Terminal methylene phosphonium ions: precursors for transient monosubstituted phosphinocarbenes

Isolable singlet carbenes are among the most important tools in chemistry, but generally require the interaction of two substituents with the electron deficient carbon atom. We herein report a synthetic approach to monosubstituted phosphinocarbenes via deprotonation of hitherto unknown diprotic terminal methylene phosphonium ions. Two methylene phosphonium salts bearing bulky N-heterocyclic imine substituents at the phosphorus atom were isolated and fully characterized. Deprotonation studies indicate the formation of transient monosubstituted carbenes that undergo intermolecular cycloadditions or intramolecular Buchner ring expansion to afford a cycloheptatriene derivative. The reaction mechanism of the latter transformation was elucidated using DFT calculations, which reveal the ambiphilic nature of the phosphinocarbene enabling the insertion into the aromatic C–C bond. Additional computational studies on the role of substituent effects are presented.


Preparation of 2a
Bis((1,3-di-tert-butylimidazolidin-2-ylidene)amino)phosphenium chloride ([1a]Cl) (4.36 mmol, 2.00 g, 1.00 eq.) was suspended in tetrahydrofuran (50 mL). The mixture was cooled to -78°C and a solution of methylmagnesium chloride in tetrahydrofuran (3 M, 1.45 mL, 1.00 eq.) was quickly added. The reaction mixture was immediately allowed to warm up to 21 °C and was stirred for 16 h. All volatiles were removed in vacuo. The crude product was extracted with n-hexane (50 mL). After the solvent was removed in vacuo, the product was obtained as a white crystalline powder.
Note: The NMR signals were assigned using 2D-NMR experiments (vide infra).

Preparation of 2b
To a suspension of [1b]Cl (1.15 mmol, 1.00 g, 1.00 eq.) in tetrahydrofuran (30 mL) methylmagnesium chloride in tetrahydrofuran (3 M, 0.38 mL, 1.00 eq.) was added at 21 °C. The solution was stirred for 12 h. Subsequently, all volatiles were removed in vacuo. The residue was suspended in a mixture of toluene and nhexane (1:1, 50 mL) and the suspension was filtrated. All volatiles were removed in vacuo and the product was obtained as a pale yellow solid.
Note: The NMR signals were assigned using 2D NMR experiments (vide infra).

Preparation of [3a]I
2a (3.96 mmol, 1.74 g, 1.00 eq.) was dissolved in diethyl ether (50 mL). The clear solution was cooled to -78°C via a dry ice/acetone cooling bath. While vigorously stirring the solution, a freshly prepared stock solution of iodine in diethyl ether (0.442 M, 3.96 mmol, 1.00 eq.) was added dropwise directly into the vortex of the stirred mixture over a time span of 30 minutes. The suspension was stirred for 16 h while keeping it in the cold bath, concurrently allowing the reaction mixture to warm up to 21 °C over a time span of several hours. The white precipitate was isolated via filtration and washed subsequently with tetrahydrofuran (2x10 mL) and diethyl ether (2x10 mL). The residue was dried in vacuo at 21 °C for 2 h. The product was obtained as a white, slightly sticky powder.
Note: The NMR signals were assigned using 2D-NMR experiments (vide infra). Too weak stirring will result in the formation of an unidentified byproduct. A slight excess of iodine will result in the formation of red [3a]I3, which can be partially washed out with tetrahydrofuran in the workup (vide infra).

Preparation of [4a]I
[3a]I (2.88 mmol, 2.00 g, 1.00 eq.) was suspended in tetrahydrofuran (50 mL) and cooled to -78°C. While stirring the suspension, a solution of KHMDS (588 mg, 2.95 mmol, 1.02 eq) in tetrahydrofuran (3 mL) was quickly added and the mixture was immediately allowed to warm up to 21 °C. While warming up, the yellow mixture turned white. The mixture was further stirred for 3 h at 21 °C. Afterwards, all volatiles were removed in vacuo. The crude product was extracted in CH2Cl2 (5 mL). To crystallize the product, diethyl ether was diffused into the solution for 16 h to afford colorless blocks, which were isolated by pipetting off the mother liquor and drying the crystals in vacuo at 21 °C for 2 h.

Preparation of [4a]BArF24
[4a][I] (1.58 mmol, 890 mg, 1.00 eq.) was dissolved in CH2Cl2 (5 mL) and added to NaBArF24 (1.58 mmol, 1.40 g, 1.00 eq.). The mixture was stirred at 21°C for 3 h. Afterwards, the suspension was passed through a glass filter and the precipitate was discarded. All volatiles of the solution were removed in vacuo. The product was obtained as a white, powdery solid.

Crude 31 P NMR spectrum containing [4b]OTf
Figure S 69: 31 P NMR (162 MHz, 300 K) spectrum of the crude mixture containing [4b]OTf in C6D6/fluorobenzene. The signal marked with a section sign ( §) can be assigned to structural isomers of [4b]OTf within the Dipp group due to isomeric impurities in the 2,6-diisopropylaniline employed for its synthesis. This observation was already reported in a previous study using the same starting materials. 2 §

Characterization data of [7]BArF24
[4a]BArF24 (0.075 mmol, 98 mg, 1.0 eq.) was dissolved in tetrahydrofuran (2 mL) and filled into a Schlenk tube. The solution was cooled to -78°C. While stirring, KHMDS (0.075 mmol, 15 mg, 1.0 eq.) in tetrahydrofuran (2 mL) was added via a syringe. Immediately, the reaction was allowed to warm up to 21°C. The mixture was stirred at 21°C for 17 h. Afterwards, the volatiles were removed in vacuo. The product was not isolated. Mass of crude product: 73 mg.
Note: The NMR signals were assigned using 2D NMR experiments (vide infra).

Deprotonation study of [4a]BArF24
General procedure: [4a][BArF24] was dissolved in the respective solvent. The solution was brought to the respective temperature. The base was quickly added and the reaction was allowed to warm up to 21°C. Afterwards, the reaction was analyzed via 31 P and 31 P{ 1 H} NMR. The results are summarized in Table S 1.

Preparation of 8
To a mixture of [3b]OTf (0.08 mmol, 92 mg, 1.0 eq.) and KOtBu (0.36 mmol, 40 mg, 4.5 eq.), diethyl ether (3 mL) was added at 21 °C and the suspension was stirred for 16 h. Subsequently, all volatiles were removed in vacuo. The residue was extracted with n-hexane (2x5 mL) and the obtained yellow solution was concentrated until crystal formation. The mixture was heated again until dissolution of the crystals, then slowly cooled to 21 °C and then stored at -40 °C.
The product was isolated as yellow crystals.
Note: The NMR signals were assigned using 2D NMR experiments (vide infra).

X-ray Diffraction Studies
General: Single-crystal X-ray diffraction data were collected on a Bruker AXS detector using Mo-K radiation ( = 0.71073 Å). Crystals were selected under oil, mounted on glass capillaries and then immediately placed in a cold stream of N2 on a diffractometer. Using Olex2, 3 the structures were solved with the Superflip 4 structure solution program using Charge Flipping, SIR2004 5 using direct methods or ShelXT 6 using Intrinsic Phasing and refined with the ShelXL 7 refinement package using Least Squares minimisation. 8 Crystallographic  Figure S87: The structure is an inversion twin. The asymmetric unit contains two molecules of 2b. One N2PC fragment, two isopropyl groups and one methyl group are disordered over two positions (see atom labels).    Figure S93: The asymmetric unit contains two molecules of [4b]OTf. One isopropyl group is disordered over two positions with a ratio of 3:7 and one OTfanion is disordered over three positions (0.71:0.15:0.14).

2.9
Crystal structure data of compound 8

Computational studies 3.1 General
All calculations were executed using Gaussian16 9 employing the B3LYP 10 functional in conjunction with def2-TZVP 11 basis sets and empirical GD3BJ dispersion correction. 12 Calculations in implicit solvent were done employing the SMD solvation model. 13 Figure S95: Optimized geometries of the reaction G(left)→ GH ‡ 1−2 → H(right) obtained at B3LYP-GD3BJ/def2-TZVP level of theory, the upper transition state is targeting the methyl-bound carbon atom of the phenyl ring, the lower is targeting the nitrogen-bound carbon leading to the cyclopropane formation in H.           Table S4-S6 and the corresponding electrostatic surface potential plots are depicted in Figure S99. The NBO partial charges of the phosphorus atoms in [3a] + and [3b] + are 1.842e and 2.238e, respectively, suggesting a higher electrophilicity for [3b] + . This finding is in line with the assumption of electron transfer to the P atom as an alternative reaction pathway for deprotonation of the methyl group attached to phosphorus. Note that the hydrogen atoms of the methyl group at the phosphorus atom feature higher positive partial charges (Mulliken and NBO analysis) than other hydrogen atoms in the molecule, which is a direct indication of higher acidity.