Recent progress on the functionalization of white phosphorus in China

ABSTRACT Direct synthesis of organophosphorus compounds from white phosphorus represents a significant but challenging subject, especially in the context of ongoing efforts to comprehensively improve the phosphorus-derived chemical industry driven by sustainability and safety concerns. China is the world's largest producer of white phosphorus, creating a significant demand for the green transformation of this crucial feedstock. This review provides an overview of advancements in white phosphorus activation by Chinese research teams, focusing on the direct construction of P‒C/N/O/S/M bonds from white phosphorus. Additionally, we offer some insights into prospective directions for the activation and transformation of white phosphorus in the future. This review paper aims to attract more researchers to engage in this area, stimulating follow-up exploration and fostering enduring advances.


INTRODUCTION
Organophosphorus compounds (OPCs) are ubiquitous in daily life, and have numerous applications in pharmaceuticals, food additives, pesticides, flame re tard ants, electro lytes and de tergents [1 -5 ].They also contribute significantly to fundamental research, particularly in synthetic chemistry [6 -8 ], materials science [9 ] and abiogenesis [10 ], propelling the evolution of chemistry and life science (Fig. 1 A).The present-day synthesis of OPCs predominately relies on white phosphorus (P 4 ), discovered by German alchemist Hennig Brand in 1669 [11 ].And now, as the main feedstock chemical, P 4 is obtained annually in excess of 1 mi l lion tons through the reduction of phosphate rock [12 ].In conventional processes, (oxy)chlorination of P 4 results in the formation of PCl 3 , PCl 5 and OPCl 3 , each posing a considerable environmental risk due to their volatile and hazardous liquid nature.Subsequent stages entail the generation of HCl or salt, culminating in the production of a diverse array of valueadded fine chemicals [13 -15 ].Regrettably, this approach not only requires the utilization of toxic liquid chemicals but also confronts challenges associated with the generation of large amounts of waste acids and salts, along with tedious work-up procedures.Another approach toward OPCs is that the reaction of P 4 with a strong base generates PH 3 , which is then functionalized by reactions with alkenes [14 ,15 ].This method suffers from the wasteful utilization of phosphorus atoms, the inherent toxicity and the challenge in handling of PH 3 gas (Fig. 1 B).
In light of the urgent environmental concerns associated with conventional approaches, an alternative route directly converting P 4 into OPCs has garnered both scientific significance and practical value.Remarkable progress has been made toward the formerly elusive goal of selectively transforming the P 4 molecule in order to avoid the production of downstream chlorinated chemicals [16 -19 ].The pioneering efforts in this direction date back to the 1960s, employing specific organic molecules and simple organometallic reagents to activate P 4 and yield certain OPCs [20 ].Nevertheless, these methods encountered challenges of low yields and poor selectivity.In subsequent stages, metal-mediated P 4 activation emerged as the predominant approach [21 -23 ].The allure of this methodology lies in its potential for achieving metal-catalyzed P 4 transformation through the coordination and activation of P 4 by a metal complex.While early transition metal (TM)mediated P 4 activation can lead to the formation of P-H and P-C bonds, the metal-catalyzed process remains a distant prospect.In the past 15 years, the introduction of highly active species, such as carbenes and their analogs, has enabled selective P 4 activation [24 ].Despite the significant progress in the field of P 4 activation making OPCs or organometallic phosphorus compounds, it is sti l l a highly challenging research area.In fact, it generally suffers from: (i) the high electrophilic reactivity of the P 4 tetrahedron; (ii) the low selectivity for the P-P bond rupture after the first P-P bond cleavage; and (iii) the low conversion efficiency of the phosphorus atoms in P 4 [25 ].Consequently, the controllable and atomefficient functionalization of P 4 to construct directly OPCs or organometallic phosphorus compounds is highly desirable.Currently, there are over 30 research groups actively engaged in P 4 activation and transformation internationally, mainly distributed in the United States [26 -33 ], Germany [34 -44 ], Russia [45 -47 ], France [48 ,49 ], the Netherlands [50 ,51 ], the United Kingdom [52 -58 ] and other countries [59 -66 ].China presently contributes over 70% to the global production of P 4 .However, the research of P 4 activation and transformation in China lags behind.Our group first launched the study in this field in 2014, and the first paper entiteld "Direct Synthesis of Phospholyl Lithium from White Phosphorus ˮ was published in 2016 [67 ].Since then, we have reported a series of works on direct functionalization of P 4 to constuct P-C bonds [68 -77 ].In the past 5 years, 10 research groups in China have been involved in P 4 activation and transformation [78 -100 ].Although some reviews have summarized the activation and transformation of P 4 from different perspectives [16 -25 ], there is no specific review summarizing progress in China.This timely review outlines the contributions of Chinese research teams in the field of P 4 activation (Fig. 1 C), and discusses the significance of P 4 chemistry along with possible directions for future research.The objective of this review is to inspire increased involvement from researchers in advancing environmentally sustainable methods for P 4 activation, fulfilling the desire to completely abandon the environmentally unfriendly industrial chlorination route in the future.

CONSTRUCTION OF P-C BONDS
The construction of P-C bonds from P 4 is of great significance in both industry and academic research.However, due to the complex P-P bond breaking patterns, it is sti l l chal lenging to construct P-C bonds from P 4 directly with good selectivity.Therefore, finding proper methods to deal with this challenge is necessary.During the past few decades, there has been some development in the construction of P-C bonds from P 4 directly, including the reactions of organometallic reagents and organic molecules with P 4 .

Reactions of P 4 with organo-di -lithium reagents
In 2016, we reported for the first time the reaction of P 4 with 1,4-dilithio-1,3-butadienes 1 , which quantitatively generated phospholyl lithiums 2 through the cooperative nucleophilic attack of two C sp2 -Li bonds on P 4 (Fig. 2 A) [67 ].Di-or tetra-substituted phospholyl lithiums with diverse alky l, ary l, or sily l groups can be prepared efficiently.Additionally, a novel cooperative insertion mechanism in the reaction of P 4 with 1 involving the release of intermediate 3 was proposed and confirmed by density functional theory calculations.The understanding of this process wi l l open a new door for the design of straightforward synthesis of OPCs from P 4 .Then, the aggregation states of phospholyl lithiums were systematically studied, revealing their potential to exist as monomers, dimers, and coordination polymers by changing the substituents and crystallization temperatures [68 ].These investigations could be helpf ul when sy nthesizing other metal complexes supported by these phospholyl ligands.Furthermore, the [LiP 3 ] n moiety 3 was isolated and characterized as a mixture of phosphorus cluster anions, including Li 3 P 7 , Li 4 P 14 , Li 2 P 16 and Li 4 P 26 based on X-ray diffraction analysis and 31 P{ 1 H} COSY NMR analysis [69 ].In 2022, the reaction of P 4 with biphenyl dilithio reagents 4 was realized to produce a series of phosphafluorenyl lithiums 5 (Fig. 2 B) [70 ].The aggregation states of phosphafluorenyl lithiums were initially studied, and the obtained phosphafluorenyl lithiums were key synthetic intermediates for phosphafluorenes.In the same year, we fur-ther achieved the derivatization of phosphafluorenyl lithiums.When the one-pot reaction among P 4 , biphenyl dilithio reagents and ArCOCl or polyfluorobenzenes was carried out, the phosphafluorenylbased acylphosphine oxides and triarylphosphines were obtained in a chlorine-free method [71 ].The acylphosphine oxides and triarylphosphines could be used as radical photoinitiators and organophosphorus ligands.

Reactions of P 4 with rare-earth metallacyclopentadienes
Considering that metallacyclopentadienes can both work as double nucleophiles and dienes, we speculated that two M-C sp2 bonds could clip out a P 1 fragment, forming a phospholyl anion via the aromatization driving force while the diene skeleton would trap the cyclo -P 3 moiety to form an organosubstituted cyclo -P 3 compound.Thus, we decided to investigate the reactions of rare-earth metallacyclopentadienes 6 with P 4 .Using this strategy, we synthesized the first series of rare-earth metal cyclo -P 3 complexes 7 and phospholyl anion 2a (Fig. 2 C) [72 ].In this process, the cleavage of three P-P bonds and formation of four P-C bonds for [3 + 1]fragmentation were observed [73 ].Complexes 7 represent the first cyclo -P 3 complexes of rareearth metals and also the first organo-substituted polyphosphides in the category of group 3 and f-block elements.The characterization of 7 suggests that dienes in 6 can trap the cyclo -P 3 moiety and confirms the existence of released [LiP 3 ] moiety in the reactions of P 4 with 1,4-dilithio-1,3-butadienes 1 .To investigate the substituent effect of lutetacyclopentadienes, the reaction of Me, trimethy lsily l (TMS)-substituted lutetacyclopentadiene with P 4 was carried out (Fig. 2 D) [74 ].The expected cyclo -P 3 lutetium complex 7d and the aggregated lithium phospholide 8 were obtained.Besides, the sandwich lutetium complex 9 was isolated as a new complex.Interestingly, an unexpected trinuclear rare-earth metal complex 10 with a bicyclo -P 6 4 − ligand was also observed in this reaction.

Reactions of P 4 with aluminacyclopentadienes
To investigate the importance of metal centers in metallacyclopentadienes for the direct functionalization of P 4 , the reactions of aluminacyclopentadienes 11 with P 4 were carried out.Unexpectedly, the cyclotetraphosphanes 12 featuring four newly formed P-C bonds and a planar square cyclo -P 4 ring was obtained selectively (Fig. 2 E) [75 ].These cyclotetraphosphanes represent an important class of organic polyphosphanes which are not easy to access by other methods.

Photo-and electrochemical transformation of P 4
Recent years have witnessed promising outcomes in the photo-and electrochemical transformation of P 4 .In 2022, the reactions of N -hydroxyphthalimide (NHPI) esters with P 4 were developed by Tang et al. (Fig. 2 F) [78 ].This process, conducted without TMs or photocatalysts, resulted in a series of dialkyl and trialkyl phosphine oxides under blue light irradiation, with yields up to 92%.This synthetic method features the simple operation, broad substrate scope and high product selectivit y.In 20 23, another approach to construct dialkylphosphines was reported (Fig. 2 G) [79 ].Using organic-dye 4CzIPN as the photocatalyst, the unactivated alkyl iodides could react with P 4 to generate dialkylphosphines in moderate to good yields.In the same year, we reported a method for the construction of tetrabenzylphosphonium bromide under blue light irridiation (Fig. 2 H) [76 ].Catalyzed by Cp 2 TiCl 2 and 4CzIPN, the reactions between P 4 and benzyl bromides produced a series of quaternary phosphonium salts, applicable in organic synthesis and pharmaceuticals.This marked the introduction of the metallaphotoredox catalysis strategy for the first time in the field of P 4 activation.Additionally, we also reported the synthesis of phosphoryltriacetates in 2023 (Fig. 2 I) [77 ].Using fac -Ir(ppy) 3 as the photocatalyst and blue LEDs (456 nm) as the light source, P 4 can react with α-bromo esters to generate phosphoryltriacetates in the one-step reaction with moderate to good yields.
Moreover, electrochemical transformation of P 4 to OPCs was reported by Liu et al. in 2022 (Fig. 2 J) [80 ].P 4 was first electro-oxidized into [P(CN) 2 ] − , which was subsequently used to synthesize the useful OPCs, such as phospholides and cyclophosphanes.Notably, this method can accomplish the activation of P 4 on a gram scale.

CONSTRUCTION OF P-S/N/O BONDS
Heteroatom-containing OPCs, such as phosphorothioates (C-S-P bonds), phosphoramidates (C-N-P bonds), or phosphates (C-O-P), have important applications in the fields of medicinal chemistry, ligands, organocatalysis and agrochemistry [101 -103 ].The synthetic methods of these compounds mainly involve two routes: (i) the substitution reactions of PCl 3 , and (ii) the classical coupling reactions, free radical reactions or substitution reactions of specific phosphorus reagents, such as (RO) 2 P(O)H, P(OR) 3 or R 2 P(O)H, etc. [104 -106 ].However, it is noteworthy that most phosphorus-containing reagents used in the currently developed methods for the synthesis of OPCs must also be pre-prepared from PCl 3.

Construction of P-S/N bonds
In 2019, Tang et al. first reported a photocatalytic reaction of P 4 for the construction of P-S bonds (Fig. 3 A) [81 ].The phosphorotrithioates were synthesized by direct reaction of P 4 and thiophenol using Na 2 EosinY as a photocatalyst.However, the substrate scope of this method was limited, which was only suitable for thiophenol, but mercaptan could not give the corresponding products.Subsequently, they reported the synthesis of phosphorotrithioates under mild conditions with KOH or K 2 CO 3 as base and air as oxidant (Fig. 3 B) [82 ].Both thiophenol and mercaptan could be tolerated, and the yields were almost quantitative.
The above methods have successfully realized the synthesis of P(SR) 3 and P(O)(SR) 3 with the same substituents, but the synthetic method of mixed phosphorotrithioates (R 1 S) 2 P(O)SR 2 was sti l l worth exploring.In 2020, they reported the synthesis of mixed phosphorotrithioates (R 1 S) 2 P(O)SR 2 by a one-pot, two-step procedure from P 4 , disulfide and alkyl halides with KOH as the base (Fig. 3 C) [83 ].The key intermediate in this process is (R 1 S) 2 P(S)OK, which was generated by the attack of RSK on S,S,S -trialkyl phosphorotrithioates and subsequent C-S bond cleavage (Michaelis-Arbuzov-like dealkylation reaction).In addition, they considered that penta-coordinate ionic species may be formed during the reaction, which may exchange with KOH to form the P = O bond.To explore this feasibility, amines were introduced in this reaction, which may exchange with the -SPh group to form a P-N bond.Based on this, they reported the efficient four-component synthesis of phosphoramidodithioates from P 4 , disulfides, amines and KOH (Fig. 3 D) [84 ].KOH serves both as the base in the reaction and as the source of oxygen atoms in the products.After that, they further synthesized (R 1 S) 2 P(S)SR 2 with NaSH instead of KOH under reaction conditions similar to Fig. 3 C.The NaSH provided the sulfur atoms in the products (Fig. 3 E) [85 ].

Construction of P-O bonds
In 2021, Tang et al. envisioned that the catalytic activation of P 4 with (RSe) 2 might produce P(SeR) 3 species, which can undergo further nucleophilic substitution with ArOH, eventually leading to P(OAr) 3 products.Based on that, using (PhSe) 2 as the catalyst and dimethyl sulfoxide (DMSO) as both the solvent and oxidant, they realized the synthesis of triaryl phosphites and triaryl phosphates from P 4 and aryl phenol with almost quantitative yield (Fig. 3 F) [86 ].The triaryl phosphites could be oxidized with H 2 O 2 or S 8 to afford the corresponding oxidation products triaryl phosphates and triaryl thiophosphates.While this work provided a straightforward synthesis of triaryl phosphites, the substrate scope is limited to phenol compounds, and alcohols are not applicable.Dialkylphosphites are widely used as basic starting materials for the synthesis of complex phosphate-based organic compounds.Tang et al. reported the direct synthesis of dialkylphosphites from P 4 and alcohol.The reaction was mediated by KBr with KHSO 5 (oxone) as the oxidant (Fig. 3 G) [87 ].In this process, oxone and KBr were employed to in situ produce PBr 3 intermediate, thus replacing the traditional PCl 3 route.
To avoid the consumption of a large amount of oxidants, Tang et al. developed a waste-free, environmentally friendly method for the synthesis of dialkylphosphites from P 4 and alcohols.This approach utilized a combination of photoredox catalyst, nickel catalyst and halide anion under visible light (Condition A; Fig. 3 H) [88 ].The trialkylphosphate could be obtained by increasing the amount of alcohol and prolonging the reaction time (Condition B; Fig. 3 H).This photocatalytic method proved to be effective for various alcohols.Furthermore, it demonstrated suitability for the synthesis of phosphorotrithioates.
α-Aminophosphonates find broad applications in fungicides and enzyme inhibitors.In 2023, Tang et al. reported a Cu-catalyzed three-component reaction among tetrahydroisoquinolines, P 4 , and alcohols to synthesize α-aminophosphonate with air as a safe oxidant (Fig. 3 I) [89 ].Furthermore, the method was also suitable for the selective construction of P-O-P compounds (Fig. 3 J) [89 ].Recently, Tang et al. described a novel and high-yielding method for the synthesis of various phosphorothioates from P 4 , disulfides and alcohols in one step (Condition A; Fig. 3 K) [90 ].They hypothesized the formation of phoroselenoate derivatives when replacing diaryl disulfides with diphenyl diselenides.Subsequent nucleophilic substitution with ArOH would result in mixed alky l/ary l phosphates.Based on this hypothesis, they successf ully sy nthesized the corresponding mixed phosphates using diphenyl diselenides as catalyst and phenol as nucleophile (Condition B; Fig. 3 K).This method achieves the simple and efficient synthesis of phosphorothioates with diverse structures.

CONSTRUCTION OF P-M/E BONDS
In the past decade, the activation and transformation of P 4 by main group element (E) and metal (M) complexes has attracted intense attention and been subjected to extensive study in the Chinese chemistry community.This is due to their potential utility in the synthesis of OPCs and metal phosphide materials.Various P n -containing compounds with different nuclearities and geometries have been prepared.
It not only provides an environmental ly friend ly and straightforward route to synthesize high-valueadded OPCs without the utilization of poisonous and corrosive chlorine gas but also leads to the production of various metal phosphides with marvelous structures and reactivities [18 -25 ].It should be noted that the organometallic complexes-mediated P 4 activation always involves complex processes, including the cleavage and formation of several bonds.The resulting metal phosphide complexes are intimately related to the type of metal complexes and the coordination environment.Additionally, there is relatively little research on the mechanisms of these processes, highlighting an area where more investigation is needed in the future.

Construction of P-E bonds
The activation of P 4 by main group elements is an established field of chemistry [20 ].In 2023, Mo et al. reported the synthesis of an elusive homoleptic diphosphene lead complex 14 through controllable degradation of P 4 by zero-valent lead complex 13 at ambient temperature (Fig. 4 A) [91 ].Complex 14 possesses significant π bonding between the Pb atom and diphosphene ligands, with Pb→ P 2 πbackbonding and P 2 → Pb σ -donation.The utility of diphosphene as a π -electron donor to stabilize lowvalence lead complexes provides a new strategy to develop π -complexes of main group elements.
In the same year, they successf ully sy nthesized a geometrically constrained borylene 15 with the help of a rigid pincer bis(silylene)amido ligand.The reaction of 15 with P 4 afforded the product 16 in 85% yield; 16 possesses a BSiP 4 cage, which is formed by the insertion of the P 4 molecule into the Si-B bond (Fig. 4 B) [92 ].

Construction of P-TM bonds
The TM-mediated activation of P 4 has given rise to a plethora of fascinating complexes bearing versatile P n units.The synthesis of these P n -containing compounds from P 4 necessitates the cleavage of one or more P-P bonds, and possibly the formation of new P-P bonds [19 ].
In 2022, Deng et al. reported P 4 activation with three-coordinate N -heterocyclic carbene (NHC)cobalt(0)-alkene complexes 17 .This reaction selectively produces the large polyphosphorus cobalt clusters 18 bearing P 8 ligands in high yields.These Co 2 P 8 clusters feature short Co-Co bonds (2.39 Å), and P 8 ligands exhibit signet-ring type geometry that is unprecedented in synthetic P 8 complexes (Fig. 4 C) [93 ].A series of cage functionalization reactions were conducted and indicated the amphiphilicity of the P 8 ligands in 18 toward electrophiles and nucleophiles.A possible mechanism for the formation of 18 was proposed.P 4 reacts with one molecule of 17 to generate cyclo -P 4 intermediates, which can interact with a second molecule of 17 to afford the chain -P 4 species.The chain -P 4 species feature two coordinatively unsaturated cobalt centers and can interact with P 4 to produce the final products.As an alternative route, the direct dimerization of cyclo -P 4 intermediates could also give the P 8 complexes.In the same year, Xi et al. synthesized and structurally characterized the dinuclear cobalt dinitrogen complex 19 bearing cyclopentadienylphosphine ligands.The two cobalt centers of 19 could undergo oxidative addition of two individual P-P bonds in the P 4 moiety resulting in the formation of diamagnetic complex 20 with a cyclo -P 4 moiety (Fig. 4 D) [94 ].Very recently, Xu et al. reported the first example of P 4 activation by a group 12 metal-centered complex.They found that the Zn(I) −Zn(I) bonded compound 21 could serve as a two-electron reducing reagent to selectively reduce a number of small molecules, including P 4 .The reaction of 21 with P 4 gave a trinuclear zinc complex 22 , which contains a zintl -P 7 ligand (Fig. 4 E) [95 ].

Construction of P-RE bonds
A combination of coordinative unsaturation and inherent Lewis acidity of rare-earth (RE) metals, and the strong nucleophilicity of RE −C bonds, endows rare-earth organometallics with a rich reaction chemistry toward P 4 .Rare-earth metal-mediated P 4 activation can lead to the formation of P-H and P-C bonds.Hence, this approach has attracted significant interest [27 ].
In 2019, Zhou et al. synthesized for the first time a rare-earth organonometallic cyclo -P 4 complex 24 by direct functionalization of P 4 using a rare-earth metal alkyl precursor 23 .Heating 24 at 50°C in toluene for 4 days afforded the R 2 P-substituted cyclo -P 3 complex 25 in 90% yield through alkyl migration.This transformation provides a new insight into the stepwise degradation of P 4 using metal complexes (Fig. 4 F) [96 ].In 2023, they reported the reaction of yttrium hydride 26 with P 4 , which results in the formation of a trinuclear yttrium complex 27 bearing a unique pyramid-like P(PH) 3 moiety (Fig. 4 G).In contrast, the intramolecular cooperative yttrium hydride/LiPPh 2 -mediated P 4 activation results in the production of two multinuclear heterometal polyphosphorus complexes, one with cyclo -P 3 fragment ( 29 ) and the other with norborane-P 7 fragment ( 30 ) (Fig. 4 H).
These findings showcased the synergistic effect of rare-earth hydride and LiPPh 2 , introducing a new mode of P 4 activation [97 ].
Very recently, Zhou et al. successf ully sy nthesized two novel rare-earth polyphosphides through the direct P 4 activation with rare-earth metal dialkyl complexes 31 .Treatment of the yttrium dialkyl complex 31a with P 4 in toluene at ambient temperature resulted in the formation of two yttrium polyphosphorus complexes: norbornene-BnP 7 complex 32a or chain-Bn 4 P 6 complex 33a , respectively.Notably, the analogous reaction of 31b with P 4 in toluene at 40°C only gave 32b .These results i l lustrated the important influence of the metal centers on the reactivity of the organometallic compounds (Fig. 4 I) [98 ].
In 2022, Ren et al. investigated the reduction of P 4 using in situ generated lanthanum and cerium hydrides.Treatment of the lanthanocene or cerocene alky l complexes 3 4 with P 4 followed by the addition of 9-BBN afforded the trinuclear lanthanide complexes 35a , b with a μ-bridging P 7 3 − ligand (Fig. 4 J) [99 ].

Construction of P-An bonds
The study of small molecule activation by actinide (An) elements sti l l lags far behind that of maingroup elements and TMs.Reports on the P 4 activation by uranium species are rare.In 2021, Zhu et al. reported the formation of a uranium polyphosphide 37 with an E -type P 4 chain by treating the uranium chloride 36 with P 4 and KC 8 in tetrahydrofuran (THF).Computational studies showed that the U(III)-P(III) synergistic effect allows a direct six-electron reduction of P 4 (Fig. 4 K) [100 ].This study further demonstrates the ability of the synergistic strategy between metal centers and ligands to activate P −P bonds, which may inspire the design of new systems for P 4 activation.

CONCLUSION AND OUTLOOK
The direct conversion of P 4 into P-containing compounds holds paramount significance both in terms of fundamental understanding and practical applications.Over the past six decades, substantial progress has been made in directly forming OPCs from P 4 .Early efforts faced challenges of poor selectivity and low yields due to the unique tetrahedral structure and high reactivity of P 4 .The prospect of transition metal-catalyzed P 4 transformations remain unresolved challenges due to the intricate nature of the reactions between low-valence TMs and P 4 .By the delicate substrate and pattern design, some highly selective conversions of P 4 to OPCs have been developed, yet these reactions are stoichiometric.In recent years, catalytic reactions producing monophosphorus compounds from readi ly avai lable substrates and P 4 have made notable progress through photochemical and electrochemical approaches, gar-nering widespread attention.However, these intriguing reactions sti l l exhibit some draw backs, such as the need for substantial additives or substrates, difficulties in scaling up, and limited applications of the products.Therefore, the development of more efficient and environmentally friendly systems is imperative.Additionally, exploring new reaction types is essential.In this context, we propose that the following fields can be considered in the future.

Mechanistic studies on P 4 degradation
While the conversion of P 4 to mono-phosphorus compounds represents a promising direction, the progress in understanding the complex and unclear mechanism of P 4 degradation is limited.In-depth mechanistic studies through the combination of in situ characterization techniques and computational chemistry would greatly aid in the development of direct synthesis of mono-phosphorus compounds from P 4 .

New reaction systems
Most current catalytic processes for OPCs from P 4 rely on radical systems.This preference arises from the fact that, compared to other reactive species, radicals are electrically neutral, allowing a single radical to react with P 4 to produce neutral organophosphorus product without the consideration of charge conservation.This process always leads to the singularity of P-atom connecting groups.Furthermore, this strategy also suffers from the poor reactivity caused by the low efficiency of free radical formation.Exploring P 4 transformations induced by other in situ generated active species, such as carbenes, frustrated radical pairs, etc., is an intriguing research topic.

Electrochemistry
The transformation of P 4 into OPCs involves changes in the oxidation state of phosphorus atoms.In terms of redox chemistry, which is frequently encountered when forging new bonds, it is difficult to conceive of a more economical way to add or remove electrons than electrochemistry.Therefore, the development of electrochemical methods for P 4 aligns with the requirements of sustainability and economics.Meanwhile, electrochemistry serves as a potent tool for generating active species, holding great promise in the realm of P 4 functionalization.One straightforward concept is the reduction of P 4 to [P] 3 − species at the cathode, which can then react with electrophiles in the system to produce the final organic compounds.

In situ transformation via P-protonation, P-sulfenylation or P-chlorination intermediates
Inspired by the work of the conversion of P 4 into organophosphate compounds via the Psulfenylation and P-selenylation intermediates, this strategy can be further expanded.Such a strategy can capitalize on established conversion methodologies, streamlining synthetic procedures, while simultaneously preventing the formation of toxic by-products and waste acids or salts.

Merging C-H activation with P 4 transformation
Among the reported catalytic transformations of P 4 to OPCs, the prerequisite for substrates to possess leaving groups often results in diminished atom economy.While C-H bond activation has witnessed significant advancements in modern synthetic chemistry, its amalgamation with P 4 activation remains a challenging and largely unexplored area.The C-H activation-based transformations of P 4 wi l l streamline the synthetic routes to OPCs, significantly enhancing atom economy and synthetic efficiency.For instance, the conventional synthesis of triphenylphosphine involves the use of sodium and chlorobenzene.Direct synthesis of triphenylphosphine from benzene and P 4 would yield substantial economic and environmental benefits.

Machine learning for P 4 activation
The application of machine learning in the fields of chemistry and materials science is rapidly expanding, bringing unprecedented innovation and progress to these disciplines.In the realm of P 4 activation, machine learning can be employed for the design of reaction pathways, enhancement of catalyst performance, optimization of reaction conditions, etc., thereby accelerating the discovery of environmentally friendly and efficient methods for P 4 transformation.

Homogeneous-heterogeneous synergy strategy for P 4 activation
Heterogeneous chemical reactions excel at facile cleavage of inert bonds, whereas homogeneous chemical reactions are adept at synthesizing fine chemicals.In recent years, a strategy combining homogeneous and heterogeneous approaches has been successfully applied to the synthesis of nitrogencontaining compounds from N 2 [107 ,108 ].If this new strategy could be implemented in the field of P 4 activation, it would offer fresh opportunities for the direct synthesis of high-value OPCs from P 4 and simple organic molecules.

3 Figure 1 .
Figure 1.The importance of OPCs and comparison of different routes to commercial OPCs.

Figure 4 .
Figure 4. Activation and functionalization of P 4 with metal complexes.RE, rare-earth.