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. 2023 Mar 20;8(13):12565–12572. doi: 10.1021/acsomega.3c00885

Protonation of P-Stereogenic Phosphiranes: Phospholane Formation via Ring Opening and C–H Activation

Ryan M Tipker 1, Jake A Muldoon 1, Jacob Jo 1, Christopher S Connors 1, Balazs R Varga 1, Russell P Hughes 1,*, David S Glueck 1,*
PMCID: PMC10077540  PMID: 37033828

Abstract

graphic file with name ao3c00885_0009.jpg

Protonation of cyclopropanes and aziridines is well-studied, but reactions of phosphiranes with acids are rare and have not been reported to result in ring opening. Treatment of syn-Mes*PCH2CHR (Mes* = 2,4,6-(t-Bu)3C6H2, R = Me or Ph, syn-1-2) or anti-Mes*PCH2CHPh (anti-2) with triflic acid resulted in regiospecific anti-Markovnikov C-protonation with ring opening and cyclophosphination of a Mes* ortho-t-Bu group to yield the phospholanium cations [PH(CH2CH2R)(4,6-(t-Bu)2-2-CMe2CH2C6H2)][OTf] (R = Me or Ph, 3–4), which were deprotonated with NEt3 to give phospholanes 5–6. Enantioenriched or racemic syn-1 both gave racemic 3. The byproduct [Mes*PH(CH2CH2Me)(OH)][OTf] (7) was formed from syn-1 and HOTf in the presence of water. Density functional theory calculations suggested that P-protonation followed by ring opening and hydride migration to C yields the phosphenium ion, [Mes*P(CH2CH2Me)][OTf], which undergoes C–H oxidative addition of an o-t-Bu methyl group. This work established a new reactivity pattern for phosphiranes.

Introduction

Like the isoelectronic epoxides and aziridines,1 phosphiranes are potentially useful as “spring-loaded” building blocks2 in organophosphorus chemistry because of their strained three-membered rings. P-quaternization increases the strain further,3 promoting ring opening, but coordination of Lewis or Brønsted acids to phosphiranes is limited by their low Lewis basicity and proton affinity.4 In contrast to other phosphines, phosphiranes do not readily form adducts with BH3,5 and P-methylation requires the highly reactive electrophile methyl triflate.6 Similarly, protonation of phosphiranes has until recently only been observed in the gas phase, where the parent P–H phosphiranium cation [C2H4PH2]+ has been observed by mass spectrometry7 and studied computationally.8

As models for possible condensed-phase examples of phosphirane protonation,9Scheme 1 shows some reactions of three-membered rings with acids bearing a weakly coordinating anion X–. Aziridine N-protonation yields aziridinium salts.10 Cyclopropane protonation usually occurs with Markovnikov selectivity at the least substituted carbon, with C–C cleavage and ring opening generating the most stable carbocation,11 as shown for 1,1,2-trimethylcyclopropane.12 Phosphirane P-protonation would yield a P–H phosphiranium cation (route A), as with aziridines or in P-methylation with MeOTf (B). Alternatively, C-protonation might occur at the carbon with less (C) or more (D) substitution, yielding branched or linear P-substituents after ring opening with P–C cleavage to yield phosphenium ion intermediates. Instead, C-protonation followed by breaking the C–C bond could form isomeric phosphines with a carbocation substituent (E or F). However, the relative Pauling electronegativities of P and C (2.19 and 2.55) and the observation that C–C bonds are usually stronger than P–C bonds suggest that these products are unlikely.13

Scheme 1. Protonation of Aziridines and a Cyclopropane, and Possible Pathways for Phosphirane Protonation.

Scheme 1

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Finally, protonation of a phosphirane bearing a good leaving group gave a P–H bond and left the ring intact (G),14 suggesting that acid treatment of a substrate without a leaving group would yield a P–H phosphiranium cation (route A, Scheme 1), which might undergo further reactions. To test this hypothesis, we investigated phosphiranes 1–2,15 which were readily methylated with MeOTf (route B, Schemes 1 and 2),6h expecting formation of P–H phosphiranium cations (route A, Schemes 1 and 2) upon treatment with HOTf.

Scheme 2. Methylation of Phosphiranes 1–2 with MeOTf (Route B) Gave P-Me Phosphiranium Cations, So Protonation with HOTf (Route A) Was Expected To Yield P–H Phosphiranium Cations.

Scheme 2

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Although protonation of 1–2 with triflic acid occurred under very mild conditions, cations from route A were not observed. Instead, in a new type of reaction for this functional group, phosphirane ring opening and C–H activation of a t-butyl group resulted in formation of a five-membered phospholane ring in 3–4 (Scheme 3). From the results of varying phosphirane regiochemistry (syn vs anti) and stereochemistry (enantiomerically enriched vs racemic), isotopic labeling, and density functional theory (DFT) calculations, we propose a mechanism for this process via a combination of pathways A and D (Scheme 1), with initial P-protonation followed by ring opening and hydride migration to the more substituted carbon to yield a highly reactive phosphenium ion intermediate, which undergoes oxidative addition of C–H or O–H bonds.

Scheme 3. Phosphirane Protonation with Triflic Acid Gave Cyclophosphinated Phospholanium Cations 3–4.

Scheme 3

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Reaction of 1 with DOTf gave 3-D with a P-CH2CHDMe group. Minor byproduct 7 formed from syn-1 and HOTf in the presence of water and was identified by independent synthesis

Results and Discussion

Treatment of racemic syn-Mes*PCH2CHMe (syn-1, Mes* = 2,4,6-(t-Bu)3C6H2) or either diastereomer of racemic Mes*PCH2CHPh (syn-2 and anti-2) with triflic acid in pentane gave the cyclophosphinated phospholanium cations [PH(CH2CH2R)(4,6-(t-Bu)2-2-CMe2CH2C6H2)][OTf] (R = Me (3); R = Ph (4)), resulting from apparent anti-Markovnikov protonation at C (route D, Scheme 1) and C–H activation of a Mes* ortho-t-Bu group (Scheme 3). These reactions occurred in minutes at room temperature. Treatment of syn-1 with DOTf gave 3-D bearing a CH2CHDMe group, demonstrating deuteration at the CHMe ring carbon. Although 3-D should exist as a mixture of diastereomers, the same single sets of signals were observed by nuclear magnetic resonance (NMR) spectroscopy when racemic or enantiomerically enriched 1 was used. Because of their high solubility, isolation of pure cations 3–4 was difficult, but deprotonation with NEt3 gave phospholanes 5–6, which could be purified by chromatography on silica.16 Treatment of 5–6 with triflic acid regenerated cations 3–4.

When water was not rigorously excluded, phosphirane protonation gave a minor byproduct, which was identified in the reaction of 1 as the protonated secondary phosphine oxide (SPO)17 [Mes*P(H)(OH)(CH2CH2Me)][OTf] (7, Scheme 3).18 Treatment of the 3–7 mixture with NEt3 gave phospholane 5 and SPO 8, which were separated by chromatography on silica.19 The structure of 8 was confirmed by independent synthesis via hydrolysis of the chlorophosphine Mes*P(n-Pr)(Cl). Separate treatment of 8 with triflic acid regenerated cation 7.

The stereochemistry of phosphirane-to-phospholanium ring expansion was investigated using enantiomerically enriched syn-1. After deprotonation of 3, coordination of the resulting phospholane 5 to a chiral Pd-amine complex gave a 1:1 mixture of diastereomeric Pd complexes 9, as also observed for racemic 1.20 Thus, the reaction of phosphirane 1 with triflic acid destroyed both its P- and C-stereocenters to give racemic 5 (via 3) with no chirality transfer (Scheme 4).

Scheme 4. Protonation of Enantiomerically Enriched or Racemic Phosphirane syn-1 Gave Racemic Phospholanium Cation 3, As Shown by Complexation of 5 to a Chiral Pd–Amine Complex.

Scheme 4

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P-stereogenic phosphiranes 1–2 and their analogues are potentially useful in asymmetric synthesis because they can be prepared in high enantiomeric purity from commercially available chiral epoxides.15 Because protonation demolished their valuable stereocenters, applications of this reaction are severely limited, so we did not further investigate its scope. Instead, to better understand why phosphirane methylation and protonation led to different results (routes A and B, Scheme 2), we investigated potential mechanisms of phosphirane protonation by DFT calculations.

Scheme 5 shows a proposed reaction mechanism, which is consistent with the experimental observations and with DFT calculations. As in the known aziridine N-protonation and phosphirane P-methylation, reaction with acid initially results in P-protonation to yield phosphiranium cation 10. P–C cleavage and ring opening then yields secondary carbocation 11, which is preferred over primary carbocation 12. Hydride migration from the secondary phosphine to the pendant carbocation, which is precedented by intermolecular examples of hydride abstraction from primary or secondary phosphines by the trityl cation or related Lewis acids,21 then yields phosphenium ion 13.22 This reactive intermediate could undergo intermolecular O–H activation of water to yield byproduct 7,18 in competition with intramolecular C–H activation of an ortho t-Bu group to give cations 3–4. Such cyclophosphination is a common process in Mes*P chemistry, as with the phosphenium ion [Mes*PSMes*]+,23 and in protonation of the phosphaalkene Mes*P=CH2, which yielded a phospholanium cation similar to 3–4, via the proposed phosphenium intermediate [Mes*PCH3][OTf].24

Scheme 5. Proposed Mechanism of Ring Opening and Phospholanium Ion Formation via Phosphirane Protonation.

Scheme 5

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We proposed protonated phosphiranes 10 as intermediates in the synthesis of phosphiranes 1–2, where cyclophosphination was not observed.15 The explanation of this apparent contradiction lies in the anion. In phosphirane synthesis, tosylate can apparently deprotonate 10 to give 1–2. In phosphirane protonation, however, the weaker base triflate cannot deprotonate 10, enabling formation of 11 and further steps in the sequence.

Notably, we also proposed reversible formation of cations like 11, which contained PMe(Mes*) instead of PHMes*, in the isomerization of the P-Me phosphiranium cations [Mes*P(Me)CH2CHPh][OTf], where, again, cyclophosphination did not occur.6h This is consistent with a greater migratory aptitude of H over Me in this system,25 which may help to explain the observation that P-Me phosphiranium cations can be isolated,6 while P–H analogues like 10 remain unknown in solution.

Since no intermediates could be observed experimentally in these reactions, the free energy landscape was explored using DFT (B3LYP-D3/6-311G**++). Full details of all calculations and structures are provided in the Supporting Information (SI). No solvent correction was utilized since the reactions occur in pentane. The calculated pathways are shown in Scheme 6, starting from P–H phosphiranium cation 10 (R = Me) formed by protonation of syn-1. The pathway 10 → 11 → 13 is strongly favored over the alternative pathway via 12 to give the isopropyl isomer of 13, consistent with the deuteration experiments and the observed regiospecificity. Intermediates 11 and 12 could be formed directly by edge-protonation of the P–C bonds, but all attempts to model such direct pathways from syn-1 in silico led to formation of 10.

Scheme 6. DFT-Calculated (B3LYP-D3/6-311G**++) Free Energy Landscape for Rearrangement of Phosphiranium Cation 10.

Scheme 6

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H-atoms on t-Bu groups are omitted for clarity, and the migrating H is shown in green. Free energies are given in kcal/mol relative to compound 10 (0.0).

The secondary carbocation 11 is more stable than its primary analogue 12, as expected, with a significantly lower barrier to its formation. We have shown previously that carbocation 11 and P-methylated analogues are strongly stabilized by hyperconjugation with the β–P–C σ-bond.6h,15 While the activation free energies for the H-migration steps from 11 and 12 are identical (6.1 kcal/mol), the relative stability of 11 and the lower barrier to its formation from 10 provides the lower energy route to 13 in which the original chirality at P and C has been dismantled.

Once formed, phosphenium ion 13 can undergo activation of one of the C–H bonds of an o-t-Bu group via a low-energy transition structure shown in Scheme 7.

Scheme 7. DFT-Calculated (B3LYP-D3/6-311G**++) Free Energy Landscape for C–H Activation in Rearrangement of Phosphenium Cation 13.

Scheme 7

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Most t-Bu H-atoms are omitted for clarity, and the migrating H is shown in green. Free energies are given in kcal/mol relative to compound 10 (Scheme 6: 0.0).

Finally, since these reactions were carried out in pentane it seems clear that triflate anion must be ion-paired with any of the cations in Schemes 6 and 7. These ion pairs have been modeled, but we find no direct role of a triflate interaction with P in any intermediate or transition structure. While triflate does bind to P in product 13, its dissociation is required for CH activation to occur, emphasizing the importance of its reduced nucleophilicity and basicity, compared to tosylate, in the observed rearrangement.

Conclusions

Protonated phosphiranes (P–H phosphiranium cations, route A in Schemes 1 and 2) have not yet been observed in the condensed phase, presumably because their combination of ring strain and a reactive P–H bond results in further transformations. Here, we have reported a new type of reaction for the phosphirane functional group, involving ring opening with P–C cleavage and formation of a new P–C bond by activation of a t-butyl C–H group under mild conditions. These observations emphasize the high reactivity of the strained phosphirane ring in 1–2 and in proposed intermediates P–H phosphiranium cations and phosphenium ion 13(26) and the importance of the nucleophilicity/basicity of the anions in the chemistry of such cations. In comparison to stable N–H aziridinium cations (Scheme 1), the increased P–H phosphiranium cation reactivity may be a consequence of weaker P–H and P–C bonds. As with the cyclopropane protonation in Scheme 1, the proposed mechanism of phosphirane protonation involves formation of the most stable carbocation (11 vs 12) by ring opening.

Experimental Section

Please see the SI for general experimental methods and details of synthesis, characterization, and computational results. Representative procedures are given below.

Reaction of the Racemic Phosphirane syn-Mes*PCH2CHMe (syn-1) with Triflic Acid: Synthesis of Phospholanium Cation 3

To a solution of racemic syn-1 (0.050 g, 0.16 mmol, 1.0 equiv) in anhydrous pentane (5 mL, dried with activated molecular sieves), HOTf (11 μL, 19 mg, 0.13 mmol, 0.8 equiv) was added from a freshly opened bottle in a glovebox under anhydrous conditions. The solution became cloudy, and a yellow oil formed. After 18 h, the oil had disappeared; the pentane was decanted, giving a white solid, which was dried under vacuum (55 mg, 93% yield). Note: this procedure minimized the formation of the byproduct [Mes*P(n-Pr)(H)(OH)][OTf] (7, 31P{1H} NMR δ 37.5; about 4% by integration; see below for independent synthesis and characterization). Additional unidentified impurities were observed by 31P{1H} NMR (δ 71.5) and 1H NMR spectroscopy (δ 6.2) in CDCl3.

HRMS m/z calcd for C21H36P (M+): 319.2555. Found: m/z 319.2550. 31P{1H} NMR (CDCl3): δ 17.8. 31P NMR (CDCl3): δ 17.8 (d, J = 525). 19F{1H} NMR (CDCl3): δ −78.3. 1H NMR (CDCl3): δ 7.94 (br d, J = 522, 1H, PH), 7.61 (dd, J = 6, 2, 1H, Ar), 7.26 (1H, Ar), 3.06–3.00 (m, 1H, phospholane CH2), 2.78–2.71 (m, 1H, PCH2), 2.60 (dd, J = 16, 11, 1H, phospholane CH2), 2.46–2.30 (m, 1H, PCH2), 1.82–1.71 (m, 1H, PCH2CH2), 1.60–1.55 (m, 1H, PCH2CH2), 1.51 (3H, Me), 1.48 (3H, Me), 1.46 (9H, t-Bu), 1.32 (9H, t-Bu), 1.10 (t, J = 7, 3H, PCH2CH2CH3). 13C{1H} NMR (CDCl3): δ 161.5 (quat Mes*), 161.4 (quat Mes*), 160.2 (d, J = 3, quat Ar), 155.2 (d, J = 9, quat Ar), 125.9 (d, J = 10, Mes* CH), 120.5 (q, J = 319, CF3), 120.1 (d, J = 14, Mes* CH), 43.7 (quat CMe2), 37.6 (quat CMe3), 35.7 (quat CMe3), 32.5 (Me), 32.4 (Me), 32.3 (t-Bu Me), 31.0 (t-Bu Me), 30.0 (d, J = 52, phospholane CH2), 25.8 (d, J = 46, PCH2), 16.9 (d, J = 3, PCH2CH2), 15.1 (d, J = 18, PCH2CH2CH3).

Deprotonation of Phospholanium Cation 3 with NEt3: Synthesis of Phospholane 5

To a solution of phospholanium triflate 3 (76 mg, 0.16 mmol, 1 equiv, containing about 8% of the protonated SPO 7) in CH2Cl2 (1 mL), triethylamine (27 μL, 20 mg, 0.19 mmol, 1.2 equiv) was added. Deprotonation was monitored via 31P{1H} NMR spectroscopy, which showed formation of phospholane 5 (major product, δ −16.5) and SPO 8 (δ 23.5, see below for independent synthesis and characterization), along with a trace of the known secondary phosphine PHMes*(n-Pr) (δ −73.6)19c and an unidentified product (δ −35.6). The solution was concentrated under reduced pressure, and the resulting solid was dissolved in hexane (2 mL). The solution was run through a silica pipette column (42 mm × 5 mm) with hexanes as starting eluent and added CH2Cl2 in a gradient. The hexane fractions contained PHMes*(n-Pr), while the CH2Cl2 fraction contained the phospholane with a trace of the secondary phosphine. The CH2Cl2 fraction was concentrated under vacuum to yield a colorless oil containing CH2Cl2 (21 mg, 41% yield).

Anal. Calcd for C21H35P: C, 79.20%; H, 11.08%. Found: C, 79.34%; H, 11.14%. HRMS m/z calcd for C21H36P (MH+): 319.2555. Found: m/z 319.2549. 31P{1H} NMR (C6D6): δ −16.8. 31P NMR (C6D6): δ −16.8. 1H NMR (C6D6): δ 7.52 (dd, J = 4, 2, 1H), 7.19 (d, J = 2, 1H), 4.27 (CH2Cl2), 2.00 (dd, J = 19, 14, 1H, phospholane CH), 1.80 (d, J = 14, 1H, phospholane CH), 1.75–1.64 (m, 2H, PCH2), 1.62 (9H, t-Bu), 1.57–1.41 (m, 2H, PCH2CH2), 1.37 (3H, Me), 1.32 (9H, t-Bu), 1.25 (3H, Me), 0.92 (t, J = 8, 3H, PCH2CH2CH3). 13C{1H} NMR (CD2Cl2): δ 157.9 (quat Ar), 151.9 (d, J = 14, quat Mes*), 151.7 (quat Mes*), 136.3 (d, J = 22, quat Ar), 121.6 (d, J = 6, Mes* CH), 118.5 (Mes* CH), 46.5 (d, J = 6, quat CMe2), 37.9 (d, J = 9, phospholane CH2), 37.1 (quat CMe3), 34.8 (quat CMe3), 33.6 (d, J = 3, Me), 33.3 (d, J = 21, PCH2), 33.3 (Me), 32.3 (d, J = 9, t-Bu Me), 31.2 (t-Bu Me), 20.6 (d, J = 19, PCH2CH2), 15.5 (d, J = 13, PCH2CH2CH3).

Synthesis of the SPO Mes*PH(O)(n-Pr) (8)

A solution of Mes*Br (300 mg, 0.922 mmol, 1 equiv) in dry degassed tetrahydrofuran (THF) (5 mL) was cooled to −78 °C. A solution of n-BuLi (0.44 mL, 2.5 M in hexanes, 1.1 mmol, 1.2 equiv) was added at −78 °C, turning the mixture a pale yellow; it was stirred for 2 h at −78 °C. This solution was added via cannula over 30 min to a solution of n-PrPCl2 (0.149 mL, 174 mg, 1.2 mmol, 1.3 equiv) in THF (10 mL), with both solutions at −78 °C. After the addition was complete, stirring was continued for 40 min. The mixture was then warmed to room temperature and stirred overnight. The major 31P{1H} NMR signal (THF) at δ 84.2 was assigned to Mes*P(n-Pr)(Cl), by analogy to related compounds.27

To this mixture, 5 mL of degassed H2O was added. In the air, the solution was extracted with hexanes (20 mL) and the aqueous phase was washed with hexanes (20 mL). The combined organic phases were dried with MgSO4, filtered, and concentrated under reduced pressure to give a crude white solid (276 mg, 89% yield). The 31P{1H} NMR spectrum showed that the major compound present was the target SPO, Mes*PH(O)(n-Pr) (δ 22.4), with a little of the protonated SPO [Mes*PH(OH)(n-Pr)][Cl] (δ 38.3), and a trace of the secondary phosphine PHMes*(n-Pr) (δ −74.0).

A portion of this material (180 mg) was purified by chromatography on silica, using a pipette column (42 mm × 5 mm) starting with hexanes as eluent, followed by CH2Cl2, and then EtOAc. According to 31P{1H} NMR spectroscopy, the hexane fractions contained PHMes*(n-Pr) (41 mg), the CH2Cl2 fraction contained a mixture of the protonated SPO and the SPO (δ 38.2 and 23.4, plus other unidentified materials; 71 mg), and the EtOAc fraction contained the SPO (60 mg, 19% yield, or 30% yield considering only the portion that was purified by chromatography).

Anal. Calcd for C21H37OP: C, 74.96%; H, 11.08%. Found: C, 74.87%; H, 11.05%. HRMS m/z calcd for C21H36OP ((M – H)+): 335.2504. Found: m/z 335.2507. 31P{1H} NMR (CDCl3): δ 23.3. 31P NMR (CDCl3): δ 23.3 (dt, J = 480, 11). 1H NMR (CDCl3): δ 7.78 (dt, J = 476, 5, 1H, PH), 7.41 (d, J = 4, 2H, Mes* CH), 2.07–1.98 (m, 1H, P-CH2), 1.67–1.59 (m, 1H, P-CH2), 1.54 (18H, o-t-Bu), 1.41–1.33 (m, 1H, CH2Me), 1.28 (9H, t-Bu), 0.97–0.86 (m, 1H, CH2Me), 0.82 (t, J = 8, 3H, PCH2CH2CH3). 13C{1H} NMR (CDCl3): δ 156.2 (br, quat Ar), 152.7 (d, J = 3, quat Ar), 127.6 (d, J = 93, ipso quat Mes*), 123.5 (d, J = 9, Mes* CH), 38.7 (d, J = 3, quat CMe3), 35.5 (d, J = 68, PCH2), 34.9 (quat CMe3), 33.9 (br, t-Bu Me), 31.0 (t-Bu Me), 16.7 (PCH2CH2), 15.0 (d, J = 15, PCH2CH2CH3).

Acknowledgments

We thank Dartmouth College and the National Science Foundation (CHE-1954412, CHE-1562037, CHE-1265758, and CHE-1011887) for support, the Department of Education for a GAANN fellowship to J.A.M., and the Polish National Alliance for a scholarship to R.M.T.

Data Availability Statement

The data underlying this study are available in the published article and its online Supplementary Material.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.3c00885.

  • Experimental procedures, characterization data, NMR spectra, and computational results (PDF)

  • Coordinates of computed structures and transition states (XYZ)

Author Present Address

† Vanderbilt University School of Medicine, 1161 21st Avenue S # D3300, Nashville, Tennessee 37232, United States (J.J.)

Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

The authors declare no competing financial interest.

Supplementary Material

ao3c00885_si_001.pdf (2.9MB, pdf)
ao3c00885_si_002.xyz (31.8KB, xyz)

References

  1. a Yudin A. Introduction: Small Heterocycles in Synthesis. Chem. Rev. 2014, 114, 7783–7783. 10.1021/cr500323m. [DOI] [PubMed] [Google Scholar]; and other reviews in this special issue.; b Dalpozzo R.; Lattanzi A.; Pellissier H. Applications of Chiral Three-membered Rings for Total Synthesis: A Review. Curr. Org. Chem. 2017, 21, 1143–1191. 10.2174/1385272821666170221151356. [DOI] [Google Scholar]
  2. Kolb H. C.; Finn M. G.; Sharpless K. B. Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angew. Chem., Int. Ed. 2001, 40, 2004–2021. 10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
  3. a Espinosa A.; de las Heras E.; Streubel R. Oxaphosphirane-Borane Complexes: Ring Strain and Migratory Insertion/Ring-Opening Reactions. Inorg. Chem. 2014, 53, 6132–6140. 10.1021/ic500536h. [DOI] [PubMed] [Google Scholar]; b Planells A. R.; Ferao A. E. Accurate Ring Strain Energy Calculations on Saturated Three-Membered Heterocycles with One Group 13–16 Element. Inorg. Chem. 2020, 59, 11503–11513. 10.1021/acs.inorgchem.0c01316. [DOI] [PubMed] [Google Scholar]
  4. a Mathey F. Chemistry of 3-Membered Carbon-Phosphorus Heterocycles. Chem. Rev. 1990, 90, 997–1025. 10.1021/cr00104a004. [DOI] [Google Scholar]; b Heydt H.Phosphiranes, Phosphirenes, and Heavier Analogues. In Comprehensive Heterocyclic Chemistry III, Taylor R. J. K.; Katritzky A. R.; Ramsden C. A.; Scriven E. F. V., Eds.; Elsevier: Oxford, 2008; 457–481. [Google Scholar]; c Glueck D. S.Phosphiranes, Phosphirenes, and Heavier Analogues. In Comprehensive Heterocyclic Chemistry IV, Black D. S.; Cossy J.; Stevens C. V., Eds.; Elsevier: 2022; 1, 464–505. [Google Scholar]; d Aue D. H.; Webb H. M.; Davidson W. R.; Vidal M.; Bowers M. T.; Goldwhite H.; Vertal L. E.; Douglas J. E.; Kollman P. A.; Kenyon G. L. Proton affinities and photoelectron spectra of three-membered-ring heterocycles. J. Am. Chem. Soc. 1980, 102, 5151–5157. 10.1021/ja00536a004. [DOI] [Google Scholar]
  5. a Mezailles N.; Fanwick P. E.; Kubiak C. P. Synthesis and Reactivity of Phosphirane Ligands and the Structural Characterization of Cp*IrCl2(tert-butylphosphirane). Organometallics 1997, 16, 1526–1530. 10.1021/om960400o. [DOI] [Google Scholar]; b Nemeth B.; Khater B.; Guillemin J.-C.; Veszpremi T. Differences Between Amine- and Phosphine-Boranes: Synthesis, Photoelectron Spectroscopy, and Quantum Chemical Study of the Cyclopropylic Derivatives. Inorg. Chem. 2010, 49, 4854–4864. 10.1021/ic902180p. [DOI] [PubMed] [Google Scholar]
  6. a Hockless D. C. R.; McDonald M. A.; Pabel M.; Wild S. B. 1-Methyl-1-phenylphosphiranium Triflate: Synthesis, Structure and Reactivity. J. Chem. Soc., Chem. Commun. 1995, 257–258. 10.1039/c39950000257. [DOI] [Google Scholar]; b Hockless D. C. R.; McDonald M. A.; Pabel M.; Wild S. B. Facile Syntheses and Interconversions between Simple Phosphiranium and Phosphirenium Salts. J. Organomet. Chem. 1997, 529, 189–196. 10.1016/S0022-328X(96)06641-7. [DOI] [Google Scholar]; c Ficks A.; Martinez-Botella I.; Stewart B.; Harrington R. W.; Clegg W.; Higham L. J. Taming functionality: easy-to-handle chiral phosphiranes. Chem. Commun. 2011, 47, 8274–8276. 10.1039/c1cc12440d. [DOI] [PubMed] [Google Scholar]; d Kobayashi S.; Kadokawa J. Ring-opening Polymerization of 1-(2,4,6-tri-tert-butylphenyl)-Phosphirane: Direct Synthesis of a Polyphosphine Derivative. Macromol. Rapid Commun. 1994, 15, 567–571. 10.1002/marc.1994.030150618. [DOI] [Google Scholar]; e Kadokawa J.-I.; Kobayashi S. New Ring-opening Polymerization of Phosphorus-Containing Cyclic Monomers. Phosphorus Sulfur Silicon Relat. Elem. 2002, 177, 1387–1390. 10.1080/10426500212283. [DOI] [Google Scholar]; f Gasnot J.; Botella C.; Comesse S.; Lakhdar S.; Alayrac C.; Gaumont A.-C.; Dalla V.; Taillier C. Access to Stable Quaternary Phosphiranium Salts by P-Alkylation and P-Arylation of Phosphiranes. Synlett 2020, 31, 883–888. 10.1055/s-0040-1708000. [DOI] [Google Scholar]; g Gasnot J.; Botella C.; Comesse S.; Lakhdar S.; Alayrac C.; Gaumont A.-C.; Dalla V.; Taillier C. Taming the reactivity of Phosphiranium salts: Site-selective C-centered-Ring Opening for Direct Synthesis of Phosphinoethylamines. Angew. Chem., Int. Ed. 2020, 59, 11769–11773. 10.1002/anie.201916449. [DOI] [PubMed] [Google Scholar]; h Tipker R. M.; Muldoon J. A.; Pham D. H.; Varga B. R.; Hughes R. P.; Glueck D. S.; Balaich G. J.; Rheingold A. L. Configurational Lability at Tetrahedral Phosphorus: syn/anti-Isomerization of a P-Stereogenic Phosphiranium Cation by Intramolecular Epimerization at Phosphorus. Angew. Chem., Int. Ed. 2022, 61, e202110753 10.1002/anie.202110753. [DOI] [PubMed] [Google Scholar]
  7. a Staley R. H.; Corderman R. R.; Foster M. S.; Beauchamp J. L. Nucleophilic attack on protonated oxiranes in the gas phase. Identification of the C2H5O+ isomeric ion corresponding to protonated ethylene oxide. J. Am. Chem. Soc. 1974, 96, 1260–1261. 10.1021/ja00811a070. [DOI] [Google Scholar]; b Berman D. W.; Anicich V.; Beauchamp J. L. Stabilities of isomeric halonium ions C2H4X+ (X = Cl, Br) by photoionization mass spectrometry and ion cyclotron resonance spectroscopy. General considerations of the relative stabilities of cyclic and acyclic isomeric onium ions. J. Am. Chem. Soc. 1979, 101, 1239–1248. 10.1021/ja00499a032. [DOI] [Google Scholar]; c Profous Z. C.; Wanczek K. P.; Hartmann H. Ion chemistry of phosphirane and structure of the phosphirane molecular ion. Z. Naturforsch. A 1975, 30, 1470–1475. 10.1515/zna-1975-1116. [DOI] [Google Scholar]
  8. a Keck H.; Tommes P. Fragmentation and isomerization of ionized trimethylphosphine sulfide (CH3)3P(S): ion structures and ab initio MO calculations. J. Mass Spectrom. 1999, 34, 44–50. 10.1002/(SICI)1096-9888(199901)34:1<44::AID-JMS756>3.0.CO;2-B. [DOI] [Google Scholar]; b Sølling T. I.; McDonald M. A.; Wild S. B.; Radom L. Novel Pi–Ligand Exchange and Insertion Reactions Involving Three-Membered Phosphorus Heterocycles: An ab Initio Investigation. J. Am. Chem. Soc. 1998, 120, 7063–7068. 10.1021/ja980494o. [DOI] [Google Scholar]
  9. Mó O.; Yáñez M.; Decouzon M.; Gal J.-F.; Maria P.-C.; Guillemin J.-C. Gas-Phase Basicity and Acidity Trends in α,β-Unsaturated Amines, Phosphines, and Arsines. J. Am. Chem. Soc. 1999, 121, 4653–4663. 10.1021/ja982657e. [DOI] [Google Scholar]
  10. a Olah G. A.; Szilagyi P. J. Stable carbonium ions. LXXX. Protonation, alkylation, and acylation of aziridine, N-alkylaziridines, and N-acylaziridines. Aziridinium, N-alkylaziridinium, and N-acylaziridinium ions. J. Am. Chem. Soc. 1969, 91, 2949–2955. 10.1021/ja01039a021. [DOI] [Google Scholar]; b Baret P.; Rivoirard E.-M.; Pierre J.-L. Sels d’aziridinium stables C-fonctionnalisés III: Synthèse et caractérisation d’aziridines protonées épimères à l’azote. J. Heterocycl. Chem. 1980, 17, 201–204. 10.1002/jhet.5570170141. [DOI] [Google Scholar]
  11. a Collins C. J. Protonated cyclopropanes. Chem. Rev. 1969, 69, 543–550. 10.1021/cr60260a004. [DOI] [Google Scholar]; b DePuy C. H.Stereochemistry and reactivity in cyclopropane ring-cleavage by electrophiles. In Three-Membered Rings; Springer: Berlin Heidelberg: Berlin, Heidelberg, 1973; 73–101. [Google Scholar]; c DePuy C. H.; Fuenfschilling P. C.; Andrist A. H.; Olson J. M. Stereochemistry of the electrophilic ring opening of cyclopropanes. 2. Reaction of cis- and trans-1,2,3-trimethylcyclopropane with D+. J. Am. Chem. Soc. 1977, 99, 6297–6303. 10.1021/ja00461a019. [DOI] [Google Scholar]; d Battiste M. A.; Coxon J. M., Acidity and Basicity of Cyclopropanes. In The Chemistry of the Cyclopropyl Group, Rappoport Z., Ed.; John Wiley & Sons: 1987; 255–305. [Google Scholar]; e Burritt A.; Coxon J. M.; Steel P. J. Corner versus Edge Protonation of Cyclopropane. J. Org. Chem. 1995, 60, 7670–7673. 10.1021/jo00128a046. [DOI] [Google Scholar]
  12. Kramer G. M. Detection of alkylcyclopropane intermediates during carbonium ion rearrangements in antimony pentafluoride tritiated fluorosulfonic acid. J. Am. Chem. Soc. 1970, 92, 4344–4348. 10.1021/ja00717a035. [DOI] [Google Scholar]
  13. Quin L. D.A Guide to Organophosphorus Chemistry; Wiley-Interscience: New York, 2000. [Google Scholar]
  14. Riu M.-L. Y.; Eckhardt A. K.; Cummins C. C. Reactions of Tri-tert-Butylphosphatetrahedrane as a Spring-Loaded Phosphinidene Synthon Featuring Nickel-Catalyzed Transfer to Unactivated Alkenes. J. Am. Chem. Soc. 2022, 144, 7578–7582. 10.1021/jacs.2c02236. [DOI] [PubMed] [Google Scholar]
  15. Muldoon J. A.; Varga B. R.; Deegan M. M.; Chapp T. W.; Eördögh Á. M.; Hughes R. P.; Glueck D. S.; Moore C. E.; Rheingold A. L. Inversion of Configuration at the Phosphorus Nucleophile in Diastereoselective and Enantioselective Synthesis of P-Stereogenic syn-Phosphiranes from Chiral Epoxides. Angew. Chem., Int. Ed. 2018, 57, 5047–5051. 10.1002/anie.201801427. [DOI] [PubMed] [Google Scholar]
  16. Phospholane 5 was generated independently from the known cyclophosphinated chlorophospholane P(4,6-(t-Bu)2–2-CMe2CH2C6H2)(Cl) and n-PrMgCl. See:; Yoshifuji M.; Shima I.; Ando K.; Inamoto N. Thermal Reactions of (2,4,6-tri-tert-butylphenyl)phosphonous dichloride and its Derivatives; Formation of 2,3-dihydro-1H-phosphindoles. Tetrahedron Lett. 1983, 24, 933–936. 10.1016/S0040-4039(00)81569-5. [DOI] [Google Scholar]
  17. Few protonated phosphine oxides are known. For some examples, see:; Seel F.; Bassler H.-J. Über Fluoro ... onium-Verbindungen. III. Chemisches Verhalten von Monofluorophosphonium-fluoro-boraten und -arsenaten(V). Z. Anorg. Allg. Chem. 1976, 423, 67–74. 10.1002/zaac.19764230110. [DOI] [Google Scholar]
  18. For related examples of formal O-H oxidative addition on reaction of water with phosphenium ions, see:; a Olaru M.; Mebs S.; Beckmann J. Cationic Carbene Analogues: Donor-Free Phosphenium and Arsenium Ions. Angew. Chem., Int. Ed. 2021, 60, 19133–19138. 10.1002/anie.202107975. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Tay M. Q. Y.; Lu Y.; Ganguly R.; Vidović D. Oxidative Addition of Water and Methanol to a Dicationic Trivalent Phosphorus Centre. Chem. – Eur. J. 2014, 20, 6628–6631. 10.1002/chem.201402356. [DOI] [PubMed] [Google Scholar]; c Tay M. Q. Y.; Ilić G.; Werner-Zwanziger U.; Lu Y.; Ganguly R.; Ricard L.; Frison G.; Carmichael D.; Vidović D. Preparation, Structural Analysis, and Reactivity Studies of Phosphenium Dications. Organometallics 2016, 35, 439–449. 10.1021/acs.organomet.5b00763. [DOI] [Google Scholar]; d Volodarsky S.; Dobrovetsky R. Ambiphilic geometrically constrained phosphenium cation. Chem. Commun. 2018, 54, 6931–6934. 10.1039/C8CC02423E. [DOI] [PubMed] [Google Scholar]
  19. For related SPOs PHMes*(R)(O) (R = Me, CH2Ph, CH2OH), see:; a Yoshifuji M.; Takahashi H.; Toyota K. Reactions of Sterically Protected Phosphaalkenes with Some Boron Reagents. Heteroat. Chem. 1999, 10, 187–196. 10.1002/(SICI)1098-1071(1999)10:3<187::AID-HC3>3.0.CO;2-4. [DOI] [Google Scholar]; b Cowley A. H.; Kilduff J. E.; Norman N. C.; Pakulski M. The Reactivity of Diphosphenes towards Electrophilic and Nucleophilic Reagents. J. Chem. Soc., Dalton Trans. 1986, 1801–1808. 10.1039/dt9860001801. [DOI] [Google Scholar]; (c) For the secondary phosphine Mes*PH(n-Pr), see:; c Yoshifuji M.; Shibayama K.; Inamoto N. Reaction of a Diphosphene with Butyllithium. Chem. Lett. 1984, 13, 115–118. 10.1246/cl.1984.115. [DOI] [Google Scholar]
  20. a Wild S. B. Resolutions of Tertiary Phosphines and Arsines with Orthometallated Palladium(II)-Amine Complexes. Coord. Chem. Rev. 1997, 166, 291–311. 10.1016/S0010-8545(97)00046-5. [DOI] [Google Scholar]; b Glueck D. S. Applications of 31P NMR Spectroscopy in Development of M(Duphos)-Catalyzed Asymmetric Synthesis of P-Stereogenic Phosphines (M = Pt or Pd). Coord. Chem. Rev. 2008, 252, 2171–2179. 10.1016/j.ccr.2007.12.023. [DOI] [Google Scholar]
  21. a Lambert J. B.; So J.-H. Phosphonium Ions Rather than Phosphenium Ions from the Reaction of Secondary Phosphines with Trityl Cation. J. Org. Chem. 1991, 56, 5960–5962. 10.1021/jo00020a050. [DOI] [Google Scholar]; b Taylor L. J.; Bühl M.; Wawrzyniak P.; Chalmers B. A.; Woollins J. D.; Slawin A. M. Z.; Fuller A. L.; Kilian P. Hydride Abstraction and Deprotonation – an Efficient Route to Low Coordinate Phosphorus and Arsenic Species. Eur. J. Inorg. Chem. 2016, 2016, 659–666. 10.1002/ejic.201500948. [DOI] [Google Scholar]; c Dobrovetsky R.; Takeuchi K.; Stephan D. W. Metal-free Lewis Acid Mediated Dehydrocoupling of Phosphines and Concurrent Hydrogenation. Chem. Commun. 2015, 51, 2396–2398. 10.1039/C4CC09526J. [DOI] [PubMed] [Google Scholar]; d Bezombes J.-P.; Carré F.; Chuit C.; Corriu R. J. P.; Mehdi A.; Reyé C. Synthesis and characterization of functionalized phosphenium ions, stabilized by two intramolecular dative P ← N bonds. J. Organomet. Chem. 1997, 535, 81–90. 10.1016/S0022-328X(96)06938-0. [DOI] [Google Scholar]; e Carré F.; Chuit C.; Corriu R. J. P.; Mehdi A.; Reyé C. N → P intramolecular stabilization of phosphenium ions and preparation of hypercoordinated phosphanes with unusual properties. J. Organomet. Chem. 1997, 529, 59–68. 10.1016/S0022-328X(96)06659-4. [DOI] [Google Scholar]
  22. a Cowley A. H.; Kemp R. A. Synthesis and Reaction Chemistry of Stable Two-Coordinate Phosphorus Cations (Phosphenium Ions). Chem. Rev. 1985, 85, 367–382. 10.1021/cr00069a002. [DOI] [Google Scholar]; b Yoshifuji M. Product class 3: phosphenium salts. Sci. Synth. 2009, 42, 63–69. 10.1055/sos-SD-042-00065. [DOI] [Google Scholar]; c Slattery J. M.; Hussein S. How Lewis acidic is your cation? Putting phosphenium ions on the fluoride ion affinity scale. Dalton Trans. 2012, 41, 1808–1815. 10.1039/C1DT11636C. [DOI] [PubMed] [Google Scholar]
  23. a Lindner E.; Weiß G. A. Oxidative Addition einer C–H-Bindung an ein zweifach koordiniertes Phosphenium-Kation. Chem. Ber. 1986, 119, 3208–3211. 10.1002/cber.19861191027. [DOI] [Google Scholar]; For a related process, see:; b Karsch H. H.; Reisacher H.-U.; Müller G. A 2-Phosphonio-Substituted 1-Phospha-1-alkene: Resonance between PIII Alkene and PV Ylide. Angew. Chem., Int. Ed. 1986, 25, 454–455. 10.1002/anie.198604541. [DOI] [Google Scholar]
  24. a Tsang C.-W.; Rohrick C. A.; Saini T. S.; Patrick B. O.; Gates D. P. Reactions of Electrophiles with the Phosphaalkene Mes*P=CH2: Mechanistic Studies of a Catalytic Intramolecular C–H Bond Activation Reaction. Organometallics 2002, 21, 1008–1010. 10.1021/om010952t. [DOI] [Google Scholar]; b Tsang C.-W.; Rohrick C. A.; Saini T. S.; Patrick B. O.; Gates D. P. Destiny of Transient Phosphenium Ions Generated from the Addition of Electrophiles to Phosphaalkenes: Intramolecular C-H Activation, Donor-Acceptor Formation, and Linear Oligomerization. Organometallics 2004, 23, 5913–5923. 10.1021/om0495022. [DOI] [Google Scholar]
  25. a Bakhtiar R.; Holznagel C. M.; Jacobson D. B. Rearrangement of nascent α-silyl-substituted carbenium ions in the gas phase. 1,2-Hydrogen versus 1,2-methyl versus 1,2-phenyl migration. J. Am. Chem. Soc. 1992, 114, 3227–3235. 10.1021/ja00035a010. [DOI] [Google Scholar]; b Wistuba E.; Rüchardt C. Intrinsic migration aptitudes of alkyl groups in a pinacol rearrangement. Tetrahedron Lett. 1981, 22, 4069–4072. 10.1016/S0040-4039(01)82067-0. [DOI] [Google Scholar]
  26. For a recent related report of phosphirane ring opening to yield a phosphenium cation, promoted by rearrangement of a carbocation, see:; Cui M.; Feng K.; Tian R.; Duan Z. Phosphorus-Involved Wagner–Meerwein Rearrangement of Phosphiranes: An Entry to Four-Membered Phosphacycles. Org. Lett. 2023, 25, 205–209. 10.1021/acs.orglett.2c04052. [DOI] [PubMed] [Google Scholar]
  27. Brauer D. J.; Bitterer F.; Dorrenbach F.; Hessler G.; Stelzer O.; Kruger C.; Lutz F. Synthesis, Coordination Chemistry and Ligand Properties of Secondary Phosphines R(Ar*)PH with Bulky Aromatic Substituents -- Molecular Structure of Ph(Is)PH, Is2PH and ClAu[PhPMes*H]. Z. Naturforsch. B 1996, 51, 1183–1196. 10.1515/znb-1996-0819. [DOI] [Google Scholar]

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