Jordi Vila

Miquel Solà

Thierry Achard

Stéphane Bellemin-Laponnaz

Anna Pla-Quintana

Anna Roglans

Stephane Bellemin-Laponnaz

Rh(I) complexes with hemilabile thioetherfunctionalized NHC ligands as catalysts for [2+2+2] cycloaddition of 1,5-bisallenes and alkynes

Keywords: [2+2+2] cycloaddition, allene, rhodium, N-heterocyclic carbene, DFT calculation

published or not. The documents may come

Rh(I) Complexes with Hemilabile Thioether-Functionalized NHC Ligands as Catalysts for [2 + 2 + 2] Cycloaddition of 1,5-Bisallenes and Alkynes

Introduction

Transition metal-catalyzed [2+2+2] cycloaddition reactions are a useful tool for the synthesis of 6-membered carbo-and heterocyclic compounds in a one-step highly atom economic process. 1 The different types of unsaturation that can be involved in these processes open the door to a wide range of cyclic derivatives with different functionalities. Among the unsaturations that can be involved in the [2+2+2] cycloaddition reaction, allenes are particularly versatile as their two cumulated double bonds can individually participate in the cycloaddition. However, with this increased diversity comes greater difficulty in controlling chemoselectivity. 2 As the number of allenes involved in the [2+2+2] cycloaddition increases, the number of possible regioisomers also increases. After the pioneering studies by Benson and Lyndsey 3a in 1958 based on the cyclotrimerization of allene by a Ni(0) catalyst, only a couple of studies by Ma and co-workers involve three allenes in a [2+2+2] cycloaddition to obtain steroid-like scaffolds. 3b-d Initially, the group described a bimolecular [2+2+2] cycloaddition of bisallenes under rhodium catalysis giving a diene, which then underwent a Diels-Alder reaction with the remaining allene, giving precursors of steroidal structures. 3b,c A complementary approach to this process was the cycloaddition between a 1,5-bisallene and monoallenes (Scheme 1a). 3d The reaction took place chemoselectively between an internal double bond and an external double bond of the bisallene and the external double bond of the monoallene under rhodium catalysis, giving a bicyclic derivative with two exocyclic double bonds. On the other hand, if we consider the participation of two allenes with an alkyne, we can find different processes based on the nature of the allenes and the nature of the transition metal used as the catalyst. Tanaka and co-workers [START_REF] Sakashita | Rhodium-catalyzed cross-cyclotrimerization and dimerization of allenes with alkynes[END_REF] described the cross-cyclotrimerization of two monosubstituted allenes with one alkyne to afford 3,6-dimethylenecyclohex-1-ene derivatives resulting from the cycloaddition of the external double bond of the allene (Scheme 1b). In contrast, when starting with di-or trisubstituted allenes and using the same catalytic system, a b-hydrogen elimination on the rhodacyclopentene intermediate took place instead of the insertion of the second allene, affording dendralene derivatives. Arai and co-workers [START_REF] Arai | Regioselective [2+2+2] cycloaddition reaction using allene-ynes with simple allenes under nickel catalysis[END_REF] reported the cycloaddition between two different allenes and an alkyne under nickel catalysis and demonstrated by DFT calculations that the selectivity of the reaction was affected by steric effects around the p-bonds (Scheme 1c).

There are also examples involving an alkene with two allenes that have been reported by both Alexanian and co-workers 6 and our own group [START_REF] Haraburda | Stereoselective rhodiumcatalyzed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies[END_REF] . Alexanian described the stereoselective and enantioselective rhodium-catalyzed [2+2+2] cycloaddition of ene-allenes and allenoates, affording trans-fused carbocycles with four stereogenic centres (Scheme 1d). The authors postulated an initial oxidative coupling of the two allenes involving the two internal double bonds of both allenes. The alkene was then inserted into the rhodacyclopentane establishing the trans ring fusion in this step. We 7 also studied the stereoselective cycloaddition of linear allene-ene-allene substrates to afford tricyclic systems. The Wilkinson complex promoted cycloaddition involving the internal double bonds of both terminal allenes, affording the corresponding exocyclic dienes (Scheme 1e).

DFT calculations showed that initial oxidative coupling took place between the internal double bond of one of the allenes and the alkene, affording a cis ring fusion. The internal double bond of the second allene was then inserted delivering this time a trans ring fusion to afford the exocyclic hexadiene after reductive elimination. In the same study, we also reported an analogous reaction on an allene-yne-allene substrate.

Scheme 1. Metal-catalyzed [2+2+2] cycloaddition reactions of allenes.

Following on from our interest in allenes in cycloaddition reactions, we became interested in involving 1,5-bisallenes in the [2+2+2] cycloaddition reactions. This special class of allenes has shown a wide range of reactivities under transition-metal catalysis. 8 However, in our initial studies, both by reaction with alkenes and alkynes, we were unable to trigger a [2+2+2] cycloaddition reaction. Instead, very interesting reactivities were observed (Scheme 2). In the reaction of 1,5-bisallenes with alkenes, dihydroazepine-and dihydrooxepine-fused ring systems were obtained in good yields. 9 Further mechanistic study by DFT calculations showed that the reaction took place through a rhodium-catalyzed cycloisomerization/Diels-Alder cascade encompassing oxidative coupling of the rhodium to the central carbon atoms of both allenes (intermediate I) followed by a β-hydride elimination (intermediate II) and reductive elimination of the rhodium to afford a nonisolable cycloheptatriene derivative III, which gave a further Diels-Alder reaction with the alkene (Scheme 2a). In contrast, when an alkyne was used as a third component using the same catalytic system as before, 1,5-bisallenes reacted with two molecules of the alkyne to afford cis-3,4arylvinyl pyrrolidines and cyclopentanes in a totally diastereoselective manner. [START_REF] Vila | A Rh(I)-catalyzed cascade cyclization of 1,5-bisallenes and alkynes for the formation of cis-3,4-arylvinyl pyrrolidines and cyclopentanes[END_REF] Here again, DFT calculations allowed us to unveil the course of the reaction, which involves a [2+2+2] cycloaddition between two molecules of the alkyne and the external double bond of one of the two allenes of the bisallene (intermediate IV) followed by a cycloisomerization reaction involving the internal double bond of the second allene unit (intermediate V). Finally, a b-hydride elimination step followed by reductive elimination afforded the final product (Scheme 2b).

Scheme 2. Rh(I)-catalyzed cyclization reactions of 1,5-bisallenes with alkenes and alkynes performed in our group.

Still with the idea of developing a [2+2+2] cycloaddition reaction of 1,5-bisallenes, we came across the study by the Alexanian group 11 on the cycloaddition of ene-allenes and alkenes under nickel catalysis. The study nicely showed that the selectivity can be controlled by fine-tuning the catalytic system, as the use of P(OTol)3 triggered a [2+2+2] cycloaddition, an alkenylative cyclization occurred when PBu3 was used, and finally a [2+2] cycloaddition ene-allene occurred when Xantphos was the ligand of choice. In addition, 1,5-bisallenes also follow different reaction pathways under rhodium catalysis depending on the nature of the ligands. Whereas Ma and coworkers 3d described a bimolecular [2+2+2] cycloaddition of the bisallene to afford steroid-type scaffolds when the Wilkinson catalyst was used (Scheme 1a), our group, using DTBM-Segphos as ligand, described a cascade process encompassing a cycloisomerization of the 1,5-bisallene followed by a selective Diels-Alder homodimerization affording spirocyclic compounds. [START_REF] Vila | Highly selective Synthesis of seven-membered azaspiro compounds by a Rh(I)-catalyzed cycloisomerization/Diels-Alder cascade of 1,5-bisallenes[END_REF] Inspired by the results of Alexanian and our own experience, we thought of testing ligands other than bisphosphines to influence the course of the process. An alternative class of ligands are the Nheterocyclic carbenes (NHC), that often give reactivities that are complementary to those of phosphines. Several examples of transition metal-catalyzed [2+2+2] cycloadditions with NHC ligands are described in the literature. Among these, complexes of cobalt 13 and, especially, nickel 14 are the most used. Louie's research group has conducted several studies of [2+2+2] cycloadditions involving mainly hetero-unsaturations, such as isocyanates, ketenes, nitriles, aldehydes and ketones using Ni-NHCs ligands. 15 To the best of our knowledge, in the case of rhodium, there are only two previous studies reported by our group in which Rh-NHC complexes, both in homogeneous 16 and heterogeneous versions, 17 are tested for [2+2+2] cycloaddition reactions of alkynes.

NHCs are strong σ-donor ligands and hence form strong metal-ligand interactions that can prevent catalyst decomposition resulting in loss of ligands under reaction conditions. Moreover, their simple synthetic procedures and the ability to tune their steric and electronic properties by modifying the nitrogen or backbone substituents make them very attractive for rapid ligand screening. Rhodium(I) bearing monodentate NHCs have been successfully applied to several metal-catalyzed transformations such as hydrothiolation, hydrophosphination, cross coupling reaction, and dimerization reactions. 18,19 Although most NHCs are monodentate ligands, a strong interest has been shown for the past 10 years and still continues today for the chemistry of functionalized NHC carbenes in which a Lewis base moiety (often rooted on: N, P or O atom) is attached to the strongly bonded imidazolyl ring. 20 However, although the S-functionalized Nheterocyclic carbenes are less represented, [START_REF] Fliedel | Recent advances in S-functionalized N-heterocyclic carbene ligands: From the synthesis of azolium salts and metal complexes to applications[END_REF] they are also an interesting class of ligands because they can potentially provide an "on and off" dynamic chelating effect for the metal complex during a catalytic cycle. This hemilability has been particularly demonstrated for the thioether function with different metals. 22 NHC-SR metal complexes have demonstrated their catalytic activity in several transformations such as hydrosilylation of aldehydes 22e and ketones [START_REF] Wolf | Nickel(II), Palladium(II) and Rhodium(I) complexes of new NHC-thioether ligands: efficient ketone hydrosilylation catalysis by a cationic Rh complex[END_REF] , the Suzuki-Miyaura cross-coupling reaction, [START_REF] Sharma | Thioether-NHC-ligated Pd II complex for crafting a filtration-free magnetically retrievable catalyst for Suzuki-Miyaura coupling in water[END_REF] hydrogenation of double bonds, [START_REF] Gandolfi | Chelating NHC Ruthenium(II) complexes as robust homogeneous hydrogenation catalysts[END_REF] click reaction, [START_REF] Szadkowska | Synthesis, structural characterization and catalytic activities of sulfur-functionalized NHC-copper(I) complexes[END_REF] dehydrogenation of amine [START_REF] Chen | Synthesis, characterization, catalytic and biological application of half-sandwich ruthenium complexes bearing hemilabile (κ 2 -C,S)-thioetherfunctionalised NHC ligands[END_REF] and the reaction of amidation. [START_REF] Egly | Half-sandwich ruthenium complexes bearing hemilabile k 2 -(C,S)-thioether-functionalized NHC ligands : application to amide synthesis from alcohol and amine[END_REF] Only two examples were reported for NHC-SR rhodium(I) complexes, by the group of Poli 22 and the group of Lassaletta, [START_REF] Ros | cyclotrimerized [2+2+2] adduct of the acetylene dicarboxylate 2, making it impossible to measure the d.r. accurately. (35) As an experimental evidence of ligand hemilability, bromide abstraction on the neutral Rh complex RhL4 generated a cationic square planar complex with NHC acting as a bidentate ligand, as deduced from X-ray diffraction experiments[END_REF] and none of them were applied to cycloaddition reactions.

In this work, a variety of NHC-imidazole ligand precursors (monodentate and bidentate) were evaluated in the Rh(I)-catalyzed [2+2+2] cycloaddition of 1,5-bisallene and alkynes. Through extensive screening of various conditions, a catalytic system with an S-functionalized NHC-Rh complex, with a catalyst loading of 5 mol%, was developed, which for the first time promoted the efficient [2+2+2] cycloaddition of 1,5-bisallene and alkynes.

Results and discussion

Synthesis of S-functionalized imidazolium salts. All S-functionalized imidazolium salts L2-5

(Figure 1) were synthesized according to our previously reported procedure by direct reaction of the 2-bromoethyl-imidazolium derivative with the corresponding sodium thiolate. 22d,27 Considering that the size of the R thioether group can influence its ability to coordinate the rhodium center and therefore its hemilability, groups with different steric hindrances were attached to the sulfur atom in order to evaluate their influence in catalysis.

The stability of a complex formed with a bidentate ligand depends also on the size of the chelate rings. Our NHC-SR ligands L2-5 possess a flexible ethylene organic backbone, which can generate six-membered chelate rings. To evaluate this effect, the ligand L1 with a shorter N-arm was also prepared according to a literature procedure (Figure 1). Cycloaddition catalysis. We started our study with the reaction of N-tosyl-tethered bisallene 1a and dimethylacetylenedicarboxylate (DMAD) 2a (Table 1). S-functionalized imidazolium salts L1-L5 (Figure 1) were tested as ligands. In the initial tests, the rhodium complexes were generated in situ by treatment of the corresponding imidazolium salt with t BuOK as a base and the dimeric rhodium complex [Rh(cod)Cl]2. The reaction with L1 afforded three products, which were identified by NMR spectroscopy. In striking contrast to our previous studies with the same substrates (Scheme 2b), 10 a mixture of diastereoisomers trans and cis 3a, in 35% yield with a ratio of about 5:1 was formed by a [2+2+2] cycloaddition reaction between the two internal double bonds of the two allenes of 1 and the alkyne (entry 1), also in contrast to the case of Ma (Scheme 1a) in which both an internal and an terminal double bond were involved in the reaction. 3d The molecular structure and stereochemistry of the major diastereoisomer 3a, which was found to be trans, was confirmed by X-ray crystallographic analysis (Figure 2). 30 Of note, 3a bears structural similarities to the product obtained through the intermolecular [2+2+2] reaction of two allenes and one alkyne described by Tanaka and co-workers (Scheme 1b). [START_REF] Sakashita | Rhodium-catalyzed cross-cyclotrimerization and dimerization of allenes with alkynes[END_REF] A second product 4 was also obtained, although with a very low yield. This was formed by our previously described process 9 based on a cycloisomerization/Diels-Alder cascade process (see for instance Scheme 2a), in which in this case the dienophile is an alkyne (Entry 1, Table 1). Interestingly, the same reaction with the monodentate 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (IPr) provided lower selectivity and reactivity (Entry 2, Table 1). In addition, the monodentate IMes and a bidentate NHC-OH or a bis-NHC ligand also gave worse results (see Scheme S2 in Supporting Information for details). the efficiency and selectivity of the cycloaddition. Using imidazolium salt L2 with longer N-wing chain the yield of 3 improved to 51%, but the selectivity decreased (Entry 3, Table 1). As a series of unidentified compounds were observed in the crude mixture in these experiments, the reaction was performed again by decreasing the temperature to 80 ºC and the yield of 3 improved to 66%

(Entry 4, Table 1). Under these conditions, we proceeded to test the less sterically demanding NHC-SR ligands L3-5 (Entries 5-7, Table 1). Use of ligand L4 provided the best yield and selectivity (Entry 6, Table 1) and was thus selected for further tests. Performing the reaction in the absence of DCE led to an increase in the trans:cis ratio and a decrease in the formation of 4 (Entry 8, Table 1). To our delight, formation of by-product 4 could be fully suppressed by increasing the concentration of 1a from 18 mM to 36 mM (Entry 9, Table 1). Increasing and decreasing the amount of 2a (2 eq. and 10 eq. respectively) did not improve the results (Entries 10-11, Table 1).

Once the ligand was optimized, we proceeded to prepare a preformed and well-defined Rh complex RhL4, which we used as a catalyst.

The NHC-rhodium(I) complex RhL4 was prepared in a one-step process by the reaction of 2 eq. of imidazolium salt L4 with 1 eq. of [Rh(cod)Cl]2 in the presence of 2.2 eq. of t BuOK in THF (Scheme 3) following a procedure previously described by some of us. 31 The corresponding Nheterocyclic carbene complex RhL4 was obtained in high yield (above 95 %) as a yellow shiny solid, which was fully characterized. In the presence of the halogen onto the metal center, no direct evidence of the coordination of the sulfur atom to the metal center was noticed by 1 H NMR. 32

Scheme 3. Synthesis of rhodium complex RhL4.

The molecular structure of RhL4 was confirmed by X-ray diffraction studies (Figure 3). 30 The rhodium-carbene bond distance, 2.033(4) Å, is within the range reported for [RhCl(cod)(imidazol-2-ylidene)] complexes. 32,33 The Rh-C bonds located in a relative trans position to the carbene are significantly elongated (mean Rh-C 2.217Å) compared to those in trans to the bromide ligand (mean Rh-C 2.1055Å) due to the strong trans influence of the NHC ligand. The imidazol-2-ylidene ring is almost perpendicular to the coordination plane of the rhodium center (dihedral angle 88.64°) and this geometry is consistent with the 1 H NMR spectra. Different catalytic amounts of RhL4 were tested, from 1 mol% to 10 mol% (Entries 12-15, Table 1). Quantities below 5 mol% reduced the yield of 3a (Entries 12-13, Table 1) and the use of 10 mol% of RhL4 (Entry 15, Table 1) did not improve the results compared to the use of 5 mol% (Entry 14, Table 1). It should be noted that in no case the formation of by-product 4 was observed.

Therefore, the optimal reaction conditions for further studies were defined as 1a ([1a] = 36 mM), 2a (5 eq.), RhL4 (5 mol%) in toluene at 80 ºC for 2 hours (Entry 14, Table 1). In addition, two blank tests were performed. The reaction was first carried out in the presence of the rhodium dimer [Rh(cod)Cl]2 excluding the NHC ligand, and secondly in the absence of both the transition metal and the ligand. The reaction did not work in either case, and only the two starting products 1a and 2a were recovered.

Of note, bisphosphine ligands such as BINAP, Tol-BINAP, BIPHEP, DPEphos, Xantphos and Xphos were unable to provide a defined product upon reaction of 1a and 2a as studied in a previous work of the group. [START_REF] Vila | A Rh(I)-catalyzed cascade cyclization of 1,5-bisallenes and alkynes for the formation of cis-3,4-arylvinyl pyrrolidines and cyclopentanes[END_REF] The scope of the reaction was then evaluated (Scheme 4). Methyl, ethyl and tert-butyl acelylenedicarboxylates 2a, 2b, and 2c were tested in the cycloaddition affording excellent yields and high trans:cis ratios 34 of the corresponding cycloadducts 3a-3c. However, terminal nonactivated alkynes, such as monoacetylenecarboxylates and phenylacetylene analogues did not react under these conditions. The nature of the substituents at the phenyl ring of the sulfonamide tether in bisallene 1 was then explored. The reaction proceeded efficiently with both electron-donating (3d) and electron-withdrawing groups (3e), as well as with substituents at the ortho position of the phenyl ring (3f, 3g). A bisallene bearing the 5-methyl-2-pyridinesulfonyl group provided 3h in a 60% yield, indicating that the presence of a potentially coordinating nitrogen atom did not poison the catalyst. Sulfonamide tethers with aliphatic substitution (tert-butyl and trimethylsilylethyl)

were also efficient, delivering cycloadducts 3i and 3j in 79 and 58% yields, respectively. Changing the sulfonamide protecting group of the nitrogen tether to a carbamate (N-Boc bisallene), the reaction took place although cycloadduct 3k was obtained in a moderate yield and with low diastereoselectivity. Bisallenes with a carbonyl group in the quaternary carbon atom of the tether also participated in the cycloaddition, affording 3l and 3m with a 61% and 81% yields, respectively. When the carbonyl group was substituted for arylsulfonyl groups, lower yields of the cycloadducts 3n and 3o were obtained but the diastereoisomeric ratios were better. In the case of 3o, an inseparable mixture of diastereoisomers was obtained due to the chiral centre in the tether making it impossible to determine the d.r. Finally, oxygen-tethered bisallene participated in the process affording cycloadduct 3p with a 61% yield and an excellent diastereoisomeric ratio. with the sulfur chelating the rhodium. Formation of rhodacyclopentene intermediate A2 takes place with an affordable barrier of 16.7 kcal•mol -1 (A1 to TS S (A1'A2), being 7.6 kcal•mol -1 lower than its non-chelating counterpart (TS(A1'A2), ΔG ‡ = 24.3 kcal•mol -1 ). This step

A1 ⇌ A1' ® A2
is exergonic by 31.6 kcal•mol -1 . An alternative way to generate A2 could be through TS S (A1''A2), although the energy barrier for this transformation is 2.9 kcal•mol -1 higher than via TS S (A1'A2).

For these two paths, the sulfur-assisted transition states (TS S (A1'A2), TS S (A1''A2)) are lower in energy than their analogues in which the sulfur is not coordinated to the rhodium (TS(A1'A2),

TS(A1''A2

)) due to the S electron-donating character, which adds electronic density to the rhodium and facilitates its oxidation. However, in the oxidative cyclometallation from A1, coordination of S leads to a pyramidalization of the rest of the ligands coordinated to Rh.

Pyramidalization brings the ligands closer to one another and, consequently, the two coordinated double bonds in the 1,5-bisallene become perpendicularly arranged to one another. This perpendicular arrangement is destabilizing 37 and the trend in inverted. As a result, the non-chelated transition state TS(A1A2) is lower in energy than TS S (A1A2) by 5.3 kcal•mol -1 . Several reaction paths of higher ΔG ‡ for the A1 to A2 transformation were studied (see Figures S2 andS3 in the SI). A2 is a Rh(III) 18 e -complex and exhibits an octahedral geometry in which the three carbons from the reacted allene are η 3 -coordinated to the rhodium (dRh-C = 2.217, 2.129, and 2.218 Å). This type of p-allyl metallacycle intermediates have previously been postulated in cycloaddition reactions. 38 From this point, A2 needs to rearrange to set a coordination position free for the second allene unit, giving either A3t rans or A3ci s at cost of 18.0 and 24.0 kcal•mol -1 respectively. For the formation of the trans-fused rhodabicyclo intermediate A4t rans through A3t rans, the insertion (via Schore mechanism 39 ) of the internal double bond of the second allene takes place in the Rh-Csp 3 bond through TS S (A3A4)t rans. This process A2 ® A4t rans has a total Gibbs energy barrier of 24.4 kcal•mol -1 and is exergonic by 3.4 kcal•mol -1 . In contrast, for the formation of A4ci s, the insertion is found to occur in the Rh-Csp 2 bond, surpassing a Gibbs energy barrier of 27.0 kcal•mol -1 (TS S (A3A4)ci s) and releasing 12.4 kcal•mol -1 . The coordination of a second DMAD unit to A2, which would lead to our previously reported cis-3,4-arylvinyl pyrrolidine derivative (Scheme 2b), 10 was also considered. However, it was found to be disfavoured at the experimental concentration of DMAD (see Figure S5 in the Supporting information).

For the final reductive elimination step, the S-adamantyl functionality is dissociated from the rhodium center to remove electronic density, drastically reducing the Gibbs energy barriers by 8.1 kcal•mol -1 (TS(A4A5)t rans vs TS S (A4A5)t rans) and 3.9 kcal•mol -1 (TS(A4A5)ci s vs TS S (A4A5)ci s). Finally, ligand exchange from A5t rans and A5ci s releases 3a-trans and 3a-cis and gives A1 to restart the catalytic cycle. The formation of by-product 4 (Table 1) was also evaluated computationally, and the results account for its formation in minor quantities at low concentrations of 2a (see Scheme S6, and Figures S4 and S6 in the SI for the complete discussion).

In summary, the reaction follows the typical [2+2+2] cycloaddition mechanism 40 and has an overall reaction energy of -98.6 kcal•mol -1 (ΔG = G3a -[G1a + G2a]) almost identical for both diastereoisomers. For 3a-trans, the energetic span between the turnover frequency (TOF) determining intermediate (TDI, A2) and the TOF determining transition state (TDTS, TS(A3A4)t rans) is 24.4 kcal•mol -1 , and for 3a-cis, the energetic span between TDI (A4ci s) and the TDTS (TS(A4A5)ci s) is 29.0 kcal•mol -1 . 41 The allene-allene oxidative cyclometallation is found to be much higher in energy than the allene-alkyne oxidative cyclometallation (ΔΔG ‡ = 16.0 kcal•mol - 1 ), indicating that the ring fusion stereochemistry comes from the latter insertion 6b of the second allene, in which the insertion leading to the trans isomer (TS(A3A4)t rans) is preferred over the cis (TS(A3A4)ci s) by 2.6 kcal•mol -1 . This difference in energy is translated into a 98:2 trans:cis ratio using the Eyring equation, in perfect agreement with the experimental data.

In conclusion, the hemilability of NHC-SR ligands enabled an efficient rhodium-catalyzed

[2+2+2] cycloaddition of 1,5-bisallenes and alkynes. A number of N-, C-, and O-tethered 1,5bisallenes, as well as variously substituted alkynes were successfully used in the reaction. The methodology developed gives access to bicyclic 3,6-dimethylenecyclohex-1-ene derivatives.

Importantly, the exocyclic alkenes in the product scaffold provide ample opportunities of synthetic manipulation to build more complex molecules. A mechanistic investigation by means of DFT calculations has been carried out to unravel that a canonical [2+2+2] reaction manifold accounts for the observed transformation, and that the hemilabile character of the sulfur in the ligand precisely modulates the electron density in key intermediates and facilitates the overall transformation. This hemilability in the catalytic system is expected to be useful for further

  22b

Figure 1 .

 1 Figure 1. S-functionalized imidazolium salt precursors used in the cycloaddition of bisallene 1a

Figure 2 .

 2 Figure 2. ORTEP representation of 3a-trans at 50% of probability level (CCDC 2209948)

Figure 3 .

 3 Figure 3. ORTEP representation of RhL4 at 50% of probability level (CCDC: 2213801). Selected

Scheme 4 .

 4 Scheme 4. Scope of the [2+2+2] cycloaddition reaction of bisallenes 1 and alkynes 2.

  NMR spectra showed sharp resonances at room temperature and the splitting observed as two multiplets for both CH2-N and CH2-S protons at 5.00 and 4.11 ppm and 3.44 and 2.69 ppm respectively is only due to the lack of an effective plane of symmetry in the molecules due to the impeded rotation already observed for NHC-Rh complexes. For similar behaviour see: Jiménez, M. V.; Pérez-Torrente, J. J.; Bartolomé, M. I.; Gierz, V.; Lahoz, F. J.; Oro, L. A. Rhodium(I) complexes with hemilabile N-heterocyclic carbenes: efficient alkyne hydrosilylation catalysts. Organometallics 2008, 27, 224-234. (33) a) Peñafiel, I.; Pastor, I. M.; Yus, M.; Esteruelas, M. A.; Oliván, M. Preparation, hydrogen bonds, and catalytic activity in metal-promoted addition of arylboronic acids to enones of a rhodium complex containing an NHC ligand with an alcohol function. Organometallics 2012, 31, 6154-6161. (b) Yu, X. Y.; Patrick, B. O.; James, B. R. New Rhodium(I) carbene complexes from carbene transfer reactions. Organometallics 2006, 25, 2359-2363. (c) Warsink, S.; Venter, J. A.; Roodt, A. NHC-amide donor ligands in rhodium complexes: Syntheses and characterisation. J. Organomet. Chem. 2015, 775, 195-201.

Table 1 .

 1 Optimization of the rhodium(I)-NHC-catalyzed [2+2+2] cycloaddition of 1a and 2a.

	Entry	Ligand	Variation of reaction conditions	Yield (%) 3 (trans:cis) / 4 a
	1	L1		35 (83:17) /
	2	IPr		23 (78:22) /
	3	L2		51 (86:14) /
	4	L2	80 ºC, 2h.	66 (86:14) /
	5	L3	80 ºC, 2h.	61 (87:13) /
	6	L4	80 ºC, 2h.	74 (89:11) /
	7	L5	80 ºC, 2h.	61 (90:10) /
	8	L4	80 ºC, 2h., toluene	73 (93:7) /
	9	L4	80 ºC, 2h., toluene, [1a] = 36 mM	76 (93:7) /
	10	L4	80 ºC, 2h., toluene, 2a (2 eq.)	66 (91:9) /
	11	L4	80 ºC, 2h., toluene, 2a (10 eq.)	77 (92:8) /
	12	RhL4	80 ºC, 2h., toluene, RhL4 (1 mol%)	31 (91:9) /
			[1a] = 36 mM
	13	RhL4	80 ºC, 2h., toluene, RhL4 (2.5 mol%)	55 (91:9) /
			[1a] = 36 mM
	14	RhL4	80 ºC, 2h., toluene, RhL4 (5 mol%)	82 (92:8) /
			[1a] = 36 mM
	15	RhL4	80 ºC, 2h., toluene, RhL4 (10 mol%),	81 (92:8) /
			[1a] = 36 mM

a Yields and ratios calculated by 1 H-NMR from the reaction crude.

  Gade, L. H.; Bellemin-Laponnaz, S. NHC-Cobalt, -Rhodium, and -Iridium Complexes in Catalysis. In N-Heterocyclic Carbenes 2 nd Edition, RSC Catalysis Series, Editor: Diez-Gonzales, S. 2017, pp 302-335. Kühl, O. The chemistry of functionalised N-heterocyclic carbenes. Chem. Soc. Rev. 2007, 36, 592-607. (b) Zhang, W.-H.; Chien, S. W.; Hor, T. S. A. Recent advances in metal catalysts with hybrid ligands.Coord. Chem. Rev. 2011, 255, 1991-2024. (c) Hameury, S.; de Frémont, P.; Braunstein, P. Metal complexes with oxygen-functionalized NHC ligands: synthesis and applications. Chem.Soc. Rev. 2017, 46, 632-733. (d) Peris, E. Smart N-heterocyclic carbene ligands in catalysis. Chem. Rev. 2018, 118, 9988-10031. (e) using stereodirecting N,N-dialkylamino groups. Tetrahedron: Asymmetry 2010, 21, 1557-1562. (30) CCDC-2209948 and CCDC-2213801 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_-request/cif. (31) Cesar, V.; Bellemin-Laponnaz, S.; Wadepohl, H.; Gade, L. H. Designing the "search pathway" in the development of a new class of highly efficient stereoselective hydrosilylation catalysts. Chem. Eur. J. 2005, 11, 2862-2873.

	B.; Stará, I.G.; Starý, I. Oxahelicene NHC ligands in the asymmetric synthesis of
	nonracemic helicenes. Chem. Commun. 2017, 53, 4370-4373.
	(15)	Thakur, A.; Louie, J. Advances in Nickel-catalyzed cycloaddition reactions to
	construct carbocycles and heterocycles. Acc. Chem. Res. 2015, 48, 2354-2365, and
	references cited therein.
	(16)	González, I.; Pla-Quintana, A.; Roglans, A. Rhodium N-heterocyclic carbene
	complexes as effective catalysts for [2+2+2] cycloaddition reactions. Synlett 2009, 2844-
	2848.
	(17)	Fernández, M.; Ferré, M.; Pla-Quintana, A.; Parella, T.; Pleixats, R.; Roglans, A.
	Adv. Synth. Catal. 2019, 361, 1479-1499.
	(19) César, V.; (20) (a)
	development of demanding cycloaddition reactions.
	ASSOCIATED CONTENT

Rhodium-NHC hybrid silica materials as recyclable catalysts for [2+2+2] cycloaddition reactions of alkynes. Eur. J.

Org. Chem. 2014, 6242-6251. (18)

For a recent review see: Lee, J.; Hahm, H.; Kwak, J.; Kim, M. New aspects of recently developed rhodium(N-heterocyclic carbene)-catalyzed organic transformations.

Supporting information (see SI for a complete description of the computational methods and Table S1 for a justification of the density functional employed). The reaction starts with the coordination equilibrium of 1,5-bisallene and DMAD with the rhodium catalyst to give Rh(I) 16 e -square planar complexes A1, A1' and A1'' (Figure 4) (see Figure S1 for the whole set of coordination complexes). The coordination of the two internal double bonds of the 1,5-bisallene (A1) is the most exergonic process, releasing 6.6 kcal•mol -1 . For the upcoming oxidative cyclometallation, all possible orientations have been evaluated along with the dynamic

AUTHOR INFORMATION

Corresponding Authors

Anna Roglans -Institut de Química Computacional i Catàlisi (IQCC) and Departament de Química, Facultat de Ciències, Universitat de Girona (UdG), Girona 17003 Catalonia, Spain; orcid.org/0000-0002-7943-5706; Email: anna.roglans@udg.edu

Stephane Bellemin-Laponnaz -Institut de Physique et Chimie des Matériaux de Strasbourg, CNRS-Université de Strasbourg, UMR7504 23 rue du Loess BP 43, 67034 Strasbourg, France; orcid.org/0000-0001-9462-5703; Email: stephane.bellemin@ipcms.unistra.fr

Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

ACKNOWLEDGMENT

We are grateful for financial support from the Ministerio de Ciencia e Innovación (PID2020-113711GB-I00 MCIN/AEI/10.13039/501100011033), the Generalitat de Catalunya (Project 2017-SGR-39), the UdG for an IF predoctoral grant to J.V. We also thank Corinne Bailly and Dr. Lydia Chem. 2001, 617-618, 346-359. (39) Schore, N. E.

Supporting Information.

Experimental procedures, compound characterization data including NMR spectra for all new compounds, and computational data (PDF).