Crystal structure of 2-(2,6-diisopropylphenyl)-N,N-diethyl-3,3-dimethyl-2-azaspiro[4.5]decan-1-amine: a diethylamine adduct of a cyclic(alkyl)(amino)carbene (CAAC)

A diethylamine adduct of a cyclic(alkyl)(amino)carbene was synthesized and characterized by single-crystal X-ray diffraction and NMR spectroscopy.


Chemical context
Cyclic (alkyl)(amino)carbenes (CAACs) are a class of singlet carbenes featuring a carbene center flanked by one amino substituent and an alkyl substituent. Compared to N-heterocyclic carbenes (NHCs), CAACs are simultaneously stronger -donors and stronger -acceptors (Melaimi et al., 2017). These properties, along with the distinctive CAAC steric environment imparted by the quaternary carbon adjacent to the carbene center, have enabled the application of CAACs as ligands to stabilize unusual transition-metal (Roy et al., 2016) and main-group compounds (Soleilhavoup & Bertrand, 2015).
As a result of their strong electrophilicity, CAACs are capable of activating strong bonds, including H-H, N-H, P-H, Si-H, and B-H bonds (Frey et al., 2007(Frey et al., , 2010. Analogous oxidative addition reactivity has also been observed for other classes of electrophilic carbenes, including N,N 0 -diamidocarbenes (DACs) (Hudnall et al., 2010;Moerdyk et al., 2013;Chase et al., 2014;Lastovickova & Bielawski, 2016). Despite this rich reactivity, these carbene oxidative addition reactions are typically irreversible. However, a recent report demonstrated that a CAAC with a sterically demanding menthol-derived quaternary carbon substituent undergoes N-H and P-H reductive eliminations (Tolentino et al., 2019). This established the reversibility of oxidative addition and reductive elimination reaction at carbon centers, and suggests that CAACs and other electrophilic carbenes may be able to perform catalytic coupling reactions.

Structural commentary
The molecular structure of the title compound is presented in Fig. 2, and selected geometric parameters are summarized in Table 1. As expected, X-ray diffraction analysis confirmed the pyramidalization of the former carbene carbon center (the sum of the N1-C1-C2, N1-C1-N2, and C2-C1-N2 angles is 337.79 ), consistent with sp 3 hybridization. The C-NEt 2 (C1-N2) bond length [1.4675 (14) Å ] is a typical distance for a carbon-nitrogen single bond (Allen et al., 1987) and is similar to bond distances observed for previously reported CAAC N-H insertion products (see Database Survey section below).

Figure 3
View of the four molecules of the title compound in the unit cell. Displacement ellipsoids are drawn at the 50% probability level. H atoms are omitted for clarity.

Supramolecular features
Four molecules of the title compound are present in the unit cell, as shown in Fig. 3. The methylene group at the 4-position of the cyclohexyl ring is oriented towards the aryl ring of the 2,6-diisopropylphenyl group of the neighboring molecule, with a distance of 2.790 Å between the aryl ring centroid (C16-C21) and the nearest methylene hydrogen atom (H7B). The molecules are oriented such that the 3-position of the cyclohexyl ring of one molecule is adjacent to a methyl group at the gem-dimethyl position of a neighboring molecule, with a distance of 2.387 Å between nearest hydrogen atoms (H8B Á Á Á H10B) (Fig. 4).

Synthesis and crystallization
The synthesis of 2-(2,6-diisopropylphenyl)-N,N-diethyl-3,3dimethyl-2-azaspiro[4.5]decan-1-amine is summarized in Fig. 1. All solvents were dried by passage through solvent purification columns (JC Meyer) and stored over activated 3 Å molecular sieves. Lithium diethylamide (Sigma-Aldrich) and 2-(2,6-diisopropylphenyl)-3,3-dimethyl-2-azaspiro[4.5]dec-1-en-2-ium hydrogen dichloride (TCI America) were used as received. Celite (Aldrich) was dried under vacuum at 473 K for 48 h before use. The 1 H and 13 C NMR spectra were recorded on a Bruker AVANCE III 400 MHz NMR spectrometer at 298 K. The 1 H NMR spectrum was calibrated internally to resonances for the residual proteo solvent relative to tetramethylsilane. The 13 C NMR spectrum was calibrated to the solvent resonance relative to tetramethylsilane. Spectra were analyzed using MestReNova Ver. 14.2.0 software. In a nitrogen-atmosphere glovebox, a cold (258 K) solution of lithium diethylamide (99 mg, 1.3 mmol) in 8 mL of THF was added dropwise to a stirred cold (258 K) suspension of 2-(2,6diisopropylphenyl)-3,3-dimethyl-2-azaspiro[4.5]dec-1-en-2ium hydrogen dichloride (250 mg, 0.63 mmol) in 5 mL of THF. The orange solution was slowly warmed to room temperature. After 24 h, volatiles were removed in vacuo to afford a pale orange solid. After extraction with pentane (2 Â 20 mL) and filtration through Celite on a fritted funnel, evaporation of volatiles in vacuo afforded a pale orange solid. Single crystals suitable for X-ray analysis were grown by slow evaporation of a pentane solution of the crude product at 258 K, which led to the formation of colorless block-like crystals of the title compound (115 mg, 46% yield).

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. A colorless crystal of approximate dimensions 0.191 x 0.248 x 0.250 mm was mounted in a cryoloop and transferred to a Bruker SMART APEX II diffractometer. The APEX2 program package was used to determine the unitcell parameters and for data collection (25 sec/frame scan time). The raw frame data was processed using SAINT and SADABS to yield the reflection data file. Subsequent calculations were carried out using the SHELXTL program package. The diffraction symmetry was 2/m and the systematic absences were consistent with the monoclinic space group P21/n that was later determined to be correct. The structure was solved by direct methods and refined on F2 by full-matrix least-squares techniques. The analytical scattering factors for neutral atoms were used throughout the analysis. Hydrogen atoms were included using a riding model. Least-squares analysis yielded wR2 = 0.1207 and Goof = 1.018 for 270 variables refined against 6744 data (0.72 ), R1 = 0.0482 for those 5087 data with I > 2.0sigma(I).