Prof. Dr Chenxiao Qi

Guillaume Force

Prof. Dr Vincent Gandon
email: vincent.gandon@universite-paris-saclay.fr

Dr David Leboeuf
email: dleboeuf@unistra.fr

Hexafluoroisopropanol-Promoted Haloamidation and Halolactonization of Unactivated Alkenes

Pyrrolidine and piperidine derivatives bearing halide functional groups are prevalent building blocks in drug discovery as halides can serve as an anchor for post-modifications. In principle, one of the simplest ways to build these frameworks is the haloamination of alkenes. While several progresses have been made in this field, notably the development of enantioselective versions, this reaction is still fraught with limitations in terms of reactivity. Besides, a major question remaining is to understand the mechanism at work. The formation of a haliranium intermediate is typically mentioned, but limited mechanistic evidence supports it. Herein, we report an efficient metal-and oxidant-free protocol to achieve the haloamidation of olefins, which is promoted by hexafluoroisopropanol, along with a DFT investigation of the mechanism. We anticipate that these findings should guide the future development of more complex transformations in the field of halofunctionalization.

Introduction

The intramolecular difunctionalization of unactivated alkenes, such as haloamidation reactions, is a powerful tool to build molecular complexity by both creating a new ring and installing halide functionalities, which are present in manifold bioactive molecules and can also serve for further derivatizations. [START_REF]For selected reviews on halofunctionalization of olefins[END_REF] It therefore provides a rapid access to densely functionalized pyrrolidines and piperidines, which are by far the most represented 5-and 6-membered N-heterocycles in drug design (Scheme 1). [2] When it comes to intramolecular haloamidation reactions, sulfonamides have been primarily studied. [3] Yet, their deprotection to obtain the parent amine is not always straightforward, thereby limiting the utility of the transformation. On the other hand, the reactivity of more basic nitrogen functional groups such as carbamates, amides and ureas is less described, apart from few notable transition-metal-or organocatalyst-based methods. [4] One possible explanation might be that the strongly basic nitrogen functionalities compete with the alkene moiety for the electrophilic halide (N-halogenation vs C-halogenation). In consequence, it might preclude, or at least slow down, the reaction because the halide is no longer available. Another issue to take into account is the potential formation of an aziridinium given that the nitrogen functionality is more nucleophilic than a sulfonamide, which can not only lead to the formation of the 6membered ring through a ring-expansion but also to other side products. [3f,4e-f] Although a large variety of transition metals, Lewis acids or organocatalysts (used with or without an oxidant) have been employed to trigger the transformation, methods exhibiting a wide functional group compatibility are scarce. [START_REF]For selected reviews on halofunctionalization of olefins[END_REF] To overcome the current limitations tied to the haloamidation of unactivated alkenes, we envisioned a strategy that would allow to both activate the halide reagent, N-halosuccinimide (NXS) for instance, and prevent the deactivation of the halide source, while operating under mild reaction conditions to suppress the formation of piperidine derivatives. In this respect, we considered the use of hexafluoroisopropanol (HFIP) to be the solution best suited to fulfil these requirements. In the last decade, HFIP has garnered a growing attention owing to its remarkable intrinsic properties, including its ability to stabilize carbocationic species and to be a strong hydrogen bond donor, in addition to its low nucleophilicity. [5][START_REF] Colomer | For selected examples with enhancement of the reactivity of olefins due to HFIP[END_REF] One of the keys to the success of our approach would rely on the inherent capacities of HFIP, including its acidity and its H-bond donating ability, to effectively activate the N-halo succinimide reagent. In addition, we anticipated that, even if the halide is sequestered by the nitrogen functional group, especially the most basic ones, HFIP could favor its release, driving the process to turn over. [7] Moreover, its high dielectric constant and its low nucleophilicity would make it an ideal solvent to generate cations, which are commonly proposed intermediates in haloamidation processes. HFIP has already demonstrated its efficiency as a solvent in halofunctionalizations. [8] However, the reactivity described was limited to arene and oxygen nucleophiles, which are less nucleophilic than amines, hence less prone to quench the electrophile in a side reaction. In the study by the Gulder group, [8a] the mechanistic proposal was based on the putative formation of a haliranium intermediate, which was not supported by either experimental or computational studies. Scheme 1. Halofunctionalization of unactivated alkenes in the presence of HFIP Herein, we report our findings on a broadly applicable and efficient metal-and oxidant-free haloamidation of unactivated alkenes promoted by HFIP as an additive rather than a solvent, which could also be extended to halolactonization with the same efficacy. Furthermore, an in-depth investigation of this reaction by DFT computations allowed us to better understand the mechanism of this transformation and shed light on the key role played by HFIP, discarding several mechanistic pathways postulated in precedent reports on haloamidation.

Results and Discussion

In our initial investigations, we studied the reactivity of N-tosyl aminoalkene 1a to access bromo-pyrrolidine 2a (Table 1). To optimize the efficacy and the selectivity of the haloamidation, we explored a variety of reaction conditions featuring HFIP as an activating agent and different bromine sources, starting with NBS. When HFIP was employed as a solvent, the reaction reached its full conversion in less than 5 min at rt, but the diastereoselectivity was moderate (Entry 1). The selectivity could be slightly improved by conducting the reaction at 0 C (Entry 2). Because of the high cost of HFIP and its high corrosivity, we tested the possibility to use it as an additive. At the outset, we explored the reaction in a solvent mixture DCM/HFIP 5:1 (~10 equivalents of HFIP) (Entries 3-5). The best result was obtained at -40 C, providing compound 2a in 97% yield with a high diastereoselectivity (dr 6.5:1). Of note, the selectivity significantly decreased at -78 C, which might be explained by the fact that the reaction mixture froze at this temperature. Operating at a lower concentration and screening other sources of bromine did not improve the selectivity (Entries 6-8). Other combinations of solvents were also tested (Entries 9-10) and, gratifyingly, performing the reaction in toluene led to the targeted product 2a in 96% yield along with an excellent diastereoselectivity (dr 9:1). [9] On the other hand, replacing HFIP by another fluorinated alcohol such as trifluoroethanol (TFE) proved to be detrimental to both the reaction rate and the selectivity (Entry 11). Then, we evaluated the possibility to further decrease the amount of HFIP (~5 equivalents) (Entries 12-13); however, apart from slowing down the reaction, it did not have any impact on the selectivity or the yield of the transformation. To highlight the critical role of HFIP in this reaction, several control experiments were conducted (Entries 14-16). In the absence of HFIP, no reaction occurred. Switching from HFIP to O-methyl hexafluoroisopropanol (HFIPMe) to preclude any strong Hbonding with the substrates shut down completely the reactivity. Similarly, replacing HFIP by other alcohol solvents such as isopropanol and ethanol that did not possess the same H-bonding ability as HFIP did not mediate the reaction at -40 °C. [START_REF]We also attempted the reaction in the presence of a catalytic amount of a Lewis acid (Ca(NTf2)2/nBu4NPF6) or a Brønsted acid (TfOH) (5 mol%), without HFIP. While the reaction worked smoothly (full conversion in less than one hour)[END_REF] Finally, we demonstrated that the reaction could also be achieved on a [a] 0.075 M. NBS = N-bromosuccinimide. BDMS = bromodimethylsulfonium bromide. DBDMH = 1,3-dibromo-5,5-dimethylhydantoin.

Scheme 2. Scope and limitations of the halofunctionalization of unactivated alkenes.

[a] HFIP (20 equiv). [b] HFIP (5 equiv). [c] in the presence of DCDMH (1.2 equiv).

larger scale (5 mmol) to afford 1.57 g of 2a (95% yield, dr 9:1).

Then, we explored the scope of the transformation with a wide range of N-protected aminoalkenes (Scheme 2). Depending on the substrate, either DCM or toluene was employed in association with HFIP as a solvent mixture. First, we evaluated the impact of the substituents at the terminal position of the alkene. The transformation worked smoothly with arenes bearing electrondonating and, more importantly, -withdrawing groups at the paraposition to furnish the targeted products 2b-2e in high yields (92-97%). Even a highly deactivated substrate such as 1e which incorporates a far less nucleophilic para-nitrostyrene moiety, proved to be compatible with the optimized conditions, albeit at a slower reaction rate (4 h vs 15 min). The reaction was also extended to polycyclic aromatic hydrocarbons such as naphthyl to yield the corresponding products 2f and 2g in high yields (91% and 85%, respectively). The transformation is also tolerant to the presence of electron-donating and -withdrawing groups at the meta-position. However, in the case of an electron-donating group (1h), the reaction had to be conducted at a lower temperature (-40 C) to obtain 2h in a good yield (80%). The reason is that, at 0 C, we observed a partial bromination of the arene ring, resulting in the formation of 2h in 56% yield. On the other hand, in the presence of electron-withdrawing groups (1i and 1j), the reaction had to be executed at rt to reach its completion, delivering 2i and 2j in 90% and 83% yields, respectively. Of note, in the case of the trifluoromethyl group (1j), 20 equivalents of HFIP were required for activating the electrophile. Lastly, substrate with an ortho-substituent (1k) underwent the haloamidation to form 2k in 77% yield. Importantly, the reaction was expanded to sterically hindered 1,1-disubstituted alkenes such as 1l and 1m to give pyrrolidines 2l and 2m in excellent yields (96% and 91%). Bicyclic structures such as 2n were also accessed in 88% yield. Using this method enabled the preparation of piperidines, notably spirocyclic compounds (2'o, 2'p and 2's), in up to 89%yield, starting from substrates bearing either a terminal alkene or a styrene moiety. In turn, with a 1,1dimethyl substitution on the alkene (1t), a mixture of piperidine 1't and 1t was obtained. In the case of 1u, while the haloamidation worked without problem, the resulting product was not stable and compound 2''u was obtained in 89% following the elimination of bromide. With respect to this protocol, the control of 2 stereocenters was not an issue, but the control of 3 ones was more problematic and the overall selectivity was moderate (2v). It is important to stress out that the reaction was not limited to alkenes with a (Z)-configuration as alkenes with a (E)configuration such as 1w could also be subjected to the optimized conditions to afford pyrrolidine 2w in 88% yield with an excellent control of the diastereoselectivity (dr 10:1). In that case, the formation of the minor diastereoisomer might result from a synaddition to the alkene.

Then, we focused on the compatibility of the reaction with a large range of protecting groups on the nitrogen (1a-1i). This protocol offers a remarkable scope regarding nitrogen functional groups, from sulfonamide to amides, carbamates and even ureas with yields ranging from 62% to 96%. Nonetheless, in the case of substrate 1g, which is more prone to generate an aziridinium species, we had to slightly modified the reaction conditions by using 5 equivalents of HFIP at -40 °C, which yielded 4g as a sole product in 79% yield. In addition, our standard reaction conditions could also be applied to unsaturated carboxylic acids to provide bromo-lactones 5a-5d in high yields (up to 96%).

Encouraged by these results, we considered the iodoamidation process, using N-iodosuccinimide as an iodide source, and the intermolecular bromoamidation of p-fluorostyrene. In each case (7a-7b and 8), the haloamidation reaction was accomplished in high to excellent yields (75%-95%). Regarding the limitations of this method, we failed to execute the chloroamidation reaction. In the presence of N-chlorosuccinimide, no reaction occurred, and, by replacing it by 1,3-dichloro-5,5-dimethylhydantoin (DCDMH), we only observed the chlorination of the sulfonamide. Both chloride sources appeared to be not sufficiently electrophilic to trigger the targeted reaction. Additionally, in the case of a N-tosyl amide functional group, the carbonyl ended up being more nucleophilic than the sulfonamide and a subsequent elimination of bromide led to furan 10 in 84% yield. [START_REF] Jaganathan | [END_REF] While the transformation displayed a wide scope under our standard protocol, the critical point was to determine the mechanism of the haloamidation, which has been less studied than that of halolactonization. [START_REF] Denmark | For selected examples[END_REF] Several mechanisms have been postulated but they are not based on experimental or computational evidences. In our case, DFT computations were performed at the OPBE/6-31G (d,p) level of theory to gain insight into the reaction mechanism. [START_REF] Swart | Since high and low spin species have been studied, the OPBE functional has been used[END_REF] A full discussion is presented in the Supporting Information (SI) and only the main conclusions are outlined here. The model substrate A (corresponding to 1a above) was used in this study, as shown in Scheme 3. At first, we envisioned that its reaction with NBS B might lead to the bromination of the nitrogen atom as in C, or to that of the alkene moiety to give either bromonium E or E'. Those are commonly proposed intermediates for the haloamidation of alkenes. The computed free energy is slightly negative for the former (-0.3 kcal/mol) and very high for the others (34.2 and 19.3 kcal/mol respectively). Based on those results, we evaluated the feasibility of the cyclization from the N-Br product C (Scheme 4). The direct formation of the final product G could be computed by reacting the nitrogen with the internal alkene carbon of C', which is a preorganized isomer of C, resulting in a formal insertion of the C=C bond into the N-Br bond. While being markedly exergonic by 37.2 kcal/mol, this process requires to overcome a high activation barrier of 42.2 kcal/mol and can thus be ruled out. Addition of the terminal alkene carbon to give ammonium H also faces an unsurmountable barrier of 39.3 kcal/mol. Then, a radical pathway was studied. Intermediate C' was re-optimized in the triplet state to give the diradical species C''. Although its cyclization could be modeled through TSdirad, C'' already lies too high on the energy surface to make this approach viable (34.1 kcal/mol). [START_REF]UV irradiation or traces of a transition metal could generate traces of radical C'' from C and trigger a radical chain mechanism through I[END_REF] We also re-investigated the cyclization under either neutral, ionic or radical pathways, but could not model the formation of the final product G (see the SI).

Scheme 4. Computed neutral and diradical pathways towards the final product G from N-tosylaminoalkene C (G233, kcal/mol; S: singlet; T: triplet).

On this basis, we suppose that, even if it is formed during the reaction, the N-Br species C may not be a viable intermediate towards G. [START_REF]We are yet aware that intramolecular haloamidations starting from N-halo precursors are feasible, see inter alia: a) I[END_REF]16] We thus hypothesized that the bromination of the alkene moiety of A could be productive via either E or E'. We found that if bromonium E' forms, it readily eliminates through a very low-lying transition state (Scheme 5). As for E, we found that its cyclization into the diastereomeric ammoniums P or P' is a straightforward process that is only based on the conformational change of the alkyl chain. A simple rotation around the C-C bond is enough to trigger the cyclization.

Scheme 5. Computed evolution of bromoniums E and E' (G233, kcal/mol).

With E as best candidate, it remained to explain how it could be formed efficiently. As shown in Scheme 3, the formation of E from A and B is endergonic by as much as 34.2 kcal/mol, but the possible role of HFIP was only considered through the SMD solvent model, not as explicit molecules. We added incrementally H-bonded HFIP molecules to see their effect on the alkene bromination step. One HFIP significantly lowered the free energy to 25.8 kcal/mol, and, with up to six H-bonded HFIP molecules, the free energy of this step was dramatically reduced to 13.1 kcal/mol (Scheme 6). Thus, this co-solvent provides a powerful stabilization of the succinimidate. At this point, the following free energy profile involving a 6-unit HFIP cluster was proposed. Of course, more HFIP molecules could be involved, but it already provides a reasonable picture. Compound A reacts with NBS Hbonded to a (HFIP)6 cluster to give bromonium E and the corresponding succinimidate F•(HFIP)6 lying at 13.1 kcal/mol on the free energy surface. A simple rotation around the C-C bond triggers the cyclization to ammonium P. This step requires only 2.6 kcal/mol of free energy of activation and is exergonic by 29.0 kcal/mol (placing P at -15.9 kcal/mol). TSanti is 2.1 kcal/mol lower in energy TSsyn, which is consistent with the experimentally observed diastereoselectivity (see Table 1). A proton exchange between P and succinimidate F•(HFIP)6 to give the final product G and succinimide is exergonic by 19.3 kcal/mol. The bromination of the nitrogen atom of A to give C is exergonic by 2.4 kcal/mol when using H-bonded NBS. It is thus logical to isolate such products when the cyclization cannot take place. However, this process is easily reversible, and the bromine can be shifted to the C=C bond.

At this point, what was missing was a transition state connecting A and B•(HFIP)n to E and F•(HFIP)n. Despite all our efforts, we did not find a transition state forming a bromonium intermediate. In fact, it has been demonstrated that olefins are often incompetent to capture an electrophile such as Cl + , and that the assistance of a nucleophile to activate the alkene can be required. [12b] The proximity of a nucleophile compensates the loss of electron density during the attack and favors the formation of the C-Cl bond. In our case, we tried to use the oxygen atoms of the SO2 Scheme 6. Incomplete bromonium pathway (G233, kcal/mol) of the bromocyclization of N-tosylaminoalkene A in the presence of a 6-unit HFIP cluster.

moiety, but it did not promote the bromination. We then used the nitrogen atom and, gratifyingly, we could locate a transition state connecting A and B to ammonium P and succinimidate F (n = 0) (Scheme 7). Of note, the ammonium intermediate has 3 stereogenic centers (2 C and 1 N) and thus 4 diastereomers are expected. Only the most energetically favorable option is shown here. The complete sequence involves first the formation of an adduct between A and B, in which the alkene provides electron density to the bromine -hole. [START_REF] Turunen | [END_REF] This weak non-covalent interaction has a maximum electron density between the alkene and the bromine of max = 0.0135 e.Å 3 , which does not provide sufficient energy to compensate the entropic factor, hence the endergonicity of 5.5 kcal/mol for the formation of adduct [A•B]. Conformer [A•B]', preorganized for cyclization, is less stable by a few kcal/mol. The non-covalent interaction between NBS and the alkene involves more electron density, a value of max = 0.0233 e.Å 3 being obtained. The bromonium transfer is achieved though [TScyclization] 0 , which also involves the concomitant formation of the C-N bond. The free energy of activation is of 20.9 kcal/mol and the formation of ammonium P is endergonic by 0.9 kcal/mol. Proton exchange between P and succinimidate F liberates 38.4 kcal/mol of free energy, generating the final products G and D (at -37.5 kcal/mol on the potential energy surface). We then introduced explicit HFIP molecules in the system (from n =1 to 6, see the SI), which considerably lowered the free energy of activation with an optimum of 3. In the case of a 3-unit HFIP cluster H-bonded to a NBS carbonyl, the free energy of the cyclization transition state [TScyclization] 3 dropped to 14.2 kcal/mol, while this step became appreciably exergonic (-14.9 kcal/mol). [START_REF] Goerigk | The OPBE functional has been the subject of some recent criticisms[END_REF] Of note, replacing HFIP by TFE resulted in a higher cyclization barrier of 19.3 kcal/mol. This is in line with the experimental results, which revealed that TFE is a fine additive for the reaction, albeit at slower rate than the one in HFIP (Table 1, entry 11). Thus, the lower pKa of TFE makes it less effective than HFIP for the ionization of the N-Br bond.

In agreement with the work of Berkessel, [19] and our own findings on the alkoxylate walk in H-bonded alcohol clusters, [20] it seems probable that the acidity of HFIP increases after forming a Hbonding network, so that the cluster can accommodate the negative charge of succinimidate D. Thus, the role of HFIP in this reaction is to facilitate the ionization of the N-Br bond of NBS, notably by stabilizing the resulting succinimidate, and trigger a cationic cyclization. What is true for NBS might also be true for the N-bromination of substrates, whose formation may quench the C-bromination process. Of course, in solution, more HFIP molecules can be involved but our computations reveal, at least qualitatively, a positive effect of the formation of a H-bonded NBS rather than a free NBS in triggering a nucleophile-assisted alkene bromination.

Conclusion

In summary, we have developed a broadly applicable haloamidation of unactivated alkenes to provide a convenient route to pyrrolidine and piperidine derivatives, as well as lactones. This transformation was efficiently and rapidly promoted by HFIP as an additive under mild conditions and exhibits a remarkable functional group tolerance, whether at the nitrogen or alkene moiety. A key feature of this study is also our in-depth investigations of the mechanism, including the role played by HFIP, which was carried-out by means of DFT computations. In contrast with previous reports, which suggested either the formation of a haliranium or a N-bromoamide intermediate, our investigations lean towards an activation of the alkene assisted by a nitrogen nucleophile in order to trigger the cyclization, which is in agreement with previous reports on halolactonization. Further applications of this approach are underway in our laboratory, including its to chlorofunctionalizations.

Scheme 3 .

 3 Scheme 3. Free energies (G233, kcal/mol) of various bromine exchange reactions between N-tosylaminoalkene A and NBS B.

Scheme 7 .

 7 Scheme 7. Free energy profile (G233, kcal/mol) of the bromo-cyclization of Ntosylaminoalkene A without HFIP or in the presence of a 3-unit HFIP cluster.

Table 1 .

 1 Reaction optimization for the formation of pyrrolidine 2a.

	Entry	Br + source	Solvent	T [°C]	t [h]	Conversion [%] (yield, trans/cis)
	1	NBS	HFIP	20	0.05	100 (2.7:1)
	2	NBS	HFIP	0	0.2	100 (3.3:1)
	3	NBS	DCM/HFIP (5:1)	0	0.2	100 (4.9:1)
	4	NBS	DCM/HFIP (5:1)	-40	1	100 (97%, 6.5:1)
	5	NBS	DCM/HFIP (5:1)	-78	6	100 (4.4:1)
	6	NBS	DCM/HFIP (10:1) [a]	-40	1	100 (6.3:1)
	7	BDMS	DCM/HFIP (5:1)	-40	1	100 (5.3:1)
	8	DBDMH	DCM/HFIP (5:1)	-40	1	100 (4.4:1)
	9	NBS	MeNO2/HFIP (5:1)	-40	4	100 (6.2:1)
	10	NBS	Toluene/HFIP (5:1)	-40	3	100 (96%, 9:1)
	11	NBS	Toluene/TFE (5:1)	-40	16	100 (5.6:1)
	12	NBS	DCM/HFIP (10:1)	-40	2	100 (6.4:1)
	13	NBS	Toluene/HFIP (10:1)	-40	8	100 (95%, 9:1)
	14	NBS	DCM	-40	1	<5
	15	NBS	Toluene	-40	3	<5
	16	NBS	Toluene/HFIPMe (5:1)	-40	3	<5
	17	NBS	Toluene/iPrOH (5:1)	-40	3	<5
	18	NBS	Toluene/EtOH (5:1)	-40	3	<5

Acknowledgements

We gratefully thank the China Scholarship Council (CSC), the CNRS, the Université Paris-Saclay and the Ecole Polytechnique for the support of this work. This work was granted access to the HPC resources of CINES under the allocation 2020-A0070810977 made by GENCI.

Keywords: halofunctionalization • hexafluoroisopropanol • DFT computations • unactivated alkenes • heterocycles

Entry for the Table of Contents

Less but better: The use of hexafluoroisopropanol as an additive enables the halofunctionalization of unactivated alkenes with a remarkable functional group tolerance under mild reaction conditions. DFT computations were carried out to shed light on the mechanism of haloamidation featuring as a key step an alkene activation assisted by a nitrogen nucleophile.

Institute and/or researcher Twitter usernames: @djpleboeuf and @vincent_gandon


Lucile Marin

Soufyan Jerhaoui

Emilie Kolodziej

Régis Guillot

Vincent Gandon

Françoise Colobert

Emmanuelle Schulz
email: emmanuelle.schulz@universite-paris-saclay.fr

Joanna Wencel-Delord
email: wenceldelord@unistra.fr

David Leboeuf
email: dleboeuf@unistra.fr

Sulfoxide-Controlled Stereoselective Aza-Piancatelli Reaction

Keywords: aza-Piancatelli cyclization, calcium, chiral sulfoxide, hexafluoroisopropanol, 4aminocyclopentenones

The development of a novel stereoselective aza-Piancatelli reaction to access 4aminocyclopentenones is reported. This transformation relies on the use of chiral o-sulfinyl anilines as chiral inductors to afford the targeted products in good to excellent yields. Remarkably, the high value-added cyclopentenones could be obtained in excellent drs (up to > 95:5) depending upon the furan substitution pattern.

The Nazarov cyclization represents an extremely versatile and powerful synthetic tool for a straightforward, atom-and step-economical construction of complex molecular scaffolds. [1] Among the Nazarov-type electrocyclizations, the aza-Piancatelli reaction has a unique place due to the simplicity with which it is possible to introduce nitrogen functionalities. [2] In particular, this transformation enables a rapid access to 4aminocyclopentenones from 2-furylcarbinols and nitrogen-containing derivatives such as anilines. Those compounds are of high interest for synthetic chemists as direct precursors of aminocyclopentitols, which are key motifs in manifold natural and bioactive molecules, including pactamycin, peramivir and trehazolin (Scheme 1a). Despite its significant potential, achieving stereocontrol during this electrocyclization remains highly challenging. To date, only few enantioselective versions of this reaction have been reported, using mainly chiral phosphoric acids and phosphoramides (Scheme 1b). [3] These methods exploit H-bonding to induce the enantioselectivity during the 4-conrotatory electrocyclization. However, they have a limited flexibility regarding the furan substitution pattern.

In this context, devising new strategies towards a more general access to these molecules still represents a compelling challenge to be tackled. As part of our continuing interest in the development of the aza-Piancatelli reaction, [4] we hypothesized that an efficient, general and highly stereocontrolled reaction could be achieved by combining a classical Lewis acid catalysis featuring calcium(II) salts to trigger the transformation and the use of a chiral inductor prompt to generate H-bonding with the amine moiety. [5] Such H-bonding should allow to lock the configuration of the aniline in order to control the torquoselectivity of the electrocyclization (Scheme 1c). In addition, this strategy would provide access to new sulfoxidecontaining scaffolds. This aspect seems particularly appealing as not only the introduction of the sulfoxide motif in bio-active molecules has become increasingly popular in drug discovery as illustrated by sulindac and omeprazole, but also chiral sulfur is a valuable motif in biology. The reason behind is that sulfoxides impart an enhanced water-solubility and fast metabolism when compared to their sulfide counterparts, while providing a possibility of confining a chiral character. [6] Despite a rather common use of chiral auxiliaries in intramolecular Nazarov cyclizations, [1] as reported by Scheme 1. Biologically relevant aminocyclopentitols and stereocontrolled induction for the aza-Piancatelli reaction.

the group of Flynn using Evans' chiral auxiliary, [7][8] it remains surprisingly scarce regarding intermolecular reactions and is usually limited to chiral allenyl ethers, as exemplified by the Tius group. [9] In order to fill this gap, we embarked on the development of a stereoselective aza-Piancatelli reaction by exploiting the potential of chiral o-sulfinyl anilines as chiral auxiliaries. The sulfoxide moiety has established itself as a powerful chiral auxiliary with numerous applications, [10] such as stereoselective reductions of -ketosulfoxides, conjugate additions to unsaturated sulfoxides, additions of sulfinyl carbanions to imines, cycloadditions and even atroposelective Ullmann type N-arylation. [11] More recently, o-sulfinyl anilines, which are easily accessible in one step, have emerged as remarkable chiral bi-coordinating directing groups for asymmetric C(sp 3 )-H activation. [12] Herein, we demonstrate that we can extend the range of applications of chiral osulfinyl anilines to stereoselective electrocyclizations, using the aza-Piancatelli reaction as a springboard.

To validate this concept, our investigations started by focusing on 2-furylcarbinol 1a and various racemic osulfinyl anilines 2a-2c as model substrates to evaluate the efficiency of such process and the influence of o-sulfinyl anilines on the diastereoselectivity of the reaction (Table 1). First, we performed the reaction using our standard catalytic system for the aza-Piancatelli reaction (Ca(NTf2)2/nBu4NPF6 (5 mol%)) [4a,13] in common solvents with o-(ptolylsulfinyl)aniline 2a as a nucleophile (entries 1-4). While, in each case, the full conversion was rapidly reached at 80 °C, the diastereomeric ratio (dr) remained low (at best 1.5:1 in toluene, entry 3), arguably due to the weak H-bonding at high temperature. Thus, we turned our attention to hexafluoroisopropanol (HFIP), [START_REF] For | [END_REF] which has proven to be highly efficient in the aza-Piancatelli reaction, allowing the cyclization to proceed at lower temperature. [4b] In that case, the reaction could be conducted at 20 °C, but the diastereoselectivity remained disappointing (dr 1.1:1, entry 4). The reason Table 1. Reaction optimization for the formation of 4aminocyclopentenones 3a-5a. [a] entry [b] 2 2a 1,2-DCE 80 0.15 3a, 100 (1.4:1) [b] 3 2a Toluene 80 0.15 3a, 100 (1.5:1) [b] 4 2a HFIP 20 3 3a, 100 (1.1:1) [b] 5 2a 1,2-DCE/HFIP (4:1) 20 3 3a, 100 (1.5:1) [b] 6 2a Toluene/HFIP (4:1) 20 0.6 3a, 100 (2.2:1) [b] 7 2a Toluene/HFIP (8:1) 20 3.5 3a, 100 (1.9:1) [b] 8 2a Toluene/HFIP (4:1) 0 32 3a, 100 (2.8:1) [b] 9 2b Toluene/HFIP (4:1) 20 16 4a, 100 (1.1:1) [b] 10 [c] 2c Toluene/HFIP (4:1) 20 2 5a, 99 (3.9:1) [d] 11 [c] 2c Toluene/HFIP (2:1) 0 54 5a, 97 (3:1) [d] 12 [e] 2c Toluene/HFIP (4:1) 0 54 5a, 98 (3.1:1) [d] [a] Reactions conditions: 2-furylcarbinol 1a (1 equiv) and aniline 2a-2c (1.3 equiv) in the indicated solvent (0.25 M) in the presence of Ca(NTf2)2 (5 mol%) and nBu4NPF6 (5 mol%) at the indicated temperature until full conversion was reached. [b] dr determined by 1 H NMR on the crude reaction mixture. [c] 2-furylcarbinol 1a (1.3 equiv) and aniline 2c (1 equiv). [d] Isolated yields. [e] 2-furylcarbinol 1a (1.3 equiv) and aniline 2c (1 equiv) in the presence of Ca(NTf2)2 (10 mol%) and nBu4NPF6 (10 mol%).

2 solvent T [°C] t [h] conversion 3 [%] (dr) 1 2a MeNO2 80 1 3a, 100 (1.3:1)
behind is likely the H-bonding formation between the HFIP solvent and the sulfoxide. [15] Consequently, as the amine moiety is not involved in the weak bonding, a loss of selectivity during the electrocyclization step is observed. [16] Based on these results, we hypothesized that the use of a solvent mixture, and, thus, a decreased amount of HFIP, should allow maintaining the high reactivity at 20 °C while preventing the undesirable participation of HFIP in Hbonding with the o-sulfinyl aniline (entries 5-8).

Gratifyingly, this approach increased the dr from 1.5:1 to 2.2:1 by employing a mixture toluene/HFIP 4:1 (entry 6), and even to 2.8:1 when performing the reaction at lower temperature (0 °C, entry 8). Subsequently, other o-sulfinyl anilines were screened (entries 9-12). In the case of a mesityl substituent, a significant decrease of the dr was observed (entry 9). On the other hand, o-(tert-butylsulfinyl)aniline 2c led to the corresponding 4-aminocyclopentenone 3c in 99% yield with a dr of 3.9:1 (entry 10). The reaction required an excess of 2-furylcarbinol (1.3 equiv) to ensure the complete conversion of 2c as both 2c and 5a have the same Rf on TLC. Of note, at 0 °C, no further improvement in stereoselectivity was witnessed and the reaction required either a larger amount of HFIP (entry 11) or of the catalyst (entry 12) to reach the full conversion.

With these reaction conditions in hand, we then focused on the stereocontrolled version of this transformation using (S)-o-(tert-butylsulfinyl)aniline 2c (er 95:5) (Table 2). The reaction with 2furylcarbinol 1a furnished the desired compounds 5a and 5'a in 74% and 19% yields (dr 3.9:1), respectively.

To our delight, the diastereomeric products 5a and 5'a could be separated by flash column chromatography and the chiral information of the o-chiral sulfinyl aniline was retained. The configuration of the major product 5a was determined by X-ray crystallography.

Remarkably, the reaction could be carried out on a large scale (5 mmol) to provide 5a in a further improved yield (80%). Then, we explored the scope of the reaction, mainly the influence of the substitution at the positions either C-3 or C-4 of the furan. In the case of a phenyl substitution at C-3 and C-4, the diastereomeric ratios were moderate (2.5:1 and 2:1), but the overall yields were excellent (combined yields of 91% and 89%). In particular, the major compounds 5b and 5c were obtained in high yields (65% and 61%) and were separated from the minor compounds 5'b and 5'c by flash column chromatography. In the case of substrate 1c, a decreased amount of HFIP was used (toluene/HFIP 16:1 mixture) due to the instability of 1c in the standard solvent mixture. The reaction was compatible with the presence of alkyl substituents at the position C-4, delivering the products 5d and 5e in good yields and diastereomeric ratios. Of note, the dr Table 2. Scope of 2-furylcarbinols 1a-1h with aniline 2c. [a] [a] Reactions conditions: 2-furylcarbinol 1a-1h (1-2.3 equiv) and aniline 2c (1-1.5 equiv) in toluene/HFIP (4:1, 0.25 M) in the presence of Ca(NTf2)2 (5 mol%) and nBu4NPF6 (5 mol%) at 20 °C for 0.75-36 h. [b] in toluene/HFIP (16:1, 0.25 M). ORTEP drawing of compound 5a (thermal ellipsoids at 50% probability level), CCDC 1906328.

was greatly improved in the presence of an alkyne moiety at C-4 (1f and 1h), providing products 5f and 5h in high yields (97% in both cases). Moreover, the reaction of the tertiary 2-furylcarbinol 1g, incorporating two different substituents, could also be achieved with an excellent selectivity and the expected product was afforded in 72% yield.

Encouraged by the excellent stereoselectivities observed for the substrates 1f and 1h bearing an alkyne moiety at C-4 position, the reactivity of alkynesubstituted 2-furylcarbinols was examined (Table 3). The reaction occurred smoothly for a large variety of substrates bearing both electron-rich and electron-poor aryls, (6a-6b), sterically hindered aryls (6c), heteroaryl (6d), cyclopropyl (6e) and alkyl (6f) groups at the carbinol moiety. Apart from 6f, the corresponding 4aminocyclopentenones were generated in high yields and good to excellent drs (up to > 95:5). Additionally, the reaction was compatible with various functional groups at the alkyne moiety, such as alkyl, trimethylsilyl and thienyl groups, and even with a terminal alkyne (6g-6k). It is also noteworthy that electron-donating and -withdrawing groups (2d and 2e) could be also introduced on the o-sulfinyl aniline to yield the desired products (7l/7'l and 7m/7'm) with 1. Scope of 2-furylcarbinols bearing an alkyne moiety 6a-6k with anilines 2c-2e. [a] [a] Reactions conditions: 2-furylcarbinol 1 (1-1.3 equiv) and aniline 2c (1-1.5 equiv) in toluene/HFIP (4:1, 0.25 M) in the presence of Ca(NTf2)2 (5 mol%) and nBu4NPF6 (5 mol%) at 20-40 °C for 2-36 h. Mes = 1,3,5-trimethylbenzene. excellent yields and good overall drs.

Among other applications possible, we succeeded in accessing a densely functionalized tetrahydrobenzo [b]azepine 5i following an aza-Piancatelli/Michael addition (Equation 1). [4e] While the selectivity remains moderate, the yield is nearly quantitative (97%).

To further highlight the synthetic utility of the newly accessed complex molecules presenting three stereocenters, post-modifications of 5a were undertaken. In the presence of benzylthiol under basic conditions, the Michael addition occurred smoothly to deliver 8 and 8' in 89% yield with a dr of 2.4:1. Rewardingly, both diastereomers were easily separated in 63% and 26% yields, respectively. Subsequent reduction of 8 in the presence of NaBH4 followed by in situ protection gave the ether-silyl congener 9 in 61% yield, offering a pathway to analogs of mannostatin A, a glycosidase inhibitor. [17] Compound 10 featuring an all-carbon quaternary stereocenter was also successfully prepared in 91% yield with an excellent control of the diastereoselectivity. Finally, when treating 5a with Scheme 2. Post-modifications.

NaBH4 and cerium(III) chloride heptahydrate, followed by addition of benzoyl chloride, ester 11 was generated in 71% yield and, unexpectedly, oxidation of the sulfoxide moiety took place to provide the corresponding sulfone. Then, to illustrate the removable character of our o-sulfinyl aniline auxiliary, the mixture of 7l:7l' was first reduced to the corresponding thioether and, then, treated with cerium ammonium nitrate (CAN). A subsequent acidic treatment led to the expected highly substituted aminederived cyclopentenone in 48% yield over three steps.

In order to rationalize the stereoselectivity of this electrocyclization, the origin of the torquoselectivity has been investigated by means of DFT computations at the M06-2X/6-311+G (d,p) level of theory (see the Supporting Information for details). A proton has been used as model catalyst. Since a mixture of solvents has been used, we will first discuss the gas phase Gibbs free energies. Four conrotatory 4-electrocyclization transition states that would lead to the diastereomeric compounds 5a and 5'a are shown in Figure 1. Their G ‡ 298 (kcal/mol) are indicated in parentheses. TS1 and TS2 display the same helicity of the pentadienyl carbocationic fragment. Both would produce the experimentally observed stereoselectivity in 5a. However, the orientation of the chiral auxiliary is less favorable in TS2 because of the steric clash between the Ph and tBu groups. In TS3 and TS4, the helix has the opposite configuration compared to the previous two transition states. This time, as they point in opposite directions, the Ph/tBu clash becomes much less important. Having the tBu outward remains the best option, but TS3 lies higher in energy than TS1. In addition to these steric considerations, the preference for TS1 in the gas phase can be explained by analyzing the non-covalent interactions. While each transition state exhibits a N-H … O-S hydrogen bond, only TS1 can establish additional hydrogen bonds between the sulfoxide oxygen and protons of the -extended pentadienyl-phenyl carbocation. The maximum electron density in these two C-H … O-S areas is max = 0.010 e.Å -3 , which is quite appreciable (about a third of the N-H … O-S hydrogen bond (max = 0.033 e.Å -3 ), but twice). Taking HFIP as solvent (SMD method), the difference between TS1 and TS3 drops to 0.2 kcal/mol, which is in line with the absence of selectivity reported in Table 1, entry 3. With toluene as solvent, the G ‡ 298 between TS1 and TS3 is computed to be 1.4 kcal/mol. There is indeed a slight preference for 5a under toluene-only conditions (Table 1, entry 4). Thus, the torquoselectivity appears to be governed by both the steric hindrance brought about by the bulky t-Bu group and non-covalent interactions that will be strongly affected by the reaction medium. [18] In conclusion, we reported herein the first examples of stereoselective aza-Piancatelli reaction using enantiopure o-sulfinyl anilines as nucleophiles, which allows the synthesis of highly substituted cyclopentenones bearing two C-stereocenters with up to 98% yield and 95:5 dr. The synthetic value of this approach was further illustrated by postderivatizations of the newly accessed scaffolds, thus, paving the way towards versatile molecules of interest for potential pharmaceutical applications.

Figure 1 .

 1 Figure 1. Computed TS1-TS4 for compounds 5a and 5'a (G ‡ 298, kcal/mol).

Acknowledgements

We gratefully thank the CNRS, the Ministère de l'Enseignement Supérieur et de la Recherche (funding for LM), the Université Paris-Saclay, the Ecole Polytechnique and the ANR (ANR-14-CE06-0009-01, funding for SJ) for their support of this work. We gratefully thank Guillaume Force for the preparation of (S)-o-(tert-butylsulfinyl)-N-methylaniline and the corresponding attempt at the cyclization.

UPDATE


Asmaa Harmouzi

Mohammed Bouachrine

Philippe Guionneau

Alexandre Fargues

Abdesselam Belaaraj

Optical properties of (C2H5-C6H4-NH2)2ZnBr2 complex material: Experimental and TD-DFT studies

Keywords: Absorption bands, Frontier molecular orbitals, Band gap energy, TD-DFT

This study aims to develop a new type of semiconductor materials. In this context, the coordination complex (CH 3 -CH 2 -C 6 H 4 -NH 2 ) 2 ZnBr 2 material was subjected to UV-Vis spectroscopy and the dependent theoretical density functional theory (TD-DFT) studies. The optical properties such optical absorption, band gap and molecular orbital energies are determined and discussed. The experimental results and theoretical conclusions appear to be in good agreement. Although we checked that the experimental molecular geometry is predicted correctly using the (TD-DFT) method. The molecular electrostatic potential (MEP) was calculated to predict physicochemical properties. The molecular composition of HOMO-LUMO and their band gap energies are represented in order to explain the activity of the title compound. So, the studied material seems to have a semiconductor behavior.

Introduction

In the increasingly-wide context of research on inorganic-organic hybrid materials, and according to their important and diversified physicochemical properties originating in the association of the organic and inorganic properties [START_REF] Houel | Revêtements polyesters hybrides organiques-inorganiques par voie sol-gel[END_REF], we currently focus on the design and investigation of coordination complexes [START_REF] Harmouzi | [END_REF][3][4]. Metal-organic coordination complexes, combining simple synthesis along with tunable optical properties had a lot of concern over the latest decades, due to their vast potential application in optoelectronic devices [5][6][7]. For example, with the relevant set of optoelectronic properties, metal-organic complexes may lead off to the next generation of solar energy conversion, replacing fragile and high-temperature processing semiconductor materials. The inorganic-organic coordination is completed at the level of the metal ion. Consequently, the Zn 2+ ion has an electron configuration [Ar] 3d10; therefore, the coordination links are created by involvement of the unoccupied 4s and 4p AOs. By reason of the coordination, a quasi-tetrahedral complex of zinc is formed, corresponding bonds are represented in a simple way by the means of four electron pairs that occupy sp3 hybrid orbitals. From the optical point of view, there are two bands in the far UV corresponding to the ligand (R-NH2) and one band corresponding to the transition of the metal to a ligand charge-transfer (MLCT) as well as two other bands which correspond to the transition from halogen to metal. It is well known that the band gap energy between HOMO and LUMO is a decisive parameter in the determination of the electrical transport properties of molecules [8]. In addition, the band gap energy has effectively been of use to prove the bioactivity from intermolecular charge transfer [9,10]. Furthermore, a molecular complex with a slight frontier orbital gap have higher polarizability and it is mostly associated to a high chemical reactivity and a low kinetic stability [11]. In the present work, the optical properties of the complex dibromidobis(4-ethylaniline-kN)Zinc of chemical formula (CH3-CH2-C6H4-NH2)2ZnBr2 (hereinafter called 4EA-ZnBr2), like band gap energy, activation energy and absorption wavelength, are reported and discussed.Results and Discussion

Experimental optical study

The UV-Vis diffuse absorbance spectroscopy (Figure 1) was performed on a crystalline powder of the 4EA-ZnBr2 structure of a previous work [START_REF] Harmouzi | [END_REF] at room temperature, on a VARIAN Cary 5000 double beam spectrophotometer in the spectral range 200-800 nm. The absorption spectrum F(R) calculated from the reflectance R spectrum using the Kubelka-Munk function:

F(R) = (α/S) (1-R) 2 /(2R).
Where α, S are respectively the absorption and scattering coefficients [12.13].

Figure1: UV-vis absorption spectrum of 4EA-ZnBr 2

Figure 1 shows the UV-visible absorption spectrum of 4EA-ZnBr2 measured at room temperature. Five strongest absorption bands centered at 236, 275, 338, 425 nm and 580 nm, are observed. The high intense absorption peak at 236 nm is due to (π→π*) electronic transition while the second peak at 275 nm is due to (n→π*) electronic transition. So the intense band in the visible region is assigned the metal to ligand charge-transfer (MLCT) [14] which is associated with Zn(II)-4ethylaniline (λ=338nm).This metal to ligand charge transfer transition arises from the (t2g6) on the Zn(II) to the empty π* orbitals on 4-Ethylaniline ligands (t2g6 → π *) [15][16][17]. The peak at 580 nm is attributed to the transition from the initial electronic state of the Br-3p valence band to the Zn-4p. The second peak at 425nm comes from the transition between the Br-3p valence band and Zn-4s conduction band [18][19][20]. We have also determined the band gap by transformed Kubelka-Munk spectrum (Figure 1) and the photon energy axis. The obtained value is found to be about 2.15 eV, which agrees very well with that of the hybrid perovskite compound CH3NH3SnBr3 [21]. This result indicates that the studied compound is a wide band gap semiconductor.

Optical properties calculations

To determine the structural and optoelectronic characteristics of the studied molecule, we have started by optimizing the structure of this molecule using DFT quantum chemistry calculations and especially the Lee -Yang -Parr LYP (B3LYP) method [22][23][24][25][26]. In the same vein, we have used the 6-311G base (d, p) [27] which is widely applied and cited by many authors for its effectiveness in the study of macromolecular systems [28]. A frequency calculation has been carried out to ensure that it is an absolute minimum corresponding to the most stable conformation. Electronic properties such as HOMO, LUMO and band gap energy are determined from the fully optimized structure. The SCXRD experimental data [START_REF] Harmouzi | [END_REF] were used as a beginning point for optimizing the atomic positions. In order to determine the absorption properties and the electronic transitions, we have adopted the method of the functional theory of density versus time (TD-DFT) [START_REF] Gross | Density functional theory II[END_REF] starting from the optimized structure obtained by the B3LYP/6-311G base (d, p) method. All the quantum chemistry calculations performed in this work were done using the Gaussian (03) program [START_REF] Frisch | Gaussian 03[END_REF]. The calculations of the simulated absorption spectra were realized using the SWIZARD program [START_REF] Gorelsky | SWizard program[END_REF]. The corresponding simulated UV-Vis absorption spectrum data (Figure 2) like energy of activation, wavelength absorption λabs (nm) and oscillator strength (O.S), calculated using TD/DFT theory are given in Table1, where MO is the molecular orbital. As it can be seen, the calculated wavelength λabs of the studied compound shows a maximum at 604.001, 445.215, 347.721, 294.008 and 236.542 nm. As illustrated in Table 1, this could be regarded as an electron transition process which is the reverse of the absorption corresponding respectively to H-2 ->LUMO, H-8 ->LUMO, H -9->LUMO, H-10 ->LUMO and H-2 ->L+1 electron transitions configurations. In addition, it is worth noting that the broader absorption peak means that there is a distribution of energy level corresponding to the π→π*, n -π* or halogen-metal transition. These interesting points are seen both from experimental and theoretical absorption results.

The molecular orbital study

The optimization of molecular geometry was made at B3LYP/6-311G (d,p) level in gas phase.

The structure calculated is presented in Figure 3. So, to obtain an indication of excitation properties, the molecular orbital contribution of the complex materials must be understood, which explains the relative arrangement of the occupied and virtual orbits. As observed in Figure 4, the HOMO and LUMO are respectively an antibonding and binding character between the subunits. Further, the electron distributions of HOMOs are essentially localized on conjugation spacer moiety between halogen and metal, but in the LUMOs both of them are distributed between metal and halogen and in the aromatic cycle. We present in Table 2 the calculated values of the HOMO/LUMO and band gap energies. The band gap energy (Eg) was evaluated theoretically as the difference between the HUMO and LOMO energies (Eg = EHOMO -ELUMO). The obtained value Eg= 2.22 eV agree very well with the experimental one, mentioned above, and confirms the semiconductor behavior of the studied compound.

Analysis of molecular electrostatic potential

In this part, we are interested in the study of the electrostatic molecular potential (MEP) in order to identify the reactive sites for the electrophilic and nucleophilic attack and to predict the physicochemical properties. We calculated Le (MEP) of the studied molecule was calculated using the same method previously used B3LYP / 6-311G (d, p). MEP is a method of correlating electronegativity and partial charges with the chemical reactivity of molecules [START_REF] Chengjun | [END_REF]. It is a threedimensional visualization that makes it possible to understand the net electrostatic effect of a molecule by means of a graphical representation of the electrostatic potential mapped in the constant electron density surface. It also serves to study and confirm the relative polarity of the compounds. The electrostatic potential values at the surface are represented by different colors.

The color code of the map is in the range between -5.459 e-2 (deepest red) and 5.459 e-2 (deepest blue); where red color denotes the negative electrostatic potential or electron rich area and blue region corresponds to the positive electrostatic potential or electron deficient region.

It is understood from the MEP map (Figure 5) that hydrogen atoms of phenyl and nitrogen group exhibit electropositive, this indicates that this group can act as a good donor which consequently expected to be vulnerable site for nucleophilic attack. On the other hand, the negative electrostatic potential region is mainly localized on the groups located on the other side of the molecule especially in the bromine groups, which is possible site for electrophilic attack.

Confrontation between the theoretical and experimental results

Molecular geometry

A comparison between the calculated selected parameters and the experimental data [START_REF] Harmouzi | [END_REF] was done to validate the theory level used. The molecular structure of the studied compound (Figure 6), along the c-axis has a form as V, which constitutes two benzene rings, with an angle α between the two planes (P1^P2) of the benzene rings of about 86.22° for the experimental one, and 66.22° for theoretical one. The experimental and theoretical length of the molecule (L) along the crystallographic b axis were found to be 14.85 Å and 14.13 Å respectively. 3.

Optical properties

The comparison between the experimental and theoretical spectra evidences good agreements, but also some discrepancies. The intense absorption peak measured at 236 nm is in good agreement with the calculated peak at 236.54 nm which is due to (π→π*) electronic transition originating in the excitation from the highest occupied molecular orbital (HOMO-2) to the second level of unoccupied molecular orbital LUMO+1. The second experimental peak at 275 nm significantly deviates from the calculated peak at 294 nm which is due to HOMO-10→ LUMO electronic transition. The HOMO-10 and LUMO have large contributions from the n and π* respectively of the ligand 4-Ethylaniline.

An intense calculated absorption band with a maximum at 347.72 nm, slightly different from the experimental maximum at about 338 nm, corresponds to the excitation from HOMO-9 equivalent of t2g6 (ZnII) to the second level LUMO (π*) orbital of 4-Ethylaniline, this absorption band is due to the transition metal-ligand charge-transfer (MLCT). The other two electronic transitions calculated at 445.21 nm and 604 nm correspond to those observed experimentally at 425nm and 580 nm respectively, showing slight discrepancies between calculation and observation. The first transition corresponds to the excitation from HOMO-8 to the LUMO accompanying the 3p-MO of Br to the 4s-MO of Zn, and the second transition corresponds to the excitation from HOMO-2 (3p of Br) to the LUMO (4p of Zn). The observed differences are probably due to the nature of the investigated sample. The latter is in the form of single-crystals, the molecular structure is therefore impacted, at some extend, by the crystal packing. Despite the above slight differences, the calculated band gap Eg= 2.22 eV is close from that obtained by experimental UV-VIS spectrum (Eg= 2.15eV). The slight difference between these values can also probably be attributed to the fact that DFT calculations are performed for gas phases and not for solids. Disorganized system tends to increase the gap value while in the solid state the system is organized in most cases as crystals and the value of the band gap is expected slightly lower than that obtained from quantum calculations as found in the present study; note that the difference of 0.07 eV between gas and solid phases band gap energies agrees with the value reported in the literature [33][34][35][36].

Conclusions

An experimental and theoretical comparative study of optical features of the complex (CH3-CH2-C6H4-NH2)2ZnBr2, has been carried out, using experimental UV-Vis spectroscopy and TD-DFT-B3LYP theory. The experimental energy gap is found to be 2.15 eV, in good agreement with the calculated value (2.22 eV), which reveals that the studied complex presents a semiconductor character. Consequently, this kind of material appears of interest to give a new access in the researching field of semiconductor materials. Incidentally, the comparison between the theoretical and experimental values gives also a comparison between the gas phase and the solid phase, for this compound. The studied molecule provides similar features at the level of the absorption bands and the gap in energy of molecules studied in gas and in solid. Some differences can be noted, but globally this molecule adopts a similar behaviour in solid and in gas phases. At the level of the geometric correlation of the molecular, we can notice that the molecule is moving a little when it passes from the solid state to the gas state. This change of state is the cause of finding some different geometrical parameter between the theory and the experimental one, like the angles of torsion formed between C (3) -C (4) -C (7) -C (8) and C (5) -C (4) -C (7) -C (8), as well as for the angle α (P1 ^ P2). The other geometrical parameters are close between the values in gas phase (theory) and in solid phase (experimental). We conclude that the correlation between the theory and the experimental shows that the molecule keeps the same optical properties despite its small difference at the structural level.

On the other hand, the molecular electrostatic potential (MEP) calculation showed that the hydrogen atoms of phenyl and nitrogen group can act as a good donor which consequently expected to be vulnerable site for nucleophilic attack. While the negative electrostatic potential region is mainly localized in the bromine groups, which is possible site for electrophilic attack.

Figure 2 :

 2 Figure 2: Simulated UV-Vis absorption spectrum of 4EA-ZnBr 2

Figure 3 :Figure 4 :

 34 Figure 3: Optimized and theoretical molecular structure of 4EA-ZnBr 2 obtained at B3LYP/6-311G (d,p) level.HOMO LUMO

Figure5:

  Figure5: Molecular Electrostatic Potential Maps of 4EA-ZnBr2 (Fused system) showing the blue and red coloras the positive and negative potential respectively and the green color indicates the intermediate region.

Figure 6 :

 6 Figure 6: Optimized and experimental molecular structure of 4EA-ZnBr 2 along the c-axis and b-axis (α: angle between the two planes P1et P2/ L: length of molecule). The experimental bonds values C(4)-C(7) (1.5 Å) and C(7)-C(8) (1.39 Å) are in good agreement with the calculated bonds 1.51, and 1.54 Å respectively. The corresponding distances and angles values around the zinc atom in N-Zn, Br-Zn, N1-Zn-N2, Br1-Zn-Br2, N1-Zn-Br2 and C1-N1-Zn are also similar. In addition, the angles C2-C1-N1, C6-C1-N1, C3-C4-C7, C5-C4-C7 and C8-C7-C4 have the same values in both experimental and theoretical studies. However, we have not observed any significant changes in intermolecular distances and angles between the theory and the experimental, except for torsion angles which are 131° and -50° for the experimental C3-C4-C7-C8 and C5-C4-C7-C8, and 90° and -87.63° for the corresponding calculated torsions angles. The intermolecular interactions are represented in the π stacking along the c-axis by the distance CH ... C, and the interaction along the b-axis, which is called side by side, by the distance NH ... Br. Both interactions are hydrogen interactions that have the same experimental and theoretical values. The results are recapitulated in the Table3.

Table 1 :

 1 Absorption spectra data obtained by TD-DFT methods at B3LYP/6-311 G (d,p) optimized geometry.

	No.	Excitation energies (eV)	λmax(nm)	Oscillator Strengths	MO/character	% (Major contributions

Table 2 :

 2 The calculated values of the HOMO/LUMO energies and band gap energies for 4EA-ZnBr2.

	E(HOMO) (eV)	E(LUMO) (eV)	Egap (eV)
	-6.20	-3.98	2.22

Table 3 :

 3 Summarizes the selected parameters obtained at the level of the theory B3LYP / 6-311-G (d, p) and those of SCXRD for the molecule 4EA-ZnBr2.

	Complex formula	(C2H5-

C6H4-NH2)2ZnBr2 Experimental(SCXRD) Theory (TD/DFT)

			L
			C
			N
			Zn
			Br
			H
	The interactions (NH…Br)	2.73/ 2.81 Å	2.70/2.80 Å
	The interactions (C-H…C)	2.79Å	2.85 Å
	N-Zn	2.05 Å	2.14 Å
	Br(2)-Zn(1)	2.38 Å	2.34 Å
	N(1)-C(1)	1.45 Å	1.44 Å
	C(4)-C(7)	1.50 Å	1.51 Å
	C(7)-C(8)	1.39 Å	1.54 Å
	N1-Zn-N2	115.85°	101.17°
	Br1-Zn-Br2	110.56°	107.21°
	N(1)-Zn(1)-Br(2)	108.28°	112.85°
	N(1)#1-Zn(1)-Br(2)	106.96°	109.88°