Towards the Preparation of Stable Cyclic Amino(ylide)Carbenes

Cyclic amino(ylide)carbenes (CAYCs) are the ylide-substituted analogues of N-heterocyclic Carbenes (NHCs). Due to the stronger π donation of the ylide compared to an amino moiety they are stronger donors and thus are desirable ligands for catalysis. However, no stable CAYC has been reported until today. Here, we describe experimental and computational studies on the synthesis and stability of CAYCs based on pyrroles with trialkyl onium groups. Attempts to isolate two CAYCs with trialkyl phosphonium and sulfonium ylides resulted in the deprotonation of the alkyl groups instead of the formation of the desired CAYCs. In case of the PCy3-substituted system, the corresponding ylide was isolated, while deprotonation of the SMe2-functionalized compound led to the formation of ethene and the thioether. Detailed computational studies on various trialkyl onium groups showed that both the α- and β-deprotonated compounds were energetically favored over the free carbene. The most stable candidates were revealed to be α-hydrogen-free adamantyl-substituted onium groups, for which β-deprotonation is less favorable at the bridgehead position. Overall, the calculations showed that the isolation of CAYCs should be possible, but careful design is required to exclude decomposition pathways such as deprotonations at the onium group.


N-(2,6-Diisopropylphenyl)-3-methylthiopyrrol 10
A) A solution of 1.14 g (3.04 mmol, 1.00 eq) dimethyl-(N-(2,6-diisopropylphenyl)pyrrol)sulfonium tetrafluoroborate 9 in 10 mL THF was cooled to -78 °C and 3.40 mL (68.74 mg, 3.13 mmol, 1.03 eq) of a 0.92 M methyllithium solution in diethyl ether were added. After this, the solution turned brown, a solid precipitated and an evolution of gas was observed. After slowly warming the mixture to room temperature, the reaction was stirred for another 16 h. All volatile compounds were removed in vacuo and the brown crude product was purified by column chromatography (SiO2, nhexane/ethylacetate gradient). The product was thus obtained as colourless oil in 47 % (0.39 g, 1.42 mmol) yield.

Tricyclohexyl-(N-(2,6-diisopropylphenyl)pyrrol)phosphonium iodide 11
The compound was synthesized similar to a known procedure. [6] 2.46 g (879 mmol, 1.00 eq) tricyclohexylphosphine and 120.9 mg (439.5 μmol, 0.05 eq) bis(cycloocta-1,5-dien)nickel(0) were dissolved in 5 mL of ethanol. 3.11 g (8.79 mmol, 1.00 eq) N-(2,6diisopropylphenyl)-3-iodopyrrol were dissolved in 25 mL ethanol and added to the solution. The mixture was then heated to reflux for 16 h, resulting in a color change to red. The solution was diluted with 100 mLwater and extracted with DCM (3 x 100 mL). The combined organic layers were dried over magnesium sulphate and all volatile compounds removed in vacuo. The resulting solid was purified by column chromatography (n-hexan/ethyl acetate: gradient). The crude product was again dissolved in dichloromethane and precipitated with diethyl ether. The product was obtained as a colorless solid in 61 % (3.40 g, 5.37 mmol) yield. Single crystals suitable for X-ray diffraction analysis were obtained by diffusion of diethyl ether into a solution of the product in dichloromethane.

Dipp-Pyrr-PCy2=C6H10 12
A) 1.00 g (1.58 mmol, 1.00 eq) tricyclohexyl-(N-(2,6-diisopropylphenyl)pyrrol)-phosphonium iodide 11 was suspended in 30 mL of toluene and cooled to -100 °C. After addition of 1.72 mL (34.68 mg, 1.58 mmol, 1.0 eq) of a 0.92 M solution of methyllithium in diethylether, the mixture was allowed to warm to room temperature and stirred for 16 hours. After filtration all volatiles were removed in vacuo. The product 11 was obtained as yellow solid in 60 % (480.5 mg, 950.0 μmol) yield. The synthesis can also be performed in tetrahydrofuran. In this case the solvent must be exchanged to toluene before filtration. Single crystals suitable for X-ray diffraction analysis were obtained by diffusion of n-hexane in a solution of 12 in THF.
A) 126.74 g (200.0 μmol, 1.00 eq) tricyclohexyl-(N-(2,6-diisopropylphenyl)pyrrol)phosphonium iodide 11 was suspended in 2.5 mL of toluene and cooled to -70 °C. After addition of 0.1 mL (21.43 mg, 200.0 μmol, 1.0 eq) of a 2.0 M solution of lithium diisopropylamide in tetrahydrofurane/heptane/ethylbenzene, the mixture was allowed to warm to room temperature and stirred for 16 hours. Volatile compounds were removed in vacuo and the residue was dissolved in toluene. After filtration all volatiles were removed in vacuo. The crude product 11 was obtained as orange solid in 60 % (60.0 mg, 118.6 μmol) yield, containing 18 % of 11.

General
All computational studies were carried out without symmetry restrictions. If it was not possible to obtain starting coordinates from crystal structures either GaussView 3.0 [13] or GaussView 6.0 [14] were used. Calculations were performed either with the Gaussian09 Revision E.01 [15], the Gaussian16 Revision B.01 [16] or the Gaussian16 Revision C.01 [17] program packages using Density-Functional Theory (DFT) [18,19]. Energy optimizations were carried out with the PBE0 [20] functional and def2svp basis set [21] together with GRIMMES D3 dispersion correction with Becke-Johnson damping [22][23][24]. To determine the nature of the structure harmonic vibrational frequency analyses were performed on the same level of theory. [25] No imaginary frequencies were observed for the ground states, for transition states one imaginary frequency corresponding to the translational motion was observed.