Straightforward convergent access to 2-arylated polysubstituted benzothiazoles

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Introduction
The benzothiazole core is considered a privileged fused bicyclic heterocycle in light of its applications in pharmaceutical, agrochemical, and materials chemistry. [1][2][3] This has driven the development of increasingly efficient methodologies towards the synthesis of functionalised 2-arylated benzothiazole scaffolds. [4][5][6] More recently, these scaffolds have found applications in organocatalyzed (de)hydrosilylation reactions where they function as carbon-centred Lewis acids in the activation of Si-H  bonds. [7] Substituted 2 benzothiazoles are also involved in important applications in organic light-emitting devices (OLEDs). [8][9][10] Similar to other benzazoles, [11][12][13][14] they quite commonly exhibit interesting photochemical properties including processes such as Excited State Intramolecular Proton Transfer (ESIPT). [15,16] These molecules have also been intensively studied for their dual action potential as metal chelators and as intercalating compounds targeting pathological peptidic aggregates that of interest for imaging various dementias e.g. Alzheimer's Disease. [17,18]

Figure 1: Benzothiazole scaffolds integrated into various applications
Considering that the nitrogen atom of the benzothiazole is key in all the applications mentioned and illustrated above, we focused our attention on modulating its environment by introducing substituents on position 2 and 4 of the benzothiazole core in a convergent fashion. Although numerous strategies have been designed to access substituted benzothiazoles, in nearly all cases, strategies have required non-versatile and non-modular syntheses. [1] One major path relies on the cyclisation of functionalised arylthioamides or arylthioureas. Such starting materials require time-consuming However, drawbacks with these approaches are readily appreciated by considering the poor shelf-life of many aldehydes, the high-reactivity of acid halides, as well as the poor availability of functionalized 2-aminothiophenols, which are themselves air-sensitive and easily decomposed.
A more facile and highly convergent approach, based on readily-available and stable building blocks, would be to leverage the extensive portfolio of boronic acids to access polysubstituted benzothiazole derivatives through Suzuki-Miyaura cross coupling starting with a suitable 2-iodobenzothioazole as a readily accessed coupling partner.
Moreover, taking advantage of the C-2 activated position of the heterocycle might prove sufficiently selective for orthogonal coupling thus providing diversely polysubstituted benzothiazoles in a highly convergent and straightforward fashion. Herein, we present a preliminary report that establishes this strategy as a viable route to polysubsituted benzothiazoles. To test this hypothesis, we envisioned a practical and convergent strategy involving 4-bromo-2-iodobenzothiazole 3 (Scheme 1) as a key intermediate that would enable regio/chemoselective coupling to deliver a series of C2/C4 arylated benzothiazoles. This strategy is attractive as it is highly modular as it allows for considerable synthetic versatility considering the expansive library of aryl boronic acids and derivatives available, both commercially and synthetically, as suitable coupling partners. [19,20] Herein, we describe the swift synthesis of versatile intermediate 3, substituted with two different halogens that, as part of our design, demonstrates efficient access to the said benzothiazoles via chemoselective and regioselective functionalisation with various aromatic substituents.

Synthesis of di-halogenated intermediate
We sought a simple, efficient, and high-yielding synthetic route with an eye to utilizing affordable and common laboratory reagents. Starting from commercially-available 2bromoaniline, thiourea 1 was obtained following standard protocol. [21,22]

Photophysical Properties
Given the increasing interest and application of the absorptive and emissive properties of benzothiazoles, we briefly studied the photophysical properties of these novel benzothiazoles. As a general trend, these benzothiazoles exhibit similar absorption spectra, consisting of large bands in the UV region of the spectrum; they absorb strongly with absorption maxima ranging from 339 to 405 nm that are attributed to characteristic -* transitions. However, on closer inspection it becomes evident that the nature of the aromatic group at C-2 determines the absorption profile, while the      versatile, allowing selective structural elaboration firstly at the C-2 position, in high yields, followed by functionalisation at the C-4 position; the scaffold can also be difunctionalised in one-pot at both the C-2 and C-4 positions. This strategy gives rapid access to a diverse family of benzothiazoles with tuneable photophysical properties.
Although our synthesis is somewhat limited in scope, we have demonstrated that this reaction manifold is readily amenable to preparing a large number of tricyclic compounds starting with (hetero)arylboronic acids. Hence, in this preliminary report, we acknowledge this methodology serves as a proof of concept for its expansion towards the functionalisation of other positions on the benzothiazole core in a similar fashion. It is readily anticipated more densely functionalized bromoanilines will readily submit to this reaction scheme. The novel benzothiazoles derivatives reported here accessible through 3, or derivatives thereof, are further anticipated to be of interest for photophysical studies in both solution and the solid-state, as well as their investigation as Lewis acid catalysts and as chelators for various metal cations. Studies towards these goals are currently underway.

Supporting Information
Supporting information including extensive experimental details and compounds characterizations (IR, 1 H and 13 C NMR, HRMS) are provided.