Dinuclear Gold Complexes Supported by Wide Bite Angle Diphosphines for Preorganization-Induced Selective Dual-Gold Catalysis

The synthesis, reactivity, and potential of well-defined dinuclear gold complexes as precursors for dual-gold catalysis is explored. Using the preorganizing abilities of well-known wide bite angle diphosphine ligands, DBFPhos and DPEPhos, dinuclear Au(I)–Au(I) complexes 1 and 2 are used as precursors to form well-defined monocationic species with either a chloridoor acetylido-ligand bridging the two gold centers. These compounds are active catalysts for the dual-gold heterocycloaddition of a urea-functionalized alkyne, and the preorganization of both Au-centers affords efficient σ,π-activation of the substrate, even at high dilution, significantly outperforming benchmark mononuclear catalysts.


Results and Discussion
The straightforward reaction of L1 (DBFPhos) and L2 (DPEPhos) with AuCl(SMe2) in a 1:2 ratio provided white solids 1 ( 31 P NMR: δ 23.3) and 2 ( 31 P NMR: δ 21.6).The respective 1 H NMR spectra were suggestive of C2 symmetric species (Scheme 1).Single crystals suitable for X-ray structure determination of 2 were obtained by slow vapor diffusion of acetone into a solution of 2 in CHCl3 (Figure 2), while for 1 only a connectivity plot could be reliably obtained (from single crystals grown from CH2Cl2-pentane; see Section 3, materials and methods).Complex 2 displays an aurophilic d 10d 10 interaction [39][40][41] with an intramolecular Au1•••Au2 distance of 3.0116(4) Å, while in 1 this Au•••Au distance was approximately 7.57 Å.It should be noted that these structures complement known ones for both compounds, with different (amounts and/or combinations of) lattice solvents present [30,31].We herein report on the formation of µ-chlorido and σ,π-alkynide derivatives of Au 2 Cl 2 (κ 2 -P;P-DBFPhos) and Au 2 Cl 2 (κ 2 -P;P-DPEPhos) and catalytic activity of these well-defined dinuclear species vs. mononuclear benchmarks in the intramolecular hydroamidation of functionalized amido-alkenes.This study emphasizes the positive effect of preorganization of two gold centers for reactions that proceed via simultaneous σand π-activation of a carbon-based π-system in a substrate.This effect is illustrated via a dilution study with mono-and di-nuclear catalysts.

Results and Discussion
The straightforward reaction of L1 (DBFPhos) and L2 (DPEPhos) with AuCl(SMe 2 ) in a 1:2 ratio provided white solids 1 ( 31 P NMR: δ 23.3) and 2 ( 31 P NMR: δ 21.6).The respective 1 H NMR spectra were suggestive of C 2 symmetric species (Scheme 1).Single crystals suitable for X-ray structure determination of 2 were obtained by slow vapor diffusion of acetone into a solution of 2 in CHCl 3 (Figure 2), while for 1 only a connectivity plot could be reliably obtained (from single crystals grown from CH 2 Cl 2 -pentane; see Section 3, materials and methods).Complex 2 displays an aurophilic d 10 -d 10 interaction [39][40][41] with an intramolecular Au1•••Au2 distance of 3.0116(4) Å, while in 1 this Au•••Au distance was approximately 7.57 Å.It should be noted that these structures complement known ones for both compounds, with different (amounts and/or combinations of) lattice solvents present [30,31].

Results and Discussion
The straightforward reaction of L1 (DBFPhos) and L2 (DPEPhos) with AuCl(SMe2) in a 1:2 ratio provided white solids 1 ( 31 P NMR: δ 23.3) and 2 ( 31 P NMR: δ 21.6).The respective 1 H NMR spectra were suggestive of C2 symmetric species (Scheme 1).Single crystals suitable for X-ray structure determination of 2 were obtained by slow vapor diffusion of acetone into a solution of 2 in CHCl3 (Figure 2), while for 1 only a connectivity plot could be reliably obtained (from single crystals grown from CH2Cl2-pentane; see Section 3, materials and methods).Complex 2 displays an aurophilic d 10d 10 interaction [39][40][41] with an intramolecular Au1   When exploiting a gold-halide precursor for gold-mediated catalysis, a prerequisite is the generation of a vacant coordination site via halide abstraction.Addition of one equivalent of AgNTf2 or related silver salts such as AgSbF6 or AgPF6 to 1 or 2 led to new species 3 and 4, respectively, according to 31 P NMR spectroscopy, with signals at δ 15.6 and 20.1 ppm, respectively.The relatively large difference in the 31 P chemical shifts observed for 1 and 3 may be related to significant reorientation of the phosphorus atoms upon formation of the single halide bridgehead.Single crystals suitable for X-ray structure determination were obtained by layer-diffusion of pentane into a CH2Cl2 solution of complex 3.The resulting molecular structure (Figure 3) shows that both gold centers were bridged by a single chlorido ligand, leading to an acute ∠Au1-Cl1-Au2 of 78.79(7)°.Relative to "open" complex 1, the intramolecular Au•••Au distance in 3 was significantly decreased (Δd ± 4.58 Å) due to increased directional positioning of the phosphorus lone pairs, despite the large natural bite angle.To the best of our knowledge, the existence of a single chlorido bridgehead between two Au I centers is relatively rare [42][43][44][45][46][47][48].Notably, this is only the second example of an intramolecular Au-Cl-Au bridge stabilized by a single dinucleating ligand, the first being our work with the ligand PN H P iPr .Attempts to characterize complex 4 via X-ray crystallography unfortunately failed, but spectroscopic data support formulation of this species as [Au2(μ-Cl)(κ 2 -P,P-DPEPhos)] + .When exploiting a gold-halide precursor for gold-mediated catalysis, a prerequisite is the generation of a vacant coordination site via halide abstraction.Addition of one equivalent of AgNTf 2 or related silver salts such as AgSbF 6 or AgPF 6 to 1 or 2 led to new species 3 and 4, respectively, according to 31 P NMR spectroscopy, with signals at δ 15.6 and 20.1 ppm, respectively.The relatively large difference in the 31 P chemical shifts observed for 1 and 3 may be related to significant reorientation of the phosphorus atoms upon formation of the single halide bridgehead.Single crystals suitable for X-ray structure determination were obtained by layer-diffusion of pentane into a CH 2 Cl 2 solution of complex 3.The resulting molecular structure (Figure 3) shows that both gold centers were bridged by a single chlorido ligand, leading to an acute ∠Au1-Cl1-Au2 of 78.79 (7) • .Relative to "open" complex 1, the intramolecular Au•••Au distance in 3 was significantly decreased (∆d ± 4.58 Å) due to increased directional positioning of the phosphorus lone pairs, despite the large natural bite angle.To the best of our knowledge, the existence of a single chlorido bridgehead between two Au I centers is relatively rare [42][43][44][45][46][47][48].Notably, this is only the second example of an intramolecular Au-Cl-Au bridge stabilized by a single dinucleating ligand, the first being our work with the ligand PN H P iPr .Attempts to characterize complex 4 via X-ray crystallography unfortunately failed, but spectroscopic data support formulation of this species as [Au 2 (µ-Cl)(κ 2 -P,P-DPEPhos)] + .Scheme 1. Synthesis of well-defined Au2-complexes 3-5 from Au(I)-Au(I) precursors 1 and 2, generated by reaction of ligands L1 and L2 with 2 equivalent of AuCl(SMe2).When exploiting a gold-halide precursor for gold-mediated catalysis, a prerequisite is the generation of a vacant coordination site via halide abstraction.Addition of one equivalent of AgNTf2 or related silver salts such as AgSbF6 or AgPF6 to 1 or 2 led to new species 3 and 4, respectively, according to 31 P NMR spectroscopy, with signals at δ 15.6 and 20.1 ppm, respectively.The relatively large difference in the 31 P chemical shifts observed for 1 and 3 may be related to significant reorientation of the phosphorus atoms upon formation of the single halide bridgehead.Single crystals suitable for X-ray structure determination were obtained by layer-diffusion of pentane into a CH2Cl2 solution of complex 3.The resulting molecular structure (Figure 3) shows that both gold centers were bridged by a single chlorido ligand, leading to an acute ∠Au1-Cl1-Au2 of 78.79(7)°.Relative to "open" complex 1, the intramolecular Au•••Au distance in 3 was significantly decreased (Δd ± 4.58 Å) due to increased directional positioning of the phosphorus lone pairs, despite the large natural bite angle.To the best of our knowledge, the existence of a single chlorido bridgehead between two Au I centers is relatively rare [42][43][44][45][46][47][48].Notably, this is only the second example of an intramolecular Au-Cl-Au bridge stabilized by a single dinucleating ligand, the first being our work with the ligand PN H P iPr .Attempts to characterize complex 4 via X-ray crystallography unfortunately failed, but spectroscopic data support formulation of this species as [Au2(μ-Cl)(κ 2 -P,P-DPEPhos)] + .Complex 3 was amenable to reaction with 1-propynylmagnesium bromide, forming σ,π-coordinated alkynide-bridging complex 5, akin to our previous report using the PN H P iPr scaffold.The 31 P NMR spectrum of 5 displayed a singlet at 23.8 ppm and the elemental composition as [Au 2 (µ-CCMe)(κ 2 -P,P-DBFPhos)] + was corroborated by high-resolution electron spray ionization mass spectrometry (ESI-MS).X-ray structure determination of a minute amount of adventitious crystalline material obtained from cyclopentane-CHCl 3 showed direct evidence of the dual interaction of the -C≡CMe ligand with both gold centers (i.e., σ-coordination of the terminal C37 carbon to Au2 and π-coordination of the triple bond to Au1; Figure 4).To the best of our knowledge, this is only the second crystallographically-characterized intramolecular Au 2 (σ,π-acetylide) complex supported by a diphosphine ligand, and an illustration that preorganization of two gold centers may lead to selective σ,π-coordination of the alkyne moiety.Complex 4 is envisioned to initially react with 1-propynylmagnesium bromide in a similar fashion to provide putative complex 6, postulated as [Au 2 (µ-CCMe)(κ 2 -P,P-DPEPhos)] + .However, this species and analogues generated by using 4-ethynyl-α,α,α-trifluorotoluene proved to be highly sensitive to water, precluding its spectral characterization.
Complex 3 was amenable to reaction with 1-propynylmagnesium bromide, forming σ,πcoordinated alkynide-bridging complex 5, akin to our previous report using the PN H P iPr scaffold.The 31 P NMR spectrum of 5 displayed a singlet at 23.8 ppm and the elemental composition as [Au2(μ-CCMe)(κ 2 -P,P-DBFPhos)] + was corroborated by high-resolution electron spray ionization mass spectrometry (ESI-MS).X-ray structure determination of a minute amount of adventitious crystalline material obtained from cyclopentane-CHCl3 showed direct evidence of the dual interaction of the -C≡CMe ligand with both gold centers (i.e., σ-coordination of the terminal C37 carbon to Au2 and πcoordination of the triple bond to Au1; Figure 4).To the best of our knowledge, this is only the second crystallographically-characterized intramolecular Au2(σ,π-acetylide) complex supported by a diphosphine ligand, and an illustration that preorganization of two gold centers may lead to selective σ,π-coordination of the alkyne moiety.Complex 4 is envisioned to initially react with 1propynylmagnesium bromide in a similar fashion to provide putative complex 6, postulated as [Au2(μ-CCMe)(κ 2 -P,P-DPEPhos)] + .However, this species and analogues generated by using 4ethynyl-α,α,α-trifluorotoluene proved to be highly sensitive to water, precluding its spectral characterization.Having established that ligands L1 and L2 can facilitate pre-activation of C≡C bonds in a σ,πfashion, we wondered about their activity in the heterocyclization (intramolecular hydroamination) of urea-functionalized alkyne A. Previously, Paradies and co-workers compared AuCl(Xantphos), Au2Cl2(Xantphos), and AuCl(PPh3) for the intermolecular hydroamidation of cyclohexene (and analogs thereof) and toluene sulfonamide in the presence of stoichiometric amounts of silver salts as halide abstracting agents [17].This study concluded that [Au2(Xantphos)] 2+ and the corresponding species [Au2(Xantphos)2] 2+ , which forms from the former, were both catalytically inactive.
We were curious whether dinuclear σ,π-activation could result in anti-Markovnikov hydroamidation of substrate A (Scheme 2).This reaction was previously reported by Medio-Simón and co-workers to form five-membered indole B via σ,π-activation, using two equivalents of the mononuclear gold complex AuCl(P t Bu3) as the best catalyst [49].Using 2.5 mol % of either dihalide precursors 1 or 2 with two equiv. of AgSbF6, or species 3 or 4 with one equiv.of AgSbF6, in N,N'-DMF at 60 °C for 5 h led to full conversion and high regioselectivity to B (95-100%), as determined by 1 H Having established that ligands L1 and L2 can facilitate pre-activation of C≡C bonds in a σ,π-fashion, we wondered about their activity in the heterocyclization (intramolecular hydroamination) of urea-functionalized alkyne A. Previously, Paradies and co-workers compared AuCl(Xantphos), Au 2 Cl 2 (Xantphos), and AuCl(PPh 3 ) for the intermolecular hydroamidation of cyclohexene (and analogs thereof) and toluene sulfonamide in the presence of stoichiometric amounts of silver salts as halide abstracting agents [17].This study concluded that [Au 2 (Xantphos)] 2+ and the corresponding species [Au 2 (Xantphos) 2 ] 2+ , which forms from the former, were both catalytically inactive.
We were curious whether dinuclear σ,π-activation could result in anti-Markovnikov hydroamidation of substrate A (Scheme 2).This reaction was previously reported by Medio-Simón and co-workers to form five-membered indole B via σ,π-activation, using two equivalents of the mononuclear gold complex AuCl(P t Bu 3 ) as the best catalyst [49].Using 2.5 mol % of either dihalide precursors 1 or 2 with two equiv. of AgSbF 6, or species 3 or 4 with one equiv.of AgSbF 6 , in N,N -DMF at 60 • C for 5 h led to full conversion and high regioselectivity to B (95-100%), as determined by 1 H NMR spectroscopy, in accordance with a selective σ,π-acetylide mechanism.All four Au 2 systems outperformed the mononuclear benchmark AuCl(P t Bu 3 ) in the presence of one equiv.of AgSbF 6 (80% B).When no AgSbF 6 was added, significantly lower regioselectivity and conversion was observed for each system, presumably due to slower generation of the σ,π-acetylide species.The high regioselectivity achieved with these dinuclear catalysts is attributed to the ligand-enforced proximity of the two Au(I) centers.High resolution mass spectra of 1:1 mixtures of 3 or 4 (with or without additional AgSbF 6 ) and substrate A, measured ten minutes after dissolution of the two solids in DMF, suggested formation of σ,π-complexes with formal loss of HCl.
Inorganics 2018, 6, x 5 of 13 NMR spectroscopy, in accordance with a selective σ,π-acetylide mechanism.All four Au2 systems outperformed the mononuclear benchmark AuCl(P t Bu3) in the presence of one equiv.of AgSbF6 (80% B).When no AgSbF6 was added, significantly lower regioselectivity and conversion was observed for each system, presumably due to slower generation of the σ,π-acetylide species.The high regioselectivity achieved with these dinuclear catalysts is attributed to the ligand-enforced proximity of the two Au(I) centers.High resolution mass spectra of 1:1 mixtures of 3 or 4 (with or without additional AgSbF6) and substrate A, measured ten minutes after dissolution of the two solids in DMF, suggested formation of σ,π-complexes with formal loss of HCl.We hypothesized that the high local concentration of gold(I) centers provided by these dinuclear gold complexes should render the regioselectivity of the complexes independent of the catalyst loading [50,51].Dilution studies to investigate the effect of decreased catalyst loadings on the level of regiocontrol for the conversion of A to B and C clearly validated this hypothesis, as the consistently high regioselectivity to B with catalyst 4 in the presence of one equivalent of AgSbF6 was not dependent on the concentration of gold centers (ranging from 5 to 0.5 mol %) (Figure 5).In contrast, dilution experiments with mononuclear AuCl(P t Bu3) in the presence of an equimolar amount of AgSbF6 resulted in a sharp drop in selectivity, particularly below 1 mol % of catalyst loading, to around 40% yield of B [52].These results demonstrate the benefits of well-defined pre-organization of two gold centers to enforce selective σ,π-activation and to mediate regioselective dual-gold catalysis with functionalized alkynes, even at low catalyst loadings.We hypothesized that the high local concentration of gold(I) centers provided by these dinuclear gold complexes should render the regioselectivity of the complexes independent of the catalyst loading [50,51].Dilution studies to investigate the effect of decreased catalyst loadings on the level of regiocontrol for the conversion of A to B and C clearly validated this hypothesis, as the consistently high regioselectivity to B with catalyst 4 in the presence of one equivalent of AgSbF 6 was not dependent on the concentration of gold centers (ranging from 5 to 0.5 mol %) (Figure 5).In contrast, dilution experiments with mononuclear AuCl(P t Bu 3 ) in the presence of an equimolar amount of AgSbF 6 resulted in a sharp drop in selectivity, particularly below 1 mol % of catalyst loading, to around 40% yield of B [52].These results demonstrate the benefits of well-defined pre-organization of two gold centers to enforce selective σ,π-activation and to mediate regioselective dual-gold catalysis with functionalized alkynes, even at low catalyst loadings.
Inorganics 2018, 6, x 5 of 13 NMR spectroscopy, in accordance with a selective σ,π-acetylide mechanism.All four Au2 systems outperformed the mononuclear benchmark AuCl(P t Bu3) in the presence of one equiv.of AgSbF6 (80% B).When no AgSbF6 was added, significantly lower regioselectivity and conversion was observed for each system, presumably due to slower generation of the σ,π-acetylide species.The high regioselectivity achieved with these dinuclear catalysts is attributed to the ligand-enforced proximity of the two Au(I) centers.High resolution mass spectra of 1:1 mixtures of 3 or 4 (with or without additional AgSbF6) and substrate A, measured ten minutes after dissolution of the two solids in DMF, suggested formation of σ,π-complexes with formal loss of HCl.We hypothesized that the high local concentration of gold(I) centers provided by these dinuclear gold complexes should render the regioselectivity of the complexes independent of the catalyst loading [50,51].Dilution studies to investigate the effect of decreased catalyst loadings on the level of regiocontrol for the conversion of A to B and C clearly validated this hypothesis, as the consistently high regioselectivity to B with catalyst 4 in the presence of one equivalent of AgSbF6 was not dependent on the concentration of gold centers (ranging from 5 to 0.5 mol %) (Figure 5).In contrast, dilution experiments with mononuclear AuCl(P t Bu3) in the presence of an equimolar amount of AgSbF6 resulted in a sharp drop in selectivity, particularly below 1 mol % of catalyst loading, to around 40% yield of B [52].These results demonstrate the benefits of well-defined pre-organization of two gold centers to enforce selective σ,π-activation and to mediate regioselective dual-gold catalysis with functionalized alkynes, even at low catalyst loadings.Encouraged by this proof-of-concept demonstration of ligand-induced preorganization of two gold centers for dual-gold catalysis, we explored the structurally related substrate D featuring an additional methylene unit between the phenyl ring and the urea fragment (Scheme 3, reaction I).This substrate was quantitatively converted via selective 6-endo-dig cyclization to yield product E when using pre-activated dinuclear catalyst 3 or 4 in the presence of AgSbF 6 .Substrate F, the thiourea-derivative of substrate A, did not provide the corresponding N-phenyl-1H-indole-1-carbothioamide.Instead, product G was selectively obtained via 6-exo-dig cyclization (Scheme 3, reaction II), which is in line with observations by Shi et al., who speculated on σ,π-activation of a propargylic thiourea and subsequent N-attack to obtain the same type of cyclic 6-membered compound [53].Finally, unlike the complex [Au 2 (BIPHEP)](NTf 2 ) 2 [54], which despite its dinuclear nature cannot accommodate σ,π-coordination because of steric constraints, digold complexes 3 and 4 do not dimerize 2-ethynylaniline but rather induced selective cyclization to form indole H (Scheme 3, reaction III), suggesting that σ,π-coordination of one molecule of 2-ethynylaniline was energetically more favorable than σ-coordination of two molecules of 2-ethynylaniline with wide bite angle diphosphine frameworks that do allow bridging ligation of acetylenic substrates.Encouraged by this proof-of-concept demonstration of ligand-induced preorganization of two gold centers for dual-gold catalysis, we explored the structurally related substrate D featuring an additional methylene unit between the phenyl ring and the urea fragment (Scheme 3, reaction I).This substrate was quantitatively converted via selective 6-endo-dig cyclization to yield product E when using pre-activated dinuclear catalyst 3 or 4 in the presence of AgSbF6.Substrate F, the thioureaderivative of substrate A, did not provide the corresponding N-phenyl-1H-indole-1-carbothioamide.Instead, product G was selectively obtained via 6-exo-dig cyclization (Scheme 3, reaction II), which is in line with observations by Shi et al., who speculated on σ,π-activation of a propargylic thiourea and subsequent to obtain the same type of cyclic 6-membered compound [53].Finally, unlike the complex [Au2(BIPHEP)](NTf2)2 [54], which despite its dinuclear nature cannot accommodate σ,πcoordination because of steric constraints, digold complexes 3 and 4 do not dimerize 2-ethynylaniline but rather induced selective cyclization to form indole H (Scheme 3, reaction III), suggesting that σ,πcoordination of one molecule of 2-ethynylaniline was energetically more favorable than σcoordination of two molecules of 2-ethynylaniline with wide bite angle diphosphine frameworks that do allow bridging ligation of acetylenic substrates.

General Comments
P( t Bu)3AuCl, AgSbF6, AgNTf2, and 1-propynylmagnesium bromide (0.5 M in THF) were purchased from commercial suppliers and used without further purification.Compound A was prepared according to a literature procedure [49].AuCl(SMe2) was either purchased from Sigma Scheme 3. Other catalytic reactions with complexes 3 and 4 with (thio)urea-containing phenylacetylenic substrates D, F, and 2-ethynylaniline to support the σ,π-activation of acetylenic substrates.

General Comments
P( t Bu) 3 AuCl, AgSbF 6 , AgNTf 2 , and 1-propynylmagnesium bromide (0.5 M in THF) were purchased from commercial suppliers and used without further purification.Compound A was prepared according to a literature procedure [49].AuCl(SMe 2 ) was either purchased from Sigma Aldrich (St. Louis, MO, USA) or synthesized by reacting HAuCl 4 .3H 2 O with an excess of dimethylsulfide in ethanol at room temperature for ten minutes.1-Propynylmagnesium bromide was titrated in triplo with I 2 /LiCl in THF.Tetrahydrofuran and pentane were distilled from sodium benzophenone ketyl.Dichloromethane was distilled from CaH 2 .All reactions were carried out in flame-dried or oven-dried glassware under a nitrogen atmosphere, unless otherwise stated.Flash column chromatography was performed with silica gel (Screening Devices, 60Å, particle size 0.040-0.063µm).Eluent mixtures are reported as v/v %.Products were visualized by UV light.NMR spectra ( 1 H, 31 P{ 1 H}, 13 C{ 1 H}) were measured at room temperature on Bruker DRX 500, AV 400, DRX 300 and AV 300 instruments (Bruker, Billerica, MA, USA) and referenced against SiMe 4 , external H 3 PO 4 or solvent.NMR chemical shifts are reported in ppm, coupling constants (J) are reported in Hertz.High resolution mass spectra were recorded on a JEOL AccuTOF LC JMS-T100LP mass spectrometer (JEOL, Tokyo, Japan) using electron spray ionization (ESI) or field desorption (FD).GC-MS spectra were recorded on an Agilent 5973 Network Mass Selective Detector (Agilent, Santa Clara, CA, USA) equipped with a 6890N Network GC System.

Syntheses of New Complexes
Complex 1, Au 2 Cl 2 (DBFPhos).DBFPhos (1 equiv.)and AuCl(SMe 2 ) (2 equiv.)were dissolved in CH 2 Cl 2 and stirred at room temperature for a couple of hours, depending on the scale.The resultant white suspension was concentrated to ca. 0.5 mL.Pentane (20 mL) was added, leading to formation of a white precipitate.The suspension was stirred vigorously for 5 min, after which the precipitate was allowed to settle.The colorless supernatant was removed and the residue was dried under vacuum, yielding 1 as a white solid in quantitative yield.Single crystals suitable for X-ray diffraction were obtained by layering ca.1.5 mL of pentane on top of a solution of ca. 4 mg of complex 1 in ca.0.3 mL of CH 2 Cl 2 in a 2 mL vial. 31 Complex 2, Au 2 Cl 2 (DPEPhos).DPEPhos (1 equiv.)and AuCl(SMe 2 ) (2 equiv.)were dissolved in CH 2 Cl 2 and stirred at room temperature for several hours.The resultant white suspension was concentrated to ca. 0.5 mL.Pentane (20 mL) was added, leading to formation of a white precipitate.The resultant suspension was stirred vigorously for 5 min, after which the precipitate was allowed to settle.The colorless supernatant was removed and the white residue was dried under vacuum, yielding 2 as a white solid in yields around 75%. Single crystals suitable for X-ray diffraction (transparent needles) were obtained by slow vapor diffusion of acetone into a solution of complex 2 in CHCl 3 . 31P{ 1 H} NMR (162 MHz, CD 2 Cl 2 , ppm): δ 21.6 (s). 1 H NMR (400 MHz, CD 2 Cl 2 , ppm): δ 7.61-7.27(m, 18H), 7.24-7.12(m, 6H), 7.05 (dd, J = 8.3, 5.3 Hz, 2H), 6.83-6.69(m, 2H). 13

Complex 3, [Au 2 (µ-Cl)(DBFPhos)](X).
Inside a nitrogen-filled glovebox, AgSbF 6 or AgNTf 2 (1 equiv.) was added to complex 1 (1 mol.equiv.)and the reaction vessel was covered in aluminum foil.In air, the mixture was suspended in CH 2 Cl 2 or THF and the suspension was stirred for several hours.The reaction mixture was filtered over 2-3 cm of Celite on top of a frit filter, and the filtrate was evaporated until dry to yield complex 3 as a white solid.Colorless single crystals suitable for X-ray diffraction of the triflimide derivative were obtained by layering ca.1.5 mL of pentane on top of a solution of ca. 4 mg of complex 3 in ca.0.5 mL of CH 2 Cl 2 in an NMR-tube. 31 ).Inside a glovebox, AgSbF 6 (or a related Ag-salt; 1 mol.equiv.) was added to complex 2 and the reaction vessel was covered in aluminum foil.In air, the mixture was suspended in CH 2 Cl 2 or THF and the suspension was stirred for a couple of hours.
The reaction mixture was filtered over ca. 1 cm of Celite on top of a frit filter and the filtrate was evaporated until dry to yield complex 4 as a white solid (average yield 81%).All attempts to grow single crystals of complex 4 failed. 31P{ 1 H} NMR (121 MHz, CD 2 Cl 2 , ppm): δ 20.1 (s). 1 H NMR (300 MHz, CD 2 Cl 2 , ppm): δ 7.66-7.35(m, 24H), 7.13 (t, J = 7.6 Hz, 2H), 6.83 (ddd, J = 12.7, 7.8, 1.4 Hz, 2H). 13 ) was added and the resultant orange solution was stirred for ca.15 min at −78 • C followed by 5 h at room temperature.The reaction mixture was quenched with a saturated aqueous solution of NaHCO 3 and the product was extracted three times into CH 2 Cl 2 .The aqueous layer was extracted two times with CH 2 Cl 2 .The combined organic layers were dried over MgSO 4 and the solvent was removed under reduced pressure.Sonication with toluene was then performed for 30 min, followed by filtration over paper, and concentration of the filtrate afforded 5 as a white solid.Single crystals (tiny transparent needles) suitable for X-ray diffraction were obtained by layering ca.1.5 mL of cyclopentane on top of a solution of ca. 4 mg of complex 5 (in its orange form) in ca.0.3 mL of CHCl 3 in a 2 mL vial. 31

General Information on Catalytic Studies
Synthesis of Substrate D. A solution of (2-ethynylphenyl)methanamine, prepared following a literature procedure [55], (0.84 g, 6.40 mmol) in CH 2 Cl 2 (16 mL) was added to phenyl isocyanate (695 µL, 6.40 mmol).The resultant red suspension was "stirred" for ca.1.5 h (formation of a solid soon impeded stirring) before being added to a second batch of phenyl isocyanate (695 µL, 6.40 mmol) and stirred for ca.16 h.The resultant brown suspension was concentrated, impregnated on silica, and purified by column chromatography (ca.30 cm of silica gel, Ø NS 29/32, hexane/ethyl acetate 3:1) to yield D as a beige solid (0.92 g, 57% yield). 1  Synthesis of Substrate F. To CH 2 Cl 2 (2 mL) was added 2-ethynylaniline (142 µL, 1.25 mmol) and phenyl isothiocyanate (150 µL, 1.25 mmol).The mixture was stirred for 30 min at room temperature and then heated to reflux for 4 h.The solution was allowed to cool down to room temperature and all volatiles were removed, yielding a light orange solid that was dried under vacuum.The crude product was impregnated on silica and purified by column chromatography (ca.28 cm of silica gel, Ø NS 29/32, hexane/ethyl acetate 3:1, Rf 0.38) to yield substrate F (202 mg, 64%). 1  General Procedure for Catalytic Studies with Substrates A, D and F.An oven-dried 4 mL vial was charged with the substrate (50 µmol) and a digold complex (2.5 mol %; 1.25 µmol).The solids were dissolved in anhydrous N,N -DMF (0.5 mL) and stirred in air at 60 • C for 5 h.If AgSbF 6 was added, this was done either by addition of the dry solid inside a nitrogen-filled glovebox or by addition of a stock solution of AgSbF 6 in N,N -DMF.The reaction mixture was transferred to a round-bottom flask with CH 2 Cl 2 or CHCl 3 and all solvent was evaporated under reduced pressure.NMR spectra were recorded in CDCl 3 or acetone-d 6 .

Single Crystal X-ray Crystallography
Complex 5. X-ray intensities were measured on a Bruker D8 Quest Eco diffractometer equipped with a Triumph monochromator (λ = 0.71073 Å) and a CMOS Photon 50 detector at a temperature of 150(2) K. Intensity data were integrated with the Bruker APEX2 software [56].Absorption correction and scaling was performed with SADABS [57].The structures were solved using intrinsic phasing with the program SHELXT [56].Least-squares refinement was performed with SHELXL-2013 [58] against F 2 of all reflections.Non-hydrogen atoms were refined with anisotropic displacement parameters.The H atoms were placed at calculated positions using the instructions AFIX 13, AFIX 43, or AFIX 137, with isotropic displacement parameters having values 1.2 or 1.5 times Ueq of the attached C atoms.C 39 H 29 OP 2 Au 2 SbF 6 , F w = 1205.28,colorless block, 0.364 × 0.115 × 0.095 mm, monoclinic,  (Sheldrick, 2015) and was refined on F 2 with SHELXL-2014/7 (Sheldrick, 2015).Analytical numeric absorption correction, using a multifaceted crystal model, was applied using CrysAlisPro.The temperature of the data collection was controlled using the system Cryojet (manufactured by Oxford Instruments).The H atoms were placed at calculated positions using the instructions AFIX 13, AFIX 43, or AFIX 137, with isotropic displacement parameters having values 1.2 or 1.5 times Ueq of the attached C atoms.2: The structure was partly disordered.The asymmetric unit contained a disordered mixture of lattice solvent molecule (CHCl3 and Acetone) at one site.The occupancy factors for the chloroform and acetone molecules were refined to 0.279(3) and 0.721(3), respectively.The crystal that was mounted on the diffractometer was twinned.The two twin components were related by a twofold axis along the reciprocal vector 0.9040a* − 0.0000b* − 0.4276c*.The BASF scale factor was refined to 0.3272 (7).3: The structure was ordered.The crystal that was mounted on the diffractometer was twinned.The two twin components were related by a twofold axis along the reciprocal vector 0.0001a* + 0.0004b* + 1.0000c*.The BASF scale factor was refined to 0.4368 (7).
CCDC 1893603 (5), 1894224 (2), and 1894225 (3) contain the supplementary crystallographic data for this paper (see Supplementary Materials).These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Conclusions
In summary, we demonstrate that the wide bite-angle diphosphine ligands, DBFPhos and DPEPhos, provide good platforms for the formation of catalytically relevant bis-gold complexes, featuring a bridging halide or alkynide ligand upon selective halide abstraction and follow-up manipulation.Preorganization of both gold centers allows for selective σ,π-activation of functionalized alkynes.The well-defined dinuclear Au I complexes are excellent precatalysts for dual-gold catalysis involving selective σ,π-activation, inducing high regioselectivity in, for instance, the gold-catalyzed heterocyclization of urea A. Dilution experiments show that the dinuclear catalysts retain high selectivity at decreased catalyst loadings, unlike mononuclear Au(I) catalysts, which are typically employed for this reaction.These results underline the benefits of preorganization of gold centers to invoke selective substrate activation in dual-gold catalysis.

Figure 1 .
Figure 1.Left: Strategy for the preorganization of two gold-centers for σ-π-coordination of hydrocarbon π-systems using a diphosphine platform.Right: previous and current work on bis-gold chemistry with specific diphosphine ligands.

Figure 1 .
Figure 1.Left: Strategy for the preorganization of two gold-centers for σ-π-coordination of hydrocarbon π-systems using a diphosphine platform.Right: previous and current work on bis-gold chemistry with specific diphosphine ligands.

Figure 1 .
Figure 1.Left: Strategy for the preorganization of two gold-centers for σ-π-coordination of hydrocarbon π-systems using a diphosphine platform.Right: previous and current work on bis-gold chemistry with specific diphosphine ligands.

Figure 3 .
Figure 3. Displacement ellipsoid plot (50% probability level) of one of the two crystallographically independent cationic parts of 3. The SbF6 counterion and hydrogen atoms have been omitted for

Figure 3 .
Figure 3. Displacement ellipsoid plot (50% probability level) of one of the two crystallographically independent cationic parts of 3. The SbF6 counterion and hydrogen atoms have been omitted for

6 Figure 5 .
Figure 5.Comparison of regioselectivity to indole B under various dilution conditions, obtained with dinuclear catalyst 4 in the presence of one equiv.of AgSbF 6 vs. mononuclear benchmark AuCl(P t Bu 3 ) with one equiv.AgSbF 6 .
Comparison of regioselectivity to indole B under various dilution conditions, obtained with dinuclear catalyst 4 in the presence of one equiv.of AgSbF6 vs. mononuclear benchmark AuCl(P t Bu3) with one equiv.AgSbF6.