Convenient and Scalable Synthesis of Aryldichlorophosphines and Primary Arylphosphines via Perthiophosphonic Anhydrides

SYNTHESIS0039-78 1 437-210X Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart 2023, 55, A–H special topic Synthetic Advancements Enabled by PhosSynthesis A Special Topic D. Picthall et al. Convenient and Scalable Synthesis of Aryldichlorophosphines and Primary Arylphosphines via Perthiophosphonic Anhydrides Daniel Picthalla Brian A. Surgenorb Petr Kilian*a Ar-H P4S10 S no solvent Ar 150-190 °C 0-016379-026 P S S Ar P S COCl2 (soln. in toluene) LiAlH4 Et2O 0 °C to RT a EaStChem School of Chemistry, University of St. Andrews, St. Andrews, Fife, KY16 9ST, UK pk7@st-andrews.ac.uk b Treatt Plc, Bury St Edmunds, IP32 7FR, UK Ar PH2 DCM 0 °C to RT 6 examples up to 52% yield Ar PCl2 6 examples up to 90% yield all steps scalable to multigram quantities minimum purification required Published as part of the Special Topic Synthetic Advancements Enabled by Phosphorus Redox Chemistry Petr Corresponding EaStChem eMail Kilian pk7@st-andrews.ac.uk School of Author Chemistry, University of St. Andrews, St. Andrews, Fife KY16 ST, UK Received: 12.09.2022 Accepted after revision: 07.12.2022 Published online: 07.12.2022 (Accepted Manuscript), 09.01.2023 (Version of Record) DOI: 10.1055/a-1994-2301; Art ID: SS-2022-08-0422-ST License terms: © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution and reproduction, so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Abstract A scalable synthetic route to both primary arylphosphines ArPH2 and aryldichlorophosphines ArPCl2 is reported. The C–P bond formation was performed in a highly regiospecific manner through electrophilic substitution of selected aromatic hydrocarbons (ArH) with phosphorus pentasulfide. The resultant perthiophosphonic anhydrides Ar2P2S4 were then reacted with LiAlH4 to give primary phosphines ArPH2. Subsequent reaction of ArPH2 with phosgene solution gives dichlorophosphines ArPCl2. Each reaction step requires minimum purification and uses commercially available and economical precursors. The scope of the reaction was shown to include alkoxy and phenoxy substituted benzenes as well as naphthalene and fluorene as starting materials. Key Words primary phosphine, chlorophosphine, organophosphorus synthesis, 31P NMR Both primary phosphines RPH2 and dichlorophosphines RPCl2 have a rich chemistry and are valuable reagents in reactions such as hydrophosphinations, dehydrocoupling and P–C bond formation.1–3 This is facilitated by the reactive nature of P–H and P–Cl bonds, respectively. However, this also means that primary phosphines, particularly those with a low molecular weight and minimal steric bulk protecting the -PH2 moiety, are extremely pyrophoric, rendering them difficult to synthesise and manipulate. Typically, primary phosphines are synthesised by the reaction between either alkyl/aryl dichlorophosphines (Scheme 1, route (i)) or phosphonates (Scheme 1, route (ii)) and a strong reducing agent.4–6 Dichlorophosphines appear to be ubiquitous within synthetic organophosphorus chemistry;7–12 despite this, the commercial availability of aryldichlorophosphines is limited and so laboratory-scale syntheses have to be employed where access to a wider range of these compounds is required. A major challenge to overcome in these syntheses is the need for a highly selective formation of the desired species, which is crucial due to the limited options for postsynthetic purification, generally limited to fractional distillation (for sufficiently volatile species). Other options (in particular chromatography) are generally not accessible due to the very reactive nature of dichlorophosphines towards both oxygen and moisture. P–C bond formation is a crucial step in the synthesis of aryldichlorophosphines. Early examples involved reacting aromatic hydrocarbons or anisol derivatives with PCl3 in the presence of a Lewis acid catalyst such as AlCl3 or SnCl4 (Scheme 2, route (i)).13,14 Later examples used the reaction of PCl3 with respective Grignard (or organolithium) reagent (Scheme 2, route (ii)) and this method is still routinely employed.15,16 The disadvantage of this synthetic route is that due to the high reactivity of the Grignard (or organolithium) reagent, often the products of multiple substitution (Ar2PCl and Ar3P) are formed in significant amounts, impacting the yield of the dichlorophosphine. This synthetic route also suffers from poor functional group tolerance. LiAlH4 (i) PCl2 PH2 P(O)Et2 OMe LiAlH4 PH2 OMe Scheme 1 Examples of primary phosphine syntheses © 2022. The Author(s). Synthesis 2023, 55, A–H Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany (ii) B Synthesis Ar H PCl3 LA catalyst (i) Ar PCl2 PCl3 Ar X Mg Special Topic D. Picthall et al. Ar PCl2 ( + Ar2PCl + Ar3P ) (ii) Ar MgX (X = Cl, Br, I; R = Alkyl) ClP(NR2)2 Ar P(NR2)2 HCl (g) (excess) R PCl2 (iii) bond-forming step, in which the perthiophosphonic anhydride Fc2P2S4 is formed from ferrocene and P4S10, proceeds fully regioselectively with high yield (>80%).19 Herein, we report the expansion of this synthetic route to make a selection of primary and dichloroaryl phosphines. Perthiophosphonic Anhydrides Synthesis – (NR2)2NH·HCl R Br R nBuLi Li ZnCl2 R ZnCl R PCl3 (iv) PCl2 R = aryl Scheme 2 Selected literature syntheses of dichlorophosphines To prevent the formation of byproducts due to multiple substitution, a protective group strategy was devised in which PCl3 was replaced with ClP(NR2)2 (Scheme 2, route (iii)). The intermediate aminophosphinyl species ArP(NR2)2 is formed, which is isolated and then reacted with excess HCl gas to form the dichlorophosphine.4,17 While this synthetic route does prevent multiple substitution from occurring, a new challenge is presented through the use of HCl gas and separation of the dichlorophosphine from the coformed dialkylammonium chloride. More recently a systematic investigation of the synthesis of aryl- and heteroaryldichlorophosphines was reported by Karaghiosoff18 in which organozinc reagents were employed in the place of Grignard or organolithium reagents (Scheme 2, route (iv)). Lower polarity of C–Zn vs. C–Mg and C–Li bonds resulted in more controlled reactivity of organozinc species compare to Grignard reagents and organolithiums. Whilst this route presents improvement over the more conventional routes as it does avoid multiple substitution products and offers good functional group tolerance, it requires observing the right stoichiometry carefully, and distillation (or recrystallisation for solids) of the highly reactive product as a final purification step. As outlined above, the synthesis of dichlorophosphines is not straightforward, with multiple issues presented for each synthetic method. Our recent investigations required a synthesis of a series of aryldichlorophosphines to allow for fine tuning of electronics of a target phosphorus-containing molecule. This prompted the synthesis of a series of aryldichlorophosphines, each in multigram quantities, with differing aryl groups. To synthesise these we have expanded on our previously reported ‘niche’ synthetic route, originally used to form dichloroferrocenylphosphine FcPCl2, via the perthiophosphonic anhydride, Fc2P2S4 (Scheme 3).19 This unique method offers a route to a previously difficult to access dichlorophosphine FcPCl2 in high yield, is easily scalable, uses economical commercially available precursors, and does not require complex purification. The P–C The synthetic route towards primary and dichloroaryl phosphines (Scheme 4) begins with the synthesis of the perthiophosphonic anhydride compounds 1A–F. These six compounds were selected due to the ease with which they can be synthesised; this is achieved by a simple heating of P4S10 with the related hydrocarbon precursor - anisole, phenetole, 2-tert-butylanisole, diphenyl ether, fluorene and naphthalene, respectively, at high temperature (150–190 °C, reaction time 1–5 hours). All of these compounds have previously been reported in the literature,20–22 with the exception of the fluorene derivative 1F. The arene reactants served also as solvents for the reaction; hence, the molar ratio of reactants 1:2 to 1:2.5 was used (P/ArH). The reactions were performed under a gentle stream of nitrogen and the exhaust gasses were bubbled through an aqueous NaOH solution to remove H2S formed as a by-product. The liquid mixtures obtained after heating were left to cool to room temperature and the formed solid products were filtered off, washed with dichloromethane or diethyl ether and dried in vacuo. Compounds 1A–F form as yellow or white solids in yields in the range of 31–65% (see Table 1). They can be manipulated in air; however, they hydrolyse slowly, hence long-term storage requires well-sealed vials. While other routes exist for the synthesis of perthiophosphonic anhydrides, these are generally more complex and require several steps, hence are less suitable to prepare starting materials for the synthetic sequence in this work.23,24 An important point to make is that the arenes selected in this work contain no functional groups that will provide additional reactivity toward P4S10, such as ketones, esters and alcohols.25,26 On the other hand, the presence of electron-donating groups (such as OMe) on the aromatic ring results in improved yields and shorter reaction times. Due to the inherent insolubility of perthiophosphonic anhydrides, no NMR data could be collected for 1A–F. Nevertheless, the follow-on reactivity (see below) indicates the P–C bond formation is fully regiospecific in the reactions of Fe Fe P4S10 S P S S LiAlH4 P S Fe PH2 COCl 2 PCl2 Fe Fe FcPH2 FcPCl2 Scheme 3 Synthesis of FcPH2 and FcPCl2 reported previously by us Synthesis 2023, 55, A–H C Synthesis Special Topic D. Picthall et al. P4S10 S Ar-H 150–190 °C Ar P S S 1A-F Ar = COCl2 (2.1 equiv) (soln. in toluene) Ar LiAlH4 (4 equiv) S P Ar PCl2 Ar PH2 Et2O 0 °C to RT O A O B 2A-F O DCM 0 °C to RT 3A-F D E C O F tBu Scheme 4 Synthetic route used for the synthesis of primary phosphines 2A–F and dichlorophosphines 3A–F P4S10 with both activated and non-activated arenes used in this study, with no other regioisomers detected by 31P{1H} NMR analysis in the phosphines 2A–F formed from 1A–F in the next step. Reduction to Primary Phosphines With the desired Ar2P2S4 compounds in hand, the next step was to reduce these with LiAlH4 (4 equiv of LiAlH4 per Ar2P2S4 were used) to the corresponding primary phosphines ArPH2 (2A–F). Both Ar2P2S4 and LiAlH4 were suspended in Et2O, and the two suspensions were added together slowly at 0 °C. The resulting suspension was filtered, degassed water was added, and the mixture was filtered a second time. In both filtrations, efficient washing of the solid on the filter was essential to achieve good yields. The filtrate and washings were collected, and the volatiles were removed in vacuo to yield the desired primary phosphines. No further purification was performed, and phosphines 2A–D were obtained in good purity and reasonable yields (33–52%). The naphthalene species 2F was obtained in 8% yield only and small amount of naphthalene (formed in the reduction step rather than carried over from previous step) was present, as shown by 1H NMR analysis. Also, the reduc- tion of 1E led to partial cleavage of the C–P bond, with small amounts of fluorene being detected by 1H NMR analysis alongside the major product 2E. Despite this, both 2E and 2F were of sufficient purity for further synthetic use and were used as obtained in the preparations of respective dichlorophosphines as described below. Other reducing reagents (NaH and NaBH4) were tested for the reduction of 2A–F; however, no phosphine was produced even at elevated temperatures in ethereal solvents. Interestingly, of the six primary phosphine compounds synthesised in this work, only two have been previously reported in the literature (2A and 2F),27,28 demonstrating the ability of this synthetic route to provide access to a wider range of primary phosphines. Despite the lack of steric bulk protection, phosphines 2E and 2F showed remarkable stability in air in both the solid state and in solution, with minimal oxidation observed. This enhanced stability to oxidation could be due to the conjugated aromatic system of naphthalene and fluorene, as the additional conjugation has been shown to stabilise primary phosphines against oxidation.27,29 Analysis via 31P{1H} NMR spectroscopy showed 2A–F to display low-frequency singlets within a very narrow shift range of –121.9 to –126.4 ppm (Table 1); these split into triplets of triplets in the 31P NMR spectra with 1JPH Table 1 Isolated Yields, Purity and 31P{1H} Chemical Shifts of Synthesised Perthiophosphonates 1A–F, Primary Phosphines 2A–F and Dichlorophosphines 3A–F Ar 1 (Ar2P2S4) Yield (%) 2 (ArPH2) 3 (ArPCl2) a Yield [purity] (%) P (ppm) Yield [purity]a (%) P (ppm) p-MeOC6H4 A 65 51 [97] –126.4 74 [90] 162.0 p-EtOC6H4 B 57 52 [92] –125.9 81 [92] 160.5 3-tBu-4-MeOC6H3 C 60 33 [94] –125.3 82 [92] 163.6 p-PhOC6H4 D 47 36 [87] –122.9 90 [90] 162.7 2-Fluorenyl E 94 33 [97] –121.9 78 [93] 160.1 1-Naphthyl F 31 8 [86] –126.1 46 [92] 161.8 a Purity as assessed by 31P{1H} NMR analysis. Synthesis 2023, 55, A–H D Synthesis Special Topic D. Picthall et al. of 199–202 Hz as expected. The purity of the products was further assessed by 1H and 13C{1H} NMR analysis. In addition to multinuclear NMR spectroscopy, the novel compounds 2B–E were characterised by MS analysis. The spectroscopic data obtained by us for the previously reported species (2A and 2F) were in agreement with the literature (see Experimental Section). For 2B, 2D and 2F, minor impurities were observed in the 31P{1H} spectra as two singlets at approximately P –70 ppm (2–4% of integral intensity). These were assigned as the respective diphosphines ArP(H)–P(H)Ar, which, due to the presence of two chiral P atoms, exist in two diastereomeric forms (meso and rac).30 In the 31P NMR spectra, these minor signals split into symmetrical multiplets with pattern consistent with a AA′XX′ spin system (A, A′ = P, X, X′ = H). Spin system simulations were carried out to replicate the observed splitting pattern for selected examples (Figure 1).31 These simulations yielded 1JPP =150 Hz, 1JPH = 150 Hz and 2JPH = 10 Hz for one of the diastereomers of ArP(H)P(H)Ar (Ar = p-EtOC6H4), which is fully consistent with the suggested diphosphine structure. Note the contribution of the ortho protons from the aryl groups has been omitted from the simulated spectrum due to the extra complexity this presents. The diphosphine impurities presented no issues for the subsequent chlorination step as they were present in very small amounts and were converted into the same end product (ArPCl2) on chlorination. Hence, no attempt was made to remove these through further purification. Chlorination to Dichlorophosphines In the last step of the synthetic sequence shown in Scheme 4, the primary phosphines 2A–F were chlorinated to the aryldichlorophosphines 3A–F. A commercially available solution of phosgene in toluene (slight excess, 2.1 equiv) was added slowly, at –10 °C, to the solution of primary phosphine. The reaction mixture was left to stir overnight and subsequent removal of the volatiles in vacuo afforded 3A–F. The dichlorophosphines were isolated in yields of 74–90% and were obtained as oils, except for 3F, which was isolated in 46% yield as an off-white solid. The 31 P{1H} spectra of 3A–F were as expected (singlets within a narrow range of P 160–164 ppm) and showed that all the primary phosphine starting material had been consumed during the chlorination step, with no other phosphoruscontaining species present. The purity of the products was further confirmed by 1H and 13C{1H} NMR analysis, which indicated some fluorene was present in the sample of 3E, whilst the purity of the other samples was very good. This represents a marked improvement on previously reported methods, where vacuum distillation was required as a final purification step. Stoichiometric amount of triphosgene was used as an alternative chlorinating reagent at room temperature for selected examples of primary phosphines, giving full conversion into the respective dichlorophosphines as judged by 31P{1H} NMR analysis. Syntheses of 3B–E have not been reported previously. In addition to multinuclear NMR spectroscopy (as discussed above) the compounds were also characterised by MS analysis. The spectroscopic data obtained by us for previously reported species (3A and 3F) agreed with the literature (see experimental section). In summary, a multigram synthesis of a series of primary arylphosphines and aryldichlorophosphines has been reported. All steps use convenient, commercially available, and economical reagents. Each step requires minimum purification, which is of importance due to the highly reactive Figure 1 Top: Partial 31P NMR spectrum of diphosphine ArP(H)-P(H)Ar (Ar = p-EtOC6H4) present as minor impurity in p-EtOC6H4PH2 (2B). Bottom: simulated 31P NMR spectrum. Synthesis 2023, 55, A–H E Synthesis Special Topic D. Picthall et al. nature of both compound types. The initial step (formation of perthiophosphonic anhydrides) proceeds highly regiospecifically, and the nature of subsequent steps means multiple substitution is avoided, hence employing protection and subsequent deprotection strategies is not required. Future work will look to further extend the scope of this reaction to other R2P2S4 compounds. Belleau’s Reagent (4-PhOC6H4)2P2S4 (1D) 1D was synthesised according to a reported literature procedure.21 Diphenyl ether (57.4 g, 337 mmol) and P4S10 (15.0 g, 33.7 mmol) were heated under reflux at 180 °C for 3 hours. The liquid mixture was cooled to r.t. to afford an off-white solid. The solid was isolated by filtration, washed with ether (3 × 50 mL) and dried in vacuo. Yield: 16.6 g (31.4 mmol, 47%). Flu2P2S4, Flu = 9H-fluoren-2-yl, (1E) All manipulations (unless indicated otherwise) were performed under an atmosphere of nitrogen using standard Schlenk line techniques or under an atmosphere of argon in a Saffron glove box. Diethyl ether and dichloromethane (DCM) were collected from an MBraun solvent purification system and stored over activated 4Å molecular sieves. 2tert-Butylanisole was prepared according to a literature method;32 all other reagents were commercially available. All new compounds were characterised via 1H, 31P{1H} and 13C{1H} NMR spectroscopy including the measurement of H–H COSY, H–C HSQC, H–C HMBC, and H–P HMBC. 13C NMR spectra were recorded using the DEPT-Q pulse sequence. All spectra were recorded at 25 °C with either a Bruker Avance III (500 MHz) spectrometer or a Bruker Avance II (400 MHz) spectrometer. In vacuo refers to pressure of ca. 0.01–0.1 mbar. MS were acquired with a Micromass LCT (electrospray ionisation) from solutions of the analyte in methanol. Fluorene (28.6 g, 172 mmol) and P4S10 (10.0 g, 22.4 mmol) were heated under reflux at 190 °C for 4 hours. The liquid mixture was then allowed to cool to r.t., giving a solid clump. DCM (30 mL) was added to form suspension after stirring. The pale-yellow solid 1E was filtered off, washed with DCM (2 × 20 mL) and dried in vacuo. Yield: 21.9 g (42 mmol, 94%); mp 232–234 °C MS (EI+): m/z (%) = 259.98 (100) [M/2]+. MS (CI+): m/z (%) = 261.0 (100) [M/2 + H]+, 520.98 (85) [M + H]+. HRMS (CI+): m/z calcd for C26H19P2S4 [M + H]+ 520.9839; found: 520.9835 IR (KBr): 1610m (C=C), 1446m (C-H), 835m, 770m, 693s (P=S) cm–1. Raman (sealed capillary): 3020w (Ar–H), 2906w (C–H), 1606s (C=C), 1480w (C=C), 703m (P=S) cm–1. Nap2P2S4, Nap = naphth-2-yl, (1F) Synthesis of Perthiophosphonic Anhydrides 1A–F All syntheses in this section were performed under a gentle stream of nitrogen, and the exhaust gasses were bubbled through aqueous NaOH solution to remove H2S formed as a by-product. The subsequent workup was performed in air (in a well ventilated fumehood). Lawesson’s Reagent, (4-MeO-C6H4)2P2S4 (1A) 1A was synthesised according to a reported literature procedure.20 Anisole (48.7 g, 450 mmol) and P4S10 (20.0 g, 45.0 mmol) were heated under reflux at 150 °C for 5 hours. The liquid mixture was allowed to cool to r.t. and a pale-yellow crystalline solid precipitated out, which was isolated by vacuum filtration. The solid was washed with ether (2 × 25 mL) and dried in vacuo. Yield: 23.6 g (58.4 mmol, 65%). (4-EtOC6H4)2P2S4 (1B) 1B was synthesised by adapting a reported literature procedure.20 Phenetole (22.0 g, 180 mmol) and P4S10 (10.0 g, 22.5 mmol) were heated under reflux to 165 °C for 2 hours. The liquid mixture was allowed to cool to r.t. Upon cooling, an off-white solid precipitated. The solid 1B was filtered off, washed with ether (2 × 30 mL) and dried in vacuo. 1F was synthesised by adapting a reported literature procedure.20 Naphthalene (27.7 g, 216 mmol) and P4S10 (12.0 g, 27 mmol) were heated to 190 °C under reflux for 3 hours. The liquid mixture was allowed to cool slowly to r.t., at which point a yellow solid began to precipitate. The solid 1F was filtered off, washed with DCM (3 × 20 mL) and dried in vacuo. Yield: 7.51 g (16.9 mmol, 31%). General Procedure for the Synthesis of Primary Phosphines (2A–F) The respective perthiophosphonic anhydride 1A–F was suspended in diethyl ether (150 mL) and cooled to 0 °C. A suspension of LiAlH4 (4 equiv) in ether (50 mL) was added in small portions with vigorous stirring. The resulting mixture was stirred for 1 hour at 0 °C. The mixture was then filtered to remove the insoluble solids, which were washed with ether (2 × 10 mL). The filtrate and washings were collected, cooled to 0 °C and degassed water (2 mL) was added cautiously dropwise. The resulting suspension was filtered again to remove the insoluble solids that had formed, and the solid on the filter was washed with DCM (2 × 20 mL). The filtrate and washings were collected, and the volatiles were removed in vacuo to yield the desired primary phosphines 2A–F. Yield: 11.2 g (25.9 mmol, 57%). 4-Methoxyphenylphosphine (2A) (3-tBu-4-MeOC6H3)2P2S4 (1C) Starting from 1A (6.00 g, 14.8 mmol), 2A was isolated as a colourless oil (2.12 g, 15.1 mmol, 51%). 1C was synthesised according to a reported literature procedure.22 2tert-Butylanisole (27.0 g, 164 mmol) and P4S10 (10.0 g, 22.5 mmol) were combined and heated to 180 °C with stirring for 1 hour. The solution was then allowed to cool to r.t. A crystalline pale-yellow solid precipitated out of solution, which was collected by vacuum filtration, washed with ether (50 mL) and dried in vacuo. 1 H NMR (400.1 MHz, C6D6):  = 7.28–7.23 (2 H, m, H2PCCH), 6.62 (2 H, m, 3JHH = 8.6 Hz, OCCH), 3.90 (2 H, d, 1JHP = 198.9 Hz, PH2), 3.22 (3 H, s, CH3). 31 P{1H} NMR (162.0 MHz, C6D6):  = –126.4 (s). 31 P NMR (162.0 MHz, C6D6):  = –126.4 (tt, 1JPH = 199.0 Hz, 4JPH = 7.0 Hz). Yield: 13.9 g (26.9 mmol, 60%). Synthesis 2023, 55, A–H F Synthesis Special Topic D. Picthall et al. 13 C{1H} NMR (100.6 MHz, C6D6):  = 160.2 (s, MeOC), 136.5 (d, 2JCP = 17.4 Hz, H2PCCH), 118.1 (d, 1JCP = 5.8 Hz, H2PC), 114.1 (d, 3JCP = 6.9 Hz, OCCH), 54.1 (s, H3CO). 9H-Fluoren-2-ylphosphine (2E) MS (ESI): m/z (%) = 335.06 (35) [((CH3OC6H4PH2O)2Na)+], 179.02 (90) [(CH3OC6H4PH2ONa)+], 157.04 (100) [(CH3OC6H4PH2OH)+], 141.05 (5) [(C7H10OP)+, (M + H)+] Mp 86–88 °C Compound 2A has been reported previously28 but no characterisation data were provided. 4-Ethoxyphenylphosphine (2B) Starting from 1B (8.00 g, 18.5 mmol), 2B was isolated as a clear colourless oil (1.77 g, 5.83 mmol, 52%). 1 H NMR (400.1 MHz, C6D6): 7.30–7.24 (2 H, m, PCCH), 6.64 (2 H, m, JHH = 7.8 Hz, OCCH), 3.89 (2 H, d, 1JHP = 198.9 Hz, PH2), 3.53 (2 H, q, 3 JHH = 7.0 Hz, CH2), 1.09 (3 H, t, 3JHH = 6.9 Hz, CH3). 3 31 P{1H} NMR (162.0 MHz, C6D6):  = –126.1 (s). 31 P NMR (162.0 MHz, C6D6):  = –126.1 (tt, 1JPH = 198.8 Hz, 4JPH = 6.8 Hz). 13 C{1H} NMR (100.6 MHz, C6D6):  = 159.6 (s, qC), 136.7 (d, 2JCP = 17.4 Hz, H2PCCH), 117.9 (d, 1JCP = 5.5 Hz, qC), 114.7 (d, 3JCP = 6.9 Hz, OCCH), 62.8 (s, CH2), 14.4 (s, H3C). MS (ESI): m/z (%) = 363.09 (25) [((C2H5OC6H4PH2O)2Na)+], 193.04 (35) [(C2H5OC6H4PH2ONa)+], 171.06 (100) [(C2H5OC6H4PH2OH)+], 155.06 (5) [(C8H12OP)+, (M + H)+]. Starting from 1C (8.00 g, 15.4 mmol), 2C was isolated as a clear colourless oil (2.00 g, 10.2 mmol, 33%) 1 H NMR (400.1 MHz, C6D6):  = 7.58–7.52 (1 H, m, Ar-H) 7.31–7.24 (1 H, m, Ar-H) 6.44–6.41 (1 H, m, Ar-H) 4.01 (2 H, d, 1JHP = 198.0 Hz, PH2) 3.22 (3 H, s, OCH3) 1.41 (9 H, s, C(CH3)3). P{1H} NMR (162.0 MHz, C6D6):  = –125.3 (s). 31 1 1 H NMR (400.1 MHz, C6D6):  = 7.66–7.54 (1 H, m, Ar-H), 7.49–7.10 (6 H, m, Ar-H), 3.96 (2 H, d, 1JHP = 198.7 Hz, PH2), 3.38 (2 H, s, CH2). 31 3 P NMR (162.0 MHz, C6D6):  = –125.3 (tt, JPH = 198.6 Hz, JPH = 7.7 Hz). 13 C{1H} NMR (125.8 MHz, C6D6):  = 159.1 (s, H3COC), 138.1 (d, 3JCP = 6.3 Hz, C-tBu), 134.5 (d, 2JCP = 18.2 Hz, MeOCHCH), 133.8 (d, 2JCP = 16.9 Hz, tBuCCH), 117.8 (d, 1JCP = 5.0 Hz, H2PC), 111.8 (d, 3JCP = 7.8 Hz, H3COCCH), 54.2 (s, H3C-O), 34.7 (s, C(CH3)3), 29.2 (s, C(CH3)3). MS (ESI): m/z (%) = 431.21 (100) [((MeO)(tBu)C6H3P)((HO)(tBu)C6H3P)(OH)2+Na+], 251.14 (10) [(MeO)(tBu)C6H3P(=O)(OH)H+Na+], 213.10 (20) [(MeO)(tBu)C6H3P(=O)H2+H+]. P{1H} NMR (162.0 MHz, C6D6):  = –122.9 (s). 31 P NMR (162.0 MHz, C6D6):  = –122.9 (tt, 1JPH = 199.0 Hz, 4JPH = 7.1 Hz). 13 C{1H} NMR (100.6 MHz, C6D6):  = 143.4 (d, 3JCP = 6.6 Hz, qC), 143.1 (s, qC), 141.9 (s, qC), 141.3 (s, qC), 133.2 (d, 2JCP = 17.0 Hz, H2PCCH), 131.5 (d, 2JCP = 15.8 Hz, H2PCCH), 126.9 (s, CH), 126.7 (s, CH), 126.1 (d, 1 JCP = 7.5 Hz, H2PC), 124.9 (s, CH), 120.0 (s, CH), 119.7 (d, 3JCP = 7.0 Hz, H2PCCHCH), 36.3 (s, CH2). MS (ESI): m/z (%) = 451.10 (44) [((C6H4CH2C6H3PH2O)2Na)+], 237.04 (52) [(C6H4CH2C6H3PH2ONa)+], 215.06 (100) [(C6H4CH2C6H3PH2OH)+]. Naphthalen-2-ylphosphine (2F) Starting from 1F (7.20 g, 16.2 mmol), 2F was isolated as an off-white solid (400 mg, 2.50 mmol, 8%) Mp 66–68 °C. 1 H NMR (400.1 MHz, CDCl3):  = 7.80–7.74 (1 H, m, Ar-H), 7.57–7.37 (3 H, m, Ar-H), 7.34–7.18 (3 H, m, Ar-H), 3.95 (2 H, d, 1JHP = 202.4 Hz, PH2). 31 3-t-Butyl-4-methoxyphenylphosphine (2C) 31 Starting from 1E (6.00 g, 11.5 mmol), 2E was isolated as a white solid (1.50 g, 7.56 mmol, 33%). P{1H} NMR (162.0 MHz, CDCl3):  = –121.9 (s). 31 P NMR (162.0 MHz, CDCl3):  = –121.9 (1 H, tt, 1JPH = 202.3 Hz, 4JPH = 7.1 Hz). Values are in agreement with literature data.27 General Procedure for the Synthesis of Dichlorophosphines 3A–F The respective primary phosphine (2A–F) was dissolved in DCM (150 mL) and cooled to –10 °C. A solution of phosgene (20% solution in toluene, 2.1 equiv) was added dropwise over 30 minutes. The resulting solution was allowed to warm to r.t. and stirred for a further 5 hours. The volatiles were removed in vacuo to yield the desired dichlorophosphine 3A–F. Safety note: Phosgene and carbon monoxide (evolved in the chlorination reaction) are highly toxic, use of a well-ventilated fumehood is essential for this step. Dichloro(4-methoxyphenyl)phosphine (3A) 4-Phenoxyphenylphosphine (2D) Starting from 2A (2.00 g, 14.3 mmol), 3A was isolated as a yellow oil (2.22 g, 10.6 mmol, 74%). Starting from 1D (8.00 g, 15.1 mmol), 2D was isolated as a colourless oil (2.22 g, 11.0 mmol, 36%). 1 3 1 H NMR (400.1 MHz, C6D6):  = 7.19–7.11 (2 H, m, Ar-H), 7.08–6.98 (2 H, m, Ar-H), 6.97–6.65 (5 H, m, Ar-H), 4.02 (2 H, d, 1JHP = 202.4 Hz, PH2). 31 P{1H} NMR (162.0 MHz, C6D6):  = –125.9 (s). 31 P NMR (162.0 MHz, C6D6):  = –125.8 (tt, 1JPH = 199.0 Hz, 4JPH = 7.0 Hz). 13 C{1H} NMR (100.6 MHz, C6D6):  = 157.9 (s, qC), 157.1 (s, qC), 136.6 (d, 3JCP = 16.8 Hz, PCCHCH), 129.8 (s, CH), 123.4 (s, CH), 121.8 (d, 1JCP = 8.1 Hz, H2PC), 119.1 (s, CH), 118.8 (d, 2JCP = 6.7 Hz, H2PCCH). MS (ESI): m/z (%) = 459.09 (58) [((C6H5OC6H4PH2O)2Na)+], 241.04 (74) [(C6H5OC6H4PH2ONa)+], 219.06 (100) [(C6H5OC6H4PH2OH)+]. H NMR (400.1 MHz, C6D6):  = 7.54–7.49 (2 H, m, Ar-H), 6.50 (2 H, m, JHH = 8.7 Hz, Ar-H), 3.08 (3 H, s, CH3). 31 P{1H} NMR (162.0 MHz, C6D6):  = 162.0 (s). All values are in agreement with literature data.13 Dichloro(4-ethoxyphenyl)phosphine (3B) Starting from 2B (1.50 g, 9.73 mmol), 3B was isolated as a pale-yellow oil (2.19 g, 3.68 mmol, 81%). 1 H NMR (400.1 MHz, C6D6):  = 7.52 (2 H, m, Ar-H), 6.54 (2 H, d, 3JHH = 7.3 Hz, Ar-H), 3.39 (2 H, q, 3JHH = 7.0 Hz, CH2), 1.00 (3 H, t, 3JHH = 7.0 Hz, CH3). 31 P{1H} NMR (162.0 MHz, C6D6):  = 162.3 (s). Synthesis 2023, 55, A–H G Synthesis Special Topic D. Picthall et al. 13 C{1H} NMR (100.6 MHz, C6D6):  = 162.7 (s, qC), 132.1 (d, 2JCP = 34.2 Hz, PCCH), 131.5 (d, 1JCP = 50.9 Hz, qC), 114.4 (d, 3JCP = 9.8 Hz, OCCH), 63.7 (s, CH2), 14.1 (s, H3C). MS (ESI): m/z (%) = 249.07 (100) [(C2H5OC6H4PCl(OMe)2)+], 201.07 (6) [(C2H5OC6H4POMeOH2)+]. Dichloro(3-tert-butyl-4-methoxyphenyl)phosphine (3C) Starting from 2C (2.00 g, 10.2 mmol), 3C was isolated as a pale-yellow oil (2.20 g, 8.30 mmol, 82%). 1 Conflict of Interest The authors declare no conflict of interest. Funding Information The authors acknowledge EastChem School of Chemistry for funding. EastChemScholfChemistry() H NMR (400.1 MHz, C6D6):  = 7.92–7.78 (2 H, m, Ar-H), 7.05–7.00 (1 H, m, Ar-H), 3.96 (3 H, s, CH3), 1.47 (9 H, s, C(CH3)3). Supporting Information 31 Supporting information for this article is available online at https://doi.org/10.1055/a-1994-2301. Data Availability Statement: The research data (NMR and MS data) supporting this publication can be accessed at https://doi.org/10.17630/29cff64a-cb08-48ab-b2fd-edd2284d9df5 P{1H} NMR (162.0 MHz, C6D6):  = 163.6 (s). 13 C{1H} NMR (100.6 MHz, C6D6):  = 162.1 (s, H3COC), 138.7 (d, 3JCP = 8.9 Hz, C-tBu), 131.3 (d, 1JCP = 50.6 Hz, Cl2PC), 130.3 (d, 2JCP = 34.5 Hz, MeOCHCH), 128.8 (d, 2JCP = 35.0 Hz, tBuCCH), 111.6 (d, 3JCP = 10.1 Hz, H3COCCH), 54.3 (s, H3CO), 35.2 (s, C(CH3)3), 28.9 (s, C(CH3)3). MS (ESI): m/z (%) = 273.13 (14) [(MeO)(tBu)C6H3P(O)(OMe)2+H+], 243.11 (100) 257.13 (32) [(MeO)(tBu)C6H3P(OMe)2+H+], [(MeO)(tBu)C6H3P(OH)(OMe)+H+]. Dichloro(4-phenoxyphenyl)phosphine (3D) Starting from 2D (2.22 g, 11.0 mmol), 3D was isolated as a pale-yellow oil (2.67 g, 9.89 mmol, 90%). 1 H NMR (400.1 MHz, C6D6):  = 7.51–7.38 (1 H, m, Ar-H), 7.09–6.50 (8 H, m, Ar-H). 31 P{1H} NMR (162.0 MHz, C6D6):  = 160.5 (s). 13 C{1H} NMR (100.6 MHz, C6D6):  = 161.6 (s, qC), 155.4 (s, qC), 133.7 (d, 1JCP = 51.8 Hz, PC), 132.3 (d, 2JCP = 33.8 Hz, PCCH), 129.9 (s, CH), 124.4 (s, CH), 120.1 (s, CH), 117.7 (d, 3JCP = 9.1 Hz, OCCH). MS (ESI): m/z (%) = 401.13 (7) [((C6H5OC6H4P)2H)+], 201.07 (100) [(C6H5OC6H4PH)+]. Dichloro(9H-fluoren-2-yl)phosphine (3E) Starting from 2E (2.20 g, 11.1 mmol), 3E was isolated as an off-white solid (2.32 g, 8.68 mmol, 78%). Mp 66–68 °C. 1 H NMR (400.1 MHz, C6D6):  = 7.75–7.57 (2 H, m, Ar-H), 7.53–7.33 (2 H, m, Ar-H), 7.30–7.08 (3 H, m, Ar-H), 3.27 (2 H, s, CH2). 31 P{1H} NMR (162.0 MHz, C6D6):  = 162.7 (s). 13 C{1H} NMR (100.6 MHz, CDCl3) 146.5 (s, qC), 143.8 (d, 3JCP = 8.2 Hz, qC), 143.2 (s, qC), 141.7 (s, qC), 138.2 (d, 1JCP = 52.0 Hz, Cl2PC), 129.3 (d, 2JCP = 37.9 Hz, Cl2PCCH), 128.3 (s, CH), 127.1 (s, CH), 126.7 (d, 2JCP = 28.4 Hz, Cl2PCCH), 125.3 (s, CH), 120.9 (s, CH), 120.0 (d, 3JCP = 10.1 Hz, Cl2PCCHCH), 36.9 (s, CH2). MS (ESI): m/z (%) = 281.07 (36) [(C6H4CH2C6H3P(OMe)2Na)+], 259.09 (58) [(C6H4CH2C6H3P(OMe)2H)+], 245.07 (100) [(C6H4CH2C6H3P(OMe)OH2)+]. Dichloro(naphthalene-2-yl)phosphine (3F) Starting from 2F (383 mg, 2.39 mmol), 3F was isolated as a pale-yellow solid (250 mg, 1.09 mmol, 46%). 1 H NMR (300.1 MHz, C6D6):  = 7.95–7.70 (1 H, m, Ar-H) 7.56–6.89 (6 H, m, Ar-H). 31 P{1H} NMR (121.5 MHz, C6D6):  = 160.1 (s). 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