# Reaction of Nitrones with phosphinylallenes: DFT mechanistic investigations

Rayhane Hammami, Pascale Maldivi, Sébastien Carret, Soufiane Touil,

Jean-françois Poisson, Benjamin Darses

► To cite this version:

Rayhane Hammami, Pascale Maldivi, Sébastien Carret, Soufiane Touil, Jean-françois Poisson, et al. Reaction of Nitrones with phosphinylallenes: DFT mechanistic investigations. European Journal of Organic Chemistry, 2025, 28 (28), pp.e202500359. 10.1002/ejoc.202500359. hal-05164967

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# Reaction of Nitrones with Phosphinylallenes: DFT Mechanistic Investigations

Rayhane Hammami,ª,ᶜ Pascale Maldivi,ᵇ* Sébastien Carret,ª Soufiane Touil,ᶜ* Jean-François Poissonª* and Benjamin Darsesª*

ª Univ. Grenoble Alpes, CNRS, DCM, 38000 Grenoble, France

ᵇ Univ. Grenoble Alpes, CEA, CNRS, IRIG-SyMMES, 38000 Grenoble, France

ᶜ University of Carthage, Faculty of Sciences of Bizerte, Laboratory of Hetero-Organic Compounds and Nanostructured Materials, LR18ES11,7021 Jarzouna, Tunisia

**Abstract.** The reaction between phosphinylallenes and nitrones efficiently leads to 4-phosphinylpyrrolidin-3-ones. The mechanism of this transformation was investigated theoretically to elucidate the overall pathway and the stereochemical outcome. The process begins with a (3+2) cycloaddition between the nitrone and the allene delivering an isoxazolidine ylidene intermediate. This intermediate, that has never been isolated, spontaneously rearranges to the final 4-phosphinylpyrrolidin-3-one

via homolytic cleavage of the N–O bond, followed by rotation and C–N recombination of the biradical intermediate. The computational results provide valuable insights for achieving diastereo- and enantioselective synthesis of 4-phosphinylpyrrolidin-3-ones through careful selection of substituents on the nitrone and allene.

**Keywords:** Nitrones, allenes, cycloaddition, rearrangement, DFT calculations, mechanism

## Introduction

The 1,3-dipolar cycloadditions between dipolarophiles and 1,3-dipoles are versatile transformations for accessing a broad array of valuable products with different scaffolds.[1] Nitrones, in particular, have proven to be efficient 1,3-dipoles capable of yielding isoxazolidines,[2] isoxazolines,[3] β-lactams,[4] or acylaziridines[5] in the presence of unsaturated partners. Among these, acylaziridines can be formed through the cycloaddition of nitrones with alkynes, generating isoxazolines that undergo a Baldwin rearrangement. (Scheme 1a).[6] This rearrangement has been proposed to proceed *via* a 1,3-sigmatropic shift rather than a homolytic cleavage of the N–O bond and a biradical recombination, based on stereochemical evidence.[7] In contrast, the 1,3-dipolar cycloaddition of nitrones with functionalized allenes to generate pyrrolidin-3-ones remains relatively underexplored,[8] particularly in terms of its mechanistic pathway. While the initial step is generally accepted to involve a (3+2) cycloaddition, the subsequent rearrangement of the transient 5-(ylidene)-isoxazolidine remains controversial. Proposed mechanisms include heterolytic cleavage of the N–O bond, in which electron density is retained by either the nitrogen or the oxygen atom,[9] as well as homolytic cleavage involving radical intermediates (Scheme 1b).[8a, 10]

In a previous study on the synthesis of phosphinylpyrrolidin-3-ones *via* (3+2) cycloaddition between N-alkylnitrones and phosphinylallenes, we conducted preliminary Density Functional Theory (DFT) calculations using a simplified model with an unsubstituted nitrone.[8i] These studies indicated that the rearrangement of the intermediate isoxazolidine proceeded *via* the homolytic cleavage of the N–O bond followed by recombination. However, the studied system was not involving stereochemical consideration. We therefore decided to fully describe

both the (3+2) cycloaddition step and the subsequent rearrangement for the reaction between substituted

a. Nitrone-alkyne (3+2) cycloaddition and Baldwin rearrangement

<figure><img src="image_2.png" /></figure>

b. Mechanisms proposed in the literature for the rearrangement of 5-(ylidene)-isoxazolidine

<figure><img src="image_3.png" /></figure>

**Scheme 1.** (3+2) cycloaddition of nitrones with alkynes and allenes, and rearrangements.nitrones and phosphinylallenes by DFT calculations.

## Results and Discussion

<figure><img src="image_4.png" /></figure>

**Scheme 2.** Reaction between nitrone 1 and phosphinylallene 2: previous report.
To gain deeper insight into the different steps involved in this transformation, we investigated the reaction between the N-methyl-C-phenylnitrone **1** and the chiral phosphinylallene **2** (used as a racemate in our previous report).[81] Experimentally, the reaction conducted in cyclohexane at 150 °C under microwave irradiation yielded a 60% mixture of diastereoisomeric pyrrolidin-3-ones **3** and **4** in a 65:35 ratio, favoring compound **3**. Pyrrolidin-3-ones **3** and **4** exhibit *trans*²,⁴/*trans*⁴,⁵ and *cis*²,⁴/*trans*⁴,⁵ stereochemistry, respectively, for the stereogenic centers at positions 2, 4 and 5 (Scheme 2).

The initial step of this sequence is a (3+2) cycloaddition between the nitrone and the allene, affording isoxazolidine intermediates. When C-substituted nitrones and chiral allenes are employed, four stereoisomeric isoxazolidines can form: two *trans*³,⁴-configured diastereoisomers (**5** and **6**), each with either *E* or *Z* geometry across the alkene, and two *cis*³,⁴-configured counterparts (**7** and **8**), also with respective *E* or *Z* configurations (Figure 1). Each of these four diastereoisomers is obtained as a racemate since a racemic chiral allene is used.

To rationalize the formation of these four stereoisomers, four distinct orientations between the reacting partners must be considered (Scheme 3). The nitrone can approach either the less hindered (Me) or more hindered (Et) face of the allene. Additionally, the electron-withdrawing phosphinyl substituent may either align with the C=N–O moiety of the nitrone (*endo* approach), or project away from it (*exo* approach). These different arrangements account for the four diastereoisomeric isoxazolidines.

DFT calculations were conducted to evaluate the likelihood of each stereoisomer forming (see computational details in SI).

DFT computations of the initial cycloaddition step, forming the isoxazolidine core, indicated that its energy profile was sensitive to the conformations of the PO(Ph)₂ group on the allene. We systematically analyzed three possible conformers across all approaches (see Supporting Information, Figure S1 and Table S1). In the case of the endo approach from the Me face, which leads to the *trans*³,⁴/*E* isomer **5**, the most favorable conformation featured the P=O group oriented toward the nitrone (Conf.2, Figure 2). This arrangement likely minimizes steric interactions

between the phenyl rings of PO(Ph)₂ and the incoming nitrone. The activation free energy for this pathway was determined to be 31.8 kcal.mol⁻¹, whereas the less favorable conformations exceeded 35 kcal.mol⁻¹. Notably, for all other geometrical approaches, the same PO(Ph)₂ conformation (Conf.2) yielded the lowest activation energy (Supporting Information, Table S1).

<figure><img src="image_5.png" /><figcaption>**Figure 1.** Diastereoisomeric isoxazolidines accessible from the reaction between **1** and **2**.</figcaption></figure>

DFT computations of the initial cycloaddition step, forming the isoxazolidine core, indicated that its energy profile was sensitive to the conformations of the PO(Ph)₂ group on the allene. We systematically analyzed three possible conformers across all approaches (see Supporting Information, Figure S1 and Table S1). In the case of the endo approach from the Me face, which leads to the *trans*³,⁴/*E* isomer **5**, the most favorable conformation featured the P=O group oriented toward the nitrone (Conf.2, Figure 2). This arrangement likely minimizes steric interactions between the phenyl rings of PO(Ph)₂ and the incoming nitrone. The activation free energy for this pathway was determined to be 31.8 kcal.mol⁻¹, whereas the less favorable conformations exceeded 35 kcal.mol⁻¹. Notably, for all other geometrical approaches, the same PO(Ph)₂ conformation (Conf.2) yielded the lowest activation energy (Supporting Information, Table S1).

<figure><img src="image_6.png" /><figcaption>**Scheme 3.** Different possible approaches between nitrone **1** and phosphinylallene **2** and resulting cycloadducts.</figcaption></figure>
<figure><img src="image_7.png" /><figcaption>**Figure 2.** Different conformations of the PO(Ph)₂ moiety in the *endo* approach of the nitrone toward the Me face of the allene: energy profiles obtained by DFT calculations. Geometry optimizations and frequencies were carried out in gas phase with the B3LYP functional and the D3 Grimme dispersion, and energies were computed based on single points using a solvation CPCM model for cyclohexane, using *def2-tzvp* basis sets.</figcaption></figure>

We then studied the other cycloaddition approaches leading to the three other stereoisomers. Starting with the second *endo* approach, on the Et face, which delivers the *trans*<sup>3,4</sup>/Z stereoisomer **6** (Figure 3), the same PO(Ph)₂ conformation (Conf. 2) involves a transition state requiring 32.3 kcal.mol<sup>-1</sup>. The moderate increase of only 0.5 kcal.mol<sup>-1</sup> compared to the *trans*<sup>3,4</sup>/E case, likely reflects minor differences in steric hindrance between a methyl and an ethyl substituent. Similar calculations for the two *exo* approaches produced activation energies of 31.5 and

32.8 kcal.mol<sup>-1</sup> for the formation of the *cis*<sup>3,4</sup>/E and *cis*<sup>3,4</sup>/Z isomers (**7** and **8**) respectively. Again, the Et face proved slightly more disfavored than the Me face. Overall, all four transition states displayed activation free energies within a narrow range of 31.5 to 32.8 kcal.mol<sup>-1</sup>, differences that are relatively minor at the DFT level. Nonetheless, the trend indicates a slight preference for nitrone attack from the Me face, leading to the formation of the *trans*<sup>3,4</sup>/E and *cis*<sup>3,4</sup>/E stereoisomers (**5** and **7**).

<figure><img src="image_8.png" /><figcaption>**Figure 3.** Energy profiles obtained by DFT calculations for each approach of the nitrone **1** on each face of the allene **2**, with the conformation Conf.2 of the allene. Geometry optimizations and frequencies were carried out in gas phase with the B3LYP functional and the D3 Grimme dispersion, and energies were computed based on single points using a solvation CPCM model for cyclohexane, using *def2-tzvp* basis sets.</figcaption></figure>
The transformation of the different diastereoisomeric isoxazolidines was next investigated to rationalize the formation of the observed pyrrolidin-3-ones. The intermediate **5** with a *trans*<sup>3,4</sup>*E* stereochemistry was analyzed first. In our previous study, we demonstrated that spontaneous homolytic cleavage of the N–O bond is followed by a radical recombination between the *N*-centered and *C*-centered radicals. The initial homolysis generates a vinylic oxygen radical, leading to a spin-density distribution predominantly localized on the conjugated carbon. However, prior to recombination, the alkenyl fragment must undergo rotation around the C5–C4 bond axis, either clockwise (a) or anti-clockwise (b). These respective rotations yield pyrrolidin-3-one **3** (*trans*<sup>2,4</sup>*/trans*<sup>4,5</sup>) product and **4** (*cis*<sup>2,4</sup>*/trans*<sup>4,5</sup>) as shown in scheme 4.

<figure><img src="image_9.png" /><figcaption>**Scheme 4.** Rearrangement of isoxazolidine **5** by homolytic cleavage, rotation and recombination to give either **3** or **4**.</figcaption></figure>

DFT calculations were employed to compare the two reaction pathways leading to diastereoisomeric products. Figure 4 shows four scenarios —derived from *endo* or *exo* approaches on either the methyl or ethyl faces— were analyzed, using the most favorable PO(Ph)₂ conformer (Conf.2).[11] 3D displays of the intermediates and products are shown in figures S2-S7 (Supporting Information). For the clockwise rotation (a) of the C<sup>5</sup>–C<sup>4</sup> bond, the rearrangement proceeds through two transition states, with the rate-determining step requiring 16.4 kcal.mol<sup>-1</sup>. In contrast, the anti-clockwise pathway (b) proceeds *via* a single transition state, but at a higher barrier of 22.1 kcal.mol<sup>-1</sup>. The additional 5.7 kcal.mol<sup>-1</sup> energy cost in pathway (b) likely arises from increased steric interactions between the alkenyl and the diphenylphosphine oxide moieties in this sense of rotation. These results strongly support the formation of isomer **3** (*trans*<sup>2,4</sup>*/trans*<sup>4,5</sup>) as the predominant species from the rearrangement of the *trans*<sup>3,4</sup>*E* isoxazolidine **5**. Importantly, the activation energy of the rearrangement is 15.4 kcal.mol<sup>-1</sup> lower than the activation energy of the (3+2) cycloaddition, suggesting that the isoxazolidine intermediate cannot be isolated under the reaction conditions.

<figure><img src="image_10.png" /><figcaption>**Figure 4.** Energy profiles obtained by DFT calculations for the rearrangement of each isoxazolidine **5-8** in a clockwise (a) or anti-clockwise (b) direction. Geometry optimizations and frequencies were carried out in gas phase with the B3LYP functional and the D3 Grimme dispersion, and energies were computed based on single points using a solvation CPCM model for cyclohexane, using def2-tzvp basis sets.</figcaption></figure>
We extended this analysis to the rearrangement of isoxazolidines **6–8** (*trans*³,⁴/Z, *cis*³,⁴/E and *cis*³,⁴/Z, respectively). For all cases, energy profiles are referenced to the isoxazolidine intermediates, with the starting point corresponding to the nitrone + allene complex.

In the case of isoxazolidine **6** (*trans*³,⁴/Z), the energy landscape was similar to that of **5** (*trans*³,⁴/E). The favorable pathway (a) again involved two transition states, whereas the anti-clockwise path (b) involved only one. The barrier for the preferred route was slightly higher than for **5** (17.4 vs 16.4 kcal.mol⁻¹), but still significantly lower (by 13.4 kcal.mol⁻¹) than the cycloaddition step. Interestingly, the major and minor products from **5** and **6** correspond to enantiomeric pairs (**3**/*ent*-**3** and **4**/*ent*-**4**), further highlighting the stereochemical symmetry of the system.

The rearrangement of isoxazolidines **7** and **8** (*cis*³,⁴/E and *cis*³,⁴/Z) followed a different pattern. Both pathways involved two transition states. However, the second transition state in each case was much lower in energy, rendering the first activation barrier the key determinant. For isoxazolidine **7**, the clockwise route (a) had a slightly lower barrier than the anti-clockwise path (17.8 vs 19.5 kcal.mol⁻¹). This modest energy difference (1.7 kcal.mol⁻¹) was insufficient to favor exclusive formation of **9** or **10**. Similarly, for isoxazolidine **8**, the anti-clockwise path (b) was slightly preferred over the clockwise route (a), with activation energies for the determining transition steps of 17.7 kcal.mol⁻¹ and 18.4 kcal.mol⁻¹ respectively. The negligible difference again precludes selective formation of either *ent*-**9** or *ent*-**10**, the enantiomers of the products accessible from **7**.

Although conformers **1** and **3** of PO(Ph)₂ are not favored during the initial cycloaddition, they were also investigated (Tables S2–S4). As observed for conformer **2**, the rearrangement pathways showed no significant deviations across conformers.

Importantly, the rate determining step is the cycloaddition itself, with barriers exceeding 30 kcal.mol⁻¹ which is consistent with the reaction temperature (150 °C). Activation energies for both the cycloaddition and rearrangement pathways are insufficient to fully explain the product distribution under these experimental conditions. Nonetheless, only *trans*⁴,⁵ pyrrolidin-3-ones were isolated experimentally; no trace of *cis*⁴,⁵ isomers was detected.

This outcome is consistent with calculated thermodynamic preferences, as the *trans*⁴,⁵ products are more stable than their *cis* counterparts by up to 4.6 kcal.mol⁻¹ (for Conf.2) and as much as 10.5 kcal.mol⁻¹ when considering all conformers (Table S5). These findings suggest that epimerization of the *β*-ketophosphine oxide *via* an enol form is plausible.[12] The feasibility of such transformation was estimated by computing possible pathways consistent with the high temperature experimental conditions. We chose to study the epimerization from *ent*-10 diastereoisomer to **3** (Scheme 5), with the assumption that other stereoisomers would follow similar pathways. Very interestingly, an intramolecular proton transfer from the *C*⁴ atom to the *N* atom of the pyrrolidinone may occur with a Gibbs free energy barrier of 38.0 kcal.mol⁻¹ compatible with the high experimental temperature (Supporting Information, Scheme S1).[13] The zwitterionic species thus generated bears a basic site thanks to the enolate formed and an ammonium group able to donate a proton. Although the pKas of such positions cannot be computed, the Gibbs free energy resulting from acid-base reactions can be obtained. We thus determined thermodynamically consistent acid-base reactions able to yield the most energetically favored **3** diastereoisomer, as shown in scheme S1. Therefore, following the (3+2) cycloaddition, rearrangement of isoxazolidines and possible isomerization of *cis*⁴,⁵ pyrrolidin-3-ones, only two pairs of enantiomers (**3**/*ent*-**3**, and **4**/*ent*-**4**) are expected, each defined by either *trans*²,⁴/*trans*⁴,⁵ or *cis*²,⁴/*trans*⁴,⁵ stereochemistry (Scheme 5). Consistent with this, NMR analysis revealed only two major products.[⁸¹] Furthermore, the calculated energy profiles support the predominance of **3** and *ent*-**3**, which aligns with the experimentally observed 65:35 diastereomeric ratio of *trans*²,⁴/*trans*⁴,⁵ and *cis*²,⁴/*trans*⁴,⁵ pyrrolidin-3-ones.

Although our earlier study employed racemic allenes, this mechanistic analysis highlights the difficulty to obtain enantiopure phosphinylpyrrolidin-3-ones using enantiopure allenes. The low energy differentiation between the four approach pathways, endo or exo, from the Me or Et face, would result in modest diastereoselectivity for the *trans*²,⁴/*trans*⁴,⁵ isomer and nearly racemic mixtures even with an enantiopure allene.
<figure><img src="image_11.png" /><figcaption>**Scheme 5.** Summary of the different pathways for the rearrangement of isoxazolidines 5-8.</figcaption></figure>

## Conclusion

The reaction between an *N*-alkylnitrone and a phosphinylallene to afford phosphinylpyrrolidin-3-ones is far more complex than it may initially appear. Multiple products can arise not only from the initial (3+2) cycloaddition but also from the subsequent rearrangement, with potential convergence toward identical or enantiomeric stereoisomers. This convergence complicates the unambiguous assignment of stereochemical outcomes. Moreover, the observed distribution of stereoisomers, when coupled with possible epimerization, can lead to an apparent erosion of the enantiopurity in products featuring three stereogenic centers, even when starting from an enantiopure allene. Nonetheless, greater differentiation among the transition states involved in the (3+2) cycloaddition step could mitigate these issues. For example, increasing the steric disparity between the geminal substituents on the allene (Me vs.

Et in our study) is expected to enhance the *E/Z* selectivity of the resulting isoxazolidines. Additionally, amplifying the steric repulsion between the nitrone *C*-substituent (*Ph*) and the electron-withdrawing group on the allene (*Ph*₂*PO*) would more strongly favor the formation of the *trans* 3,4-configured isoxazolidines over their *cis* counterparts. Such control would significantly bias the reaction toward the formation of the *trans* 3,4/E isoxazolidine 5 ultimately favoring the production of the diastereo- and enantioenriched pyrrolidin-3-one 3 with *trans* 2,4/*trans* 4,5 relative stereochemistry. Importantly, the mechanism pathway described in this study differs markedly from the closely related formation of aziridines from isoxazolines *via* the Baldwin rearrangement. While the latter has been proposed to proceed *via* a sigmatropic shift, our DFT investigations indicate that the rearrangement of isoxazolidines into pyrrolidin-3-ones proceeds through a radical mechanism involving homolytic N–O bond cleavage and recombination.
Acknowledgements

We wish to thank the Labex ARCANE and CBH-EUR-GS (ANR-17-EURE-0003), for their financial support. The authors are also thankful for support from the Ministry of Higher Education and Scientific Research of Tunisia (grant for R. H.) and from ICMG FR 2607, Grenoble, through which analyses have been performed. P. M. wishes to acknowledge GENCI for providing high performance computing resources, under project number 0807648.

References

[1] a) S. E. Beutick, P. Vermeeren, T. A. Hamlin, Chem. – Asian J. **2022**, *17*, e202200553; b) M. Breugst, H.-U. Reissig, Angew. Chem., Int. Ed. **2020**, *59*, 12293–12307; c) M. S. Singh, S. Chowdhury, S. Koley, *Tetrahedron* **2016**, *72*, 1603–1644.

[2] a) A. D. Jones, D. W. Knight, S. R. Thornton, *J. Chem. Soc., Perkin Trans. 1* **1999**, 3337–3344; b) T. Saito, T. Yamada, S. Miyazaki, T. Otani, *Tetrahedron Lett.* **2004**, *45*, 9585–9587; c) P. Jiao, D. Nakashima, H. Yamamoto, *Angew. Chem. Int. Ed.* **2008**, *47*, 2411–2413; d) L. Xie, H. Bai, J. Li, X. Yu, Z. Zhang, B. Fu, *Tetrahedron* **2017**, *73*, 2923–2930; e) E. Opoku, G. Arhin, G. B. Pipim, A. H. Adams, R. Tia, E. Adei, *Theor. Chem. Acc.* **2020**, *139*, 16.

[3] a) X. Cai, C. Wang, J. Sun, *Adv. Synth. Catal.* **2012**, *354*, 359–363; b) B. Chandrasekhar, S. Ahn, J.-S. Ryu, *Synthesis* **2016**, *49*, 1569–1574; c) B. Chakraborty, G. P. Luitel, M. S. Chhetri, *Indian J. Chem.* **2016**, *55B*, 1259–1266; d) B. Chakraborty, *J. Heterocyclic Chem.* **2020**, *57*, 477–485.

[4] a) A. Basak, S. C. Ghosh, *Synlett* **2004**, *9*, 1637–1639; b) Y. Kumar, P. Singh, G. Bhargava, *New J. Chem.* **2016**, *40*, 8216–8219; c) Y. Takayama, T. Ishii, H. Ohmiya, T. Iwai, M. C. Schwarzer, S. Mori, T. Taniguchi, K. Monde, M. Sawamura, *Chem. Eur. J.* **2017**, *23*, 8400–8404.

[5] a) J. E. Baldwin, R. G. Pudussery, A. K. Qureshi, B. Sklarz, *J. Am. Chem. Soc.* **1968**, *90*, 5325–5326; b) R. Grée, R. Carrié, *J. Am. Chem. Soc.* **1977**, *99*, 6667–6672; c) K. Tanaka, M. Ohsuga, Y. Sugimoto, Y. Okafuji, K. Mitsuhashi, *J. Fluorine Chem.* **1988**, *39*, 39–45; d) X. Dai, M. W. Miller, A. W. Stamford, *Org. Lett.* **2010**, *12*, 2718–2721; e) H. Abda, K. Aouadi, J. Brahmi, M. Msaddek, S. Vidal, C. R. Chimie **2016**, *19*, 275–278; f) S. Tangara, C. Aupic, A. Kanazawa, J.-F. Poisson, S. Py, *Org. Lett.* **2017**, *19*, 4842–4845.

[6] S. Tangara, A. Kanazawa, S. Py, *Eur. J. Org. Chem.* **2017**, 2017, 6357–6364.

[7] a) R. Grée, R. Carrié, *J. Am. Chem. Soc.* **1977**, *99*, 6667–6672.

[8] a) A. Padwa, Y. Tomioka, M. K. Venkatramanan, *Tetrahedron Lett.* **1987**, *28*, 755–758; b) P. Parpani, G. Zecchi, *J. Org. Chem.* **1987**, *52*, 1417–1421; c) A. Padwa, D. N. Kline, K. F. Koehler, M. Matzinger, M. K. Venkatramanan, *J. Org. Chem.* **1987**, *52*, 3909–3917; d) A. Padwa, M. Matzinger, Y. Tomioka, M. K. Venkatramanan, *J. Org. Chem.* **1988**, *53*, 955–963; e) A. Padwa, W. H. Bullock, D. N. Kline, J. Perumattam, *J. Org. Chem.* **1989**, *54*, 2862–2869; f) B.-X. Zhao, S. Eguchi, *Tetrahedron* **1997**, *53*, 9575–9584;

g) X.-J. Wang, J.-T. Liu, *Chin. J. Chem.* **2007**, *25*, 649–652; h) U. Amrutha, B. P. Babu, S. Prathapan, *J. Heterocycl. Chem.* **2019**, *56*, 3236–3243; i) R. Hammami, P. Maldivi, C. Philouze, S. Carret, B. Darses, S. Touil, J.-F. Poisson, *Adv. Synth. Catal.* **2023**, *365*, 1385–1390; j) R. Hammami, L. Mele, S. Touil, D. Virieux, T. Ayad, J.-F. Poisson, B. Darses *Eur. J. Org. Chem.* **2025**, DOI: 10.1002/ejoc.202500390.

[9] M. C. Aversa, G. Cum, N. Uccella, *J. Chem. Soc. D, Chem. Commun.* **1971**, 156–157; b) G. Cum, G. Sindona, N. Uccella, *J. Chem. Soc. Perkin Trans. 1* **1976**, 719–721.

[10] J. J. Tufariello, S. A. Ali, H. O. Klingele, *J. Org. Chem.* **1979**, *44*, 4213–4215.

[11] Activation energies for conformers 1 to 3 are detailed in Tables S2-S4 (see supporting information). Notably, for Conf.1 and Conf.3, some variations in PO(Ph)₂ group conformation were observed during the cleavage/recombination steps.

[12] The assistance of the slightly basic *N*-methylpyrroline-type products is probable. For pka of *N*-methylpyrroline = 10.46, see S. Searles, M. Tamres, F. Block, L. A. Quarterman, *J. Am. Chem. Soc.* **1956**, *78*, 4917–4920.

[13] H. Ryu, J. Park, H. K. Kim, J. Y. Park, S. T. Kim, M. H. Baik, *Organometallics* **2018**, *37*, 3228–3239.