Tuan-Anh Nguyen

E Daiann

Sosa Carrizo

Hélène Cattey

Paul Fleurat-Lessard

Julien Roger

Jean-Cyrille Hierso
email: jean-cyrille.hierso@u-bourgogne.fr

Dr T.-A Nguyen

E D Sosa

Dr H Carrizo

Prof. Dr P Cattey

Dr J Fleurat-Lessard

Prof. Dr J.-C Roger

Hierso

Tetranuclear Dicationic Aurophilic Gold(I) Catalysts in Enyne Cycloisomerization: Cooperativity for a Dramatic Shift in Selectivity

Keywords: Gold catalysis, polynuclear complexes, alkyne activation, gold cluster, azabicyclo-hept-4-enes

In comparison to mononuclear gold Lewis-acid catalysts, digold complexes and dual-gold catalysis have illustrated a distinct and powerful potential for the activation of carbon-carbon multiple bonds. Herein, we pushed this concept further by designing novel tetranuclear gold(I) dicationic complexes structurally supported by strongly stabilizing constraint diphosphinoferrocenyl ligands and attractive closed-shell Au•••Au aurophilic interactions. The use of a molecularly-defined tetranuclear dicationic aurophilic gold(I) precatalyst for the selectivity-challenging cycloisomerization of lowsubstituted 1,6-enynes favors the formation with high selectivity of strained azabicyclo[4.1.0]hept-4-enes -even in the complete absence of activating/orienting substituents on alkyne and olefin reactive functions. This selectivity is not achieved by the reported phosphine-and carbene-stabilized mono-and dinuclear cationic gold(I) complexes, including the ones formed from the same ligands. More importantly this selectivity differs also from nanoparticles and heterogeneous gold catalysts reported to date. DFT studies correlated to experimental mechanistic investigations support an unprecedented "cluster-like" reactivity from polynuclear cooperation at the origin of this peculiar selectivity where the aurophilic interactions preexist, and pre-organize, gold cluster reactive intermediates.

Introduction

Transition metal-catalyzed enyne cycloisomerization is a powerful strategy for the synthesis of functionalized cyclic and polycyclic structures. [1][2][3][4][5] The building of structural complexity starting with fairly simple acyclic subunits containing alkyne and olefin moieties has motivated this success (Figure 1, top). Accordingly, gold(I) species are very powerful for the construction of complex molecular architectures under very mild conditions and in short reaction time [START_REF] Hashmi | For a pioneer gold-catalysed cycloisomerization of a substrate with an enyne-substructure[END_REF][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] via skeletal rearrangement of enynes by Lewis-acidic induced cyclization. [22- 26] The outcome of the cycloisomerization reaction and its selectivity is strongly influenced by the substitution pattern of the starting enyne and the nature of the catalyst used. On the other hand, digold complexes and dual-gold catalysis have recently illustrated a distinct and powerful potential for the activation of carbon-carbon multiple bonds. [27][28][29][30][31][32][33][34][35][36][37][38][39] This gave the impetus for designing novel digold(I) complexes based on strongly stabilizing ligands such as tertiary mono-and diphosphines or heterocyclic carbenes, [27,[37][38][39][40][41] while the attractive closed-shell interactions between d 10 -d 10 pairs of gold atomsknown as Au•••Au aurophilic interaction - [42] might further assist the structuring of digold complexes. [40] Regarding gold-catalyzed cycloisomerization of 1,6-enynes, mostly mononuclear cationic species have been reported as being useful, whereas the performances of well-defined aurophilic digold(I) complexes have been only recently illustrated. [41] To the best of our knowledge, the competence of molecularly-defined higher rank polynuclear complexes, and clusters has never been reported in cycloisomerization of 1,6enynes, despite the conceivable benefit of pre-organizing gold centers in a constrained environment regarding selectivity outcome in such reactions. This issue is all the more pertinent that, surprisingly, very high but divergent selectivity is also achieved at the surface of heterogeneous gold catalysts and from nanoparticle catalysts. [43][44][45] Herein, we report the use of a molecularly-defined tetranuclear dicationic aurophilic gold(I) catalyst for the selectivity-challenging cycloisomerization of lowsubstituted 1,6-enynes (Figure 1, bottom). We show that such tetranuclear Au(I) species specifically favors the formation of strained azabicyclo[4.1.0]hept-4-enes with high selectivity -even in the complete absence of activating/orienting substituents on alkyne and olefin reactive functions-, which is usually hardly achieved by phosphine-and carbene-stabilized mono-and dinuclear cationic gold(I) complexes or heterogeneous gold catalysts.

Results and discussion

The bis(dicyclohexyl)phosphino-ferrocene ligand rac L1 displays a versatile coordination chemistry with gold(I) salts that we exploited in order to synthesize the well-defined complexes 1-5 (Scheme 1) having various gold nuclearity, generally stabilized by aurophilic interactions, and being either neutral or cationic.

Scheme 1.

Neutral and polynuclear cationic gold(I) complexes of bis(dicyclohexylphosphino)-ferrocene rac L1.

From complexes 1 and 2, [41] the straightforward formation of cationic gold complexes 3 and 4 was respectively achieved by total or partial chloride abstraction using one equivalent of AgSbF6 in acetonitrile [0.01 M] at rt for 1 h. The complexes 3 ( 31 P NMR 53.7 ppm) and 4 (46.1 ppm) crystallized as pure orange solid in 97% and 65% yield, respectively. The formation of the related dicationic digold complex 5 was achieved by reacting dinuclear complex 2 with 2 equiv of AgSbF6 in CH3CN (Scheme 1). Comparatively to 3 and 4, the complex 5 that is isolated as a dark orange solid (86% yield, 31 P NMR 41.3 ppm) was found to be less stable and degraded in solution overtime, forming gold mirror.

Single crystal X-ray diffraction analysis of the cationic 3-5 complexes was conducted (Figure 2). Gold tetranuclear bischloride-bridged structure organized such as complex 4 was rarely reported. [27] Complex 4 is structurally related to tetranuclear species recently reported by the van der Vlugt group from a tridentate diarylamino-bisphosphine ligand (PN H P iPr , Figure S1), [37] and by the Tamm group from N-heterocyclic carbene-phosphinidene species (IPr•PPh, Figure S2). [46] Interestingly, the PN H P iPr -complex was suggested to be in equilibrium with its neutral dinuclear counterpart that is a precursor for a digold cationic species catalytically active in dual ,-alkyne activation. [37] More importantly, the tetranuclear cationic complex [(IPr•PPh)2Au4Cl2][BArF]2 that was directly tested in enyne cycloisomerization was found to promote the formation of five-or six-membered ring dienes of I and III type (Figure 1), with a moderate selectivity (66% to 75%). Diffusion-ordered NMR Spectroscopy (DOSY 1 H NMR) experiments conducted for 2 and 4 in CD2Cl2 solution at 298 K, correlated the dinuclear and tetranuclear structure of the complexes with coefficients of 8.57x10 -10 and 6.92x10 -10 m 2 s -1 , respectively. 1,6-Enyne cycloisomerization from aurophilic cationic tetranuclear complexes. The Echavarren group reported that gold-based catalysts were very effective for accomplishing a series of 1,6-enyne cycloisomerization. [22] The catalyst was generated by treatment of Au(PPh3)Cl with AgSbF6, which resulted in the formation of highly reactive cationic Au(PPh3) + species. With the gold catalyst, various 1,6-enynes were converted into five-membered dienes (type I, Figure 1) at rt; this completed the known reactivity of palladium, platinum, and ruthenium, previously identified for such cyclopentenes formation. [47][48][49] Following this milestone work, mononuclear cationic gold complexes have been shown to promote mostly the formation of either five and/or six-membered dienes (type I-III, Figure 1), sometimes with a troublesome selectivity. [23,[50][51][52][53][START_REF] Homs | abstraction of chloride anion from Au(I) complexes such as JohnPhosAuCl (JohnPhos = di-tbutyl(2-biphenyl)phosphine) in noncoordinating solvents with 1 equiv of a Ag salt, or even larger amounts, gives chloride-bridged dinuclear Au(I) complexes [JohnPhos-Au-Cl-Au-JohnPhos]X-irrespective of the counteranion[END_REF][START_REF] Arumugam | [END_REF][56][57][58][59][60][61] Au(I) catalytic systems are occasionally able to form bicyclic strained structures such as bicyclo[4.1.0]hept-4-enes (type IV, Figure 1) and cyclobutenes (type V-VI, Figure 1). In these cycloisomerization reactions using 1,6-enyne substrates, a high substrate-dependence is observed for the final selectivity. In particular, alkyl groups at the olefin function, [22,41,53,62] and/or bulky aromatic groups at the alkyne [63][64][65] assist the cyclopropyl formation. However, while Pt-based catalysts promote the formation of bicyclo[4.1.0]hept-4-enes IV (Figure S3), [66] for gold catalysts the competition to form isomeric dienes is conversely found very strong in the absence of such substituents on the enyne. [START_REF] Chao | The formation of oxabicyclo[4.1.0hept-4-enes is a noticeable exception, see for instance elegant asymmetric cyclopropanation[END_REF] Since the vast majority of defined cationic gold complexes tested in 1,6-enyne cycloisomerization are preformed mononuclear species, we were eager to screen the activity and selectivity obtained from the well-defined complexes 1-5, among which cationic aurophilic di-and tetranuclear species, unexploited to date, are present. We performed this preliminary approach using the low-substituted N-propargyl-N-allyl-toluene-4-sulfonylamine 6 (unsubstituted at the olefin and terminal alkyne, Table 1), assuming that this simple 1,6-enyne a priori does not strongly influence the cycloisomerization selectivity outcome by its own structure. Our starting conditions had been previously optimized to form selectively 7a from the dinuclear aurophilic complex 2 (Table 1, entry 2), [41] by in situ cationization with 2.5 equiv of [AgSbF6], while the same operation on the mononuclear counterpart 1 was mostly unproductive (Table 1, entry 1). dichloroethane. b Triplicate experiments insured this result, notably, at the end of these reactions using tetranuclear complex 4 a limpid solution is obtained without any precipitation of gold. c Freshly prepared complex 5 is used in these conditions, while storage during one day or one week progressively reduced both the conversion and selectivity, confirming the weaker stability of 5.

d Experiments performed for 15, 30, and 60 min showed that the same products distribution is conserved along the reaction, which achieves 85% conversion after 15 min.

When using the tetranuclear dicationic complex 4, we observed a dramatic shift in selectivity to the full formation of the strained azabicyclo[4.1.0]hept-4-ene 7c (99%, entry 4), albeit with low conversion, providing thus from cycloisomerization of 6 a selectivity neither observed previously using any ferrocenylphosphine stabilized mononuclear and dinuclear complexes. [41] This selectivity was not observed using the defined cationic complexes 3 and 5 (Table 1, entries 3 and 5). A solvent change to dichloroethane (DCE) allowed us to access higher temperatures of activation, and enhanced the conversion while conserving a high selectivity in 7c (entries 6 and 7). These changes in solvent and temperature were applied with the other complexes 1-3 (entries 8-10), and led to the loss of either the activity or the selectivity to bicyclo[4.1.0]hept-4-ene 7c. This confirmed the specific activity and selectivity of tetranuclear dicationic complex 4. Beside the fact that the well-defined dinuclear cationic complex 5 does not favor a good selectivity to 7c (entry 11), we observed that the addition of 2 to 10 mol% of [AgSbF6] to gold tetranuclear 4 induced the progressive disappearance of 7c in favor of the formation of the five and sixmembered dienes 7a and 7b (entry 12, and comparison of entry 4 with entries 13-16). This was presumably attributed to the breakdown of the tetranuclear motif due to further chloride abstraction. To further challenge this hypothesis, we achieved the synthesis of the analogous tetranuclear compounds 4a-4f (XRD analyses and molecular structures of 4b-4f are provided in Supporting Information), and we tested those well-defined complexes similarly into the cycloisomerization of 6 (Table 2). The cycloisomerization results all confirmed that the tetranuclear scheme is essential in the formation of 7c with a selectivity above 60% (Table 2, entries 1-7). However, the structure changes operated with 4a-f, regarding the cousin structure of 4, deserve some comments. Despite a slight selectivity loss, a high activity in the conversion from 6 to 7c was conserved when the phosphino substituents introduced on the ferrocene ligand were phenyl (4a, entry 2, 93%) and i-propyl groups (4b, entry 3, 92%). This remarkable activity is strongly in favor of the conservation of the gold centers in a constrained pre-organized environment. Indeed, mono-and dinuclear cationic gold complex counterparts provided with these ferrocenylphosphine ligands very different synthetic issues. [START_REF]We reported for these complexes a selectivity towards the six-membered 7a and weaker conversions[END_REF] Conversely, a noticeable drop of activity was due to the counteranion change from SbF6 -(4, entry 1, 98%) to NTf2 -(4d, entry 5, 67%) and BF4 -(4c, entry 4, 52%) while a high selectivity in 7c is conserved above 75%. The presence of the -chloro bridges was found to be even more determining for the activity of the complexes since their replacement for -iodo in 4e (entry 6, 11%) and 4f (entry 7, 4%) provided unproductive catalysts. The question of the structural advantage of a smaller bridge size and higher strength of the separation bridge is thus open.

Computational approach of the selectivity induced by aurophilic cationic tetranuclear complexes. To decipher the origin of this unexpected selectivity from tetragold catalysts, we used computational chemistry to investigate the formation of azabicyclo[4.1.0]hept-4-ene. Previous studies have shown that 7c is mainly formed from the 6-endo-dig cyclization, while 7b mainly comes from the 5-exo-dig cyclization and 7a can be formed from both intermediates. [22a,69] Electronic structure and non-covalent interactions (NCI) were analyzed at the DFT level (AIM and NCI analyses in Supporting Information) for the 6endo-dig transition states with aurophilic pre-catalysts dinuclear 2 and tetranuclear 4 (Figure 3). Consistent with experimental XRD data, we identified a stabilizing aurophilic interaction between the two gold atoms in 2 and TS-2. This aurophilic interaction is also present in 4 and TS-4 between the paired gold atoms Au1…Au2 and Au3…Au4 (NCI analysis in Figure Sth1). Computing the Gibbs free energies for the cyclization steps, we found that the -TsNenyne linker favors the formation of the 5-exo-dig cycle with digold 2 (Figure Sth2), in agreement with previous reports. [22a,69,15,70] Conversely, with tetragold 4, the 6endo-dig cyclization leading to 7c (Figure 4) is favored both from kinetic and thermodynamic perspective (TS-endo found at 9.9 kcal mol -1 and int2 endo stabilized at -12.9 kcal mol -1 ). The Gibbs free energy difference between the endo and the exo TS (10.6 kcal mol -1 ) we identified corresponds to a 70:30 7c:(7b,a) ratio, in good agreement with our experiments for tetragold catalysts (Table 2).

Electronic structure and non-covalent interactions were analyzed more in depth in TS-4 endo and exo (Figure 5) regarding this inversion of stability Actually, in addition to the stabilizing aurophilic interactions between the gold atoms Au1…Au2 (2.98 Å) and Au3…Au4 (2.96 Å), the supplementary interaction which takes place between the gold atoms Au2 and Au3 (in addition to chlorine bridge, Au2…Au3 = 3.08 Å, Figure 3) leads to the formation of a metallic structure as a folded tetranuclear linear chain solidarizing the two moieties of the catalyst. In addition, the analysis of the non-covalent interactions reveals an Au3-alkyne interaction that stabilizes the 6-endo-dig TS with respect to the 5-endo-dig one. One can also note a strong interaction of one chlorine atom with the substrate. The set of weak interactions evidenced from TS-4 highlights a polynuclear cooperative behavior that is not achievable from lower rank mono-and dinuclear systems. Alkyne bridging-interaction within gold tetranuclear motifformation of a gem gold cluster. From the computational results and the experiments gathered in Table 2 (and notably the tests using dinuclear 4 in the presence of AgSbF6 as halide extractor, entries 12-15 in Table 1), the selectivity towards lowsubstituted azabicyclo[4.1.0]hept-4-enes is clearly attributed to the persistence of the gold tetranuclear motif. To further assess the structural role of the tetragold catalysts, we experimentally examined the interaction of tetranuclear motif with a model alkyne 4-methoxyphenylacetylene. The isolation of pertinent alkyne (or enyne) intermediate species from direct reaction with the precatalyst 4 was found to be difficult, presumably because of the high reactivity of the intermediates. However, we first observed that dicationic complex can be obtained from fragmentation of 4 by adding AgSbF6 for chloride bridge removal. Then, after Cl abstraction, 5 reacted with one equiv of methoxyphenylacetylene and quantitatively formed a new tetragold organometallic cluster 4g bridged by two alkynes (Scheme 2). The presence of a base for alkyne deprotonation is needed to form this very stable species that was characterized by XRD in the solid state (Figure 6 bottom). This species differ from the dinuclear van der Vlugt intramolecular Au2(,πacetylide) complex with a diphosphine ligand [d Au1…Au2 = 3.1110(2)], 37 Further crystallographic details of 4g are given in SI. Beside its unique and very original bis(diphosphine)polyaurophilic cluster structure, compound 4g illustrates that tetranuclear gold preorganization can be potentially conserved upon interaction with alkyne. This definitely establish the interest of constraint diphosphine ligands for assembling tetra gold complexes. Such cluster formation would be also structurally advantageous for promoting polynuclear cooperativity and lead to selectivity alterations from mono-or digold catalysis.

Synthesis of low-substituted azabicyclo[4.1.0]hept-4-enes.

Having confirmed the propensity of these tetranuclear Au(I) catalysts to form the bicyclic strained structure 7c with a high and unexpected selectivity, we further examined the activity of complex 4 on variously aryl-substituted N-propargyl-N-allyl-arylsulfonylamines 8-14 (Table 3). These low-substituted substrates are of particular interest to examine since with current gold catalysts cyclopropyl formation from 1,6-enynes cycloisomerization is generally reported using enynes holding substituents at the olefin, [10,22,41,53,62] or at the alkyne moiety. [10,[63][64][65] The current state-of-the art, whatever the conditions, including Rh, Ru, Ir or nonmetal, does not describe high-yield general synthesis of low-substituted azabicyclo[4.1.0]hept-4-enes. [58,[71][72][73][74] We were glad to observe high conversion, above 97%, and consistent selectivity, above 72%, for the formation of 3-phenylsulfonyl-3azabicyclo[4.1.0]hept-4-ene 8c (Table 3, entry 2) and variously phenyl-substituted new sulfonyl-3-azabicyclo[4.1.0]hept-4-enes 9c-12c (entries 3-6). These were isolated in moderate to good yields (37-74%). The catalytic system tolerated electrondonating and electron-withdrawing substituents: 3-[(4-tertbutylphenyl)sulfonyl]-3-azabicyclo[4.1.0]hept-4-ene 9c and 4-(methoxyphenyl)sulfonyl analogue 10c were isolated in 50% and 37%, respectively. 4-Trifluoromethylphenylsulfonyl-substituted 11c and 4-nitrophenylsulfonyl 12c were isolated in 74% and 57% yield, respectively. Alkylsulfonyl3-azabicyclo[4.1.0]hept-4enes were equally accessible with the benzyl-substituted 13c isolated in 49% yield and the methyl-substituted 14c isolated in 62% yield.

Besides the formation of these previously undescribed azabicyclo[4.1.0]hept-4-enes, we assessed the performances of the gold tetranuclear 4 in the cycloisomerization of more classical alkyl-subsisted 1,6-enynes (Scheme 3). Using enyne substrates methylated at various positions, an excellent activity with conversions above 98%, was conserved for reactions achieved within 1 to 40 h. The faster cycloisomerization reactions were accompanied with a slight loss in selectivity, found between 61-72% for 15c-18c. We were glad to observe the major formation of azabicycloheptenes 19c and 20c, [56,62,75,76] albeit in slower reaction with the need to increase gold catalyst loading for optimized conversions. The preferential formation of the sixmembered ring 21a isolated in 70% yield (90% selectivity, 99% enyne conversion) is consistent with a fast reactivity (0.5 mol% of 4, 1h) and a strong influence of gem-methyl groups on the olefin; it has been repeatedly reported. [52,56,60] From dimethyl allyl(propargyl)malonate the five-membered 22b was isolated in 41% yield (79% selectivity, 99% enyne conversion). The selective cycloisomerization of dimethyl allyl(propargyl)malonate is usually challenging, and gold homogeneous catalysts often achieved mixtures of six and five-membered cyclic dienes. [22,26,45] Notably, very high selectivity from this malonate precursor to the five-membered 22b has been recently achieved at the surface of ultra-small gold nanoparticles (NPs, sizing 1.3 nm, > 99% selectivity in 22b). [45] It is tempting to hypothesize some structural relationship between the reactivity at the surface of ultra-small gold NPs and the present gold polynuclear species in this substrate case.

Conclusion

Molecularly-defined tetranuclear dicationic aurophilic gold(I) precatalysts used in cycloisomerization of 1,6-enynes favors the formation with high selectivity of strained azabicyclo[4.1.0]hept-4-enes, even in the absence of activating or orienting substituents on alkyne and olefin functions. The bis(dicyclohexyl)phosphino-ferrocene supporting ligand 1 for tetragold complex is the most efficient for a general high cycloisomerization yield and selectivity. Strained azabicyclo[4.1.0]hept-4-enes are not formed by mono-and dinuclear neutral or cationic gold(I) complexes stabilized with the same class of phosphine ligands, evidencing for the first time the importance of a gold tetranuclear scheme in this selectivity. DFT studies correlated to experimental mechanistic investigations support an unprecedented "cluster-like" reactivity from polynuclear cooperation at the origin of this peculiar selectivity. Herein, the aurophilic interactions preexist, and pre-organize, gold cluster reactive intermediates. Accordingly, and more importantly, the selectivity observed also differ from nanoparticles and heterogeneous gold catalysts reported to date. Crystallographic data deposition numbers: 2128908 (for 3), 2128909 (for 4), 2128910 (for 5), 2128911 (for 4g), as well as 2144186 (for 4b), 2144187 (for 4c), 2144188 (for 4d), 2144189 (for 4e), and 2144190 (for 4f) contain the supplementary crystallographic data for this paper. These data are provided free of charge by The Cambridge Crystallographic Data Centre.

Figure 1 .

 1 Figure 1. Top: general five-or six-membered ring dienes and bicyclic corestructures achievable by 1,6-enyne cycloisomerization. Bottom: unique selectivity to challenging strained azabicyclo[4.1.0]hept-4-ene promoted by tetranuclear Au4 2+ complexes (this work).

Figure 2 .

 2 Figure 2. Molecular views of XRD structures of the cationic part of gold(I) complexes 3-5 (counter anions, solvent and hydrogen atoms are omitted for clarity). For 4, two cyclohexyl groups are disordered over two positions with occupation factors converged to 0.71:0.29 (details in Supporting Information); symmetry code: (i) 1-x, 1-y, 1-z.

Figure 3 .

 3 Figure 3. (a) General mechanism of the 6-endo-dig cyclization step. (b) Transition state DFT geometry with catalyst 2. (c) Transition state geometry with catalyst 4. Geometries were optimized at the BP86-D3(BJ)/def2SVP level in CH2Cl2 (internuclear distances are given in Å).

Figure 4 .

 4 Figure 4. Gibbs free energies for the cyclization steps from tetragold 4. Geometries were optimized at the BP86-D3(BJ)/def2SVP level in CH2Cl2, internuclear distances are given in Å.

Figure 5 .

 5 Figure 5. Non-covalent interactions (NCI) analysis in a) TS-4 endo, b) TS-4 exo for catalyst 4. Contour plots of the reduced density gradient isosurfaces (density cutoff of 0.04 au for Au…Au interactions and 0.02 for all others). The green surfaces indicate weak attractive interactions (NCI). The visualization is focused on interactions near to the Au atoms, complete views are given in SI.

  since each acetylide is equally shared for bridging gold pairs, inducing very close distances [d Au1 i …Au2 = d Au2 i …Au1 = 2.9525(2) Å]. Very interestingly, the change from chloride to carbon bridging induces a contraction of the tetranuclear motif in which additional shorter aurophilic interactions are observed with d Au1…Au2 = d Au1 i …Au2 i = 3.0561(2) Å, d Au2…Au2 i = 3.0888(3) Å, d Au1…Au1 i = 3.1015(3) Å. Notably, these internuclear distances fully matches the computed values for enyne activation above reported.

Scheme 2 .

 2 Scheme 2. Dialkyne-bridged diphosphine tetragold cluster 4g formation.

Figure 6 .

 6 Figure 6. Molecular structure (top) and cluster core (bottom) of the dialkynebridged diphosphine tetragold cluster 4g. Symmetry Code: (i) 1-x, y, 3/2-z.

Table 1 .

 1 Intramolecular cycloisomerization of 1,6-enyne 6.

	a

a Conditions: enyne 6 (0.1 mmol), [Au] (4 mol%), 1.5 mL solvent [0.067 M in enyne], 1 H NMR conversion are given from triplicate experiments. DCE:

Table 2 .

 2 Effect of tetranuclear complexes 4a-4f in Intramolecular cycloisomerization of 1,6-enyne 6.

	Entry	Catalyst
	1	4	98	8% / 17% / 75%
	2	4a	93	12% / 26% / 62%
	3	4b	92	12% / 20% / 69%
	4	4c	52	11% / 13% / 76%
	5	4d	67	6% / 15% / 79%
	6	4e	11	22% / 0% / 78%
	7	4f	4	0% / 0% / 100%

([Au] 4 mol%) Conversion in 7a,b,c (%) Selectivity 7a / 7b / 7c a Conditions: enyne 6 (0.1 mmol), [Au] (4 mol%), 1.5 mL DCE [0.067 M in enyne], 85 °C, 3 h, 1 H NMR conversion are given from duplicate experiments.

Table 3

 3

		.	Intramolecular	cycloaddition	of	N-propargyl-N-allyl-aryl-
	sulfonylamines 8-14. a
	Entry 1,6-Enyne / R group	Enyne		7c-14c/	Isolated Yield
				Conversion		Selectivity	of 7c-14c
				(%)		(%)	(%)
	1	6/(C6H4)-4-Me	98		7c/75	46
	2	8/C6H5	97		8c/78	48
	3	9/(C6H4)-4-t-Bu	99		9c/75	50
	4	10/(C6H4)-4-OMe	99		10c/72	37
	5	11/(C6H4)-4-CF3	99 b		11c/85	74
	6	12/(C6H4)-4-NO2	99 b		12c/78	57
	7	13/CH2(C6H5)	97		13c/76	49
	8	14/CH3	99 b		14c/72	62
	a Conditions: enyne 6, 8-14 (0.2 mmol), 4 (1 mol%, i.e. [Au] = 4 mol%), 3 mL
	dichloroethane (DCE, 0.067 M in enyne), 85 °C, 3 h, conversion from NMR
	yield. b 16 h. Isolated yields averaged from triplicate experiments.

Scheme 3 .

 3 Intramolecular cycloaddition of 1,6-enyne 15-22.

		a Conditions:
	enyne 15-22 (0.2 mmol), Au(I) tetranuclear cationic complex 4 (1 mol%), 3.0
	ml DCE [0.067 M in enyne], 85 °C,	1 H NMR conversion and isolated yield (in
	brackets) are given from triplicate experiments.

b 4 (2 mol%). c 4 (0.5 mol%).

Acknowledgements

his ork as supported by the C R , the Université de Bourgogne, the Conseil Régional de Bourgogne-Franche-Comté (CHIMENE project, PhD grant for T.-A. N.), the PIAexcellence ISITE-BFC program (COMICS: Chemistry of Molecular Interactions Catalysis and Sensors, for JCH), ANR JCJC 2018 FITFUN (ANR-18-CE07-0015, for RJ) and the Fonds uropéen de éveloppement Régional (FEDER). Calculations were performed using HPC resources from CCUB (Université de Bourgogne). This work was granted access to the HPC resources of CINES under the allocation A0090807259 made by GENCI, for PFL.

Conflict of interest

The authors declare no conflict of interest.

Entry for the Table of Contents

Towards specific "cluster-like" reactivity? Ligands pre-organizing gold centers in a constrained environment, assisted with aurophilic interactions, push further the selectivity not achieved by mono-and digold complexes from previously unseen cooperative tetragold catalysis.

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