[​4+2] versus [​2+2] Homodimerization in P(V) Derivatives of 2,4-Disubstituted Phospholes

Phosphole P(V) derivatives are interesting building blocks for various applications from ligand synthesis to material sciences. We herein describe the preparation and characterisation of new 2,4-disubstituted oxo-, thiooxo-, and selenooxophospholes. The nature of the substituents on the phosphole ring determines the reactivity of these compounds towards homodimerization reactions. Aryl and trimethylsilyl substituted oxophospholes undergo selective [4+2] dimerization, whereas, for thiooxo- and selenooxophospholes, light-induced, selective [2+2] head-to-head dimerization occurs in the case of aryl substituents. DFT calculations provide some insights on these differences in reactivity.

Some years ago, we reported the synthesis of a series of 2,4-disubstituted phospholes 1 through a highly selective transformation of a mixture of 2,4-and 2,5-disubstituted zirconacyclopentadienes (Scheme 1) [19]. In this reaction, the addition of PPhCl 2 led only to the formation of phospholes 1; no other regioisomer was observed. Quenching the reaction mixture with HCl yielded the 1,4-disubstituted 1,3butadienes, which could be readily separated from 1. This methodology was successfully applied to aryl, alkyl, and trimethylsilyl groups on the phosphole ring.
We herein show that the oxidation of some of these heterocycles to the corresponding oxo-, thiooxo-, and selenooxophospholes can lead to various reactivity behaviours with respect to homodimerization processes, i.e., [4+2] or [2+2] cycloaddition reactions.

General Considerations.
Dichloromethane was collected under argon from a PURSOLV MD-3 (Innovative Technologie Inc.) solvent purification unit. m-chloroperbenzoic acid, sulphur, and selenium were purchased from Aldrich or Alfa Aesar. Phospholes 1a-d were prepared according to the literature procedure [19]. 1 H, 13 C, 19 F, 29 Si, 31 P, and 77 Se NMR spectra were recorded in CDCl 3 , unless specified, on a 500 MHz Bruker Avance III spectrometer equipped with a BBFO+ probe. Chemical shifts are reported in delta ( ) units, expressed in parts per million (ppm). High resolution ESI-MS spectra were recorded on a hybrid tandem quadrupole/timeof-flight (Q-TOF) instrument, equipped with a pneumatically assisted electrospray (Z-spray) ion source (Micromass, Manchester, UK) operated in positive mode. High resolution EI-MS spectra were obtained on a GCT-TOFmass spectrometer (Micromass, Manchester, UK) with EI source. Single crystals of 6d were coated in Paratone-N oil and mounted on a loop. Data were collected at 150.0(1) K on a Nonius Kappa CCD diffractometer using a Mo K ( = 0.71070Å) X-ray source and a graphite monochromator. All data were measured using phi and omega scans. The crystal structure was solved using SIR 97 and refined using Shelx 2016 [20,21]. DFT calculations were performed using the Gaussian09 suite of software (full details are provided in the SI (available here)).

General Procedure for the Synthesis of Oxophospholes 2 and the [4+2] Dimers 3.
In a flask equipped with a magnetic stir bar, phosphole 1a-c (5 mmol), dichloromethane (5 mL), and m-chloroperbenzoic acid (mCPBA) (6 mmol) were introduced. After stirring for 5 minutes at room temperature, the solution was filtered and the solvent evaporated under reduced pressure. The 31 P NMR spectrum (CDCl 3 ) of the crude residue showed complete conversion of starting phosphole and formation of oxophospholes 2a-c and several nonidentified by-products. After a given time (several hours to days) compounds 2a,b transform to the dimers 3a,b in solution or in the solid state.

General Procedure for the Synthesis of Thiooxophospholes 4 and the [2+2]dimers 5.
In a flask equipped with a magnetic stir bar, phosphole 1a-d (5 mmol), elemental sulphur (S 8 ) (1 mmol), and dichloromethane (5 mL) were introduced. After stirring overnight at room temperature, the solution was filtered, and then the solvent evaporated under reduced pressure. The 31 P NMR spectrum (CDCl 3 ) of the crude product showed complete conversion to 4a-d. Under the influence of natural light, compounds 4a,d transformed to the dimers 5a,d after several days in solution in a classical NMR tube or in the solid state.        1 (500 MHz, 3

Results and Discussion
3.1. Oxophospholes. The reaction of phospholes 1 with mchloroperbenzoic acid (mcpba) in dichloromethane at room temperature led immediately to the formation of 2,4disubstituted oxophospholes 2 as shown by 31 P NMR spectroscopy (Scheme 2, Table 1). Within several hours, the arylsubstituted compound 2a transformed to the corresponding [4+2] cycloadduct 3a in a highly selective endo-anti fashion. For 2b containing two trimethylsilyl groups, the dimerization took several days, whereas with the bulky tert-butyl groups in 2c no dimerization occurred. The values observed in the 31 P NMR spectrum for 2 and 3 are close to other values in the literature [22,23]. The oxidation of 1a and 1c produced nonidentified sideproducts, which did not allow a full characterisation of these compounds and the dimer 3a. In contrast, compound 3b could be obtained as a pure product and was fully characterized by multinuclear NMR spectroscopy. In Table 2, the 13 C NMR data of product 3b is compared to the previously described [4+2] dimer of 3-methylphosphole oxide A, which had also been characterized by X-ray diffraction analysis [22]. The good correlation of the data between compounds 3b and A led us to the assumption that in our case the same endo-anti product was formed as major product.

3.2.
Thiooxophospholes. The oxidation of phospholes 1 with sulfur in dichloromethane was complete after one night stirring at room temperature, as shown by 31 P NMR spectroscopy, yielding the corresponding thiooxophospholes 4 (Scheme 3, Table 3). In the case of aryl-substituted compounds 4a and 4d, a new signal appeared in the 31 P NMR spectrum after workup. This singlet increased steadily upon leaving the sample exposed to natural light with a concomitant decrease of the signal for 4 until nearly full conversion after several days. No other products appeared in the spectrum. The new products could be identified as [2+2] head-to-head dimers 5a and 5d through multinuclear NMR spectroscopy and X-ray diffraction studies for 5d. In the case of 4b and 4c, no further reaction was observed. When compounds 4a and 4d were stored in the dark the corresponding products 5a and 5d did not form, whereas exposure to direct sunlight accelerated the reaction.
The 31 P NMR values for 4 are in agreement with literature data [24][25][26][27]. A comparison of the 1 H and 13 C NMR data of      compounds 1d, 4d, and 5d is shown in Table 4 confirming the head-to-head dimerization of compound 4d. Interesting observations are the changes in the coupling constants 1 J P-C for C 훼 and C 훼 ' upon oxidation from 1d (0 and 1.8 Hz) to 4d (86.4 and 74.0 Hz) [24]. Upon dimerization to 5d, the 1 J P-C for C 훼 ' is most impacted (down to 3.3 Hz), whereas for C 훼 a high value remains (65.4 Hz). Crystals of compound 5d suitable for X-ray diffraction studies were obtained through slow evaporation of the chloroform solvent. 5d crystallised in the monoclinic space group C2/c with one disordered solvent molecule in the unit cell ( Figure 1). The tricyclic [5;4;5] pattern shows a syn-anti arrangement with respect to the phosphole units and the substituents on the cyclobutene ring. There are only two other structurally characterised compounds with this arrangement in the literature, i.e., the dimerised helical phosphoindole oxides which have no substituents on the C1 and C2 position, reported by Marinetti and Voituriez [28]. The cyclobutane ring in 5d is quasi-rectangular (angles C1-C2-C2a 88.32 (8) Scheme 4: Phosphole oxidation with Se then [2+2] dimerization. Table 4: Chemical shifts (ppm) and coupling constants (Hz) of 1d, 4d, and 5d.

Selenooxophospholes.
When selenium was employed for the oxidation of phospholes 1 in dichloromethane the corresponding selenooxophospholes 6 were obtained quantitatively after 18h at room temperature (Scheme 4). The substituents on the phosphole ring influence strongly the 31 P NMR shifts and, in this case, also the 77 Se NMR values (Table 5). Leaving compound 6a in a standard NMR tube for several days exposed to natural light led to a good but not full conversion to the [2+2] head-to-head dimer 7a as shown by 31 P NMR. It has previously been shown that the coupling constant 1 J Se-P can provide information on the -donor ability of phospholes [4][5][6][7][29][30][31][32]. According to Table 5, phosphole 1b having the trimethylsilyl groups in positions 2 and 4 is the strongest -donor as 6b has the smallest coupling constant with 716 Hz, close to the value for 1phenyl-3,4-dimethylphosphole (713 Hz). The value for compound 6a is smaller compared to the corresponding 1,2,5triphenylselenooxophosphole (742 Hz) [4][5][6][7], indicating a certain influence of the position of the ring substituents on the -donor ability. Interestingly, the dimer 7a has a considerably higher coupling constant with 759 Hz.   [37]. In our case, the 2,4-disubstituted phosphole oxides are just borderline: with aryl groups and the bulky, but flexible trimethylsilyl groups homodimerization occurs, albeit slowly, whereas the bulky tbutyl group prevents this reaction. A very good regioselectivity with the formation of mainly one [4+2] dimer, the endoanti isomer, is observed.

[2+2]
Dimerization. Until recently, thermal or lightinduced [2+2] dimerization reactions were mainly restricted to phosphole derivatives coordinated to metals [38][39][40][41]. In 2012, Marinetti and Voituriez reported the first metal-free, head-to-head [2+2] photocyclizations with nonsubstituted helical phosphoindole oxides [28]. More recently, a helical phosphinamide substituted in the C2 position was examined, providing the head to tail [2+2] dimer in solution under sunlight. Furthermore, the reaction took also place in the solid state under sunlight or X-ray radiation [42]. In our case, the 2,4-disubstituted thiooxo-and selenooxophospholes 4a, 4d and 6a are the first examples for phosphole P=S and P=Se derivatives to undergo metal-free head-to-head [2+2] homodimerization reactions, despite the presence of substituents in the C2 position. These transformations are highly regio-and stereoselective, yielding a single isomer. The aryl groups have a crucial role in this case, as they allow the absorption of visible light by the phosphole moiety and, as can be seen from the DFT calculations, they lower the HOMO-LUMO gaps just under the threshold for visible light energy, so that [2+2] dimerization can occur. In contrast, trimethylsilyl or t-butyl substituted phospholes 4b,c and 5b,c do not absorb in the visible light region and, in most cases, have too wide HOMO-LUMO gaps for visible light mediated reactions. These findings open the way to further light-driven transformations of phosphole P(V) derivatives.

Conclusions
We have shown that P(V) derivatives of 2,4-disubstituted phospholes have intriguing properties with respect to [4+2] and [2+2] homodimerization reactions, which are highly dependent on (a) the heteroatom on phosphorus (O vs S, Se) and (b) the substituents on the phosphole ring (aryl vs. trimethylsilyl vs. t-butyl). Their reactivity and their properties lie in-between the corresponding 2,5-and 3,4-disubstituted phospholes, as, for example, shown with the 1 J PSe coupling constants. Particularly, the light-driven [2+2] photocyclization requires further in-depth studies to explore its full potential towards other derivatization reactions. Further transformations of the new [2+2] dimers (reduction of the P=S bond and chiral resolution) could provide the platform for a new family of chiral ligands for asymmetric catalysis.

Data Availability
The NMR spectra, X-ray data, and computed structures used to support the findings of this study are included within the supplementary information file(s).