Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

The homolytic cleavage of the PV(O)–PIII bond in tetraphenyldiphosphine monoxide simultaneously provides both pentavalent and trivalent phosphorus-centered radicals with different reactivities. The method using V-40 as an initiator is successfully investigated for the regio- and stereoselective phosphinylphosphination of terminal alkynes giving the corresponding trans-isomers of 1-diphenylphosphinyl-2-diphenylthiophosphinyl-1-alkenes in good yields. The protocol can be applied to a wide variety of terminal alkynes including both alkyl- and arylalkynes.

(Ph 2 PCH=CHPPh 2 , dppen) is among bidentate diphosphine ligands having a rigid structure and has increased attention as a useful and effective ligand in coordinating with various metals [19,20]. (Z)-Ph 2 PCH=CHPPh 2 is very important as a bidentate ligand for many mononuclear complexes [21][22][23]. On the other hand, (E)-Ph 2 PCH=CHPPh 2 acts as a monodentate ligand for mononuclear complexes, but it is highly attractive because a hierarchical structure can be constructed by cross-linking between two metals [24][25][26]. Considering the characteristics of the coordination form between the (E)-and (Z)-isomers, the development of a synthetic method for the highly selective synthesis of the (E)-or (Z)-isomers is strongly desired [27][28][29][30]. Furthermore, since it was reported that the introduction of a substituent into the ethylene moiety has a great effect on the catalytic activity [31], it is considered important to synthesize derivatives having various substituents on the ethylene moiety. In particular, synthetic methods that do not use metal catalysts and reagents are expected to be very effective in manufacturing precision materials and pharmaceuticals [32][33][34][35][36][37]. To develop metal-free methods for the synthesis of 1,2-bis(diphenylphosphino)ethylenes, we have recently been conducting systematic research on the radical addition of P-P bond compounds to unsaturated carbon-carbon bonds [38][39][40][41][42][43][44]. Early studies have found that the radical addition of tetraphenyldiphosphine (Ph 2 PPPh 2 ) to alkynes using a radical initiator such as 1,1'azobis(cyclohexane-1-carbonitrile) (V-40) (Scheme 1a) [45] or upon photoirradiation (Scheme 1b) [38] yields vic-bis(diphenylphosphino)alkenes in good yields. Unfortunately, this photoinduced reaction of Ph 2 PPPh 2 was not applicable to alkenes [42]. To change the reactivity of the P-P bond, therefore, when the combination of pentavalent phosphorus and trivalent phosphorus was examined, it was found that the desired radical addition of Ph 2 P(X)PPh 2 (X = O, S) to alkenes successfully occurred [42,43] (Scheme 1c and 1d).
However, in the case of Ph 2 P(O)PPh 2 , its absorption is located at a shorter wavelength (λ max = 318 nm) and the absorption intensity is lower than those of Ph 2 PPPh 2 and Ph 2 P(S)PPh 2 [46]. Indeed, the photoinduced addition of Ph 2 P(O)PPh 2 to alkynes required prolonged reaction times (>40 h), and the scope of this alkyne addition was unexamined. Thus, we examined in detail the radical addition of Ph 2 P(O)PPh 2 to alkynes and found that the desired radical addition proceeds efficiently using a radical initiator instead of light irradiation, providing 1-(diphenylphosphinyl)-2-(diphenylphosphino)-1-alkenes (Scheme 1e).

Results and Discussion
First, a mixture of Ph 2 P(O)PPh 2 (1, 0.6 mmol) and 1-octyne (2a, 0.4 mmol) was irradiated with a xenon lamp. After 40 hours, sulfurization of the addition product was performed to afford the phosphinylphosphination product 3a in 45% yield, confirmed by 31 P NMR spectroscopy (Scheme 2) [47]. Next, the reaction was carried out varying the reaction parameters such as the light source and the ratio of the radical initiator (V-40)/2a (Table 1). Using a xenon lamp as an artificial solar source [48,49], 3a was produced in 45% yield ( Table 1, entry 1). Using UV light irradiation with a high-pressure mercury lamp [50], 3a was produced in 28% yield (  lamp irradiation, the reaction did not proceed because 1 was less soluble in benzene than CDCl 3 (Table 1, entry 4). The radical initiator, V-40, was found to be an appropriate initiator for the generation of phosphorus-centered radicals [38,42]. The ratio of V-40/2a was important to depress the formation of selfpolymerization of 2a (Table 1, entries 5-7). The results showed that the best amount of V-40 toward 2a was 10 mol %. Besides, the side product 3a' is found up to 8% yield under photoirradiation. Considering that in our previously reported radical addition reactions of Ph 2 P(S)PPh 2 and Ph 2 P(S)P(S)Ph 2 to alkynes [44], the E/Z ratios were about 9:1 and 8:2, respectively, it should be noted that the present addition of Ph 2 P(O)PPh 2 1 to alkynes afforded (E)-isomers with an excellent stereoselectivity (greater than 95:5) [60].
We also investigated the phosphinylphosphination of some internal alkynes, 2p and 2q, with Ph 2 P(O)PPh 2 , but did not afford any adduct (the starting alkynes were recovered unchanged) (Scheme 4). This is most probably because the internal alkynes are sterically bulkier than terminal alkynes, and therefore, the addition did not proceed (Scheme 4, reaction 1). On the other hand, reaction 2 in Scheme 4 indicates an example of the phosphinylphosphination of a terminal alkyne. The detailed analysis of the products in this reaction revealed the formation of 8% of the addition product 3n', which might be formed by the addition of Ph 2 P• to the alkyne. Noteworthy is that the capture of carbon radicals occurred only at the trivalent phosphorus site of Ph 2 P(O)PPh 2 . Therefore, the initiation step might also proceed via the attack of the carbon radical generated from V-40 at the trivalent phosphorus site to form Ph 2 P(O)• selectively.
With this information in mind, a plausible reaction pathway is shown in Scheme 5. Decomposition of the radical initiator (V-40) generates In•, which attacks selectively at the trivalent phosphorus atom of Ph 2 P(O)PPh 2 to form Ph 2 P(O)•. Then, Ph 2 P(O)• adds to the terminal carbon of an alkyne to afford the carbon-centered radical A1. Radical A1 is captured by Ph 2 P(O)PPh 2 to provide A2, regio-and stereoselectively [62].

Conclusion
In conclusion, a highly regio-and stereoselective phosphinylphosphination of alkynes with Ph 2 P(O)PPh 2 has been successfully developed. The radical initiator V-40 can be used to selectively generate Ph 2 P(O)• as an important species to regioselectively afford 1-phosphinyl-2-phosphinoalkenes. This method can be applied to a wide range of terminal alkynes. We believe that the excellent stereoselectivity to give (E)-isomers is effective for the stereoselective synthesis of (E)-bis(diphenylphosphino)ethylenes.

Experimental General comments
Unless otherwise state, materials were obtained from commercial suppliers and purified by distillation. 1 H NMR spectra were recorded on a JEOL JNM-ECS400 (400 MHz) spectrometer or JEOL JNM-ECX400 (400 MHz) FT spectrometer in CDCl 3 as the solvent with tetramethylsilane (TMS) as an internal standard. 13  General procedure for the phosphinylphosphination of alkynes Ph 2 P(O)PPh 2 (1, 0.6 mmol) and an alkyne (2, 0.4 mmol) were placed in a Schlenk tube with CDCl 3 or benzene (super dehydrated) under argon atmosphere. V-40 was added to the mixture, and then the reaction was heated at 80 °C and stirred for 22 h. After the reaction was complete, sulfur (3 equiv) was added under inert atmosphere and then the mixture was stirred at 60 °C for 6 h to provide the stable adduct 3. The purification of the products was performed by silica gel column chromatography using isohexane/MeOAc as an eluent.

Supporting Information
Supporting Information File 1 Characterization data and copies of NMR spectra.