Romain Duwald

Simon Pascal

Johann Bosson

Stephane Grass

Céline Besnard

Thomas Bürgi

Jérôme Lacour

Stéphane Grass

Enantiospecific Elongation of Cationic Helicenes by Electrophilic Functionalization at Terminal Ends

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Organic helicenes, which are helical derivatives made of ortho-fused aromatic rings, [1] usually feature a minimum of five consecutive rings to ensure large enough helical pitch and configurational stability at room temperature. Higher order helicenes, including axially [START_REF] Martin | [END_REF] or laterally extended derivatives, [3] present greater racemization barriers and, importantly, modified properties brought by the extension of the helical framework. Strategies have thus been developed to extend helicene scaffolds by, for instance, additions of ortho-fused rings at terminal ends of preexisting skeletons (Scheme 1a). [4] However, due to the inherent difficulty to post-functionalize helicenes regioselectively, and at terminal ends in particular, such efforts have been limited so far. [5] Herein, using the intrinsic reactivity of cationic 1, 13dimethoxy[4]helicenes 1 towards electrophiles and strongly acidic conditions for thermodynamic control, an orthogonal mode of late stage functionalization at terminal rings is reported. In fact, contrary to classical electrophilic aromatic substitutions that occur at position 6 of compounds 1 (Scheme 1b), [6] reactions performed in polyphosphoric acid (PPA) or with Eaton's reagent (7.5% P2O5 in CH3SO3H) [7] lead over time to derivatives 2 or 3 carrying functional groups at position 2 or at positions 2 and 12 exclusively (Scheme 1c). Extension of this reactivity to cationic [6]helicenes affords compounds 4. With substitutions happening next to the terminal MeO groups in 2 or 3, elongation strategies could be developed to yield extended [5] and [6]helicenes, products 5 and 6 respectively (Scheme 1d). Importantly, these configurationally stable cationic derivatives (G ‡ > 36 kcal/mol, 180 °C) [8] can be generated with high enantiospecificity (es up to 99%) from M-1 or P-1 precursors providing a general access to a variety of enantiopure elongated helicenes.

Diaza[4]helicenes of type 1, cationic derivatives related to triangulenium salts, [9] are prepared in two steps from 1,3dimethoxybenzene (R = alkyl, 60-77% overall yield). These helicenes can be isolated as single enantiomers on gram-scale using established resolution procedures. [10] Thanks to a high configurational stability (ΔG ‡ racem ~42 kcal.mol -1 ), [11] compounds 1 can be handled at high temperature conveniently. They display fluorescence within the transparency window of biological media [12] and have proven their ability to selectively bind DNA [13] or behave as chiroptical switch. [14] Of most relevance to this study, helicenes 1 react under nitration or Vilsmeier-Haack conditions to afford products of electrophilic substitution at position 6 exclusively (Scheme 1b). While useful for the tuning of physicochemical properties, these reactions did not open a synthetic access to elongated helicenes. Alternative protocols that would allow electrophilic substitutions of the terminal rings exclusively were thus looked for. [a] Entry Product PPA [b] Eaton's reagent [c] In this context, combinations of strong Brønsted acids and dehydrating agents, such as PPA or Eatons' reagent (7.5% P2O5 in CH3SO3H), had been reported to promote Friedel-Craft alkylations and acylations. [7] It was also established that strong acids can provoke the general isomerization of substituted arenes; molecular rearrangements leading to interconversions of constitutional isomers. [15] It was then conceivable that such conditions could lead to efficient electrophilic functionalizations of [4]helicene 1 but with a markedly different regioselectivity. Salt [1][BF4] (R = n-Pr) was thus treated with benzoic acid in PPA at 80 °C for 2h (Table 1). To our satisfaction, salt [2a][BF4] was obtained in excellent yield as a single isomer (91%, entry 1); the regioselectivity of which was ascertained by NMR spectroscopy and X-ray diffraction analysis. [START_REF]The presence of the benzoyl group forces a change in conformation for the neighboring MeO that is no more coplanar with the aromatic ring (torsion angle: 62.1°)[END_REF] Using p-toluenesulfonic acid as reagent, sulfone 2b was isolated in 75% yield. With bisarylcarbinol reagents (3 equiv), double alkylations at the terminal rings occurred leading to products 3c and 3d in excellent yields (89-93%, Ar = Ph, pMe2NC6H4, entries 3 and 4). These results were encouraging but scale-up was difficult in viscous PPA. Eaton's reagent was selected as substitute. Satisfactorily, products 2a, 2b, 3c and 3d were isolated in good to excellent yields (70-89%).

Recently, it was shown that cationic diaza[6]helicenes react with electrophiles, like [4]helicenes 1, spontaneously on the central (top) benzene ring (eq S1, supporting information). [6] It was then conceivable that a different regioselectivity would occur in PPA or Eaton's reagent. To our satisfaction, products 4a, 4b, 4c of functionalization at terminal rings were isolated in low to good yields (17-89%, Table 1, entries 5 to 7).

With these results showing a separate regioselectivity in strong acid conditions, a series of control experiments was performed to rationalize the reactivity. The results are detailed in Table 2. First, acylation of 1 with benzoic acid was performed at 30 °C instead of 60 °C for 1h (entry 1). Three components were detected in the crude mixture: starting material 1, adduct 2a and, interestingly, regioisomer 7 in relatively equal proportions; longer reaction time or higher temperatures leading to a larger amount of 2 over 7 (entries 2 & 3). Isomer 7 was submitted to Eaton's reagent for 1h at 60 °C in the absence of benzoic acid. [17] Significantly, an essentially complete transformation of 7 into [4]helicene 1 and regioisomer 2a was observed (entry 4). Finally, product 2a was submitted to the same conditions (Eaton's, 60 °C). After 1h, 2a remained the major component of the crude along with 1; adduct 7 being only a minor component (entry 5). All together, these experiments indicate that the formation of 2a occurs under thermodynamic control while the formation of "classical" isomer 7 is kinetically preferred. Terminal ring functionalization is thus clearly favored by higher temperatures and longer reaction times under strongly acidic conditions. [START_REF] Schubert | This interconversion of the acyl group through acid catalysis probably occurs with the intermediacy of ipso arenium ions, see ref[END_REF] Table 2. Thermodynamic vs. kinetic control in the formation of 2a in Eaton's reagent. [a] Substrate Additive Temp Time 1 2a 7 4 [b] 7 -60 °C 1h 75% 21% 4%

1 1 PhCO2H ( 3
5 [b] 2a -60 °C 3h 33% 59% 8%

[a] Proportions determined by 1 H-NMR spectroscopy on crude reaction mixtures. Average of two reactions. [b] Compounds 2a or 7 were heated without PhCO2H.

Care was then taken to tackle the goal of the project, ie the elongation of 1 to [5] and possibly [6]helicene derivatives (Scheme 2). To that effect, substrate 1 was treated in Eaton's reagent with salicylic acid at 50 °C for 24h to afford synthetic intermediate 8 (X = OH) which was engaged immediately under basic conditions to provoke an intramolecular SNAr cyclization. [START_REF]MeO groups of quinacridiniums 1 are readily substituted by nucleophiles thanks to the electron-withdrawing ability of the central cationic core[END_REF] In fact, treatment of 8 with an excess of Et3N in acetonitrile at 65 °C afforded [5]helicene 5a in 56% combined yield (two steps). The procedure is general as sulfur-containing 5b was isolated in 58% combined yield starting from 1 and thiosalicylic acid. Using sterically hindered 1-hydroxy-2-naphthoic acid as reagent, it was necessary to adopt more forcing conditions for the cyclization step 2a X-ray (aq. NaOH, 0.1 M in acetonitrile) and compound 5c was isolated in 23% only due to the steric encumbrance. Finally, with 5b in hand, the (inside) sulfur atom was oxidized with m-CPBA. The corresponding sulfoxide 5d was isolated in excellent yield (95%) as a single diastereomer (d.r. > 49:1). The relative configuration was established by X-ray diffraction analysis (Figure 1, left). Clearly, the peracid approaches the less hindered side of the sulfur atom, ie the pro-R lone pair for an M configuration of 5b. [START_REF] Aillard | Functionalizations of stereogenic heteroatoms embedded in helical frameworks are often highly stereoselective[END_REF] Scheme 2. Reaction conditions: [a] Eaton's reagent, 50 °C, 3-24h, 3 equiv ArCO2H. [b] 2.5:1 mixture of MeCN:Et3N, 65 °C, 2-6h. [c] 2:1 mixture of MeCN:aq. NaOH (0.1M), reflux, 8h. Isolated yields [%] for the combined steps.

For the homologation to [6]helicene scaffolds, the use of more (electron-poor) o-fluorobenzoic acid 9 was necessary as compounds 5a or 5b did not react with salicylic or thiosalicylic acids under above-described conditions. Even with 9, acylation of 5a was Eaton's reagent (15% conv after 3 days at 50 °C). The use of even more acidic conditions was required. [21] In fact, treatment of 5a with 9 for 15 min at 80 °C in trifluoromethanesulfonic acid (TfOH) containing P2O5 (18% wt.) resulted in acylated intermediate 10a (Scheme 3). This compound was engaged immediately in demethylating conditions with lithium iodide in DMF at 140 °C to form dioxa 6aa (36%, Figure 1, right). In this case, the in-situ generated phenoxide of type 11 reacts ipso to the fluorine atom by intramolecular SNAr to ensure the final ring closure after fluoride anion elimination (Scheme 3, path 1). With 5b as substrate, the same conditions afforded intermediate 10b and then mixed oxathia 6ab in 53% yield. Finally, to prepare dithia 6bb (54%), intermediate 10b was treated with sodium sulfide (3.6 equiv) in presence of CuI (40 mol%) in DMF (80 °C, 16h). An intermolecular substitution of the fluorine by a sulfur atom occurs to generate intermediate 12 prior to an intramolecular SNAr of the MeO group (Scheme 3, path 2). This second type of approach will be beneficial for the enantiospecificity (see below). At that stage, all reactions had been performed in racemic series and it was questionable whether the helicene growth would be enantiospecific. In fact, ring expansions 1 → 5 or 5 → 6 occur by reactions at terminal methoxy groups. These moieties are essential for the helical pitch and the configurational stability of the helicene framework. It was then conceivable that their replacement by other groups could lead to a racemization. Care was thus taken to perform the elongations using enantiopure M-1 or P-1 as substrates. Satisfactorily, as analyzed by chiral stationary phase (CSP) HPLC (Figures S2-S8), extended [5]helicenes 5a and 5b were obtained in excellent enantiomeric purity (ee > 98%) while 5c was isolated with a 90% ee. Clearly, in this later case, the harsher ring closure conditions are responsible for the moderate loss of enantiospecificity. The compounds display a very high configurational stability (G ‡ > 36 kcal/mol) as shown by the lack of racemization of 5a at 180 °C in DMSO (VT-ECD monitoring, 21-180 °C, Figure S9-S11). [8c] Electronic circular dichroism (ECD) spectra present symmetrical curves in the 240 to 700 nm region (Figures S12-S18). VCD analysis of (-) and (+)-5a (optical rotations measured at 365 nm at 20 °C) establishes unambiguously P and M configurations [START_REF] Al | [END_REF] for the helicenes made 5d 6aa

from P-1 and M-1 respectively (Figure 2). [START_REF]Compounds 1-6 are effective dyes that absorb light from the UV to ca. 650 nm[END_REF] As it could be expected, retention of helical configuration happens upon terminal ends elongation. Finally and significantly, depending on the synthetic route, the second ring elongation leads to either full racemization or complete enantiospecificity (Scheme 3, path 1 or path 2). This dual behavior can be explained mechanistically. In path 1, after formation of 11, the loss of enantiomeric purity is due to the transient formation of an achiral (planar) diazaoxatriangulenium intermediate 13 by an intramolecular attack of the phenoxide anion onto the extended ring (eq 1). Such a racemization process cannot occur following path 2. This was demonstrated in the enantiospecific synthesis of 6ab that occurs, though this second route, in excellent enantiomeric purity (ee 99%, yield 47 % for two steps).

In summary, in PPA or Eaton's reagent, direct late-stage functionalizations at terminal ends of cationic diaza helicenes have been achieved. Thanks to the strongly acidic conditions that permit reversible electrophilic substitutions, acylations, sulfonylations or alkylations occur at the extremity(ies) of the helical core. This exclusive regioselectivity was used to generate extended [5] or [6]helicenes from [4]helicenes in successive onepot processes. Retention of configuration and excellent enantiospecificity (up to 99%) can be further obtained for the helicene elongation in the enantiopure series.

Experimental Section

Synthetic procedures and spectral characterization of new compounds 2-6 are reported in the electronic supporting information. CCDC XXXXX-XXXXXX, products 2a, 5b, 5c, 5d, 6aa and 6bb, contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

  Scheme 1. a) Helicene growth by terminal ends elongation. b) Reported regioselective electrophilic aromatic substitutions of [4]helicenes 1. c) Orthogonal regioselectivity by thermodynamically-driven functionalizations in PPA or Eaton's reagent. d) Enantiospecific syntheses of extended helicenes 5 and 6. Numbers in italic indicate substituent positions.

Figure 1 .Scheme 3 .

 13 Figure 1. ORTEP views of sulfoxide [5]helicene 5d (left) and dioxa [6]helicene 6aa (right). M-configurations displayed arbitrarily. H-atoms and anionic counterions are removed for clarity.

Figure 2 .

 2 Figure 2. Experimental VCD spectra (CD2Cl2, 298K) of (+) (blue) and (-) (red) enantiomers of 5a (optical rotations measured at 365 nm). The calculation (green spectrum) was done on the P-enantiomer.

Table 1 .

 1 Terminal ring(s) functionalization of [4] and [6]helicenes

Acknowledgements

We thank the University of Geneva and the Swiss NSF for financial support. We also acknowledge the contributions of the Sciences Mass Spectrometry (SMS) platform at the Faculty of Sciences, University of Geneva. Keywords: Carbenium ions • Helicenes • Regioselectivity • SEAr • SNAr • Thermodynamic control • SNAr • Thermodynamic control


Gabriele Boschetto
email: gabriele.boschetto@lirmm.fr

Stefania Carapezzi

Aida Todri-Sanial

Ab Initio Simulations of Defective Metal Contacts in Beyond-CMOS Devices Based on Single-layer MoS2: Impact of Small and Extended Defects

Atomically thin single-layer molybdenum disulfide (MoS2) is a two-dimensional material with highly desirable mechanical, electronic, and optical properties. These, combined with its reduced dimensionality and ultra-thin size, could enable the fabrication of a new generation of very compact and low-power devices which go beyond the conventional CMOS technology. At present, wafer-scale production of MoS2 is mainly achieved via CVD and PVD growth techniques, however, films have not yet reached the level of purity typical of the silicon technology. Small and extended defects are inevitably introduced in the material, and are expected to significantly affect not just the properties of MoS2 itself but also the quality of the metal contact. For instance, poor electron injection and Fermi level pinning at the MoS2-metal interface could lead to large Schottky barriers and contact resistances, which limit the device performance by introducing unwanted parasitic elements [START_REF] Allain | Electrical Contacts to Two-Dimensional Semiconductors[END_REF]. This is detrimental for devices like field-effect transistors (FETs). On the other hand, the functionality of some devices, such as memristors based on monolayer MoS2, may even depend on the presence and nature of such defects [START_REF] Ge | Atomristor: Nonvolatile Resistance Switching in Atomic Sheets of Transition Metal Dichalcogenides[END_REF]. Here, with the aim of bridging the gap between material's properties and device physics, we investigate defective single-layer MoS2 in top contact with a metal electrode. To do so, we carry out ab initio computer simulations in the framework of Density Functional Theory (DFT) coupled with surface simulations based on the Green's function formalism [START_REF] Smidstrup | First-Principles Green's Function Method for Surface Calculations: A Pseudopotential Localized Basis Set Approach[END_REF]. Such a simulation scheme allows us to construct realistic MoS2-metal interfaces and to carry out accurate interface simulations. To model the metal electrode, we choose the chemical inert Au as it is commonly employed at the lab scale to fabricate devices. We explore the impact of experimentally-observed vacancies and substitutions on the properties of MoS2-Au contacts, and we predict relevant interface properties such as electron injection rates and tunnelling barriers. Ultimately, our study constitutes the first step of a more comprehensive multi-scale modelling approach, in which the aim is to construct a full atomistic-to-device level model that can aid us in elucidating the physics of 2D devices based on single-layer MoS2.