ORCID Lingyu Kong

Bohdan Biletskyi

Didier Nuel

Hervé Clavier
email: herve.clavier@univ-amu.fr

Cobalt(III

HAL is a

The development of direct functionalization of aromatic C-H bonds catalysed by transition metal complexes has increased tremendously over the past decade [START_REF]For recent selected reviews[END_REF] to reach now a status of powerful synthetic methodology for the preparation of natural compounds, pharmaceuticals, agrochemical products, polymers and commodity and specialty chemicals. 2 Among the various functionalizations, C-H allylations are of interest since allyl moieties can be straightforwardly manipulated to afford a wide range of useful functionalities. 3 Various transition metalbased catalytic systems enable direct C-H allylation such as 3d (iron, cobalt, nickel), 4d (ruthenium, palladium, rhodium) or 5d (iridium) metals. For quite some time Rh was considered to be superior to other metals regarding its reactivity. Recently, research has demonstrated cobalt complexes, in particular high-valent species, 4,[START_REF]For a rare example of low-valent cobalt-catalyzed C-H allylation[END_REF] represent efficient catalysts for C-H functionalization 6 including C-H allylation. For example, a Cocatalysed C-H allylation using unactivated olefin partners was recently developed (Scheme 1a). 7 A major catalytic breakthrough was accomplished in this field with the development of Cp*Co(III)-type complexes. 8,[START_REF]For comprehensive reviews[END_REF] With this catalyst, Glorius and Matsunaga and Kanai reported independently C-H allylation processes with allylic derivatives involving carboncarbon double bond insertion and subsequent -oxygen elimination. 10 From an atom economy point of view, the release of a leaving group is not desirable. Therefore, Li and coworkers explored successfully the possibility to perform C-H allylation with vinyloxirane (Scheme 2b). 11 Importantly, allylated products were obtained as mixture of Eand Z-isomers with ratios spanning from 3.2 to 1.7 to 1. Prior to this work, Ackermann had described that activated vinylcyclopropanes could be used as allylating partners. 12 The -carbon elimination being highly selective, mainly Z-isomers were isolated. Of note, these two reactions were successfully performed with enamides substrates. 13 As a part of our interest for the metal-catalysed activation of small rings, 14,[START_REF] Wang | For selected reviews on TM-catalysed reactions involving small rings[END_REF] we report now herein the use of vinylaziridines to carry out the Cp*Co(III)-cobalt catalysed direct C-H allylation involving a -nitrogen elimination step. [START_REF] Zell | During the redaction of this manuscript, a C-H allylation process with a -F elimination was reported[END_REF] We have optimized the cobalt-catalyzed C-H allylation using the benchmark substrates 2-phenylpyridine 1a and tosyl-containing vinylaziridine 2a and determined that, through the appropriate choice of conditions, the reaction can be achieved with good

Please do not adjust margins

Please do not adjust margins a Reaction conditions: 1a (36 L, 0.25 mmol), vinylaziridine 2a (56 mg, 0.25 mmol, 1 equiv.), Cp*Co(CO)I2 (6.0 mg, 5 mol%), silver salt (10 mol%), additive (10 mol%), solvent (0.5 mL). b Determined by 1 H NMR.

efficiency but unfortunately low E/Z selectivity (Table 1). Thus, during all the experiments of this optimization study, only inseparable mixtures of Eand Z-isomers of allylation products in the range of 0.8 to 1.3:1 3aa were observed. AgSbF6 was found competent to generate the cationic active species from the well-defined Cp*Co(CO)I2. [START_REF] Chirila | For a study by DFT calculations highlighting the need of cationic Cp*Co species[END_REF] With NaOAc as additive, the catalytic system allowed for the formation of 63% of the expected allylation product 3aa in only 2 h at 40 °C in 1,4dioxane (entry 1). With other silver salt such as AgBF4, AgPF6 or AgOTf only small quantities of 3aa were isolated (entries 2-4).

The Co-catalyzed C-H allylation can be carried out in other solvents than 1,4-dioxane, but in slightly lower yields (entries 5-7). Without carboxylate additive, only tiny amount of 3aa were isolated (entry 10). Among the various carboxylate salts we have tested, NaOAc was the most effective (entries 1 and 10-14). Instead of carboxylate salts, carboxylic acids have been evaluated as additive (entries 15-17). The use of pivalic acid -10 mol% being the optimum quantity -allowed to reach 75% of 3aa (entries 17-19).

Having established the optimal reaction conditions, we investigated further the scope of the catalytic system with a range of arenes bearing various directing groups (DG) (Table 2). The Co-catalyzed C-H allylation was successfully applied to several para-functionalized 2-phenylpyridines and the expected products were obtained in good to excellent yields but again contained almost equal quantities of Eand Z-isomers. Importantly, with these substrates no traces of diallylation a Reaction conditions: Arene 1 (0.25 mmol), vinylaziridine 2a (56 mg, 0.25 mmol, 1 equiv.), Cp*Co(CO)2I (6.0 mg, 5 mol%), AgSbF6 (8.6 mg, 10 mol%), PivOH (2.4 mg, 10 mol%), 1,4-dioxane (0.5 mL). E/Z ratio determined by 1 H NMR.

products were detected, highlighting a high mono/di selectivity.

With the same conditions, benzo [h]quinolone 1f reacted to afford 3fa in moderate yield (52%). Furthermore, the scope of arene substrates was broadened to heterocycles such as indole 1g and thiophene 1h. Noticeably, product 3ga was obtained with a significantly higher ratio in favour of the E-isomer. Not only the pyridine moiety could be used as directing group since pyrazole-containing product 3ia and acetanilides 3ka and 3la were isolated albeit in moderate yields. Despite repeated attempts with increase of the reaction temperature, 2phenylbenzoxazole 1j was found unreactive.

Whereas the works of Ackermann 12 and Li 11 on vinylcyclopropanes and 2-vinyloxirane respectively were limited to 1 or 2 examples, we were wondering if this cobalt-catalyzed allylation could be extended to other vinylaziridines 2. The scope and limitations of vinyaziridines are depicted in Table 3.

Overall, sulfonyls as electron-withdrawing groups are well tolerated with yields spanning from 55% for the bulky (2,4,6triisopropylphenyl) sulfonamide derivative 3ae to 88% for 3ad bearing a (phenyl)sulphonamide group. To our delight, vinylaziridines with diphenylphosphinyl and phtalimide groups 1f and 1g reacted well to afford the expected products in 41 and 65% respectively. The use of these different electronwithdrawing groups seems to have no significant influence of the E/Z ratio of the allylated compounds. No C-H allylation Please do not adjust margins Please do not adjust margins Reaction conditions: 1a (36 L, 0.25 mmol), vinylaziridine 2 (0.25 mmol, 1 equiv.), Cp*Co(CO)I2 (6.0 mg, 5 mol%), AgSbF6 (8.6 mg, 10 mol%), PivOH (2.4 mg, 10 mol%), 1,4dioxane (0.5 mL). E/Z ratio determined by 1 H NMR. Ns = 4-nitrobenzenesulfonyl.

occurred with vinylaziridine 2h; since under the reaction conditions used, 2h was converted into the more stable vinyloxazoline. Unfortunately and despite harsher reaction conditions, when the carbon-carbon double bond of the vinylaziridine was substituted by a methyl, either in terminal or internal position, 2i and 2j respectively, no formation of the expected allylation products was observed. In the case of allylating reagents bearing a leaving group, this type of substitution did not shut down the reaction; 10b-d but this point was not discussed for vinylcyclopropane and vinyloxirane. 11,12 Considering recent related mechanistic studies, 10b,12,18 a plausible mechanism is shown in Scheme 2. Formation of catalytically active species A is followed by C-H activation process giving rise to cobaltacycle B. Olefin insertion leads to intermediates C and C' (only one enantiomer depicted) and subsequent syn -N eliminations afford D and D' respectively. Of note, -H elimination process seems to be disfavoured since the formation of alkylideneaziridine was never detected. A protonolysis step releases products 3 and regenerates active species A. The low or no selectivity in the formation of Eand Zisomers seems to indicate that the selective-determining step, olefin insertion, cannot be selectively achieved. Thus, intermediates C and C' are formed in almost equal amounts.

To illustrate the synthetic usefulness of allylated compounds 3, 3aa was treated with iodine in toluene at 25 °C (Scheme 3). After only 30 min, the starting material was completely consumed and pyridinium salt 4 was obtained as a separable mixture of diastereomers with a ratio anti/syn (0.8:1) corresponding to the E/Z ratio of 3aa. [START_REF]After separation by column chromatography, anti-4 and syn-4 were converted into PF6 salts to perform analyses[END_REF] This of note that the 6,7dihydro-benzo[a]quinolizinium moiety of compounds 4 is present in the skeleton of various natural products such as Berberine and related alkaloids. [START_REF] Bentley | [END_REF] Please do not adjust margins Please do not adjust margins

Conclusions

In summary, we have developed a Co-catalysed direct C-H allylation of arenes using vinylaziridines to prepare various allylated aromatic and heteroaromatic compounds overall in good yields. Despite a low E/Z selectivity, this reaction occurring under mild reactions conditions was found relatively broad in scope for both arenes and vinylaziridines. The reaction pathway probably involves a C-H activation step carried out by the versatile cationic cobalt(III) complex, olefin insertion that determines the formation of either Eor Z-isomer, and subsequent -nitrogen elimination that triggers the aziridine ring-opening. A synthetic application of the allylation products has been achieved. Further developments are currently underway in our laboratory and will be reported in due course.

Scheme 1

 1 Scheme 1 Co-catalysed C-H allylation.

Table 1

 1 Optimization of the reaction conditions a

Table 2

 2 Substrate scope and limitation of various arenes a

Table 3

 3 Substrate scope and limitations of various vinylaziridines a a

J. Name.,2013, 00, 1-3 | 3

Scheme 3 Iodocyclisation of C-H allylation product 3aa. Scheme 2 Proposed mechanism.

J. Name.,2013, 00, 1-3 | 4

Acknowledgements

L.K. thanks the China Scholarship Council for a Ph.D. grant. This work was supported by the Ministère de l'Enseignement Supérieur et de la Recherche (B. B. Ph.D. grant), the CNRS, AMU, and Centrale Marseille. We thank Christophe Chendo and Dr. Valérie Monnier for mass spectrometry analyses (Spectropole, Fédération des Sciences Chimiques de Marseille). Dr A. Tenaglia is gratefully acknowledged for helpful discussions.

Conflicts of interest

There are no conflicts to declare.

Notes and references