New Insight into the Reactivity of S,S-Bis-ylide

The present work focuses on the reactivity of S,S-bis-ylide 2, which presents a strong nucleophilic character, as evidenced by reactions with methyl iodide and CO2, affording C-methylated salts 3 and betaine 4, respectively. The derivatization of betaine 4 affords the corresponding ester derivative 6, which is fully characterized by using NMR spectroscopy and X-ray diffraction analysis. Furthermore, an original reaction with phosphenium ions leads to the formation of a transient push–pull phosphino(sulfonio)carbene 8, which rearranges to give stabilized sulfonium ylide derivative 7.


Introduction
Since the discovery of ylides in the 1920s [1,2], their chemistry has experienced important growth [3][4][5], and they have become very important synthetic tools [6][7][8][9]. Bisylides, which are the combination of two ylide functions on a single carbon atom, have attracted significant attention from many research groups [10][11][12][13][14][15][16]. Indeed, since the first synthesis of carbodiphosphoranes I by Ramirez in the 1960s [17], many models have been developed (Figure 1). Among them, we can mention carbodicarbenes II prepared by Bertrand's group [18], after initial theoretical predictions by Frenking [19]; mixed carbophosphinocarbene III, initially synthesized by Fürstner and Alcarazo and later by Ong et al. [20][21][22]; and mixed phosphonio/sulfonio IV and phosphonio/sulfoxonio V (X = O) bis-ylides prepared by our group [23][24][25]. Finally, major contributions were made by Fujii's group with various combinations of selenium/sulfur-or sulfur/sulfur-stabilized carbones V-VIII [26][27][28][29][30]. Naturally, the diversity of these structures has brought considerable knowledge on these species, which exhibit very diverse reactivity, ranging from their use as ligands in organometallic chemistry [15] to the activation of small molecules [21] and even their application as atomic carbon sources [23]. The main application of bis-ylides remains their use as ligands because of the peculiar environment of the central carbon atom. In particular, the presence of two lone pairs located on a single carbon atom [10][11][12][13][14][15][16] offers unique coordination modes for transition metals. Indeed, Stephen took advantage of the presence of the two lone pairs to stabilize certain transition metals, achieving high efficiency in hydrogenation reactions [31]. Ong's group has evidenced that the unexpected accepting character of carbodicarbenes at the N-heterocyclic carbene fragments was beneficial for ambiphilic-type reactivity allowing the activation of small molecules [32,33]. It is obvious that the reactivity and applications of bis-ylides are directly linked to the combination of the two ylide functions, but overall remain rare.
In 2010, we reported the first stable and isolable mixed P,S-bis-ylide IV [23], which can be used as an atomic carbon reagent to introduce one carbon atom into various organic molecules [34]. In particular, the labile character of the sulfide ligand in IV facilitates substitution reactions at the central carbon atom and, thus, atomic carbon transfer reactions. Therefore, S,S-bis-ylide VI consisting of two labile sulfide moieties should be an excellent  48 phonio/sulfonio bis-ylides IV, phosphonio/sulfoxonio or phosphonio/iminosulfonio bis-ylides V, 49 sulfonio/sulfonio bis-ylides VI, selenio-or sulfonio-/iminosulfonio VII and bis iminosulfanebis- 50 ylides VIII. 51 52 In 2010, we have reported the first stable and isolable mixed P,S-bis-ylide IV [23] 53 which can be used as atomic carbon reagent to introduce one carbon atom into various 54 organic molecules [34]. In particular, the labile character of sulfide ligand in IV facilitates 55 substitution reactions at the central carbon atom and thus atomic carbon transfer reac-56 tions. Therefore, S,S-bis-ylide VI constituted of two labile sulfide moieties should be an 57 excellent atomic carbon reagent. However, probably due to the thermal instability of VI, 58 only a few reactions with Au(I), demonstrating its carbone character were described [30] 59 and no reaction with organic reagents has been reported to date. In this article, we report 60 original reactions of S,S-bis-ylide VI with CO2 and phosphenium ions (Figure 1). 61

62
Synthesis 63 Monoprotonated precursor 1 (Scheme 1) has been prepared according to the method 64 previously described by Fujii [30]. The spectroscopic data are in good agreement with the 65 reported values. In particular, the central proton and carbon resonances of 1 appear at  = 66 3.88 ppm and  = 19.4 ppm, respectively in 1 H and 13 C NMR spectra. Because of the thermal 67 instability of S,S-bis-ylide 2, the deprotonation was then realized in THF-d8 using potas-68 sium hexamethyldisilazane at −80 °C and was analyzed at low temperature, in situ, in the 69 presence of conjugated acid. With the appearance of a bright yellow color, in the 1 H NMR 70 spectrum the C-H signal in disappeared while the central carbon in the 13 C NMR spectrum 71 was lower field shifted at  = 39.0 ppm compared to 1. Bis-ylide 2 starts to decompose at 72 −30 °C to afford black carbon precipitate and diphenyl sulfide. The formation of S,S-bis-ylide 2 was unambiguously confirmed by its methylation 79 reaction (Scheme 1). Indeed, upon addition of one equivalent of methyl iodide to a THF 80 solution of 2 at −80 °C , the yellow color immediately disappeared concomitantly with the 81 precipitation of a white solid. After treatment, the desired C-methylated salt 3 was iso-82 lated in 85% yield. The methylation was confirmed by the presence of two characteristic 83 Figure 1. Carbodiphosphoranes I, carbodicarbenes II, carbophosphinocarbenes III, phosphonio/sulfonio bis-ylides IV, phosphonio/sulfoxonio or phosphonio/iminosulfonio bis-ylides V, sulfonio/sulfonio bis-ylides VI, selenio-or sulfonio-/iminosulfonio VII, and bis iminosulfanebis-ylides VIII.

Synthesis
Monoprotonated precursor 1 (Scheme 1) was prepared according to the method previously described by Fujii [30]. The spectroscopic data are in good agreement with the reported values. In particular, the central proton and carbon resonances of 1 appear at δ = 3.88 ppm and δ = 19.4 ppm, respectively, in the 1 H and 13 C NMR spectra. Because of the thermal instability of S,S-bis-ylide 2, the deprotonation was then realized in THF-d 8 using potassium hexamethyldisilazane at −80 • C and was analyzed at low temperature, in situ, in the presence of conjugated acid. With the appearance of a bright-yellow color, in the 1 H NMR spectrum, the C-H signal disappeared, while the central carbon in the 13 C NMR spectrum was lower-field-shifted at δ = 39.0 ppm compared to 1. Bis-ylide 2 starts to decompose at −30 • C to afford black carbon precipitate and diphenyl sulfide. Carbodiphosphoranes I, carbodicarbenes II, carbophosphinocarbenes III, phosphonio/sulfonio bis-ylides IV, phosphonio/sulfoxonio or phosphonio/iminosulfonio bis-ylides V, sulfonio/sulfonio bis-ylides VI, selenio-or sulfonio-/iminosulfonio VII, and bis iminosulfanebisylides VIII.
In 2010, we reported the first stable and isolable mixed P,S-bis-ylide IV [23], which can be used as an atomic carbon reagent to introduce one carbon atom into various organic molecules [34]. In particular, the labile character of the sulfide ligand in IV facilitates substitution reactions at the central carbon atom and, thus, atomic carbon transfer reactions. Therefore, S,S-bis-ylide VI consisting of two labile sulfide moieties should be an excellent atomic carbon reagent. However, probably due to the thermal instability of VI, only a few reactions with Au(I), demonstrating its carbone character, were described [30], and no reaction with organic reagents has been reported to date. In this article, we report the original reactions of S,S-bis-ylide VI with CO2 and phosphenium ions ( Figure 1).

Synthesis
Monoprotonated precursor 1 (Scheme 1) was prepared according to the method previously described by Fujii [30]. The spectroscopic data are in good agreement with the reported values. In particular, the central proton and carbon resonances of 1 appear at δ = 3.88 ppm and δ = 19.4 ppm, respectively, in the 1 H and 13 C NMR spectra. Because of the thermal instability of S,S-bis-ylide 2, the deprotonation was then realized in THF-d8 using potassium hexamethyldisilazane at −80 °C and was analyzed at low temperature, in situ, in the presence of conjugated acid. With the appearance of a bright-yellow color, in the 1 H NMR spectrum, the C-H signal disappeared, while the central carbon in the 13 C NMR spectrum was lower-field-shifted at δ = 39.0 ppm compared to 1. Bis-ylide 2 starts to decompose at −30 °C to afford black carbon precipitate and diphenyl sulfide.

Reactivity
The formation of S,S-bis-ylide 2 was unambiguously confirmed by its methylation reaction (Scheme 1). Indeed, upon the addition of one equivalent of methyl iodide to a THF solution of 2 at −80 °C, the yellow color immediately disappeared concomitantly with the precipitation of a white solid. After treatment, the desired C-methylated salt 3 was isolated in an 85% yield. The methylation was confirmed by the presence of two characteristic signals for the methyl group at δ = 1.67 ppm and δ = 10.2 ppm in the 1 H and 13 C NMR spectra, respectively (see Supplementary Materials). C-methylated salt 3 was Scheme 1. Synthesis of S,S-bis-ylide 2 and alkylation reaction with MeI.

Reactivity
The formation of S,S-bis-ylide 2 was unambiguously confirmed by its methylation reaction (Scheme 1). Indeed, upon the addition of one equivalent of methyl iodide to a THF solution of 2 at −80 • C, the yellow color immediately disappeared concomitantly with the precipitation of a white solid. After treatment, the desired C-methylated salt 3 was isolated in an 85% yield. The methylation was confirmed by the presence of two characteristic signals for the methyl group at δ = 1.67 ppm and δ = 10.2 ppm in the 1 H and 13 C NMR spectra, respectively (see Supplementary Materials). C-methylated salt 3 was isolated in crystalline form by layering diethyl ether onto a saturated dichloromethane solution, and its structure was confirmed by X-ray diffraction analysis ( Figure 2). As expected, the S-C bond lengths in 3 (1.682 and 1.687 Å) are very similar to those of the protonated bis-ylide precursor 1 (1.685 Å and 1.676 Å) [30] and much shorter than an S-C single bond length (1.81 Å), showing the delocalization of the negative charge from the central carbon atom to the SPh 2 fragments and justifying the planar environment around the C1 atom (∑ • = 359.7 • ). The S1-C1-S2 angle is also almost identical to that of 1. isolated in crystalline form by layering diethyl ether onto a saturated dichloromethane solution, and its structure was confirmed by X-ray diffraction analysis ( Figure 2). As expected, the S-C bond lengths in 3 (1.682 and 1.687 Å) are very similar to those of the protonated bis-ylide precursor 1 (1.685 Å and 1.676 Å) [30] and much shorter than an S-C single bond length (1.81 Å), showing the delocalization of the negative charge from the central carbon atom to the SPh2 fragments and justifying the planar environment around the C1 atom (∑°= 359.7°). The S1-C1-S2 angle is also almost identical to that of 1.
It is well known that carbodiphosphoranes (P,P-bis-ylides) react with CO 2 to form zwitterionic donor-acceptor complexes that can coordinate transition metals or evolve upon heating toward phosphine oxide and phosphoranylideneketene [35][36][37][38][39]. The sulfur analog 2 also reacts with CO 2 (3 bars) at −70 • C, affording the corresponding CO 2 adduct 4 (Scheme 2). 13 C NMR analysis of the resulting solution at −20 • C shows two broad signals appearing at δ = 167.2 ppm and δ = 40.16 ppm, corresponding to the coordinated CO 2 fragment and the central carbon atom, respectively, which is in good agreement with the formation of betaine 4. However, at room temperature, zwitterionic CO 2 adduct 4 reacts slowly with the hexamethyldisilazane byproduct to afford the O-silylated ester 5 [40]. Alternatively, CO 2 adduct 4 can be trapped by adding one equivalent of MeI to generate the O-methylated salt 6, which is stable and was easily isolated in an 80% yield. Compound 6 was fully characterized by NMR spectroscopy (see experimental section and supporting information). The single crystals of 6 were grown by layering pentane onto a saturated DCM at room temperature [41] and then analyzed by X-ray diffraction, confirming the expected structure ( Figure 3). The S1-C2 and S2-C2 bond lengths (1.720(2) Å and 1.713(3) Å, respectively) are slightly longer than those of 3 (1.682 Å and 1.687 Å). The central carbon C1 shows a planar environment, and the C1-C2 bond length is short 1.437(4) Å. This bonding pattern can be explained by a major contribution of the ester fragment to stabilize the negative charge [42].

General Comments
All manipulations were performed under an inert atmosphere of argon by using standard Schlenk techniques or high-pressure NMR tube techniques. Solvents were purified with an MBraun SBS-800 purification system. Dry and oxygen-free solvents were used. 1 H, 13 C, 19 F, and 31 P NMR spectra were recorded on Brucker Avance II 300 MHz, Avance III HD 400 MHz, and Avance I and II 500 MHz spectrometers (Brucker, Karlsruhe, Germany). Chemical shifts were expressed in parts per million with residual solvent signals as internal reference ( 1 H and 13 C{ 1 H}). 19 F and 31 P NMR chemical shifts were reported in ppm relative to CFCl 3 and 85% H 3 PO 4 , respectively. The following abbreviations and their combinations were used: br-broad; s-singlet; d-doublet; t-triplet; q-quartet; hept-heptuplet; mmultiplet. 1 H and 13 C resonance signals were attributed by means of 2D COSY, HSQC, and HMBC experiments. Mass spectra were recorded on a Hewlett Packard 5989A spectrometer (Hewlett-Packard, Palo Alto, CA, USA). High-resolution MS (HRMS) spectra were realized on a Xevo G2 QTof apparatus (Waters, Milford, CT, USA). Melting points were measured in a sealed glass tube on a Stuart SMP-30 automatic melting point apparatus. All commercially available reagents were used without further purification otherwise noted. Moreover, 1 was prepared following a previously reported procedure [30].

X-ray Data
The data of the structures for 3, 5, 6-I, 6-OTf, and 7 were collected at low temperature (193 K) on a Bruker-AXS APEX II CCD Quazar diffractometer (7) equipped with a 30 W air-cooled microfocus source and on a Brucker-AXS D8-Venture diffractometer (3, 5, 6-I, and 6-OTf) equipped with a Photon III-C14 detector with MoKα radiation (wavelength = 0.71073 Å) by using phi-and omega-scans. The data were integrated with SAINT, and an empirical absorption correction with SADABS was applied [48]. The structures were solved using an intrinsic phasing method (ShelXT) [49] and refined using the least-squares method on F 2 (ShelXL-2014) [50]. All non-H atoms were treated anisotropically. All H atoms attached to C atoms were fixed geometrically, and treated as riding on their parent atoms with C-H = 0.95 Å (aromatic), 0.98 Å (CH 3 ), 0.99 Å (CH 2 ), or 1.0 Å (CH) with U iso (H) = 1.2U eq (CH, CH 2 ) or U iso (H) = 1.5U eq (CH 3 ). The structures 3 and 6-I were found to be disordered. Several restraints (SAME, SADI, SIMU, DELU) were applied to refine these disorders, and to avoid the collapse of the structure during the least-squares refinement by the large anisotropic displacement parameters.

Conclusions
In summary, S,S-bis-ylide 2 readily reacted with MeI to give the C-methylated salt 3. Moreover, 2 also reacted with CO 2 to give betaine 4, which was characterized in solution by using NMR spectroscopy at low temperatures. CO 2 adduct 4 was still reactive and underwent O-silylation and O-alkylation reactions in the presence of HMDS and MeI, respectively, to afford the corresponding salts 5 and 6. Finally, the high leaving group ability of sulfide ligand in 2 was demonstrated by an original reaction with phosphenium ions, yielding a stabilized ylide 7, probably through the transient formation of a strongly electrophilic phosphino(sulfonio)carbene 9. Efforts are currently underway to extend the potential of this type of ylide.