Pyridinylidenaminophosphines: Facile Access to Highly Electron‐Rich Phosphines

Abstract Electron‐rich tertiary phosphines are valuable species in chemical synthesis. However, their broad application as ligands in catalysis and reagents in stoichiometric reactions is often limited by their costly synthesis. Herein, we report the synthesis and properties of a series of phosphines with 1‐alkylpyridin‐4‐ylidenamino and 1‐alkylpyridin‐2‐ylidenamino substituents that are accessible in a very short and scalable route starting from commercially available aminopyridines and chlorophosphines. The determination of the Tolman electronic parameter (TEP) value reveals that the electron donor ability can be tuned by the substituent pattern at the aminopyridine backbone and it can exceed that of common alkylphosphines and N‐heterocyclic carbenes. The potential of the new phosphines as strong nucleophiles in phosphine‐mediated transformations is demonstrated by the formation of Lewis base adducts with CO2 and CS2. In addition, the coordination chemistry of the new phosphines towards CuI, AuI, and PdII metal centers has been explored, and a convenient procedure to introduce the most basic phosphine into metal complexes starting from air‐stable phosphonium salt is described.


Synthesis of phosphines 2a-d and 4a-d
General Procedure a) using excess imine as base: The pyridinium salt (2 eq.) and KHMDS (2 eq.) were suspended in THF (10 mL*mmol -1 ) and stirred for 16 h. PClR2 (1 eq.) was added dropwise at room temperature. After 3 h all volatile compounds were removed in vacuo and the residue was extracted with nhexane (3 x 20 mL) to give the corresponding phosphine. General Procedure b) using KHMDS as base: Pyridinium salt 1a (1 eq.), KHMDS (2 eq.) and PClR2 (1 eq.) were suspended in THF (10 mL*mmol -1 ). After 3 h all volatile compounds were removed in vacuo and the residue was extracted with n-hexane (3 x 20 mL) to give the corresponding phosphine.

Synthesis of 5a-b and 6a-b Compound 5a
Pyridinium salt 3a (720 mg, 3.54 mmol, 3.1 eq.) and NEt3 (1.1 mL, 8.00 mmol, 7 eq.) were suspended in DCM (25 mL). At -78 °C PCl3 (0.1 mL, 1.14 mmol, 1 eq.) was added dropwise and the solution was allowed to warm to room temperature. All volatile compounds were removed in vacuo and the residue was redissolved in a minimum amount of MeOH. NaBF4 (188 mg, 1.72 mmol, 1.5 eq.) was added and the solution was cooled to -78 °C (Note that the low temperature is necessary owing to the good solubility of 5a in MeOH). The precipitate was filtered off, washed with MeOH at -78 °C and dried at 50 °C in vacuo for 16 h. Yield: 423 mg (0.877 mmol, 77%).

Compound 10
A solution of [Pd(allyl)Cl]2 (15 mg, 0.041 mmol, 1 eq.) in THF (2 mL) was added dropwise to a solution of 6b (36 mg, 0.082 mmol, 2 eq.) in THF (5 mL) at -78 °C. The mixture was allowed to warm to room temperature and all volatile compounds were removed in vacuo to afford 10 as yellow powder in quantitative yield.

Compound 11
A solution of [CuOTf]2•toluene (24 mg, 0.046 mmol, 1 eq.) in toluene (5 mL) was added dropwise to a solution of 6b (80 mg, 0.184 mmol, 4 eq.) in toluene (5 mL) at -78 °C. The reaction mixture was allowed to warm to room temperature and all volatile compounds were removed in vacuo to afford 11 as yellow powder in quantitative yield.               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 nylon loops and then immediately placed in a cold stream of N2 on a diffractometer. Using Olex2, 9 the structures were solved with the Superflip 10 structure solution program using Charge Flipping and refined with the ShelXL 11 refinement package using Least Squares minimisation.

Single-crystal X-ray structure analysis of 2d:
Single crystals were obtained by slow cooling of a saturated n-hexane solution of 2d. A single-crystal Xray structure analysis revealed that 2d crystallizes in the monoclinic space group P21/n. The asymmetric unit contains one molecule of 2d. Figure S85: Molecular view of 2d in the solid state with thermal ellipsoid plot at the 50% levels of probability. Hydrogen atoms are omitted for clarity. Single-crystal X-ray structure analysis of 6b: Single crystals were obtained by slow cooling of a saturated n-hexane solution of 6b. A single-crystal Xray structure analysis revealed that 6b crystallizes in the trigonal space group P3 ̅ . The asymmetric unit contains ⅓ molecule of 6b. The phosphorus atom is dosordered over two positions with (95:5) relative occupancy. Figure S86: Molecular view of the asymetric unit of 6b in the solid state with thermal ellipsoid plot at the 50% levels of probability. Hydrogen atoms are omitted for clarity. Single-crystal X-ray structure analysis of 7: Single crystals were obtained by slow cooling of a saturated THF solution of 7. A single-crystal X-ray structure analysis revealed that 7 crystallizes in the monoclinic space group P21/c. The asymmetric unit contains one molecule of 7. Figure S87: Molecular view of 7 in the solid state with thermal ellipsoid plot at the 50% levels of probability. Hydrogen atoms are omitted for clarity. Single-crystal X-ray structure analysis of 8: Single crystals were obtained by slow diffusion of n-hexane into a solution of 8 in THF. A single-crystal Xray structure analysis revealed that 2c crystallizes in the monoclinic space group C2/c. The asymmetric unit contains one molecule of 8. The n-butyl group is disordered over two position with relative occupancies of 69:31. The PLATON SQUEEZE program was used to treat two severely disordered THF solvate molecules.  Single-crystal X-ray structure analysis of 9: Single crystals were obtained by slow diffusion of Et2O into a solution of 9 in DCM. A single-crystal X-ray structure analysis revealed that 9 crystallizes in the monoclinic space group P21/c. The asymmetric unit contains two molecules of 9 and one molecule of CH2Cl2. One pyridinyl-4-ylidenamino substituent is disordered over two positions (occupancies: 83% and 17%) and the CH2Cl2 molecules is distorted over three positions (occupanccies: 50%, 35% and 15%).  Single-crystal X-ray structure analysis of 10: Single crystals were obtained by slow diffusion of Et2O in a solution of 10 in DCM. A single-crystal X-ray structure analysis revealed that 10 crystallizes in the monoclinic space group P21/n. The asymmetric unit contains two molecules of 10. Figure S90: Molecular view of 10 in the solid state with thermal ellipsoid plot at the 50% levels of probability. Hydrogen atoms are omitted for clarity.