MTBE in the presence of three different arynophiles: azide 17a, cyclic urea 17b, and furan 17c. In each case, deprotonation occurred exclusively at the more acidic C4–H position, leading to products 18a–c. For products 18a and 18b, we observed only the formation of the shown regioisomers, both of which result from nucleophilic attack at C5, as predicted by DFT and the Aryne Distortion Model. The structure of 18b was further confirmed by using X-ray crystallography. Products 18a–b were the only isolable species from otherwise intractable mixtures. The [4 + 2] cycloaddition with 17c gave 18c in a fair yield. Attempts to generate aryne 16 via C5–H deprotonation of the 4-iodaneyl BTD isomer of 6 (see compound 6′ in Supporting Information) in the presence of 17c gave only traces of 18c. More broadly, aryne generation from aryliodonium salts can give lower yields than, for example, fluoride-activated ortho-silylaryl triflates,59a but the latter can be more demanding to prepare. The modest yields of 18a–b notwithstanding, the reactions in Scheme 5 confirm the viability of BTD-based arynes and the theoretical prediction of the regioselectivity with which they react. They also expand the range of approaches available for decorating BTD’s benzenoid ring as well as the portfolio of accessible heteroaryne synthons.

Conclusions

This methodology study addresses several long-standing challenges around functionalizing the BTD core. We have demonstrated a new route to diversely functionalized BTDs, which allows predictable and systematic substitutions at the C4, C5, C6, and C7 positions. These include a broad set of substitutions at C5, the first examples of directed and sequential C–H functionalization at the C4, C6, and C7 positions, and a demonstration that BTD-based arynes can be generated and captured with excellent levels of chemo- and regioselectivity.

At the root of these new possibilities is access to BTD-based organoboronate building blocks via mild and selective catalytic C–H borylation. We expect our description of their reactivity to serve as a platform for the synthesis of new functional molecules based on BTD’s unique properties. Work on the exploration of new substituent effects on the photophysical properties of BTD derivatives is ongoing in our laboratory.

Acknowledgments

We thank Carl Tryggers Stiftelse (CTS 21:1210) and the Swedish Research Council (Vetenskapsrådet, dnr 2018-03524 and 2019-05424). This study made use of the NMR Uppsala infrastructure, which is funded by the Department of Chemistry—BMC and the Disciplinary Domain of Medicine and Pharmacy. Computations were enabled by resources provided by the National Academic Infrastructure for Supercomputing in Sweden (NAISS) and the Swedish National Infrastructure for Computing (SNIC) at UPPMAX, partially funded by the Swedish Research Council through grant agreement nos. 2022-06725 and 2018-05973.

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.4c00122.

  • General information, detailed experimental procedures, characterization data, 1H NMR and 13C NMR spectra, DFT calculations, and crystallographic data (PDF)

The authors declare no competing financial interest.

Supplementary Material

jo4c00122_si_001.pdf (6.7MB, pdf)

References

  1. a Parker T. C.; Patel D. G.; Moudgil K.; Barlow S.; Risko C.; Brédas J. L.; Reynolds J. R.; Marder S. R. Heteroannulated acceptors based on benzothiadiazole. Mater. Horiz. 2015, 2, 22–36. 10.1039/C4MH00102H. [DOI] [Google Scholar]; b Wang Y.; Michinobu T. Benzothiadiazole and its π-extended, heteroannulated derivatives: useful acceptor building blocks for high-performance donor–acceptor polymers in organic electronics. J. Mater. Chem. C 2016, 4, 6200–6214. 10.1039/C6TC01860B. [DOI] [Google Scholar]
  2. For reviews see:; a Neto B. A. D.; Correa J. R.; Spencer J. Fluorescent Benzothiadiazole Derivatives as Fluorescence Imaging Dyes: A Decade of New Generation Probes. Chem.—Eur. J. 2022, 28, e202103262 10.1002/chem.202103262. [DOI] [PubMed] [Google Scholar]; b Neto B. A. D.; Carvalho P. H. P. R.; Correa J. R. Benzothiadiazole Derivatives as Fluorescence Imaging Probes: Beyond Classical Scaffolds. Acc. Chem. Res. 2015, 48, 1560–1569. 10.1021/ar500468p. [DOI] [PubMed] [Google Scholar]; For selected original studies, see:; c Yu Y.; Xing H.; Park H.; Zhang R.; Peng C.; Sung H. H. Y.; Williams I. D.; Ma C.; Wong K. S.; Li S.; Xiong Q.; Li M.-H.; Zhao Z.; Tang B. Z. Deep-Red Aggregation-Induced Emission Luminogen Based on Dithiofuvalene-Fused Benzothiadiazole for Lipid Droplet-Specific Imaging. ACS Mater. Lett. 2022, 4, 159–164. 10.1021/acsmaterialslett.1c00570. [DOI] [Google Scholar]; d de la Torre C.; Toscani A.; Marín-Hernández C.; Robson J. A.; Terencio M. C.; White A. J. P.; Alcaraz M. J.; Wilton-Ely J. D. E. T.; Martínez-Máñez R.; Sancenón F. Ex Vivo Tracking of Endogenous CO with a Ruthenium(II) Complex. J. Am. Chem. Soc. 2017, 139, 18484–18487. 10.1021/jacs.7b11158. [DOI] [PubMed] [Google Scholar]
  3. Gu H.; Liu W.; Li H.; Sun W.; Du J.; Fan J.; Peng X. 2,1,3-Benzothiadiazole derivative AIEgens for smart phototheranostics. Coord. Chem. Rev. 2022, 473, 214803. 10.1016/j.ccr.2022.214803. [DOI] [Google Scholar]
  4. a Li Q.; Wang J.; Zhang Y.; Ricardez-Sandoval L.; Bai G.; Lan X. Structural and Morphological Engineering of Benzothiadiazole-Based Covalent Organic Frameworks for Visible Light-Driven Oxidative Coupling of Amines. ACS Appl. Mater. Interfaces 2021, 13, 39291–39303. 10.1021/acsami.1c08951. [DOI] [PubMed] [Google Scholar]; b Ding X.; Chen L.; Honsho Y.; Feng X.; Saengsawang O.; Guo J.; Saeki A.; Seki S.; Irle S.; Nagase S.; Parasuk V.; Jiang D. An n-Channel Two-Dimensional Covalent Organic Framework. J. Am. Chem. Soc. 2011, 133, 14510–14513. 10.1021/ja2052396. [DOI] [PubMed] [Google Scholar]; c Dogru M.; Sonnauer A.; Zimdars S.; Döblinger M.; Knochel P.; Bein T. Facile synthesis of a mesoporous benzothiadiazole-COF based on a transesterification process. CrystEngComm 2013, 15, 1500–1502. 10.1039/c2ce26343b. [DOI] [Google Scholar]
  5. a Du J.; Biewer M. C.; Stefan M. C. Benzothiadiazole building units in solution-processable small molecules for organic photovoltaics. J. Mat. Chem. A 2016, 4, 15771–15787. 10.1039/C6TA06241E. [DOI] [Google Scholar]; b Zając D.; Honisz D.; Łapkowski M.; Sołoducho J. 2,1,3-Benzothiadiazole Small Donor Molecules: A DFT Study, Synthesis, and Optoelectronic Properties. Molecules 2021, 26, 1216. 10.3390/molecules26051216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cong P.; Wang Z.; Geng Y.; Meng Y.; Meng C.; Chen L.; Tang A.; Zhou E. Benzothiadiazole-based polymer donors. Nano Energy 2023, 105, 108017. 10.1016/j.nanoen.2022.108017. [DOI] [Google Scholar]
  7. Li S.; Liu K.; Feng X.-C.; Li Z.-X.; Zhang Z.-Y.; Wang B.; Li M.; Bai Y.-L.; Cui L.; Li C. Synthesis and macrocyclization-induced emission enhancement of benzothiadiazole-based macrocycle. Nat. Commun. 2022, 13, 2850. 10.1038/s41467-022-30121-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. For a review, see:; a Tan S. E.; Sarjadi M. S. The recent development of carbazole-benzothiadiazole-and isoindigo-based copolymers for solar cells application: A review. Polymer Science, Series B 2017, 59, 479–496. 10.1134/S1560090417050141. [DOI] [Google Scholar]; b Nie Q.; Tang A.; Guo Q.; Zhou E. Benzothiadiazole-based non-fullerene acceptors. Nano Energy 2021, 87, 106174. 10.1016/j.nanoen.2021.106174. [DOI] [Google Scholar]; c Zhu L.; Zhang M.; Xu J.; Li C.; Yan J.; Zhou G.; Zhong W.; Hao T.; Song J.; Xue X.; Zhou Z.; Zeng R.; Zhu H.; Chen C.-C.; MacKenzie R. C. I.; Zou Y.; Nelson J.; Zhang Y.; Sun Y.; Liu F. Single-junction organic solar cells with over 19% efficiency enabled by a refined double-fibril network morphology. Nat. Mater. 2022, 21, 656–663. 10.1038/s41563-022-01244-y. [DOI] [PubMed] [Google Scholar]; d Wei Y.; Chen Z.; Lu G.; Yu N.; Li C.; Gao J.; Gu X.; Hao X.; Lu G.; Tang Z.; Zhang J.; Wei Z.; Zhang X.; Huang H. Binary Organic Solar Cells Breaking 19% via Manipulating the Vertical Component Distribution. Adv. Mater. 2022, 34, 2204718. 10.1002/adma.202204718. [DOI] [PubMed] [Google Scholar]; e Gao J.; Yu N.; Chen Z.; Wei Y.; Li C.; Liu T.; Gu X.; Zhang J.; Wei Z.; Tang Z.; Hao X.; Zhang F.; Zhang X.; Huang H. Over 19.2% Efficiency of Organic Solar Cells Enabled by Precisely Tuning the Charge Transfer State Via Donor Alloy Strategy. Adv. Sci. 2022, 9, 2203606. 10.1002/advs.202203606. [DOI] [PMC free article] [PubMed] [Google Scholar]; f Wang C.; Xia D.; Yang F.; Li J.; Wu Y.; Li W. Benzothiadiazole-Based Double-Cable Conjugated Polymers for Single-Component Organic Solar Cells with Efficiency over 4%. ACS Appl. Polym. Mater. 2021, 3, 4645–4650. 10.1021/acsapm.1c00743. [DOI] [Google Scholar]; g Godfroy M.; Liotier J.; Mwalukuku V. M.; Joly D.; Huaulmé Q.; Cabau L.; Aumaitre C.; Kervella Y.; Narbey S.; Oswald F.; Palomares E.; González Flores C. A.; Oskam G.; Demadrille R. Benzothiadiazole-based photosensitizers for efficient and stable dye-sensitized solar cells and 8.7% efficiency semi-transparent mini-modules. Sustain. Energy Fuels 2021, 5, 144–153. 10.1039/D0SE01345E. [DOI] [Google Scholar]; h Wang B.; Tsang S.-W.; Zhang W.; Tao Y.; Wong M. S. Naphthodithiophene-2,1,3-benzothiadiazole copolymers for bulk heterojunction solar cells. Chem. Commun. 2011, 47, 9471–9473. 10.1039/c1cc13690a. [DOI] [PubMed] [Google Scholar]
  9. a Li M.; An C.; Pisula W.; Müllen K. Cyclopentadithiophene–Benzothiadiazole Donor–Acceptor Polymers as Prototypical Semiconductors for High-Performance Field-Effect Transistors. Acc. Chem. Res. 2018, 51, 1196–1205. 10.1021/acs.accounts.8b00025. [DOI] [PubMed] [Google Scholar]; b Bai F.; Zhang J.; Zeng A.; Zhao H.; Duan K.; Yu H.; Cheng K.; Chai G.; Chen Y.; Liang J.; Ma W.; Yan H. A highly crystalline non-fullerene acceptor enabling efficient indoor organic photovoltaics with high EQE and fill factor. Joule 2021, 5, 1231–1245. 10.1016/j.joule.2021.03.020. [DOI] [Google Scholar]; c Kafourou P.; Park B.; Luke J.; Tan L.; Panidi J.; Glöcklhofer F.; Kim J.; Anthopoulos T. D.; Kim J.-S.; Lee K.; Kwon S.; Heeney M. One-Step Sixfold Cyanation of Benzothiadiazole Acceptor Units for Air-Stable High-Performance n-Type Organic Field-Effect Transistors. Angew. Chem., Int. Ed. 2021, 60, 5970–5977. 10.1002/anie.202013625. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Ocheje M. U.; Comí M.; Yang R.; Chen Z.; Liu Y.; Yousefi N.; Al-Hashimi M.; Rondeau-Gagné S. Molecular engineering of benzothiadiazole-based polymers: balancing charge transport and stretchability in organic field-effect transistors. J. Mater. Chem. C 2022, 10, 4236–4246. 10.1039/D1TC06103H. [DOI] [Google Scholar]
  10. a Axelsson M.; Marchiori C. F. N.; Huang P.; Araujo C. M.; Tian H. Small Organic Molecule Based on Benzothiadiazole for Electrocatalytic Hydrogen Production. J. Am. Chem. Soc. 2021, 143, 21229–21233. 10.1021/jacs.1c10600. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Yang C.; Ma B. C.; Zhang L.; Lin S.; Ghasimi S.; Landfester K.; Zhang K. A. I.; Wang X. Molecular Engineering of Conjugated Polybenzothiadiazoles for Enhanced Hydrogen Production by Photosynthesis. Angew. Chem., Int. Ed. 2016, 55, 9202–9206. 10.1002/anie.201603532. [DOI] [PubMed] [Google Scholar]
  11. For brominations, see:; a Pilgram K.; Zupan M.; Skiles R. Bromination of 2,1,3-benzothiadiazoles. J. Heterocycl. Chem. 1970, 7, 629–633. 10.1002/jhet.5570070324. [DOI] [Google Scholar]; b Dyrager C.; Vieira R. P.; Nyström S.; Nilsson K. P. R.; Storr T. Synthesis and evaluation of benzothiazole-triazole and benzothiadiazole-triazole scaffolds as potential molecular probes for amyloid-β aggregation. New J. Chem. 2017, 41, 1566–1573. 10.1039/C6NJ01703G. [DOI] [Google Scholar]; c Coombs B. A.; Lindner B. D.; Edkins R. M.; Rominger F.; Beeby A.; Bunz U. H. F. Photophysical property trends for a homologous series of bis-ethynyl-substituted benzochalcogendiazoles. New J. Chem. 2012, 36, 550–553. 10.1039/C2NJ20847D. [DOI] [Google Scholar]; For a milder chlorination protocol, see:; d Zahara A. J.; Hinds E. M.; Nguyen A. L.; Wilkerson-Hill S. M. Programmed Sequential Additions to Halogenated Mucononitriles. Org. Lett. 2020, 22, 8065–8069. 10.1021/acs.orglett.0c03007. [DOI] [PubMed] [Google Scholar]; For nitration, see:; e Plyuta N.; Cauchy T.; Hauser A.; Lloret F.; Julve M.; Avarvari N. Zinc(II) and copper(II) complexes with benzothiadiazole Schiff-base ligands. Polyhedron 2022, 224, 115994. 10.1016/j.poly.2022.115994. [DOI] [Google Scholar]; f Salah S. B.; Zaier R.; Ayachi S.; Goumont R.; Boubaker T. The N-alkylation of 4-nitrobenzochalcogenadiazoles: Synthesis and theoretical approach. J. Mol. Struct. 2019, 1197, 80–86. 10.1016/j.molstruc.2019.06.091. [DOI] [Google Scholar]; g da Silva Miranda F.; Signori A. M.; Vicente J.; de Souza B.; Priebe J. P.; Szpoganicz B.; Gonçalves N. S.; Neves A. Synthesis of substituted dipyrido[3,2-a:2′,3′-c]phenazines and a new heterocyclic dipyrido[3,2-f:2′,3′-h]quinoxalino[2,3-b]quinoxaline. Tetrahedron 2008, 64, 5410–5415. 10.1016/j.tet.2008.02.097. [DOI] [Google Scholar]; h Murashima T.; Fujita K.-i.; Ono K.; Ogawa T.; Uno H.; Ono N. A new facet of the reaction of nitro heteroaromatic compounds with ethyl isocyanoacetate. J. Chem. Soc. Perkin Trans. 1 1996, 1403–1407. 10.1039/p19960001403. [DOI] [Google Scholar]
  12. Knochel P.; Zimdars S.; Langhals H. Functionalization of the Benzo[c] [1,2,5]thiadiazole Scaffold via Mg-Zn- and Mn-Intermediates. Synthesis 2011, 2011, 1302–1308. 10.1055/s-0030-1259966. [DOI] [Google Scholar]
  13. Rakitin O. A. Recent Developments in the Synthesis of 1,2,5-Thiadiazoles and 2,1,3-Benzothiadiazoles. Synthesis 2019, 51, 4338–4347. 10.1055/s-0039-1690679. [DOI] [Google Scholar]
  14. a Rogge T.; Kaplaneris N.; Chatani N.; Kim J.; Chang S.; Punji B.; Schafer L. L.; Musaev D. G.; Wencel-Delord J.; Roberts C. A.; Sarpong R.; Wilson Z. E.; Brimble M. A.; Johansson M. J.; Ackermann L. C–H activation. Nat. Rev. Methods Primers 2021, 1, 43. 10.1038/s43586-021-00041-2. [DOI] [Google Scholar]; b Zakis J. M.; Smejkal T.; Wencel-Delord J. Cyclometallated complexes as catalysts for C–H activation and functionalization. Chem. Commun. 2022, 58, 483–490. 10.1039/D1CC05195D. [DOI] [PubMed] [Google Scholar]; c Sinha S. K.; Guin S.; Maiti S.; Biswas J. P.; Porey S.; Maiti D. Toolbox for Distal C–H Bond Functionalizations in Organic Molecules. Chem. Rev. 2022, 122, 5682–5841. 10.1021/acs.chemrev.1c00220. [DOI] [PubMed] [Google Scholar]; d Liu B.; Romine A. M.; Rubel C. Z.; Engle K. M.; Shi B.-F. Transition-Metal-Catalyzed, Coordination-Assisted Functionalization of Nonactivated C(sp3)–H Bonds. Chem. Rev. 2021, 121, 14957–15074. 10.1021/acs.chemrev.1c00519. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Abrams D. J.; Provencher P. A.; Sorensen E. J. Recent applications of C–H functionalization in complex natural product synthesis. Chem. Soc. Rev. 2018, 47, 8925–8967. 10.1039/C8CS00716K. [DOI] [PubMed] [Google Scholar]; f Davies H. M. L.; Morton D. Recent Advances in C–H Functionalization. J. Org. Chem. 2016, 81, 343–350. 10.1021/acs.joc.5b02818. [DOI] [PubMed] [Google Scholar]
  15. a Tyler J. L.; Katzenburg F.; Glorius F. A focus on sustainable method development for greener synthesis. Chem. Sci. 2023, 14, 7408–7410. 10.1039/D3SC90120C. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Dhawa U.; Kaplaneris N.; Ackermann L. Green strategies for transition metal-catalyzed C–H activation in molecular syntheses. Org. Chem. Front. 2021, 8, 4886–4913. 10.1039/D1QO00727K. [DOI] [Google Scholar]; c Dalton T.; Faber T.; Glorius F. C–H Activation: Toward Sustainability and Applications. ACS Cent. Sci. 2021, 7, 245–261. 10.1021/acscentsci.0c01413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. For nitration, see:; a Punzi A.; Capozzi M. A. M.; Di Noja S.; Ragni R.; Zappimbulso N.; Farinola G. M. Solvent-Free Pd-Catalyzed Heteroaryl–Aryl Coupling via C–H Bond Activation for the Synthesis of Extended Heteroaromatic Conjugated Molecules. J. Org. Chem. 2018, 83, 9312–9321. 10.1021/acs.joc.8b01284. [DOI] [PubMed] [Google Scholar]; b Idris I.; Tannoux T.; Derridj F.; Dorcet V.; Boixel J.; Guerchais V.; Soulé J. F.; Doucet H. Effective modulation of the photoluminescence properties of 2,1,3-benzothiadiazoles and 2,1,3-benzoselenadiazoles by Pd-catalyzed C–H bond arylations. J. Mater. Chem. C 2018, 6, 1731–1737. 10.1039/C7TC05395A. [DOI] [Google Scholar]; c Zhang J.; Parker T. C.; Chen W.; Williams L.; Khrustalev V. N.; Jucov E. V.; Barlow S.; Timofeeva T. V.; Marder S. R. C–H-Activated Direct Arylation of Strong Benzothiadiazole and Quinoxaline-Based Electron Acceptors. J. Org. Chem. 2016, 81, 360–370. 10.1021/acs.joc.5b02551. [DOI] [PubMed] [Google Scholar]; d He C.-Y.; Wu C.-Z.; Qing F.-L.; Zhang X. Direct (Het)Arylation of Fluorinated Benzothiadiazoles and Benzotriazole with (Het)Aryl Iodides. J. Org. Chem. 2014, 79, 1712–1718. 10.1021/jo402675v. [DOI] [PubMed] [Google Scholar]; e Zhang J.; Chen W.; Rojas A. J.; Jucov E. V.; Timofeeva T. V.; Parker T. C.; Barlow S.; Marder S. R. Controllable Direct Arylation: Fast Route to Symmetrical and Unsymmetrical 4,7-Diaryl-5,6-difluoro-2,1,3-benzothiadiazole Derivatives for Organic Optoelectronic Materials. J. Am. Chem. Soc. 2013, 135, 16376–16379. 10.1021/ja4095878. [DOI] [PubMed] [Google Scholar]; f Ghanem T.; Vincendeau T.; Marqués P. S.; Habibi A. H.; Abidi S.; Yassin A.; Dabos-Seignon S.; Roncali J.; Blanchard P.; Cabanetos C. Synthesis of push–pull triarylamine dyes containing 5,6-difluoro-2,1,3-benzothiadiazole units by direct arylation and their evaluation as active material for organic photovoltaics. Mater. Adv. 2021, 2, 7456–7462. 10.1039/D1MA00798J. [DOI] [Google Scholar]; g Shi Q.; Tatum W.; Zhang J.; Scott C.; Luscombe C. K.; Marder S. R.; Blakey S. B. The Direct Arylation Polymerization (DArP) of Well-Defined Alternating Copolymers Based On 5,6-Dicyano[2,1,3]benzothiadiazole (DCBT). Asian J. Org. Chem. 2018, 7, 1419–1425. 10.1002/ajoc.201800232. [DOI] [Google Scholar]; For a Ru-catalyzed C–H/C–H arylation under oxidative conditions, see:; h Shome S.; Singh S. P. Access to small molecule semiconductors via C–H activation for photovoltaic applications. Chem. Commun. 2018, 54, 7322–7325. 10.1039/C8CC02706D. [DOI] [PubMed] [Google Scholar]; For a rare example of a Pd-catalyzed C–H allylation of BTD, see:; i Wang J.; Yu Y.-B.; Zhang X. Palladium-catalyzed direct allylation of fluorinated benzothiadiazoles with allyl chlorides. Tetrahedron 2018, 74, 6329–6334. 10.1016/j.tet.2018.09.033. [DOI] [Google Scholar]; For work exploiting the nitrogen atoms of BTD as directing groups to effect C–H activation of a pendant arene, see:; j Guo J.; He H.; Ye Z.; Zhu K.; Wu Y.; Zhang F. Highly Selective Palladium-Catalyzed Arene C–H Acyloxylation with Benzothiadiazole as a Modifiable Directing Group. Org. Lett. 2018, 20, 5692–5695. 10.1021/acs.orglett.8b02414. [DOI] [PubMed] [Google Scholar]; k He H.; Guo J.; Sun W.; Yang B.; Zhang F.; Liang G. Palladium-Catalyzed Direct Mono- or Polyhalogenation of Benzothiadiazole Derivatives. J. Org. Chem. 2020, 85, 3788–3798. 10.1021/acs.joc.9b03418. [DOI] [PubMed] [Google Scholar]; See also:; l Taylor D.; Malcomson T.; Zhakeyev A.; Rosair G. M.; Paterson M. J.; Marques-Hueso J.; Dalgarno S. J.; Vilela F. Regioselective electrophilic aromatic borylation as a method for synthesising sterically hindered benzothiadiazole fluorophores. RSC Adv. 2023, 13, 5826–5832. 10.1039/D2RA08319A. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. For a recent discussion on mechanistic aspects of C–H activation, see:; a Altus K. M.; Love J. A. The continuum of carbon–hydrogen (C–H) activation mechanisms and terminology. Commun. Chem. 2021, 4, 173. 10.1038/s42004-021-00611-1. [DOI] [PMC free article] [PubMed] [Google Scholar]; For a review of the role of carboxylate bases in CMD-type reactions see the following, see:; b Ackermann L. Carboxylate-Assisted Transition-Metal-Catalyzed C–H Bond Functionalizations: Mechanism and Scope. Chem. Rev. 2011, 111, 1315–1345. 10.1021/cr100412j. [DOI] [PubMed] [Google Scholar]; c Rogge T.; Oliveira J. C. A.; Kuniyil R.; Hu L.; Ackermann L. Reactivity-Controlling Factors in Carboxylate-Assisted C–H Activation under 4d and 3d Transition Metal Catalysis. ACS Catal. 2020, 10, 10551–10558. 10.1021/acscatal.0c02808. [DOI] [Google Scholar]; d Wang L.; Carrow B. P. Oligothiophene Synthesis by a General C–H Activation Mechanism: Electrophilic Concerted Metalation–Deprotonation (eCMD). ACS Catal. 2019, 9, 6821–6836. 10.1021/acscatal.9b01195. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Alharis R. A.; McMullin C. L.; Davies D. L.; Singh K.; Macgregor S. A. The Importance of Kinetic and Thermodynamic Control when Assessing Mechanisms of Carboxylate-Assisted C–H Activation. J. Am. Chem. Soc. 2019, 141, 8896–8906. 10.1021/jacs.9b02073. [DOI] [PubMed] [Google Scholar]; For computational studies, see the following:; f Yang Y.-F.; She Y. Computational exploration of Pd-catalyzed C–H bond activation reactions. Int. J. Quantum Chem. 2018, 118, e25723 10.1002/qua.25723. [DOI] [Google Scholar]; g Davies D. L.; Macgregor S. A.; McMullin C. L. Computational Studies of Carboxylate-Assisted C–H Activation and Functionalization at Group 8–10 Transition Metal Centers. Chem. Rev. 2017, 117, 8649–8709. 10.1021/acs.chemrev.6b00839. [DOI] [PubMed] [Google Scholar]; h Gorelsky S. I.; Lapointe D.; Fagnou K. Analysis of the Concerted Metalation-Deprotonation Mechanism in Palladium-Catalyzed Direct Arylation Across a Broad Range of Aromatic Substrates. J. Am. Chem. Soc. 2008, 130, 10848–10849. 10.1021/ja802533u. [DOI] [PubMed] [Google Scholar]; i Sajjad M. A.; Schwerdtfeger P.; Edwards P. J. B.; Harrison J. A.; Nielson A. J. Chasing the CMD/AMLA Mechanism C–H···Pd Interactions in the Cyclopalladation Reaction of N,N-Dimethylbenzylamine with Pd(OAc)2. Organometallics 2023, 42, 3343–3356. 10.1021/acs.organomet.3c00208. [DOI] [Google Scholar]
  18. a Hribersek M.; Méndez-Gálvez C.; Huber M.; Gates P. J.; Shakari P.; Samanta A.; Pilarski L. T. Solvent-free and Ball Mill-free Catalytic C–H Methylation. Green Chem. 2023, 25, 9138–9145. 10.1039/D3GC02411C. [DOI] [Google Scholar]; b Ni S.; Hribersek M.; Baddigam S. K.; Ingner F. J. L.; Orthaber A.; Gates P. J.; Pilarski L. T. Mechanochemical Solvent-Free Catalytic C-H Methylation. Angew. Chem., Int. Ed. 2021, 60, 6660–6666. 10.1002/anie.202010202. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Devaraj K.; Ingner F. J. L.; Sollert C.; Gates P. J.; Orthaber A.; Pilarski L. T. Arynes and Their Precursors from Arylboronic Acids via Catalytic C-H Silylation. J. Org. Chem. 2019, 84, 5863–5871. 10.1021/acs.joc.9b00221. [DOI] [PubMed] [Google Scholar]; d Kalepu J.; Gandeepan P.; Ackermann L.; Pilarski L. T. C4–H indole functionalisation: precedent and prospects. Chem. Sci. 2018, 9, 4203–4216. 10.1039/C7SC05336C. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Pilarski L.; Larsson J.; Demory E.; Devaraj K.; Sollert C. Selective Activation of Arylboronate or Aryne Reactivity as a Versatile Postfunctionalization Strategy. Synlett 2016, 27, 969–976. 10.1055/s-0035-1561248. [DOI] [Google Scholar]; f Devaraj K.; Sollert C.; Juds C.; Gates P. J.; Pilarski L. T. Ru-catalysed C-H silylation of unprotected gramines, tryptamines and their congeners. Chem. Commun. 2016, 52, 5868–5871. 10.1039/C6CC00803H. [DOI] [PubMed] [Google Scholar]; g Sollert C.; Devaraj K.; Orthaber A.; Gates P. J.; Pilarski L. T. Ru-catalysed C-H arylation of indoles and pyrroles with boronic acids: scope and mechanistic studies. Chem.—Eur. J. 2015, 21, 5380–5386. 10.1002/chem.201405931. [DOI] [PMC free article] [PubMed] [Google Scholar]; h Demory E.; Devaraj K.; Orthaber A.; Gates P. J.; Pilarski L. T. Boryl (Hetero)aryne Precursors as Versatile Arylation Reagents: Synthesis through C–H Activation and Orthogonal Reactivity. Angew. Chem., Int. Ed. 2015, 54, 11765–11769. 10.1002/anie.201503152. [DOI] [PMC free article] [PubMed] [Google Scholar]; i Sollert C.; Orthaber A.; Pilarski L. T. Crystal structure of aceto-nitrile-[η6–1-methyl-4-(1-methyl-eth-yl)benzene] [1-(pyrimidin-2-yl)-3H-indol-1-ium-2-yl-κ2N,C]ruthenium(II) bis--(hexa-fluorido-anti-monate). Acta Cryst. E 2015, 71, 1190–1192. 10.1107/S2056989015016710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. a Doloczki S.; Holmberg K. O.; Fdez Galván I.; Swartling F. J.; Dyrager C. Photophysical characterization and fluorescence cell imaging applications of 4-N-substituted benzothiadiazoles. RSC Adv. 2022, 12, 14544–14550. 10.1039/d2ra01404a. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Colas K.; Holmberg K. O.; Chiang L.; Doloczki S.; Swartling F. J.; Dyrager C. Indolylbenzothiadiazoles as highly tunable fluorophores for imaging lipid droplet accumulation in astrocytes and glioblastoma cells. RSC Adv. 2021, 11, 23960–23967. 10.1039/D1RA04419B. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Colas K.; Doloczki S.; Kesidou A.; Sainero-Alcolado L.; Rodriguez-Garcia A.; Arsenian-Henriksson M.; Dyrager C. Photophysical Characteristics of Polarity-Sensitive and Lipid Droplet-Specific Phenylbenzothiadiazoles. ChemPhotoChem 2021, 5, 632–643. 10.1002/cptc.202100040. [DOI] [Google Scholar]; d Appelqvist H.; Stranius K.; Börjesson K.; Nilsson K. P. R.; Dyrager C. Specific Imaging of Intracellular Lipid Droplets Using a Benzothiadiazole Derivative with Solvatochromic Properties. Bioconjugate Chem. 2017, 28, 1363–1370. 10.1021/acs.bioconjchem.7b00048. [DOI] [PubMed] [Google Scholar]
  20. a Bisht R.; Haldar C.; Hassan M. M. M.; Hoque M. E.; Chaturvedi J.; Chattopadhyay B. Metal-catalysed C-H bond activation and borylation. Chem. Soc. Rev. 2022, 51, 5042–5100. 10.1039/D1CS01012C. [DOI] [PubMed] [Google Scholar]; b Wright J. S.; Scott P. J. H.; Steel P. G. Iridium-Catalysed C–H Borylation of Heteroarenes: Balancing Steric and Electronic Regiocontrol. Angew. Chem., Int. Ed. 2021, 60, 2796–2821. 10.1002/anie.202001520. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Mkhalid I. A.; Barnard J. H.; Marder T. B.; Murphy J. M.; Hartwig J. F. C-H activation for the construction of C-B bonds. Chem. Rev. 2010, 110, 890–931. 10.1021/cr900206p. [DOI] [PubMed] [Google Scholar]; d Yu I. F.; Wilson J. W.; Hartwig J. F. Transition-Metal-Catalyzed Silylation and Borylation of C–H Bonds for the Synthesis and Functionalization of Complex Molecules. Chem. Rev. 2023, 123, 11619–11663. 10.1021/acs.chemrev.3c00207. [DOI] [PubMed] [Google Scholar]
  21. A small handful of literature reports refers to the use of 3a variously in the syntheses of organic materials:; a Hong J.; Xiao X.; Liu H.; Fu L.; Wang X.-C.; Zhou L.; Wang X.-Y.; Qiu Z.; Cao X.-Y.; Narita A.; Müllen K.; Hu Y. X-shaped thiadiazole-containing double [7]heterohelicene with strong chiroptical response and π-stacked homochiral assembly. Chem. Commun. 2021, 57, 5566–5569. 10.1039/D1CC01631H. [DOI] [PubMed] [Google Scholar]; b Costa C.; Farinhas J.; Velho M. F. G.; Avó J.; Matos M.; Galvão A. M.; Charas A. Band-gap tunable thiadiazolo[3,4-g]quinoxaline derivatives as non-fullerene acceptors in organic photovoltaic cells processed from low toxic ethanol/anisole mixtures. New J. Chem. 2019, 43, 14246–14256. 10.1039/C9NJ02419K. [DOI] [Google Scholar]; For the use of 3a in the synthesis of enzyme inhibitors, see:; c Boutard N.; Białas A.; Sabiniarz A.; Guzik P.; Banaszak K.; Biela A.; Bień M.; Buda A.; Bugaj B.; Cieluch E.; et al. Discovery and Structure–Activity Relationships of N-Aryl 6-Aminoquinoxalines as Potent PFKFB3 Kinase Inhibitors. ChemMedChem 2019, 14, 169–181. 10.1002/cmdc.201800569. [DOI] [PubMed] [Google Scholar]; For the use of 3a as a substrate in a methodology study:; d Haydl A. M.; Hartwig J. F. Palladium-Catalyzed Methylation of Aryl, Heteroaryl, and Vinyl Boronate Esters. Org. Lett. 2019, 21, 1337–1341. 10.1021/acs.orglett.9b00025. [DOI] [PMC free article] [PubMed] [Google Scholar]; The synthesis of 3a has been described only once (via Pd-catalyzed Miyaura borylation of 5-bromo-2,1,3-benzothiadiazole) but the yield of that reaction was based on the corresponding phenol after oxidation (i.e., over two steps without direct characterization of 3a itself):; e Wang X.; Liu W.-G.; Tung C.-H.; Wu L.-Z.; Cong H. A Monophosphine Ligand Derived from Anthracene Photodimer: Synthetic Applications for Palladium-Catalyzed Coupling Reactions. Org. Lett. 2019, 21, 8158–8163. 10.1021/acs.orglett.9b02414. [DOI] [PubMed] [Google Scholar]; The 4-B(pin)-BTD isomer has been generated via Miyaura borylation:; f Anant P.; Lucas N. T.; Jacob J. A Simple Route toward the Synthesis of Bisbenzothiadiazole Derivatives. Org. Lett. 2008, 10, 5533–5536. 10.1021/ol8022837. [DOI] [PubMed] [Google Scholar]
  22. a Takagi J.; Sato K.; Hartwig J. F.; Ishiyama T.; Miyaura N. Iridium-catalyzed C–H coupling reaction of heteroaromatic compounds with bis(pinacolato)diboron: regioselective synthesis of heteroarylboronates. Tetrahedron Lett. 2002, 43, 5649–5651. 10.1016/S0040-4039(02)01135-8. [DOI] [Google Scholar]; b Tajuddin H.; Harrisson P.; Bitterlich B.; Collings J. C.; Sim N.; Batsanov A. S.; Cheung M. S.; Kawamorita S.; Maxwell A. C.; Shukla L.; Morris J.; Lin Z.; Marder T. B.; Steel P. G. Iridium-catalyzed C–H borylation of quinolines and unsymmetrical 1,2-disubstituted benzenes: insights into steric and electronic effects on selectivity. Chem. Sci. 2012, 3, 3505–3515. 10.1039/c2sc20776a. [DOI] [Google Scholar]
  23. a Kawamorita S.; Ohmiya H.; Hara K.; Fukuoka A.; Sawamura M. Directed Ortho Borylation of Functionalized Arenes Catalyzed by a Silica-Supported Compact Phosphine–Iridium System. J. Am. Chem. Soc. 2009, 131, 5058–5059. 10.1021/ja9008419. [DOI] [PubMed] [Google Scholar]; b Kawamorita S.; Ohmiya H.; Sawamura M. Ester-Directed Regioselective Borylation of Heteroarenes Catalyzed by a Silica-Supported Iridium Complex. J. Org. Chem. 2010, 75, 3855–3858. 10.1021/jo100352b. [DOI] [PubMed] [Google Scholar]; c Konishi S.; Kawamorita S.; Iwai T.; Steel P. G.; Marder T. B.; Sawamura M. Site-Selective C–H Borylation of Quinolines at the C8 Position Catalyzed by a Silica-Supported Phosphane–Iridium System. Chem. Asian. J. 2014, 9, 434–438. 10.1002/asia.201301423. [DOI] [PubMed] [Google Scholar]
  24. For selected general reviews and discussions of the properties of organoboronate reagents, see:; a Lennox A. J. J.; Lloyd-Jones G. C. Selection of boron reagents for Suzuki–Miyaura coupling. Chem. Soc. Rev. 2014, 43, 412–443. 10.1039/C3CS60197H. [DOI] [PubMed] [Google Scholar]; b Berionni G.; Leonov A. I.; Mayer P.; Ofial A. R.; Mayr H. Fine-tuning the nucleophilic reactivities of boron ate complexes derived from aryl and heteroaryl boronic esters. Angew. Chem., Int. Ed. 2015, 54, 2780–2783. 10.1002/anie.201410562. [DOI] [PubMed] [Google Scholar]; c Berionni G.; Maji B.; Knochel P.; Mayr H. Nucleophilicity parameters for designing transition metal-free C–C bond forming reactions of organoboron compounds. Chem. Sci. 2012, 3, 878–882. 10.1039/C2SC00883A. [DOI] [Google Scholar]; d Xu L.; Ding S.; Li P. Site-Differentiated Polyboron Arenes Prepared by Direct C–H Borylation and Their Highly Selective Suzuki–Miyaura Cross-Coupling Reactions. Angew. Chem., Int. Ed. 2014, 53, 1822–1826. 10.1002/anie.201309546. [DOI] [PubMed] [Google Scholar]; e Xu L.; Zhang S.; Li P. Boron-selective reactions as powerful tools for modular synthesis of diverse complex molecules. Chem. Soc. Rev. 2015, 44, 8848–8858. 10.1039/C5CS00338E. [DOI] [PubMed] [Google Scholar]; For reviews of organotrifluoroborate salts, see:; f Volochnyuk D. M.; Gorlova A. O.; Grygorenko O. O. Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry. Chem.—Eur. J. 2021, 27, 15276. 10.1002/chem.202103751. [DOI] [PubMed] [Google Scholar]; g Molander G. A.; Ellis N. Organotrifluoroborates: Protected Boronic Acids That Expand the Versatility of the Suzuki Coupling Reaction. Acc. Chem. Res. 2007, 40, 275–286. 10.1021/ar050199q. [DOI] [PubMed] [Google Scholar]; h Darses S.; Genet J.-P. Potassium Organotrifluoroborates: New Perspectives in Organic Synthesis. Chem. Rev. 2008, 108, 288–325. 10.1021/cr0509758. [DOI] [PubMed] [Google Scholar]; For reviews of B(MIDA) organoboronates, see:; i Aich D.; Kumar P.; Ghorai D.; Kanti Das K.; Panda S. Recent advances in the synthesis and reactivity of MIDA boronates. Chem. Commun. 2022, 58, 13298–13316. 10.1039/D2CC04893K. [DOI] [PubMed] [Google Scholar]; j Gillis E. P.; Burke M. D. Iterative Cross-Couplng with MIDA Boronates: Towards a General Platform for Small Molecule Synthesis. Aldrichimica Acta 2009, 42, 17–27. [PMC free article] [PubMed] [Google Scholar]; k Lehmann J. W.; Blair D. J.; Burke M. D. Towards the generalized iterative synthesis of small molecules. Nat. Rev. Chem 2018, 2, 0115. 10.1038/s41570-018-0115. [DOI] [PMC free article] [PubMed] [Google Scholar]; For innovations on closely related boronates, see:; l Oka N.; Yamada T.; Sajiki H.; Akai S.; Ikawa T. Aryl Boronic Esters Are Stable on Silica Gel and Reactive under Suzuki–Miyaura Coupling Conditions. Org. Lett. 2022, 24, 3510–3514. 10.1021/acs.orglett.2c01174. [DOI] [PubMed] [Google Scholar]; m Noguchi H.; Hojo K.; Suginome M. Boron-Masking Strategy for the Selective Synthesis of Oligoarenes via Iterative Suzuki–Miyaura Coupling. J. Am. Chem. Soc. 2007, 129, 758–759. 10.1021/ja067975p. [DOI] [PubMed] [Google Scholar]; n Yamamoto T.; Ishibashi A.; Suginome M. Regioselective Synthesis of o-Benzenediboronic Acids via Ir-Catalyzed o-C–H Borylation Directed by a Pyrazolylaniline-Modified Boronyl Group. Org. Lett. 2017, 19, 886–889. 10.1021/acs.orglett.7b00041. [DOI] [PubMed] [Google Scholar]; o Koyanagi M.; Eichenauer N.; Ihara H.; Yamamoto T.; Suginome M. Anthranilamide-masked o-Iodoarylboronic Acids as Coupling Modules for Iterative Synthesis of ortho-Linked Oligoarenes. Chem. Lett. 2013, 42, 541–543. 10.1246/cl.130136. [DOI] [Google Scholar]; p Ihara H.; Koyanagi M.; Suginome M. Anthranilamide: A Simple, Removable ortho-Directing Modifier for Arylboronic Acids Serving also as a Protecting Group in Cross-Coupling Reactions. Org. Lett. 2011, 13, 2662–2665. 10.1021/ol200764g. [DOI] [PubMed] [Google Scholar]; q Ihara H.; Suginome M. Easily Attachable and Detachable ortho-Directing Agent for Arylboronic Acids in Ruthenium-Catalyzed Aromatic C–H Silylation. J. Am. Chem. Soc. 2009, 131, 7502–7503. 10.1021/ja902314v. [DOI] [PubMed] [Google Scholar]; r Williams A. F.; White A. J. P.; Spivey A. C.; Cordier C. J. meta-Selective C–H functionalisation of aryl boronic acids directed by a MIDA-derived boronate ester. Chem. Sci. 2020, 11, 3301–3306. 10.1039/D0SC00230E. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sun J.; Perfetti M. T.; Santos W. L. A Method for the Deprotection of Alkylpinacolyl Boronate Esters. J. Org. Chem. 2011, 76, 3571–3575. 10.1021/jo200250y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lennox A. J. J.; Lloyd-Jones G. C. Preparation of Organotrifluoroborate Salts: Precipitation-Driven Equilibrium under Non-Etching Conditions. Angew. Chem., Int. Ed. 2012, 51, 9385–9388. 10.1002/anie.201203930. [DOI] [PubMed] [Google Scholar]
  27. Knapp D. M.; Gillis E. P.; Burke M. D. A General Solution for Unstable Boronic Acids: Slow-Release Cross-Coupling from Air-Stable MIDA Boronates. J. Am. Chem. Soc. 2009, 131, 6961–6963. 10.1021/ja901416p. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. a Lehmann J. W.; Blair D. J.; Burke M. D. Towards the generalized iterative synthesis of small molecules. Nat. Rev. Chem 2018, 2, 0115. 10.1038/s41570-018-0115. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Gillis E. P.; Burke M. D. Multistep Synthesis of Complex Boronic Acids from Simple MIDA Boronates. J. Am. Chem. Soc. 2008, 130, 14084–14085. 10.1021/ja8063759. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Woerly E. M.; Roy J.; Burke M. D. Synthesis of most polyene natural product motifs using just 12 building blocks and one coupling reaction. Nat. Chem. 2014, 6, 484–491. 10.1038/nchem.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Li J.; Ballmer S. G.; Gillis E. P.; Fujii S.; Schmidt M. J.; Palazzolo A. M. E.; Lehmann J. W.; Morehouse G. F.; Burke M. D. Synthesis of many different types of organic small molecules using one automated process. Science 2015, 347, 1221–1226. 10.1126/science.aaa5414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. For a mechanistic analysis of B(MIDA) hydrolysis see:Gonzalez J. A.; Ogba O. M.; Morehouse G. F.; Rosson N.; Houk K. N.; Leach A. G.; Cheong P. H. Y.; Burke M. D.; Lloyd-Jones G. C. MIDA boronates are hydrolysed fast and slow by two different mechanisms. Nat. Chem. 2016, 8, 1067–1075. 10.1038/nchem.2571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. For a recent review, see:; a Pagett A. B.; Lloyd-Jones G. C.. Suzuki–Miyaura Cross-Coupling. Organic Reactions; John Wiley & Sons, 2019; pp 547–620. For an example of the use of brominated BTD as a building block in Suzuki-Miyaura couplings, see: [Google Scholar]; b Heiskanen J. P.; Vivo P.; Saari N. M.; Hukka T. I.; Kastinen T.; Kaunisto K.; Lemmetyinen H. J.; Hormi O. E. O. Synthesis of Benzothiadiazole Derivatives by Applying C–C Cross-Couplings. J. Org. Chem. 2016, 81, 1535–1546. 10.1021/acs.joc.5b02689. [DOI] [PubMed] [Google Scholar]
  32. For examples accessed via Suzuki-Miyaura coupling see ref (2d) and the following:; a McLay J. R. W.; Sutton J. J.; Shillito G. E.; Larsen C. B.; Huff G. S.; Lucas N. T.; Gordon K. C. Transitioning from Intraligand π,π* to Charge-Transfer Excited States Using Thiophene-Based Donor–Acceptor Systems. Inorg. Chem. 2021, 60, 130–139. 10.1021/acs.inorgchem.0c02555. [DOI] [PubMed] [Google Scholar]; b Toscani A.; Marín-Hernández C.; Robson J. A.; Chua E.; Dingwall P.; White A. J. P.; Sancenón F.; de la Torre C.; Martínez-Máñez R.; Wilton-Ely J. D. E. T. Highly Sensitive and Selective Molecular Probes for Chromo-Fluorogenic Sensing of Carbon Monoxide in Air, Aqueous Solution and Cells. Chem.—Eur. J. 2019, 25, 2069–2081. 10.1002/chem.201805244. [DOI] [PubMed] [Google Scholar]; c Curreli F.; Belov D. S.; Ahmed S.; Ramesh R. R.; Kurkin A. V.; Altieri A.; Debnath A. K. Synthesis, Antiviral Activity, and Structure–Activity Relationship of 1,3-Benzodioxolyl Pyrrole-Based Entry Inhibitors Targeting the Phe43 Cavity in HIV-1 gp120. ChemMedChem 2018, 13, 2332–2348. 10.1002/cmdc.201800534. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Gribanov P. S.; Vorobyeva D. V.; Tokarev S. D.; Loginov D. A.; Danshina A. A.; Masoud S. M.; Osipov S. N. Rhodium(III)-catalyzed Construction of D-A Type Polyheteroaromatics with Fluorinated Benzothiadiazole as a Modifiable Acceptor Block. Asian J. Org. Chem. 2022, 11, e202200603 10.1002/ajoc.202200603. [DOI] [Google Scholar]; For examples of Stille coupling, see:; e Mosleh I.; Shahsavari H. R.; Beitle R.; Beyzavi M. H. Recombinant Peptide Fusion Protein-Templated Palladium Nanoparticles for Suzuki-Miyaura and Stille Coupling Reactions. ChemCatChem 2020, 12, 2942–2946. 10.1002/cctc.201902099. [DOI] [Google Scholar]; For examples of Sonogashira coupling, see:; f Barnsley J. E.; Shillito G. E.; Mapley J. I.; Larsen C. B.; Lucas N. T.; Gordon K. C. Walking the Emission Tightrope: Spectral and Computational Analysis of Some Dual-Emitting Benzothiadiazole Donor–Acceptor Dyes. J. Phys. Chem. A 2018, 122, 7991–8006. 10.1021/acs.jpca.8b05361. [DOI] [PubMed] [Google Scholar]
  33. Partridge B. M.; Hartwig J. F. Sterically Controlled Iodination of Arenes via Iridium-Catalyzed C–H Borylation. Org. Lett. 2013, 15, 140–143. 10.1021/ol303164h. [DOI] [PubMed] [Google Scholar]
  34. Murphy J. M.; Liao X.; Hartwig J. F. Meta Halogenation of 1,3-Disubstituted Arenes via Iridium-Catalyzed Arene Borylation. J. Am. Chem. Soc. 2007, 129, 15434–15435. 10.1021/ja076498n. [DOI] [PubMed] [Google Scholar]
  35. Selected reviews of aryl iodonium reagents:; a Takenaga N.; Kumar R.; Dohi T. Heteroaryliodonium(III) Salts as Highly Reactive Electrophiles. Front. Chem. 2020, 8, 599026. 10.3389/fchem.2020.599026. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Kaur M.; Kumar R. A Minireview on the Scope of Cadogan Cyclization Reactions Leading to Diverse Azaheterocycles. Asian J. Org. Chem. 2022, 11, e202200092 10.1002/ajoc.202200092. [DOI] [Google Scholar]; c Merritt E. A.; Olofsson B. Diaryliodonium Salts: A Journey from Obscurity to Fame. Angew. Chem., Int. Ed. 2009, 48, 9052–9070. 10.1002/anie.200904689. [DOI] [PubMed] [Google Scholar]
  36. a Darzi E. R.; White B. M.; Loventhal L. K.; Zakharov L. N.; Jasti R. An Operationally Simple and Mild Oxidative Homocoupling of Aryl Boronic Esters To Access Conformationally Constrained Macrocycles. J. Am. Chem. Soc. 2017, 139, 3106–3114. 10.1021/jacs.6b12658. [DOI] [PubMed] [Google Scholar]; b Kopp J.; Brückner R. Stereoselective Total Synthesis of the Dimeric Naphthoquinonopyrano-γ-lactone (−)-Crisamicin A: Introducing the Dimerization Site by a Late-Stage Hartwig Borylation. Org. Lett. 2020, 22, 3607–3612. 10.1021/acs.orglett.0c01078. [DOI] [PubMed] [Google Scholar]
  37. Yan S.; Fu H.; Dong Y.; Li W.; Dai Y.; Zhang C. Synthesis, electrochemistry and electrochromic properties of donor-acceptor conjugated polymers based on swivel-cruciform monomers with different central cores. Electrochim. Acta 2020, 354, 136672. 10.1016/j.electacta.2020.136672. [DOI] [Google Scholar]
  38. Huang H.; Yu C.; Li X.; Zhang Y.; Zhang Y.; Chen X.; Mariano P. S.; Xie H.; Wang W. Synthesis of Aldehydes by Organocatalytic Formylation Reactions of Boronic Acids with Glyoxylic Acid. Angew. Chem., Int. Ed. 2017, 56, 8201–8205. 10.1002/anie.201703127. [DOI] [PubMed] [Google Scholar]
  39. For a 4,5,6-tricyanation via SNAr of the corresponding fluoro-BTD fragment of an n-type semiconductor, see ref (9c).
  40. Nykaza T. V.; Cooper J. C.; Li G.; Mahieu N.; Ramirez A.; Luzung M. R.; Radosevich A. T. Intermolecular Reductive C–N Cross Coupling of Nitroarenes and Boronic Acids by PIII/PV=O Catalysis. J. Am. Chem. Soc. 2018, 140, 15200–15205. 10.1021/jacs.8b10769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Review:; a Chen J.-Q.; Li J.-H.; Dong Z.-B. A Review on the Latest Progress of Chan-Lam Coupling Reaction. Adv. Synth. Catal. 2020, 362, 3311–3331. 10.1002/adsc.202000495. [DOI] [Google Scholar]; For Chan-Lam reactions of organo-B(pin) substrates specifically, see:; b Vantourout J. C.; Miras H. N.; Isidro-Llobet A.; Sproules S.; Watson A. J. B. Spectroscopic Studies of the Chan–Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity. J. Am. Chem. Soc. 2017, 139, 4769–4779. 10.1021/jacs.6b12800. [DOI] [PubMed] [Google Scholar]; c Vantourout J. C.; Law R. P.; Isidro-Llobet A.; Atkinson S. J.; Watson A. J. B. Chan–Evans–Lam Amination of Boronic Acid Pinacol (BPin) Esters: Overcoming the Aryl Amine Problem. J. Org. Chem. 2016, 81, 3942–3950. 10.1021/acs.joc.6b00466. [DOI] [PubMed] [Google Scholar]
  42. For examples of Buchwald-Hartwig aminations on the BTD core, see ref (32f) and the following:; a Ma Y.-P.; Wang G.; Zhao M.; Shi Z.-F.; Miao Y.; Cao X.-P.; Zhang H.-L. A red thermally activated delayed fluorescence emitter based on benzo[c] [1,2,5]thiadiazole. Dyes Pigm. 2023, 212, 111084. 10.1016/j.dyepig.2023.111084. [DOI] [Google Scholar]; b Wang Z.; Wang Z.; Lu P.; Wang Y. Preparation and Photoluminescent Properties of Three 5-Amino Benzothiadiazoles (5-amBTDs). Chem. Asian. J. 2020, 15, 3519–3526. 10.1002/asia.202000980. [DOI] [PubMed] [Google Scholar]; c Ruiz-Castillo P.; Blackmond D. G.; Buchwald S. L. Rational Ligand Design for the Arylation of Hindered Primary Amines Guided by Reaction Progress Kinetic Analysis. J. Am. Chem. Soc. 2015, 137, 3085–3092. 10.1021/ja512903g. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Tapu D.; Buckner O. J.; Boudreaux C. M.; Norvell B.; Vasiliu M.; Dixon D. A.; McMillen C. D. A benzothiadiazole-supported N-heterocyclic carbene and its rhodium and iridium complexes. J. Organomet. Chem. 2016, 823, 40–49. 10.1016/j.jorganchem.2016.09.016. [DOI] [Google Scholar]; For a Buchwald-Hartwig amination incorporated into a C–H/C–N dual functionalization, see:; e Kamimoto N.; Schollmeyer D.; Mitsudo K.; Suga S.; Waldvogel S. R. Palladium-Catalyzed Domino C–H/N–H Functionalization: An Efficient Approach to Nitrogen-Bridged Heteroacenes. Chem.—Eur. J. 2015, 21, 8257–8261. 10.1002/chem.201500897. [DOI] [PubMed] [Google Scholar]; For a single example of generating a carbamate at from 5-Br-BTD, see:; f Vinogradova E. V.; Park N. H.; Fors B. P.; Buchwald S. L. Palladium-Catalyzed Synthesis of N-Aryl Carbamates. Org. Lett. 2013, 15, 1394–1397. 10.1021/ol400369n. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Aminations of the BTD backbone are possible via SNAr of fluoro-BTDs see ref (32d) and the following:; a Prima D. O.; Makarov A. G.; Bagryanskaya I. Y.; Kolesnikov A. E.; Zargarova L. V.; Baev D. S.; Eliseeva T. F.; Politanskaya L. V.; Makarov A. Y.; Slizhov Y. G.; Zibarev A. V. Fluorine-Containing n-6 and Angular and Linear n-6-n’ (n, n’ = 5, 6, 7) Diaza-Heterocyclic Scaffolds Assembled on Benzene Core in Unified Way. ChemistrySelect 2019, 4, 2383–2386. 10.1002/slct.201803970. [DOI] [Google Scholar]; b Shi H.; Zou L.; Huang K.; Wang H.; Sun C.; Wang S.; Ma H.; He Y.; Wang J.; Yu H.; Yao W.; An Z.; Zhao Q.; Huang W. A Highly Efficient Red Metal-free Organic Phosphor for Time-Resolved Luminescence Imaging and Photodynamic Therapy. ACS Appl. Mater. Interfaces 2019, 11, 18103–18110. 10.1021/acsami.9b01615. [DOI] [PubMed] [Google Scholar]; c Si C.; Hu Y.-N.; Sun D.; Wang K.; Zhang X.-H.; Zysman-Colman E. The influence of nitrogen doping of the acceptor in orange-red thermally activated delayed fluorescence emitters and OLEDs. J. Mater. Chem. C 2023, 11, 12174–12184. 10.1039/D3TC02352D. [DOI] [Google Scholar]; For rare examples of C–O and C–S bond forming SNAr reactions, see:; d Creamer A.; Casey A.; Marsh A. V.; Shahid M.; Gao M.; Heeney M. Systematic Tuning of 2,1,3-Benzothiadiazole Acceptor Strength by Monofunctionalization with Alkylamine, Thioalkyl, or Alkoxy Groups in Carbazole Donor–Acceptor Polymers. Macromolecules 2017, 50, 2736–2746. 10.1021/acs.macromol.7b00235. [DOI] [Google Scholar]
  44. a Sathiyan G.; Sivakumar E. K. T.; Ganesamoorthy R.; Thangamuthu R.; Sakthivel P. Review of carbazole based conjugated molecules for highly efficient organic solar cell application. Tetrahedron Lett. 2016, 57, 243–252. 10.1016/j.tetlet.2015.12.057. [DOI] [Google Scholar]; For reviews of bioactive carbazoles, see:; b Tsutsumi L. S.; Gündisch D.; Sun D. Carbazole Scaffold in Medicinal Chemistry and Natural Products: A Review from 2010–2015. Curr. Top. Med. Chem. 2016, 16, 1290–1313. 10.2174/1568026615666150915112647. [DOI] [PubMed] [Google Scholar]; c Schmidt A. W.; Reddy K. R.; Knölker H. J. Occurrence, Biogenesis, and Synthesis of Biologically Active Carbazole Alkaloids. Chem. Rev. 2012, 112, 3193–3328. 10.1021/cr200447s. [DOI] [PubMed] [Google Scholar]
  45. a Choi T. J.Preparation of benzo[c][1,2,5]thiadiazoles for organic electroluminescent devices. KR 2018071882, 2018.; b Hyun S. Y.; Yoon Y. H.; Song J. H.. Aromatic compound as electroluminescent material and/or organic electron transport material for organic electroluminescent device. KR 2013113913, 2013.
  46. Campeau L.-C.; Parisien M.; Jean A.; Fagnou K. Catalytic Direct Arylation with Aryl Chlorides, Bromides, and Iodides: Intramolecular Studies Leading to New Intermolecular Reactions. J. Am. Chem. Soc. 2006, 128, 581–590. 10.1021/ja055819x. [DOI] [PubMed] [Google Scholar]
  47. Kaur M.; Kumar R. C.-N. C-N and N-N bond formation via Reductive Cyclization: Progress in Cadogan/Cadogan-Sundberg Reaction. ChemistrySelect 2018, 3, 5330–5340. 10.1002/slct.201800779. [DOI] [Google Scholar]
  48. Suzuki C.; Hirano K.; Satoh T.; Miura M. Direct synthesis of N-H carbazoles via iridium(III)-catalyzed intramolecular C-H amination. Org. Lett. 2015, 17, 1597–1600. 10.1021/acs.orglett.5b00502. [DOI] [PubMed] [Google Scholar]
  49. Review:; a Yang Y.; Lan J.; You J. Oxidative C–H/C–H Coupling Reactions between Two (Hetero)arenes. Chem. Rev. 2017, 117, 8787–8863. 10.1021/acs.chemrev.6b00567. [DOI] [PubMed] [Google Scholar]; Selected original papers:; b Qin X.; Liu H.; Qin D.; Wu Q.; You J.; Zhao D.; Guo Q.; Huang X.; Lan J. Chelation-assisted Rh(iii)-catalyzed C2-selective oxidative C–H/C–H cross-coupling of indoles/pyrroles with heteroarenes. Chem. Sci. 2013, 4, 1964–1969. 10.1039/c3sc22241a. [DOI] [Google Scholar]; c Dong J.; Long Z.; Song F.; Wu N.; Guo Q.; Lan J.; You J. Rhodium or Ruthenium-Catalyzed Oxidative C–H/C–H Cross-Coupling: Direct Access to Extended π-Conjugated Systems. Angew. Chem., Int. Ed. 2013, 52, 580–584. 10.1002/anie.201207196. [DOI] [PubMed] [Google Scholar]
  50. a Chen Z.; Zhang F. Recent progress on Catellani reaction. Tetrahedron 2023, 134, 133307. 10.1016/j.tet.2023.133307. [DOI] [Google Scholar]; b Wang J.; Dong G. Palladium/Norbornene Cooperative Catalysis. Chem. Rev. 2019, 119, 7478–7528. 10.1021/acs.chemrev.9b00079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Lombeck F.; Di D.; Yang L.; Meraldi L.; Athanasopoulos S.; Credgington D.; Sommer M.; Friend R. H. PCDTBT: From Polymer Photovoltaics to Light-Emitting Diodes by Side-Chain-Controlled Luminescence. Macromolecules 2016, 49, 9382–9387. 10.1021/acs.macromol.6b02216. [DOI] [Google Scholar]
  52. Akkuratov A. V.; Susarova D. K.; Moskvin Y. L.; Anokhin D. V.; Chernyak A. V.; Prudnov F. A.; Novikov D. V.; Babenko S. D.; Troshin P. A. A strong influence of the positions of solubilizing alkyl side chains on optoelectronic and photovoltaic properties of TTBTBTT-based conjugated polymers. J. Mater. Chem. C 2015, 3, 1497–1506. 10.1039/C4TC02432J. [DOI] [Google Scholar]
  53. Shaoming F.; Jigong S.; Guohao W.; Likun X.; Yonghui Z.; Junping D. 4,6–2,1,3-Benzothiadiazole: A New Block to Construct Polymer Optoelectrical Functional Materials and Multiple Performance Regulator. Chinese J. Org. Chem. 2015, 35, 1565–1569. 10.6023/cjoc201501033. [DOI] [Google Scholar]
  54. a Modern Aryne Chemistry; Biju A.; Wiley VCH, 2021. [Google Scholar]; b Wu C.; Shi F. A Closer Look at Aryne Chemistry: Details that Remain Mysterious. Asian J. Org. Chem. 2013, 2, 116–125. 10.1002/ajoc.201200142. [DOI] [Google Scholar]; c Wenk H. H.; Winkler M.; Sander W. One Century of Aryne Chemistry. Angew. Chem., Int. Ed. 2003, 42, 502–528. 10.1002/anie.200390151. [DOI] [PubMed] [Google Scholar]; d Yoshida S.; Hosoya T. The Renaissance and Bright Future of Synthetic Aryne Chemistry. Chem. Lett. 2015, 44, 1450–1460. 10.1246/cl.150839. [DOI] [Google Scholar]
  55. a Krishna R. B.; Moncy S. H.; Mohan C. Arynes as synthetic linchpins towards the construction of diversely functionalized natural product skeletons. Org. Biomol. Chem. 2023, 21, 479–488. 10.1039/D2OB01975B. [DOI] [PubMed] [Google Scholar]; b Tadross P. M.; Stoltz B. M. A comprehensive history of arynes in natural product total synthesis. Chem. Rev. 2012, 112, 3550–3577. 10.1021/cr200478h. [DOI] [PubMed] [Google Scholar]; c Gampe C. M.; Carreira E. M. Arynes and Cyclohexyne in Natural Product Synthesis. Angew. Chem., Int. Ed. 2012, 51, 3766–3778. 10.1002/anie.201107485. [DOI] [PubMed] [Google Scholar]
  56. a Garcia-Lopez J.-A.; Greaney M. F. Synthesis of biaryls using aryne intermediates. Chem. Soc. Rev. 2016, 45, 6766–6798. 10.1039/C6CS00220J. [DOI] [PubMed] [Google Scholar]; b Yoshimura T.; Onda K.-i.; Matsuo J.-i. Asymmetric Cycloaddition Reactions of Aryne Intermediates with a Chiral Carbon–Carbon Axis: Syntheses of Axially Chiral Biaryl Compounds. Org. Lett. 2023, 25, 8952–8956. 10.1021/acs.orglett.3c03983. [DOI] [PubMed] [Google Scholar]
  57. a Pozo I.; Guitián E.; Pérez D.; Peña D. Synthesis of Nanographenes, Starphenes, and Sterically Congested Polyarenes by Aryne Cyclotrimerization. Acc. Chem. Res. 2019, 52, 2472–2481. 10.1021/acs.accounts.9b00269. [DOI] [PubMed] [Google Scholar]; b Takikawa H.; Nishii A.; Sakai T.; Suzuki K. Aryne-based strategy in the total synthesis of naturally occurring polycyclic compounds. Chem. Soc. Rev. 2018, 47, 8030–8056. 10.1039/C8CS00350E. [DOI] [PubMed] [Google Scholar]; c Pérez D.; Peña D.; Guitián E. Aryne Cycloaddition Reactions in the Synthesis of Large Polycyclic Aromatic Compounds. Eur. J. Org Chem. 2013, 2013, 5981–6013. 10.1002/ejoc.201300470. [DOI] [Google Scholar]
  58. a Kamikawa K. Asymmetric reactions involving aryne intermediates. Nat. Rev. Chem 2023, 7, 496–510. 10.1038/s41570-023-00485-y. [DOI] [PubMed] [Google Scholar]; b Roy T.; Biju A. T. Recent advances in molecular rearrangements involving aryne intermediates. Chem. Commun. 2018, 54, 2580–2594. 10.1039/C7CC09122B. [DOI] [PubMed] [Google Scholar]; c Mhaske S.; Dhokale R. Transition-Metal-Catalyzed Reactions Involving Arynes. Synthesis 2018, 50, 1–16. 10.1055/s-0036-1589517. [DOI] [Google Scholar]; d Shi J.; Li Y.; Li Y. Aryne multifunctionalization with benzdiyne and benztriyne equivalents. Chem. Soc. Rev. 2017, 46, 1707–1719. 10.1039/C6CS00694A. [DOI] [PubMed] [Google Scholar]; e Asamdi M.; Chikhalia K. H. Aryne Insertion into σ Bonds. Asian J. Org. Chem. 2017, 6, 1331–1348. 10.1002/ajoc.201700284. [DOI] [Google Scholar]; f Bhunia A.; Yetra S. R.; Biju A. T. Recent advances in transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions using arynes. Chem. Soc. Rev. 2012, 41, 3140–3152. 10.1039/c2cs15310f. [DOI] [PubMed] [Google Scholar]
  59. For selected reviews, see:; a Shi J.; Li L.; Li Y. o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors. Chem. Rev. 2021, 121, 3892–4044. 10.1021/acs.chemrev.0c01011. [DOI] [PubMed] [Google Scholar]; b Yoshimura A.; Saito A.; Zhdankin V. V. Iodonium Salts as Benzyne Precursors. Chem.—Eur. J. 2018, 24, 15156–15166. 10.1002/chem.201802111. [DOI] [PubMed] [Google Scholar]; c Holden née Hall C.; Greaney M. F. The Hexadehydro-Diels–Alder Reaction: A New Chapter in Aryne Chemistry. Angew. Chem., Int. Ed. 2014, 53, 5746–5749. 10.1002/anie.201402405. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Roberts R. A.; Metze B. E.; Nilova A.; Stuart D. R. Synthesis of Arynes via Formal Dehydrogenation of Arenes. J. Am. Chem. Soc. 2023, 145, 3306–3311. 10.1021/jacs.2c13007. [DOI] [PubMed] [Google Scholar]; e Metze B.; Roberts R. A.; Nilova A.; Stuart D. R. An efficient and chemoselective method to generate arynes. Chem. Sci. 2023, 14, 13885–13892. 10.1039/d3sc05429b. [DOI] [PMC free article] [PubMed] [Google Scholar]; f Smith O.; Hindson M. J.; Sreenithya A.; Tataru V.; Paton R. S.; Burton J. W.; Smith M. D. Harnessing triaryloxonium ions for aryne generation. Nat. Synth. 2023, 3, 58–66. 10.1038/s44160-023-00408-1. [DOI] [Google Scholar]; g Dong Y.; Lipschutz M. I.; Tilley T. D. Regioselective, Transition Metal-Free C–O Coupling Reactions Involving Aryne Intermediates. Org. Lett. 2016, 18, 1530–1533. 10.1021/acs.orglett.6b00183. [DOI] [PubMed] [Google Scholar]
  60. a Nilova A.; Sibbald P. A.; Valente E. J.; González-Montiel G. A.; Richardson H. C.; Brown K. S.; Cheong P. H.-Y.; Stuart D. R. Regioselective Synthesis of 1,2,3,4-Tetrasubstituted Arenes by Vicinal Functionalization of Arynes Derived from Aryl(Mes)iodonium Salts. Chem.—Eur. J. 2021, 27, 7168–7175. 10.1002/chem.202100201. [DOI] [PubMed] [Google Scholar]; b Yoshimura A.; Fuchs J. M.; Middleton K. R.; Maskaev A. V.; Rohde G. T.; Saito A.; Postnikov P. S.; Yusubov M. S.; Nemykin V. N.; Zhdankin V. V. Pseudocyclic Arylbenziodoxaboroles: Efficient Benzyne Precursors Triggered by Water at Room Temperature. Chem.—Eur. J. 2017, 23, 16738–16742. 10.1002/chem.201704393. [DOI] [PubMed] [Google Scholar]
  61. a Medina J. M.; Mackey J. L.; Garg N. K.; Houk K. N. The Role of Aryne Distortions, Steric Effects, and Charges in Regioselectivities of Aryne Reactions. J. Am. Chem. Soc. 2014, 136, 15798–15805. 10.1021/ja5099935. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Goetz A. E.; Garg N. K. Regioselective reactions of 3,4-pyridynes enabled by the aryne distortion model. Nat. Chem. 2013, 5, 54–60. 10.1038/nchem.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Bronner S. M.; Mackey J. L.; Houk K. N.; Garg N. K. Steric Effects Compete with Aryne Distortion To Control Regioselectivities of Nucleophilic Additions to 3-Silylarynes. J. Am. Chem. Soc. 2012, 134, 13966–13969. 10.1021/ja306723r. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Goetz A. E.; Bronner S. M.; Cisneros J. D.; Melamed J. M.; Paton R. S.; Houk K. N.; Garg N. K. An Efficient Computational Model to Predict the Synthetic Utility of Heterocyclic Arynes. Angew. Chem., Int. Ed. 2012, 51, 2758–2762. 10.1002/anie.201108863. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Garg N.; Bronner S.; Goetz A. Understanding and Modulating Indolyne Regioselectivities. Synlett 2011, 2011, 2599–2604. 10.1055/s-0031-1289561. [DOI] [Google Scholar]; f Im G. Y. J.; Bronner S. M.; Goetz A. E.; Paton R. S.; Cheong P. H. Y.; Houk K. N.; Garg N. K. Indolyne Experimental and Computational Studies: Synthetic Applications and Origins of Selectivities of Nucleophilic Additions. J. Am. Chem. Soc. 2010, 132, 17933–17944. 10.1021/ja1086485. [DOI] [PMC free article] [PubMed] [Google Scholar]; g Cheong P. H. Y.; Paton R. S.; Bronner S. M.; Im G.-Y. J.; Garg N. K.; Houk K. N. Indolyne and Aryne Distortions and Nucleophilic Regioselectivites. J. Am. Chem. Soc. 2010, 132, 1267–1269. 10.1021/ja9098643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Picazo E.; Houk K. N.; Garg N. K. Computational predictions of substituted benzyne and indolyne regioselectivities. Tetrahedron Lett. 2015, 56, 3511–3514. 10.1016/j.tetlet.2015.01.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. In accordance with Bent’s RuleBent H. A. An Appraisal of Valence-bond Structures and Hybridization in Compounds of the First-row elements. Chem. Rev. 1961, 61, 275–311. 10.1021/cr60211a005. [DOI] [Google Scholar]
  64. For a discussion of how the auxiliary group might affect regioselectivity see:Stuart D. R. Unsymmetrical Diaryliodonium Salts as Aryne Synthons: Renaissance of a C–H Deprotonative Approach to Arynes. Synlett 2016, 28, 275–279. 10.1055/s-0036-1588683. [DOI] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

jo4c00122_si_001.pdf (6.7MB, pdf)

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Articles from The Journal of Organic Chemistry are provided here courtesy of American Chemical Society

RESOURCES