# Synthesis of non-symmetric ortho-functionalized azoarenes through arylation of arylazo sulfones

Rayhane Hammami, Victor Flon, Morgane Sanselme, Julien Legros, Isabelle

Chataigner, Laëtitia Chausset-Boissarie

► To cite this version:

Rayhane Hammami, Victor Flon, Morgane Sanselme, Julien Legros, Isabelle Chataigner, et al. Synthesis of non-symmetric ortho-functionalized azoarenes through arylation of arylazo sulfones. Organic Chemistry Frontiers, 2025, 12 (24), pp.6953-6960. 10.1039/D5QO00932D. hal-05407069

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# Synthesis of non-symmetric *ortho*-functionalized azoarenes through arylation of arylazo sulfones

Rayhane Hammami,ª Victor Flon,ª Morgane Sanselme,ᵇ Julien Legros,ª Isabelle Chataignerª,ᶜ and Laëtitia Chausset-Boissarie*ª

A novel protocol for the arylation of arylazo sulfones with organomagnesiums for accessing non-symmetric *ortho*-functionalized azoarenes has been successfully developped. Bench-stable substituted arylazo sulfones, which serve as masked electrophilic diazo sources, have been effectively arylated, achieving good to excellent isolated yields. This method demonstrates broad tolerance towards a wide variety of substituents. Further, the mechanism and the regioselectivity of the addition has been investigated using DFT calculations. The observed regioselectivity would arise from a combination of steric and electronic effects, as well as the presence or absence of a strongly coordinating substituent at the *ortho* position of the starting material.

## Introduction

Azoarenes represent an important class of organic compounds with a wide range of applications, including molecular photoswitches,¹ functional materials,² biomedical agents,³ organic dyes and colorants,⁴ and food additives⁵ among other uses. Particularly, substitution pattern through electronic and steric effects has a significant impact on the physical and photochemical properties of azoarenes. Thus, fine-tuning of these properties through simple structural modifications can address specific applications. Notably, *ortho*-substituted azobenzenes are particularly noteworthy.⁶ They enable the use of visible, red or even near-infrared (NIR) light while providing good absorption band separation and relatively high thermal stability of the thermodynamically less stable Z-isomer making these photo-switchable molecules excellent candidates for photo-pharmacological applications especially *in-vivo*.⁷ Consequently, the synthesis of substituted azoarenes has been widely explored.⁸ While symmetrical azoarenes are readily accessible, the synthesis of asymmetric hindered azoarenes still remains a significant challenge. Early protocols were mainly based on azo coupling with electron-rich aromatic compounds,⁹ or Baeyer-Mills reaction¹⁰ however, these approaches suffered from major drawbacks such as low yields and narrow substrate scope due to their intrinsic reaction mechanisms (Figure 1a). Oxidative coupling of anilines,¹¹ reductive coupling of nitroaromatics¹² or metal catalysed C-H functionalization of symmetrical azoarenes¹³ were also effective catalytic approaches towards the synthesis of *ortho*-substituted non-symmetric azoarenes.

a) Classical methods for the synthesis of non-symmetric *ortho*-substituted azoarenes

<figure><img src="image_2.png" /></figure>

b) Substitution-arylation of arylazo sulfones with phenols

<figure><img src="image_3.png" /></figure>

c) This work: Substitution-arylation of arylazo sulfones with grignard reagents

<figure><img src="image_4.png" /><figcaption>**Figure 1.** Approaches for the synthesis of non-symmetric *ortho*-substituted azoarenes</figcaption></figure>

Unfortunately, both of these processes require harsh reaction conditions, excess of reducing or oxidizing agents, undesirable by-products and transition metal catalysts. In addition to the above strategies, C(sp²)-N bond formation protocols using arylhydrazines¹⁴ or silylated aryl diazenes¹⁵ have been developed; however, these methods necessitate the use of expensive palladium catalyst. Another approach to unsymmetrically *ortho*-substituted azo compounds uses direct addition of organometallics such as arylmagnesium,¹⁶
aryllithium¹⁷ or diaryl zinc¹⁸ reagents to aryldiazonium salts. However, dry aryldiazonium salts are often avoided in industry due to their exothermic decomposition and potential explosive behaviour. Recently, Zhao, Jiang and co-workers reported the first example of the use of bench-stable arylazo sulfones¹⁹ as effective electrophilic diazo sources for the synthesis of azo compounds (Figure 1b).²⁰ The method is unfortunately, strictly limited to electron-rich aromatic nucleophiles like phenols, with substitution intrinsically restricted to the para positions or ortho when this position is already occupied. Herein, we disclose a novel strategy for the synthesis of diverse non-symmetric *ortho*-functionalized azoarenes using safe and easy to handle *ortho*-substituted arylazo mesylates with arylmagnesium reagents, *via* a nucleophilic addition-elimination processes.²¹ In addition, the unique feature of the regioselectivity was explored in detail by density functional theory (DFT).

## Results and discussion

Initially, arylation of (E)-1-(2-bromophenyl)-2-(methylsulfonyl)diazene (1a) was chosen as a model reaction (Table 1).

<table><caption>**Table 1.** Optimization of the reaction conditionsª</caption><thead><tr><th>Entry</th><th>Variations from optimized conditions</th><th>3aa<br>Yield<br>(%)<sup>b</sup></th><th>4aa<br>Yield<br>(%)<sup>b</sup></th></tr></thead><tbody><tr><td>1</td><td>None</td><td>87</td><td>10</td></tr><tr><td>2</td><td>-40 °C instead of -78°C</td><td>68</td><td>16</td></tr><tr><td>3</td><td>0 °C instead of -78 °C</td><td>55</td><td>39</td></tr><tr><td>4</td><td>Ts instead of Ms as leaving group</td><td>43</td><td>18</td></tr><tr><td>5</td><td>PhLi instead of PhMgBr</td><td>57</td><td>-</td></tr><tr><td>6</td><td>PhZnBr</td><td>3</td><td>2</td></tr></tbody></table>

Systematic investigation led to the identification of optimal reaction conditions: a mixture of **1a** (0.5 mmol), and phenyl magnesium bromide **2a** (0.65 mol, 1 M in THF) was stirred in THF (1.0 mL) at -78 °C for 40 min, resulting in the desired product **3aa** with an NMR yield of 87% along with 10% of diarylmethanesulfonohydrazide **4aa** as a by-product (Table 1, entry 1, see the ESI† for details). The hydrazine by-product **4aa** results from the attack of the Grignard reagent on the aryl-substituted N atom.²² The two most important factors that

influence the selectivity of the competing reaction are the temperature and the reactivity of the leaving group. Indeed, performing the reaction at -40 °C or 0 °C resulted in lower yields of **3aa** (Table 1, entries 2-3) and favoured the hydrazine formation **4aa**. By using *p*-toluene sulfonyl (Ts) substituted azo derivative as potential leaving group lowered the yield of the desired product **3aa** and slowed the reaction, while increasing the formation of by-product **4aa** (entry 4). Although phenyl lithium led to better selectivity by avoiding halogen-lithium exchange or nucleophilic attack on the azo group, the desired product **3aa** was obtained in a lower yield of only 57% (Table 1, entry 5). The evaluation of phenylzinc bromide as a nucleophilic partner yielded only a trace of azoarene **3aa**. (entry 6).

With the optimal reaction conditions in hand, we explored the scope and the generality of the method, employing a wide range of functionalized substrates (Scheme 1). The Grignard reagents tested were commercially available or readily prepared by the magnesium insertion into aryl bromides in THF. Both isomers of **3** were obtained in all reactions, but the *Z* isomer gradually isomerized into the *E* isomer at room temperature. *Ortho*-substituted aryl azosulfones with various electron-withdrawing groups such as Br, Cl, I and CF₃ reacted smoothly with phenyl magnesium and afforded the desired azobenzene derivatives **3aa**, **3ba**, **3ca** and **3da** in 77-87% yields. It is noteworthy that halo-substituted aromatic azo compounds can be further functionalized to obtain valuable derivatives. However, when using an arylazo sulfone bearing an *ortho* nitro group **1e**, the addition-elimination process failed, resulting in a complex mixture in which the expected product **3ea** was not detected. The reaction of 2-methyl-substituted substrate **1f** proved to be nonselective, yielding **3fa** in 42% yield along with 49% of hydrazine by-product **4fa** which the structure was confirmed by single-crystal X-ray crystallography (see ESI for details). Furthermore, the arylation of 2-methoxyarylazo sulfone **1g** did not produce the expected product **3ga**, but instead exclusively afforded the hydrazine product **4ga** in 75% yield, highlighting the significant influence of the *ortho* substituent's nature on the regioselectivity of the addition. In contrast, a phenyl ring is well-tolerated, giving **3ha** in 85% yield. The impact of substituents at the *para* position of the phenyl ring in 2-bromoarylazo sulfones was also evaluated. Various functional groups, including halogen (Cl), electron-withdrawing groups (CF₃, CN, CO₂Et) or electron-donating groups (Me, OMe) is well tolerated yielding the expected products **3ia-3na** in good to excellent yields (62-87%). These results indicate that the electronic properties of the ring do not play a crucial role in the reaction. The position of an alkyl substituent on the phenyl ring had no significant influence on the reaction outcome.
<figure><img src="image_5.png" /></figure>

<figure><img src="image_6.png" /><figcaption>3ia (R¹ = Br, R² = Br): 78%</figcaption></figure>

<caption>3ja (R¹ = Br, R² = CF₃): 82%</caption>

<figure><img src="image_7.png" /><figcaption>3oa 73%</figcaption></figure>

<figure><img src="image_8.png" /><figcaption>3qa 77%</figcaption></figure>

<figure><img src="image_9.png" /><figcaption>3cb 69%ᵃ</figcaption></figure>

<figure><img src="image_10.png" /><figcaption>3cd 34%ᶜ</figcaption></figure>

<figure><img src="image_11.png" /><figcaption>3cf 59%</figcaption></figure>

<figure><img src="image_12.png" /><figcaption>3ah Traces</figcaption></figure>

<caption>3aa (R = Br): 78%</caption>

<caption>5.0 mmol scale: 61%</caption>

<caption>3ba (R = Cl): 77%</caption>

<caption>3ca (R = I): 87%</caption>

<caption>3da (R = CF₃): 80%</caption>

<caption>3ea (R = NO₂): -</caption>

<caption>3fa (R = Me): 42%</caption>

<caption>3ga (R = OMe): -</caption>

<caption>3ha (R = Ph): 85%</caption>

<figure><img src="image_13.png" /><figcaption>3la (R¹ = I, R² = CO₂Me): 67%</figcaption></figure>

<caption>3ma (R¹ = Br, R² = OMe): 69%</caption>

<figure><img src="image_14.png" /><figcaption>3pa 65%</figcaption></figure>

<figure><img src="image_15.png" /><figcaption>3ra 85%</figcaption></figure>

<figure><img src="image_16.png" /><figcaption>3cc 97%ᵇ</figcaption></figure>

<figure><img src="image_17.png" /><figcaption>3ae 48%ᵈ</figcaption></figure>

<figure><img src="image_18.png" /><figcaption>3ag 58%</figcaption></figure>

<figure><img src="image_19.png" /><figcaption>3ai Traces</figcaption></figure>

Indeed, 2-bromoarylazo sulfones bearing a methyl group at the C-3 or C-5 position reacted smoothly, yielding the desired products **3oa** and **3pa** in 73% and 65% yields, respectively. We were therefore pleased to find that the success of the reactions was not affected by the incorporation of a heteroaromatic motif, as (E)-4-iodo-5-(phenyldiazenyl)benzo[d]thiazole **3qa** was obtained in 77% yield. This approach provides a mild and efficient route to obtain unsymmetrical *ortho*-substituted heteroazobenzene, which are not easily accessible through other methods. In addition, a replacement of the phenyl moiety with the *δ*-naphthyl unit was also tolerated to afford **3ra** in 85% yield. We then turned our attention towards the influence of the substituent on the Grignard reagents. Substituted aryl magnesium reagents bearing electron-donating groups like methyl or methoxy at the *para* position were successfully added to *ortho*-haloarylazo sulfones, albeit with slower reaction rates, yielding azobenzenes **3cb** and **3ae** in 69% and 48%, respectively. The position of an alkyl substituent on the aryl Grignard ring significantly influenced the selectivity of the process. While the *meta*-tolyl Grignard reagent provided the desired product **3cc** in an excellent 97% yield, the *ortho*-tolyl counterpart resulted in a poor yield, with the hydrazine by-product as the major product, likely due to steric hindrance. This method is particularly interesting since azobenzenes bearing two electron-deficient aromatic rings **3cf** and **3ag** were obtained in good yields.

<figure><img src="image_20.png" /><figcaption>1s-v</figcaption></figure>

<caption>2a-d</caption>

<figure><img src="image_21.png" /><figcaption>3sa (R = Br): 56%</figcaption></figure>

<caption>3ta (R = Cl): 52%</caption>

<figure><img src="image_22.png" /><figcaption>3va 80%</figcaption></figure>

<figure><img src="image_23.png" /><figcaption>3sc 74%ᵇ</figcaption></figure>

<caption>3vd 56%ᶜ</caption>

**Scheme 1.** Scope of the arylation of functionalized *ortho*-substituted arylazo sulfones **1a-r** with various Grignard reagents **2a-i**. Yields are of isolated products after purification by flash chromatography on silica gel. ᵃ5 h of reaction time. ᵇ4 h of reaction time. ᶜ7 h of reaction time. ᵈ9 h of reaction time.

**Scheme 2.** Scope of the arylation of functionalized *ortho-ortho'-substituted* arylazo sulfones **1s-v** with various Grignard reagents **2a-d**. Yields are of isolated products after purification by flash chromatography on silica gel. ᵃ10 h of reaction time. ᵇ1 h of reaction time. ᶜ7 h of reaction time.
Unfortunately, use of tert-butyl or vinyl magnesium bromide as nucleophiles led to complex mixtures, with only trace amounts of the desired products **3ah-i**.

To further investigate the applicability of the method, unsymmetric bis-*ortho* substituted azobenzenes were synthesized (Scheme 2). Remarkably, this procedure enables the synthesis of sterically hindered azobenzene bearing two different halides, which serve as modular building block (**3sa-3va**, **6sb-c**) with good to high yields (52-80%). As previously observed, the *ortho*-tolyl Grignard reagent **2c**, gave the product **3vd** in slightly lower than the unsubstituted Grignard reagent **2a**.

A distinctive feature of the present reaction is that the selectivity of the arylation is influenced by the nature of the *ortho* substituent on the arylazo sulfones (Scheme 3). Indeed, as observed in previous studies on the arylation of arylazo tosylates<sup>23</sup> or carbamates<sup>24</sup> with organometallic nucleophiles, the absence of substituents leads to the selective formation of the hydrazine by-products *via* nucleophilic addition on the aryl-substituted nitrogen (Pathway I). In the case of *ortho*-haloarylazo sulfones, nucleophilic addition preferentially occurs at the nitrogen atom bearing the mesylate leaving group, forming a nitrogen anion intermediate that, upon elimination of the mesylate, generates azobenzenes (Pathway II).

### Pathway I

<figure><img src="image_24.png" /></figure>

### Pathway II

<figure><img src="image_25.png" /><figcaption>**Scheme 3.** Azoarene vs. Hydrazine Formation.</figcaption></figure>

Density functional theory (DFT) calculations were carried out to gain a clearer understanding of the regioselectivity of these nucleophilic additions on arylazo sulfonyl compounds. Geometry optimizations were carried out at the ωB97X-D/6-31+G(d,p) level of theory with an implicit PCM solvation model. In these calculations, we compared the addition of the nucleophilic species to both nitrogen atoms of brominated substituted arylazo sulfone **1a** and methoxy substituted arylazo sulfone **1g**. Experimentally, these two compounds indeed resulted in different adducts as the azobenzene derivative **3aa** was obtained from **1a**, while the hydrazine compound **4ga** was formed from **1g**.

We first analyzed and compared the electronic structures of **1a** and **1g**, by performing NBO calculations. This revealed that the Natural Population Analysis (NPA) at the nitrogen atoms of these two arylazo sulfones were comparable and negative in

each case, with the charge at the N-Ms position being more negative (~-0.4 e at the N-Ms vs ~-0.1 e at the N-Ar position, Table 2, entries 1 and 2). Thus, no clear link between the electronic charges of the diazo compounds and their dichotomic electrophilic reactivity can be drawn from these data. Computing frontier molecular orbitals, revealed that the Lowest Unoccupied Molecular Orbital (LUMO) energy for the *o*-bromo compound **1a** was lower than for the *o*-methoxy one **1g** (-1.32 vs -0.98 eV, entry 3). As shown in Table 2 where the isovalues of two lowest empty orbitals for **1a** and **1g** are displayed, the LUMO biggest molecular coefficients are located on the two nitrogen atoms with similar coefficients at both positions, whatever the compound. In line with these data, **1a** had a higher global electrophilicity parameter (ω)<sup>25</sup> (1.76 vs 1.52, entry 4), suggesting that compound **1a** is more reactive than **1g** towards nucleophiles. Then, we evaluated the local electrophilic/nucleophilic character of these two arylazo sulfones, by estimating a local electrophilicity value over atoms (f+)<sup>26</sup> defined within the context of the atoms-in-molecules theory.<sup>27</sup> All these calculations have been performed with the TopChem2 package.<sup>28</sup> This revealed that if the electrophilicity at the N-Ms position is much higher for the *o*-bromo compound **1a** compared to the *o*-methoxy one **1g** (entry 6), in line with the experimental observations, the electrophilicity value remains however equal or higher at the N-Ar position, whatever the compound (compare entries 5 and 6). The regioselectivity of the nucleophilic addition process can thus not be fully accounted with these sole values.

<table><caption>**Table 2.** Structural analysis for compounds **1a** and **1g**<sup>a</sup></caption><thead><tr><th rowspan="2">Entry</th><th rowspan="2">Structural parameters</th><th colspan="2">1a</th></tr><tr><th>1g</th></tr></thead><tbody><tr><td>1</td><td>NPA Charge at N-Ar position (e)</td><td>-0.11</td><td>-0.11</td></tr><tr><td>2</td><td>NPA Charge at N- position (e)</td><td>-0.39</td><td>-0.41</td></tr><tr><td>3</td><td>LUMO energy (eV)</td><td>-1.32</td><td>-0.98</td></tr><tr><td>4</td><td>ω : Global electrophilicity parameter</td><td>1.76</td><td>1.52</td></tr><tr><td>5</td><td>Local electrophilicity (f') at N-Ar</td><td>0.29</td><td>0.29</td></tr><tr><td>6</td><td>Local electrophilicity (f') at N-Ms</td><td>0.29</td><td>0.27</td></tr></tbody></table>

<footnote><sup>a</sup>structure optimized at the ωB97X-D/6-31+G(d,p) level, with an implicit PCM solvation (THF). Population and orbital analyses were affected at the same level of theory, in the absence of implicit solvation. <sup>b</sup>Plot of the LUMO of **1a** and **1g**. <sup>c</sup> Localization domains of the Dual Descriptor and its condensed values over the atoms-in-molecules volumes for **1a** and **1g**. <sup>d</sup> Color code. red : positive (electrophilic) and blue : negative (nucleophilic).</footnote>
As these calculations do not take into account the interaction of the arylazo sulfone with the nucleophilic species, we then tried to localize and compare the transition states (TSs) of both attacks (at the N-Ar and N-Ms centres), for the two compounds **1a** and **1g**. For this quantitative energy evaluation, optimizations were performed at the same level, with an implicit solvation and were followed by single-point energy calculations using def2TZVPP basis set.

<table><caption>**Table 3.** Energy profile for the addition of phenyl lithium to N-Ar and N-Ms positions of **1a** and **1g**ª</caption><thead><tr><th colspan="2">Attack at N-Ar</th><th colspan="2">Attack at N-Ms</th><th colspan="2">MsLi Elimination</th></tr><tr><th>Entry</th><th>Pathway</th><th>With 1a</th><th>With 1g</th><th>With 1a</th><th>With 1g</th></tr></thead><tbody><tr><td>1</td><td>ΔG<sup>‡</sup> TS attack at the N-Ms position<sup>b</sup></td><td>7.3</td><td>10.6</td><td></td><td></td></tr><tr><td>2</td><td>ΔG<sup>‡</sup> TS attack at the N-Ar position<sup>b</sup></td><td>10.0</td><td>3.9</td><td></td><td></td></tr><tr><td>3</td><td>ΔG<sub>r</sub> attack at the N-Ms position<sup>c</sup></td><td>-35.6<br>(-48.6)<sup>d</sup></td><td>-38.5<br>(-39.9)<sup>d</sup></td><td></td><td></td></tr><tr><td>4</td><td>ΔG<sub>r</sub> attack at the N-Ar position<sup>c</sup></td><td>-48.3</td><td>-51.1</td><td></td><td></td></tr><tr><td>5</td><td>ΔG<sup>‡</sup> TS elimination from N-Ms adduct<sup>b</sup></td><td>-35.1<br>(13.5)<sup>e</sup></td><td>-28.8<br>(11.1)<sup>e</sup></td><td></td><td></td></tr><tr><td>6</td><td>ΔG<sub>r</sub> elimination from N-Ms adduct<sup>c</sup></td><td>-54.6<br>(-6.0)<sup>e</sup></td><td>-51.7<br>(-11.8)<sup>e</sup></td><td></td><td></td></tr></tbody></table>

Given that the solvation of organolithium compounds is often crucial in such nucleophilic addition reactions, an explicit solvation with a THF molecule was incorporated here for the localization of transition states, alongside the implicit

solvation. This was carried out in the presence of a phenyl lithium nucleophilic compound, as experimental evidence had shown that this nucleophilic species behaves similarly to phenyl magnesium bromide in terms of regioselectivity (vide infra). Different orientations were considered for both approaches, with the *ortho* substituent on the aryl group (bromo or methoxy) and the phenyl lithium cation lying on the same side or on opposite sides. With the *ortho*-bromo azo compound **1a**, the kinetically most favoured pathway involved the attack of the nucleophile at the N-Ms side (ΔG‡ = 7.3 kcal.mol⁻¹, Table 3, entry 1) compared to a more energetic TS for the attack at the N-Ar center (ΔG‡ = 10.0 kcal.mol⁻¹, entry 2).²⁹ This is in line with the experimental observation with the preferred formation of the azo compound **3aa** starting from **1a**. Thermodynamically, the N-Ms adduct resulting from the optimization of the adduct arising from the most favoured TS was significantly less stable than the N-Ar adduct. However, a more stable conformer of the N-Ar adduct was located with both the Br substituent and one oxygen atom of the Ms group close to the lithium cation (entry 3, figure in parentheses). The free energies of this N-Ms conformer and the N-Ar adduct were not significantly different (ΔG<sub>r</sub> = -48.3 and -48.6 kcal.mol⁻¹, respectively, entries 3 and 4). The situation was different with the *ortho* methoxy arylazo sulfone **1g**, for which the kinetically favoured path involved the attack at the N-Ar center (compare entries 1 and 2), with the methoxy substituent lying on the phenyl lithium side this time, a conformation which allows an extra coordination of the lithium cation (Li---OMe = 2.16 Å in the TS). A similar coordination can be envisaged with the magnesium atom when Grignard reagents are used experimentally. These values are also in good agreement with the experimental observations which showed that the adduct **4ga**, resulting from an attack at the N-Ar center was preferred with this arylazo sulfone **1g**. In both cases, the elimination step started from the N-Ms intermediate adduct where one oxygen atom of the Ms group was close to the lithium cation, and were of relatively similar energies (effective ΔG‡ = 13.5 and 11.1 kcal.mol⁻¹, entry 5). This elimination step was thermodynamically favoured with negative effective ΔG<sub>r</sub> (-6.0 and -11.8 kcal.mol⁻¹, entry 6).

Overall, the main difference between the two starting arylazo sulfones **1a** and **1g** would arise from the *ortho* substitution on the starting material (Br or OMe) and a combination of their steric and electronic effects. With the methoxy group a coordination can take place with the nucleophile counteraction, favouring the approach on the N-Ar side, while with the less coordinating bromo substituent, the N-Ms approach would be favoured.

## Conclusions

In summary, we have reported a novel and efficient procedure for the synthesis of a wide range of non-symmetric *ortho*-functionalized azoarenes bearing a broad variety of functional groups, obtained in good to excellent yields. Computational investigations revealed that the regioselectivity likely arises from a combination of steric and electronic effects, as well as the presence of a strongly coordinating substituent, such as

<footnote>ªStructure optimizations at the ωB97X-D/6-31+G(d,p) level, with an implicit PCM solvation (THF). ᵇGibbs free energy differences between the optimized transition state and the sum of substrates, in kcal.mol⁻¹. ᶜGibbs free energy difference between the optimized adducts and the sum of substrates, in kcal.mol⁻¹. ᵈin parentheses: Gibbs free energy difference between the intermediate N-Ms adduct, in its most stable conformation, after rotation around the N-SO₂Me bond and the sum of substrates. ᶠin parentheses: Gibbs free energy difference between the elimination TS or product and the starting intermediate N-Ms adduct (in its most stable conformation).</footnote>
OMe, at the *ortho* position of the starting material which directs the nucleophilic attack of the organomagnesium reagents toward the N-aryl group. However, in most cases, nucleophilic attack at the N-sulfonyl position is kinetically favoured, leading to the selective formation of the *ortho*-functionalized azoarenes with high regioselectivity.

## Author contributions

R.H. and V.F. carried out the experiment. All authors provided critical feedback and helped shape the research, analysis and manuscript.

## Conflicts of interest

There are no conflicts to declare.

## Data availability

The data supporting this article have been included as part of the ESI.

## Acknowledgements

The authors acknowledge the Region Normandy (projet émergent n° 23E02619) and the European France-(Manche)-England cross-border cooperation program INTERREG V A "SmartT", co-financed by ERDF, for financial support. This work has also been partially supported by University of Rouen Normandy, the Centre National de la Recherche Scientifique (CNRS), INSA Rouen Normandy, European Regional Development Fund (ERDF), Labex SynOrg (ANR-11-LABX-0029), Carnot Institute I2C, and the graduate school for research XL-Chem (ANR-18-EURE-0020XL CHEM). CRIANN is also acknowledged for their allocation of computer time.

## Notes and references

‡ Footnotes relating to the main text should appear here. These might include comments relevant not central to the matter under discussion, limited experimental and spectral data, and crystallographic data.

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