A combined DFT-predictive and experimental exploration of the sensitivity towards nucleofuge variation in zwitterionic intermediates relating to mechanistic models for unimolecular chemical generation and trapping of free C 2 and alternative bimolecular pathways involving no free C 2 .

Following the recent report of the chemical generation and trapping at room temperatures of C 2, generated from an alkynyl phenyl iodonium salt, a computational analysis had indicated that both unimolecular fragmentation and bimolecular substitution mechanisms for the process could be envisaged. Here a combined theoretical and experimental analysis explores how the energetics of these mechanisms and resulting experimental products respond to variation in the nucleofuge. When the phenyl iodonium nucleofuge is replaced by pyridinium, trapping products are again obtained, which we conclude favours a bimolecular mechanism involving no free C 2 . Trapped products in greater yield were also observed using dibenzothiophenium as the nucleofuge in both condensed solution phase and most significantly in a two-flask room temperature experiment in which a volatile species, presumed to be C 2 , is transferred and trapped in a second flask. The


Introduction
The long history 1 of the diatomic species C2 and its reactivity took a new turn recently with the report of room temperature generation and trapping of this species by chemical means. 2,3 The reaction was thought to proceed at ambient or low temperatures from the transient zwitterionic intermediate 2 (X = IPh), itself formed by treating precursor 1 with a source of fluoride anion. The proposed mechanism involved unimolecular fragmentation of 2 to produce X = iodobenzene and 3 (free singlet state C2, Figure 1), followed by its trapping in solution using either 9,10-dihydroanthracene or galvinoxyl radical and resulting in isolation of products 4/anthracene 5 and from which participation of free C2 was inferred ( Figure 2). 2,3 Scrambling of 13    A commentary on this report 4,5 observed that the computed thermodynamics of this reaction using three different estimates indicated that the production of free C2 and X = iodobenzene (Path 1, figure 1) was likely to be highly endoenergic, in the range of +(43-53) kcal mol -1 and therefore that room temperature production of C2 seemed unlikely. A follow up analysis 6 explored the possibility that bimolecular reactions between 2 and the traps (Path 2, Figure 1), or between 2 and itself to give ultimately polymeric carbon (Path 3, figure 1), might provide alternative mechanistic routes to the observed products and which would also rationalise the 13 C scrambling, whilst avoiding liberation of free C2. Here this study is extended to computing the bimolecular transition states and unimolecular fragmentation energies using a variety of different leaving groups X, in order to establish how the energetics of the mechanistic paths shown in Figure 1 respond to the nature of group X. As a result of these studies we felt in appropriate to then suggest that the original experiments be repeated with a new selection of leaving groups X. Accordingly, the experimental response of the putative C2 precursors 1a-d with different nucleofuges (1a: X = iodo, 1b: λ 3 -iodanyl, 1c: pyridinio, and 1d: sulfonio groups) to trapping experiments was undertaken to establish the scope of this method for generating putative 3.

Computational Details
The CHAMP portal 7 was used as an electronic notebook for managing the project, enabled with one-click FAIR data publishing to the Imperial College data repository. 8 To study the energetics and mechanism of these reactions, a calibrated 9 procedure was selected as used before; ωB97X 10 /Def2-TZVPPD 11 /SCRF 12 =dichloromethane solvent. 13 All located transition states have one negative force constant with the correct vectors, which can be inspected as 3D animated models using a FAIR-enabled version of Table 1. 18
General procedure. To a stirred solution of C2-precursor 1 (0.065 mmol) and trapping agent (50 equivalent for 9,10-dihydroanthracene and 1.2 equivalent for galvinoxyl radical) in dichloromethane (1.3 mL), tetrabutylammonium fluoride trihydrate (1.2 equivalent) was added in one portion at -78 °C and the solution was gradually warmed to room temperature for 3-72 h (disappearance of starting material was monitored by 1 H NMR, except for 1a). After concentration of the reaction mixture under a reduced pressure, the resulting residue was then analyzed by 1 H NMR (ethyl acetate as an internal standard) and APCIMS. For the trapping reaction with galvinoxyl radical, excess 1,4-cyclohexadiene was added (in order to quench remaining galvinoxyl radical) prior to 1 H NMR measurement. The formation of acetylene was confirmed by GCMS with PLOT column (Rt-U-Bond, 0.25 mm x 30 m, 30 °C) or silver nitrate testing.
Solvent-free connected flask experiment. S-(trimethylsilylethynyl)dibenzothiophenium salt 1d (33 mg, 0.077 mmol) and cesium fluoride (35.0 mg, 0.231 mmol) was placed in one of a pair of connected flasks (Flask A), and galvinoxyl radical (97 mg, 0.231 mmol) was placed in the other flask (Flask B). The reaction mixture in Flask A was vigorously stirred at room temperature for 48 hours under argon. The contents of Flask B were directly analyzed by APCI mass spectrometry. The contents of Flask A were analyzed by 1 H NMR (ethyl acetate was an internal standard).

Results and Discussion
There are two basic mechanisms for the reaction of the zwitterionic species 2, namely unimolecular fragmentation to give 3 (free C2) followed by bimolecular trapping of this species (Figure 1, Path 1) or immediate bimolecular reactions involving no free C2 (paths 2 and 3). The presence of the species 2 (X = IPh) has been confirmed during the fluorolysis of alkynyl(aryl)λ 3 -iodane with Bu4NF in dichloromethane and was stable below -30 °C. 3 One potential strategy for differentiating between these mechanistic pathways would be to vary the nature of the group X. The leaving group ability of X would be expected to impact directly upon the unimolecular fragmentation path 1, whereas its effect might be attenuated for the bimolecular trapping paths 2 or 3 ( Figure 1). To explore if this hypothesis is correct, the energetics for a variety of new leaving groups X were obtained computationally using density functional theory, with the results collected in Table 1. 18 This shows the energetics of bimolecular dimerization of species 2 (Path 3) as well as reaction of 2 with either dihydroanthracene or a phenoxy radical model as trapping agents (Path 2). The calculated free energy of the two-stage unimolecular dissociation path 1 needs correction for the error in the calculated energy of 3 itself, as described previously. 5 The difference in free energy between the dissociation path 1 and the transition states leading to bimolecular reaction via either 1,1 or 1,2 substitution 6 (paths 2 or 3) is shown in the last column of the table. It is the effect the nature of the leaving group X has on this difference that will now be discussed.
We start by noting that for the substituents X = Me3P through to MeF, the calculated free energy of unimolecular dissociation of 2 to give X and 3 (C2) spans ΔΔG = 117.6 to -2.4 kcal mol -1 . Of these, only values < ~35 kcal mol -1 would be considered as thermally accessible below ~313K. In contrast, the activation barriers for direct bimolecular reactions of 2 over this span of substituents range from ΔΔG ‡ 34.5 to 12.5 kcal mol -1 , a very much smaller span for which the entire range is potentially thermally accessible. The last column in Table 1 indicates the difference in free energy between the unimolecular dissociation path 1 resulting in the formation of 3 from 2 and the lowest energy of the two bimolecular paths 2 and 3 for reaction of 2 involving either 1,1-or 1,2-substitution. 6 We note that the relative free energy of path 1 in this column should be increased by a further ~10 kcal mol -1 to reflect the entropic penalty for the bimolecular reaction between 3 and trap, with the thermal barrier for this reaction expected to be very small or even zero. 6 For leaving groups such as X = pyridinium, the difference between the paths is so large that one might confidently state that only bimolecular paths 2 and 3 are viable. There is only one substituent for which unimolecular dissociation is actually predicted to be more favourable than the bimolecular mode, and that is X = MeF, which is not a realistic group for synthetic testing. The activation free energy of the bimolecular route for e.g. X = dibenzothiophenium is ~25 kcal mol -1 , which can be considered as falling into a thermally accessible range. This example and X = pyridinium are the ones that were selected for experimental testing. Following this theoretical evaluation, we turned to an experimental protocol for evaluating the ability of the C2 precursors 2, as potentially generated from the starting materials 1a-d representing different nucleofuges (X = iodo, λ 3 -iodanyl, pyridinio, and sulfonio groups respectively), to be trapped using our previous radical trapping protocol. 3 Firstly, the attempted reaction of (trimethylsilyl)iodoacetylene (1a, X = iodo) with a fluoride ion source (Bu4NF) in the presence of galvinoxyl radical or 9,10-dihydroanthracene was investigated ( Figure 3A), but no distinct evidence was obtained for the formation of radical-trapped products (ethynylated galvinoxyl 4a, anthracene 5) nor was acetylene detected and alkyne 1a was recovered exclusively. In sharp contrast, as expected, alkynyl-λ 3 -iodane 1b (X = λ 3 -iodanyl), which has ca. 10 12 times greater nucleofuge capability (-I(Ph)X) than an iodo group, 19 led to good yields of trapped products 4a or 5 under similar reaction conditions. This confirms the importance of the nucleofuge in this transformation ( Figure 3B).
Significantly, the theoretically evaluated pyridinium-type precursor 1c (X = 4phenylpyridinium triflate) was also found to serve as a precursor. Thus, in the presence/absence of trapping agents, not only acetylene gas but also radical-trapped products 4a or 5 were detected/obtained in low yields, being accompanied by the formation of 4-phenylpyridine ( Figure 3C). Similar to our previous report, the formation of di(galvinoxy)acetylene 4b was not observed in solution, probably due to the rapid hydrogen abstraction of transient ethynyl radical from the solvent, dichloromethane. 3,20 All of these experimental results suggest that the in-situ generation of the zwitterionic species 2 could act as a C2 synthon, even with much a much weaker leaving group such as 4-phenylpyridine. However this result does not distinguish between unimolecular and bimolecular trapping mechanisms (path 1 vs path 2). The activation free energy for path 2 bimolecular trapping is predicted to be within a thermally accessible range, whereas the energy for path 1 is computed to be 60 + ~10 = ~70 kcal mol -1 higher than that for path 2 ( Table 1).
Use of the dibenzothiophenium precursor 1d, which bears a more potent nucleofuge than pyridine, has provided further evidence in the form of higher yields of trapped products 4a and 5 as obtained under similar conditions ( Figure 3D). The computed path 2 bimolecular free energy barriers for this substituent and the pyridinium-type substrate were similar (Table 1). Based on these two trapping experiments, we consider that the rate of desilylation yielding intermediate 2 as well as the following processes has a relatively modest dependency on both the electron withdrawing-and the leaving group ability of X in the precursors 1. This is more congruent with the predicted behaviour of path 2 rather than of path 1, for which a much higher dependency on X is predicted.
Significantly however, the solid-state solvent-free connected flask experiment using sulfonium 1d also afforded a trapped product 4a, although to a small extent (Figure 4). The presence of 4a in a separated flask (Flask B) suggests that the evolution of a volatile species, presumed to be 3, would occur in Flask A, which is consistent with the previous results obtained with alkynyl-λ 3 -iodane 1b and 1b-13 C (counter ion: BF4 -). 3,19 The absence of di(galvinoxyl)acetylene 4b in Flask B might reflect the poorer ability of 1d (X= dibenzothiophenium) to act as a precursor of 3, compared with 1b (X = λ 3 -iodanyl) under the reaction conditions.
At this stage, we cannot explain the discrepancy between the (solid-state solvent-free connected flask) experimental results and theoretical estimations of the energy required to liberate a free C2 species. An alternative mechanism might be necessary to solve the conundrum.

Conclusions
The single-flask solution phase experiments indicating trapping using two different precursors 2 (X = pyridinium and dibenzothiophenium) are not inconsistent with a bimolecular mechanism (path 2) involving no free 3. The theoretical free energies of the unimolecular path 1 for X = dibenzothiophenium and particularly for pyridinium are so much higher than it seems less likely that this mechanism could be followed. A mystery remains however for the connected flask trapping experiment, which suggest that the precursor with the good nucleofuge 1d can produce an argon-borne intermediate that results in transfer to flask B and then apparent trapping of C2 (3). This seemingly indicates that path 1 is followed under these conditions, despite the contra-indications from the theoretical evaluation. More experiments to further confirm the identity of this gas-borne intermediate and perchance provide insight into the experimental/theoretical dichotomy are needed.

Conflicts of Interest
The authors declare no conflicts of interest.