Thiophosphonium–Alkyne Cycloaddition Reactions: A Heavy Congener of the Carbonyl–Alkyne Metathesis

While the metathesis reaction between alkynes and thiocarbonyl compounds has been thoroughly studied, the reactivity of alkynes with isoelectronic main group R2E=S compounds is rarely reported and unknown for [R2P=S]+ analogues. We show that thiophosphonium ions, which are the isoelectronic phosphorus congeners to thiocarbonyl compounds, undergo [2 + 2]-cycloaddition reactions with different alkynes to generate 1,2-thiaphosphete ions. The four-membered ring species are in an equilibrium state with the corresponding P=C–C=S heterodiene structure and thus undergo hetero-Diels–Alder reactions with acetonitrile. Heteroatom and substituent effects on the energy profile of the 1,2-thiaphosphete formation were elucidated by means of quantum chemical methods.


■ INTRODUCTION
Heavy analogues of carbonyl compounds are generally highly reactive and prone to spontaneous oligomerization owing to the energetic preference of heavy p-block elements in forming σ bonds instead of (p−p)π bonds. 1−4 In this respect, the thiocarbonyl group (C=S) is an exception, but it reacts, due to its rather weak C=S bond and the aptitude of sulfur to stabilize an adjacent charge or radical center, more easily in nucleophilic reactions and sigmatropic rearrangements than carbonyls. 5 Both carbonyls and thiocarbonyls undergo (thio)carbonyl− alkyne metathesis reactions, involving the [2 + 2]-cycloaddition reaction of a (thio)carbonyl with an alkyne. These reactions have been extensively utilized in synthetic chemistry. 6 The carbonyl−alkyne metathesis proceeds via a fourmembered oxete intermediate, which is usually directly transformed into the α,β-unsaturated ketone, 7−12 unless it is stabilized by strongly electron-withdrawing groups. 13−15 Due to the lower tendency of sulfur to form double bonds, thietes are more stable than oxetes, 16−21 and a dynamic equilibrium between the "closed" thiete and "open" α,β-unsaturated thioketone form was observed with thioether substituents. 22,23 Given these differences between oxetes and thietes, we became curious to explore how the introduction of another heavy main group element would affect the stability of the four-membered ring species. Although numerous examples for heavy main group carbonyls R 2 E=O and thiocarbonyls R 2 E=S have been synthesized, 24−34 the reactivity with alkynes is little developed. Stannanethiones undergo [2 + 2]-cycloaddition reactions with the particularly electron-poor alkyne dimethyl acetylenedicarboxylate in a stepwise mechanism to give 1,2-thiastannete. 35,36 The reaction mode of stannaneselone and stannanetellone was found to be similar, but ring-opening and formation of the corresponding stannabutadiene was not observed. 35,37 Similarly, in transition metal chemistry, the elusive zirconasulfide [Cp* 2 Zr=S] (Cp* = pentamethylcyclopentadienyl) was trapped via [2 + 2]-cycloadditions with alkynes yielding 1,2thiazirconabutenes. 38,39 Recently, we explored the cycloaddition reaction between oxophosphonium cations and alkynes and showed that by using strong π-donor substituents instead of alkyl groups at the phosphorus atom, the "closed" oxaphosphete and the "open" 1-phospha-4-oxa-butadiene get closer in energy. 40 Enabled by our recent success in isolating the first Lewis-base-free thiophosphonium ion [R 2 P=S] + , 41 we herein report on [2 + 2]-cycloaddition reactions of thiophosphonium salts with alkynes, yielding 1,2-thiaphosphete cations (Scheme 1b). The first neutral P V 1,2thiaphosphete was synthesized by Kawashima and co-workers containing a P-center stabilized by the Martin ligand (Scheme 1, I). 42 24 ] was used in the present study.
The formation of the four-membered heterocycle [2a] + is further confirmed by the 13 C{ 1 H} NMR spectrum, revealing a doublet at 120.3 ppm ( 1 J PC = 106 Hz) for the phosphorusbound carbon atom and a doublet at 153.4 ppm ( 2 J PC = 5 Hz) of the adjacent carbon atom, which is deshielded by the sulfur atom. The 1 H NMR resonance of the thiaphosphete ring proton appears at 3.80 ppm and is significantly shifted to lower frequency compared to that of the parent thiete C 4 H 4 S (6.50 ppm). 44 The effect can be explained by an enhanced polarization of the C=C bond of the thiaphosphete heterocycle, resulting from the negative hyperconjugation of πelectron density from the carbon atom into low-lying σ* orbitals of the phosphorus atom.  42 whereas the resonance of the P III thiaphosphete II appears at 37.5 ppm. 43 In order to explore possible substituent effects on the [2 + 2]-cycloaddition reaction, acetylene derivatives with electrondonating groups were reacted with thiophosphonium salt [ 24 ] in excellent yields. The cycloaddition reaction with electron-rich alkynes, e.g., para-(dimethylamino)phenylacetylene (entry 3) and ethoxyacetylene (entry 4), is significantly faster than that with phenylacetylene. The electron-poor alkyne 1-ethynyl-3,5-bis-(trifluoromethyl)benzene (entry 6) reacted with [2a][BArF 24 ] very slowly, even with prolonged heating at 180°C. After 16 h, only 12% conversion was observed. This accelerated cycloaddition reaction between [2a][BArF 24 ] and electron-rich alkynes can be explained by the high electrophilicity of the thiophosphonium cation and is contrary to the reactivity trend of neutral stannanethiones. 35 The same regioselectivity was observed for all [2 + 2]-cycloaddition reactions, which agrees with that of the 1,2-thiaphosphete II. 43 Single A single-crystal X-ray diffraction (XRD) study ( Figure 1) revealed that the four-membered rings of both thiaphosphete salts are perfectly planar (sum of angles: 360°). The P−S bond length of [2a] + (2.154 Å) is shorter than that in the P III 1,2thiaphosphete II (2.161 Å), 43 as expected for the more electrophilic cationic P V center. Accordingly, the elongated P− S bond (2.167 Å) in [2d] + indicates a weaker S−P interaction than in [2a] + , which is supported by our computational results (vide infra).

■ COMPUTATIONAL STUDIES
We performed DLPNO−CCSD(T)/def2-TZVPP 45 24 ] a a R = aryl, ethoxy, or methyl(p-toluenesulfonyl)amide (see Table 1). Dipp = 2,6-diisopropylphenyl.  40 this gives us the opportunity to evaluate how replacing the O atom with the S atom would influence the energy profile. In fact, the first barrier (TS1) and the second barrier (TS2) are both only ∼1 kcal/mol lower in energy for the thiophosphonium case (cf. Figure 2 and ref 40). The most notable deviation between the oxo-and thio systems is the energy difference between CF and OF. In the case of oxophosphonium, the closed form was more stable by 13.3 kcal/mol, while in the case of the thiophosphonium, the closed form was more stable by 18.4 kcal/ mol, putting the open form slightly above the transition state.
The heavy atom α,β-unsaturated ketones contain reactive double bonds and thus provide a platform for rich follow-up chemistry. Phosphabutadiene derivatives have been extensively used in cycloaddition reactions for the construction of phosphorus-containing heterocycles, 53−61 and many examples of P=C−C=O compounds reacting in hetero-Diels−Alder reactions were reported. 62,63 Since the analogous reactivity with a P=C−C=S moiety is unexplored, we attempted to identify substituent effects that would stabilize this acyclic structure. The rather low transition state with ethoxyacetylene indicates that electron-donating groups might be beneficial in this respect. Hence, the cyclization step was computed for the reaction of oxo-and thiophosphonium ions with acetylene derivatives carrying phenyl, ethoxy, and dimethylamino substituents (Figure 3). The comparison of the relative energy levels of CF and OF structures indicates that with an increasing number of heavy atoms in the system, the four-membered ring gets stabilized over the α,βunsaturated ketone structure, which is consistent with the doublebond rule, as heavy atom (p−p)π bonds are formed upon electrocyclic ring-opening. Remarkably, the ethoxy substituent is most effective in facilitating the ring-opening reaction, leading to a thermoneutral reaction for the oxaphosphete system.    The formation of the six-membered thiazaphosphinine ring in [3d] + is confirmed by the deshielded doublet of the S−C− N carbon atom at 164.6 ppm ( 2 J CP = 6 Hz) in the 13 24 ] in quantitative yield. The 31 P NMR resonance of the heterocycle appears at −34.0 ppm. The different reaction conditions for the ring expansion reactions indicate that ringopening of the thiaphosphetes is required prior to the hetero-Diels−Alder reactions, which, in agreement with the computational results, is more easily accessible for [2d] + than for [2a] + . The analogous ring expansion reaction with oxaphosphetes proceeds at lower temperature than that with thiaphosphetes, 40 which again is consistent with the energy barrier of the electrocyclic ring-opening reaction. Single
The presented heavy congener of a thioketone−alkyne metathesis is an appealing example for the diagonal relationship between carbon and phosphorus in the periodic table. The great potential of the R 2 P + fragment to act in a thermoneutral fashion in bond metathesis reactions is indicated by the ringopening reaction of the ethoxy substituted oxaphosphete. Further studies into this direction will be reported in due course.
Synthetic procedures, NMR spectra, mass spectrometry data, crystallographic data, and computational details (PDF)