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

Abstract

The homolytic cleavage of the P^V(O)–P^III 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.

Introduction

Organophosphorus compounds are an essential class of compounds in catalytic technologies, biochemistry, and materials [1–6]. In particular, in coordination chemistry and catalyst chemistry, organophosphorus compounds such as triorganylphosphines are widely used as typical monodentate ligands for many metals [7–8]. In addition, diphosphines such as 1,2-bis(diphenylphosphino)ethane (Ph₂PCH₂CH₂PPh₂, dppe) are employed as bidentate ligands and are effective in controlling important catalytic reactions such as cross-coupling reactions [9–18]. 1,2-Bis(diphenylphosphino)ethylene (Ph₂PCH=CHPPh₂, 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)-Ph₂PCH=CHPPh₂ is very important as a bidentate ligand for many mononuclear complexes [21–23]. On the other hand, (E)-Ph₂PCH=CHPPh₂ 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 [24–26]. 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 [27–30]. 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 [32–37]. 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 [38–44]. Early studies have found that the radical addition of tetraphenyldiphosphine (Ph₂PPPh₂) 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 Ph₂PPPh₂ 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 Ph₂P(X)PPh₂ (X = O, S) to alkenes successfully occurred [42–43] (Scheme 1c and 1d).

Scheme 1.

Radical addition of Ph₂PPPh₂ and Ph₂P(X)PPh₂ to unsaturated C–C bonds.

However, in the case of Ph₂P(O)PPh₂, its absorption is located at a shorter wavelength (λ_max = 318 nm) and the absorption intensity is lower than those of Ph₂PPPh₂ and Ph₂P(S)PPh₂ [46]. Indeed, the photoinduced addition of Ph₂P(O)PPh₂ 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 Ph₂P(O)PPh₂ 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 Ph₂P(O)PPh₂ (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 ³¹P NMR spectroscopy (Scheme 2) [47].

Scheme 2.

The addition of Ph₂P(O)PPh₂ (1) to 1-octyne (2a).

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 (Table 1, entry 2). However, 3a was obtained only in trace amounts upon irradiation with a tungsten lamp [51] (Table 1, entry 3). These results indicate that Ph₂P• [52–55] and/or Ph₂P(O)• [56–59] radicals were generated by the irradiation with light in the near-UV region. When benzene was used instead of CDCl₃ under xenon lamp irradiation, the reaction did not proceed because 1 was less soluble in benzene than CDCl₃ (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 self-polymerization 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 Ph₂P(S)PPh₂ and Ph₂P(S)P(S)Ph₂ to alkynes [44], the E/Z ratios were about 9:1 and 8:2, respectively, it should be noted that the present addition of Ph₂P(O)PPh₂ 1 to alkynes afforded (E)-isomers with an excellent stereoselectivity (greater than 95:5) [60].

Table 1.

Phosphinylphosphination of terminal alkyne 2a with 1 under different reaction parameters.

entry	reaction parameters	yield of 3aa (%), E/Z	yield of 3a’a (%)
1	xenon lamp, CDCl3 (0.4 mL), 40 h	45, 98:2	8
2	high-pressure mercury lamp, CDCl3 (0.4 mL), 40 h	28, 97:3	4
3	tungsten lamp, CDCl3 (0.4 mL), 40 h	trace	–
4	xenon lamp, benzene (0.4 mL), 40 h	trace	–
5	V-40 (5 mol %), benzene (0.6 mL), 80 °C, 22 h	40, 99:1	2
6	V-40 (10 mol %), benzene (0.6 mL), 80 °C, 22 h	73 (67), 99:1	3
7	V-40 (15 mol %), benzene (0.6 mL), 80 °C, 22 h	64, 100:0	5

^aDetermined by ³¹P NMR spectroscopy. V-40 = 1,1’-azobis(cyclohexane-1-carbonitrile). Isolated yield is shown in parentheses.

The phosphinylphosphination of various terminal alkynes 2 with Ph₂P(O)PPh₂ 1 was conducted under the optimization conditions (Scheme 3). Terminal alkylalkynes 2a, 2b, and 2c reacted efficiently with 1 to give the corresponding adducts 3a, 3b, and 3c in moderate to good yields (67%, 71%, and 83%, respectively) with excellent stereoselectivity (E/Z = 95:5–99:1). Terminal alkylalkynes with chloro (2d), cyano (2e), and ester (2g) groups provided the corresponding adducts 3d, 3e, and 3g in 33%, 41%, and 54% yields, respectively (E/Z = 94:6–100:0). In sharp contrast, the presence of a hydroxy group inhibited the desired phosphinylphosphination (see, alkyne 2f), probably because of the decomposition of Ph₂P(O)PPh₂. Furthermore, an electron-deficient alkyne such as methyl propiolate (2h) failed to provide the desired adduct (3h) [61]. 3-Phenyl-1-propyne (2i) and cyclohexylacetylene (2j) gave 3i and 3j in 41% and 65% yields, respectively. Again, an excellent stereoselectivity was observed. Moreover, terminal arylalkynes 2k–o were also tolerated under the conditions to afford the desired adducts 3k–o in moderate to good yields with high stereoselectivity.

Scheme 3.

Phosphinylphosphination of various terminal alkynes 2 with 1. ^aIsolated yields. V-40 = 1,1’-azobis(cyclohexane-1-carbonitrile). ^bRepeated 2 times.

We also investigated the phosphinylphosphination of some internal alkynes, 2p and 2q, with Ph₂P(O)PPh₂, 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 Ph₂P• to the alkyne. Noteworthy is that the capture of carbon radicals occurred only at the trivalent phosphorus site of Ph₂P(O)PPh₂. 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 Ph₂P(O)• selectively.

Scheme 4.

Attempted radical addition to internal alkynes and insight into the addition to 2n.

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 Ph₂P(O)PPh₂ to form Ph₂P(O)•. Then, Ph₂P(O)• adds to the terminal carbon of an alkyne to afford the carbon-centered radical A1. Radical A1 is captured by Ph₂P(O)PPh₂ to provide A2, regio- and stereoselectively [62].

Scheme 5.

A plausible reaction pathway for the radical addition of Ph₂P(O)PPh₂ to terminal alkynes.

Conclusion

In conclusion, a highly regio- and stereoselective phosphinylphosphination of alkynes with Ph₂P(O)PPh₂ has been successfully developed. The radical initiator V-40 can be used to selectively generate Ph₂P(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. ¹H NMR spectra were recorded on a JEOL JNM-ECS400 (400 MHz) spectrometer or JEOL JNM-ECX400 (400 MHz) FT spectrometer in CDCl₃ as the solvent with tetramethylsilane (TMS) as an internal standard. ¹³C NMR spectra were taken mainly on JEOL JNM-ECS400 (100 MHz) and JEOL JNM-ECX400 (100 MHz) FT spectrometers in CDCl_3. ³¹P NMR spectra were recorded on a JEOL JNM-ECX400 (162 MHz) FT spectrometer in CDCl₃ with 85% H₃PO₄ solution as an external standard or a Bruker BioSpin Ascend 400 spectrometer (162 MHz). ¹⁹F NMR spectra were recorded on a Bruker BioSpin Ascend 400 spectrometer (377 MHz). IR spectra were recorded on JASCO FT/IR-680Plus instrument. High-resolution mass spectra (HRMS) were recorded on a Bruker micrOTOF II ESI(+)/TOF instrument.

General procedure for the phosphinylphosphination of alkynes

Ph₂P(O)PPh₂ (1, 0.6 mmol) and an alkyne (2, 0.4 mmol) were placed in a Schlenk tube with CDCl₃ 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

File 1

Characterization data and copies of NMR spectra.

Funding Statement

D.P.T. is grateful for the support of the Japanese Government (Monbukagakusho: MEXT) Scholarship. This research was supported by JSPS KAKENHI (B, 19H02791), (B, 19H02756), and (19K17746), from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by Kyoto-NAIST Advanced Nanotechnology Network.