Palladium-Catalyzed Synthesis of Amidines via tert-Butyl isocyanide Insertion.

Para-substituted iodobenzenes were reacted with tert-butyl isocyanide and piperidine as nucleophiles in the presence of palladium-diphosphine catalysts. Both single and double insertion of the isocyanide was observed and the corresponding amidines and ketimine-amidines were obtained in yields of practical interest. With the increase of the tert-butyl isocyanide/iodobenzene ratio, 100% chemoselectivity toward the ketimine-amidine was achieved. The formation of the products was rationalized on the basis of a catalytic cycle analogous to that of the aminocarbonylation reactions. Clear connection was found between the activity and the electronic structure of the proposed catalyst Pd(diphosphine) by computational studies, as the more negative partial charge on palladium resulted in higher conversion. Among five isocyanide substrates, only tert-butyl isocyanide was proved to be active.

Introduction

Palladium-catalyzed migratory insertion of n class="Chemical">carbon monoxide in the presence of O- and N-nucleophiles, i.e., the alkoxycarbonylation and aminocarbonylation reactions, is among the most widely used homogeneous catalytic reactions in synthetic chemistry.[1] Their importance could be illustrated by the synthesis of simple building blocks and by the functionalization of compounds of biological relevance.[2]

Due to the isoelectronic structure of carbon monoxide and its electron-rich analogue, n class="Chemical">N-alkyl/aryl isocyanide, described by related resonance structures (Figure ), similar palladium-catalyzed homogeneous catalytic reactions resulting in amidines (carboximidamides) and imidates (carboximidates) have been described and reviewed recently.[3] The amidines and imidates, potentially available in the presence of N- and O-nucleophiles, respectively, can be considered as compounds related to the corresponding carboxamides or esters. In spite of the close analogy, the insertion of isocyanides in palladium-catalyzed reactions is less explored and has several limitations both from the side of the substrate and the isocyanide derivative.

Figure 1

Resonance structures of carbon monoxide and alkyl isocyanide.

Resonance structures of carbon monoxide and n class="Chemical">alkyl isocyanide.

A ferrocene-based n class="Chemical">rigid diphosphine, dppf, proved to be the most efficient ligand in the palladium-catalyzed imidoylative (“isonitrile insertive”) reaction of bromoaromatics.[4] Similarly, β-styryl bromide was reacted with tert-butyl isocyanide, primary/secondary amines, and alkoxides/phenoxides in the presence of the PdCl2–dppf catalyst. In the case of application of primary amines, the product exists entirely in the tautomeric form instead of the expected amidine form.[5] Bifunctional substrates possessing bromoarene functionality and a pendant arm with N- or O-nucleophile afforded cyclic amidines and imidates, respectively, in the palladium-catalyzed reaction.[6] Palladium-catalyzed double isocyanide insertion into the aryl halide bond resulted in the formation of α-iminoimidates in the presence of O-nucleophiles.[7] Recently, a palladium-catalyzed isocyanide insertion/cyclization sequence was used for the synthesis of quinazolinones.[8] Pyrazines and indols were synthesized from benzyl isocyanides via double isocyanide insertion.[9]

One of the most frequently used “isonitrile-free” methods, the nucleophilic addition of n class="Chemical">amines to nitrile functionality, was used for the synthesis of amidines in the presence of samarium(II) iodide.[10]

The use of amidines and their synthesis by conventional methods (other than homogeneous catalytic reactions) were shown by a review published as en class="Chemical">arly as 1944.[11] The high pharmacological importance of amidines (and guanidines) is reported in a book-chapter.[12] Transition metal-catalyzed N-arylation of amidines aiming at the synthesis of various compounds possessing pharmacological importance, agricultural importance, etc. was also reviewed.[13] Benzimidazole-based amidines, synthesized from the corresponding nitriles via amidate esters, have shown antibacterial and antifungal activities.[14] High-value cyclic and acyclic amidines can also be obtained according to a number of patents[15] (Scheme ). As a synthetic application of amidines, N,N′-bis(aryl) amidines were transformed into 1,2-disubstituted benzimidazoles via oxidative C–H amination.[16]

Scheme 1

Synthetic Applications for the Preparation of Amidines ((a) ref (15c), (b) ref (15b), (c) ref (15a))

As mentioned above, the close analogy of carbon monoxide and alkyl n class="Chemical">isocyanides (Figure ) encouraged us to investigate the insertion of the latter species using similar substrates. On the basis of the experiences in palladium-catalyzed carbonylation reactions,[17,18] a systematic investigation of the corresponding imidoylative reaction, i.e. the related isocyanide insertion was decided. The goal of this work was to apply this insertion reaction in a chemoselective manner toward the double insertion by careful selection of the reaction parameters and to examine the effect of para substituent on reactivity and selectivity. Ketimine–amidine derivatives have not yet been synthesized and described in previous studies. The double insertion was reported by Whitby et al.[7] and Wang et al.[8] only for the alkoxycarbonylation reaction. Our further objective was the elaboration of the influence of various bidentate phosphines upon the reaction activity and selectivity.

Results and Discussion

Investigation of the Insertion of tert-Butyl Isocyanide in the Palladium-Catalyzed Imidoylation of Iodoaromatics (1a–1q)

Para-substituted iodobenzenes were reacted with n class="Chemical">tert-butyl isocyanide and piperidine as N-nucleophiles in the presence of a palladium catalyst formed in situ from palladium(II) chloride and 1,1′-bis(diphenylphosphino)ferrocene (dppf). The mixture of two products was obtained in all cases, i.e., amidines (2a–2q) and ketimine–amidines (3a–3q) were formed due to simple and double tert-butyl isocyanide insertion, respectively (Scheme ). Other isonitriles such as 2-pentyl isocyanide, benzyl isocyanide, and 2-naphthyl isocyanide were also tested but resulted in no conversion. Although the steric effects cannot be excluded, the inactivity of isonitriles other than the tert-butyl isocyanide might be explained by the difference in the electron density distribution of the isonitrile functional group. According to Wiberg bond indices (WBIs) computed on natural atomic orbitals basis, the bond order decreases in the order of tert-butyl, 2-pentyl, benzyl, and naphthyl with the WBIs of 2.434, 2.428, 2.410, and 2.338, respectively.

Scheme 2

Palladium-Catalyzed Imidoylation of Iodoaromatics via Single and Double tert-Butyl Isocyanide Insertion

First, experiments were run to optimize the insertion reactions. It turned out that the ratio of the substrate to tert-butyl isocyanide is crucial, i.e., although close to complete conversions were achieved under the given conditions at 1:1.5 and 1:3 ratios (Table , entries 1 and 2), the conversion decreased dramatically when a 1:4 or higher ratio was used (entries 3–6). At the same time, chemoselectivity was shifted town class="Chemical">ard the ketimine–amidine derivative (3a). Compound 3a was formed in low yields but in a chemospecific reaction. Using bromobenzene (4a) instead of iodobenzene a lower conversion was achieved but the ratio of the amidine derivative (2a) was higher (entry 7). No insertion products (2a, 3a) were obtained with chlorobenzene (5a) (entry 8) as the substrate.

Table 1

Insertion of tert-Butyl Isocyanide Using Iodobenzene (1a), Chlorobenzene (4a), Bromobenzene (5a), in the Presence of the PdCl2/Diphosphine “In Situ” Catalyst and Piperidine as the N-Nucleophilea

					ratio of the insertion productsb (%)
entry	tBuNC (1a/4a/5a)	P–P	conv.b (%)	TOFc (h–1)	amidine (2a)	ketimine–amidine (3a)
1	1.5:1 (1a)	dppf	90	0.25	13	87
2	3:1 (1a)	dppf	92	0.26	38	62
3	4:1 (1a)	dppf	13	0.04	0	100
4	5:1 (1a)	dppf	10	0.03	0	100
5	6:1 (1a)	dppf	8	0.02	0	100
6	12:1 (1a)	dppf	8	0.02	0	100
7	1.5:1 (4a)	dppf	0
8	1.5:1 (5a)	dppf	58	0.16	80	20
9	1.5:1 (1a)	dppp	60	0.17	20	80
10	1.5:1 (1a)	dppe	55	0.15	13	87
11	1.5:1 (1a)	xantphos	>99	0.28	14	86
12	1.5:1 (1a)	PCy3	50	0.14	16	84
13	1.5:1 (1a)	PtBu3	61	0.17	24	76

Reaction conditions (unless otherwise stated): 1 mmol substrate (1a), 1.5–12 mmol of tert-butyl isocyanide, 5 mmol of piperidine, 0.05 mmol of PdCl2—0.05 mmol of diphosphine ((dppf), 1,3-bis(diphenylphosphino)propane (dppp), 1,2-bis(diphenylphosphino)ethane (dppe), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos)), 0.025 mmol of PdCl2—0.05 mmol of monophosphine (PPh3, PCy3, PtBu3), 2 mmol of K2CO3, 10 mL of toluene, 105 °C, reaction time: 72 h.

Determined by gas chromatography–mass spectrometry (GC–MS).

Moles of converted substrate/(moles of catalyst × time).

Reaction conditions (unless otherwise stated): 1 mmol substrate (1a), 1.5–12 mmol of tert-butyl isocyanide, 5 mmol of n class="Chemical">piperidine, 0.05 mmol of PdCl2—0.05 mmol of diphosphine ((dppf), 1,3-bis(diphenylphosphino)propane (dppp), 1,2-bis(diphenylphosphino)ethane (dppe), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos)), 0.025 mmol of PdCl2—0.05 mmol of monophosphine (PPh3, PCy3, PtBu3), 2 mmol of K2CO3, 10 mL of toluene, 105 °C, reaction time: 72 h.

A close analogy to carbonylation reactions, and especially, to aminocn class="Chemical">arbonylation reactions, can be made. As the increase of the carbon monoxide pressure (slightly) decreases the catalytic activity of the system due to the formation of palladium–dicarbonyl/tricarbonyl catalytic intermediates, the coordination of its electron-rich analogue (tert-butyl isocyanide) as a ligand (in excess) has a similar effect. At the same time, the increased concentration of the tert-butyl isocyanide resulted in double isonitrile insertion, i.e., the favored formation of 3a. (In the case of aminocarbonylation reaction, the application of elevated carbon monoxide pressure resulted in the preferred formation of 2-ketocarboxamides due to double CO insertion.)

In addition to dppf, three additional bidentate ligands, 1,3-bis(diphenylphosphino)propane (n class="Chemical">dppp), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos), and 1,2-bis(diphenylphosphino)ethane (dppe), and three monodentate ligands, triphenylphosphine (PPh3), tricyclohexylphosphine (PCy3), and tri-tert-butylphosphine (PtBu3) were tested. In all cases the formation of 3a was preferred. The catalytic activities of the Pd–dppp and Pd–dppe systems were lower than that of the xantphos-containing one (entries 9, 10 and 11). In the case of the dppe-ligand, the ratio of the products was a bit lower than in the presence of dppp, but chemoselectivity was practically the same as that obtained with dppf. The activities of Pd–PCy3 and Pd–PtBu3 systems (entries 12 and 13) were similar to those obtained with Pd–dppe and Pd–dppp systems. No conversion was obtained in the presence of PPh3.

Under the optimized conditions, a set of para-substituted n class="Chemical">iodobenzenes (1a–1q) were investigated in the same reaction (Table ). As observed for the parent substrate (1a), in general, a mixture of single and double inserted compounds (2 and 3, respectively) was obtained. Although the reaction tolerates a series of functionalities, the carboxyl and phenolic OH groups do not allow the formation of the target products.

Table 2

Insertion of tert-Butyl Isocyanide Using Four-Substituted Iodobenzenes (1a–1q) in the Presence of the PdCl2–dppf In Situ Catalyst and Piperidine as the N-Nucleophilea

					ratio of the insertion productsb (%)
entry	substrate	σp	conv.b (%)	TOFc (h–1)	amidine (2; yielde (%))	ketimine–amidine (3; yielde (%))
1	1a (H)	0	90	0.25	13 (2a; 62)	87 (3a; 68)
2	1b (NH2)	–0.66	98	0.27	65 (2b)	35 (3b; 25)
3	1b (NH2)d	–0.66	74	0.21	51 (2b)	49 (3b)
4	1c (OH)	–0.37	0	0	–(2c)	–(3c)
5	1d (OMe)	–0.27	60	0.17	20 (2d)	80 (3d; 68)
6	1e (tBu)	–0.20	69	0.19	27 (2e; 51)	73 (3e; 73)
7	1f (Me)	–0.17	98	0.27	61 (2f; 61)	39 (3f; 77)
8	1f (Me)d	–0.17	39	0.11	18 (2f)	82 (3f)
9	1g (iPr)	–0.15	63	0.18	21 (2g; 56)	79 (3g; 48)
10	1h (Ph)	–0.01	28	0.08	18 (2h)	82 (3h; 49)
11	1i (F)	0.06	99	0.28	36 (2i; 46)	64 (3i; 72)
12	1j (Cl)	0.23	25	0.07	20 (2j)	80 (3j; 62)
13	1k (Br)	0.23	78	0.22	33 (2k; 54)	67 (3k; 73)
14	1l (COOMe)	0.45	80	0.22	32 (2l; 42)	68 (3l; 45)
15	1m (COOH)	0.45	0	0	–(2m)	–(3m)
16	1n (C(O)Me)	0.50	95	0.26	43 (2n; 64)	57 (3n; 66)
17	1n (C(O)Me)d	0.50	80	0.22	26 (2n)	74 (3n)
18	1o (CF3)	0.54	98	0.28	49 (2o; 68)	51 (3o; 72)
19	1o (CF3)d	0.54	15	0.04	25 (2o)	75 (3o)
20	1p (CN)	0.66	95	0.26	50 (2p; 73)	50 (3p; 78)
21	1q (NO2)	0.78	98	0.27	50 (2q)	50 (3q; 48)
22	1q (NO2)d	0.78	37	0.10	70 (2q)	30 (3q)

Reaction conditions (unless otherwise stated): 1 mmol substrate (1a–1q), 1.5 mmol of tert-butyl isocyanide, 5 mmol of piperidine, 0.05 mmol of PdCl2, 0.05 mmol of dppf, 2 mmol of K2CO3, 10 mL of toluene, 105 °C, reaction time: 72 h.

Determined by GC–MS.

Moles of converted substrate/(moles of catalyst × time).

0.05 mmol of xantphos instead of dppf.

Yield of the isolated product based on the amount of the substrate (1a–1q).

Reaction conditions (unless otherwise stated): 1 mmol substrate (1a–1q), 1.5 mmol of tert-butyl isocyanide, 5 mmol of n class="Chemical">piperidine, 0.05 mmol of PdCl2, 0.05 mmol of dppf, 2 mmol of K2CO3, 10 mL of toluene, 105 °C, reaction time: 72 h.

0.05 mmol of xantphos instead of n class="Chemical">dppf.

Investigating the reactivity–Hammett substituent constant (σp) and the selectivity–Hammett substituent constant relations, no linear correlation can be established. High activities were obtained with substrates possessing both electron-releasing (entries 2, 7) and electron-withdrawing groups (entries 18, 21). Surprisingly low activity was observed in the case of phenyl- and chloro-substituted n class="Chemical">iodobenzenes (entries 10 and 12). These unexpected conversions might also be related to the complexity of the reaction mechanism (Scheme ). However, the lack of any correlation to Hammett substituent constants might indicate that the rate-determining step is not the oxidative addition. It should be one of the steps afterwards.

Scheme 3

Rationalization of the Formation of the Products Based on a Simplified Catalytic Cycle

Although the palladium–n class="Chemical">dppf and palladium–xantphos systems gave similar results with the parent iodobenzene (1a), the latter system featured slightly (compare entries 2 and 3, 16 and 17) or definitely lower (compare entries 7 and 8, 18 and 19) activity using para-substituted derivatives.

It is worth noting that the chloro- and bromo-substituted iodobenzenes (1j and 1k, respectively) react as an n class="Chemical">iodoarene only, i.e., no reaction occurred at the chloro- and bromoarene functionality (entries 12 and 13).

The formation of the two types of products can be rationalized on the basis of the reaction mechanism depicted in Scheme . The oxidative addition of substrate (I) is followed by tert-butyl n class="Chemical">isocyanide activation (II). The coordinated isocyanide is inserted into the Pd–aryl bond resulting in Pd-tert-butyliminoacyl intermediate (III). The coordination of the amine (HNRR1) is accompanied by HX elimination upon the influence of base (B) and Pd-tert-butyliminoacyl-amido key-intermediate (IV) is formed. There are two pathways for further reaction, i.e., either the catalytic cycle-A is closed via reductive elimination of the amidine product (2) and the coordinatively unsaturated Pd(0) complex is re-formed or the coordination of the “second” isocyanide (V) and its insertion into the Pd–N bond resulted in the formation of Pd-tert-butyliminoacyl-tert-butyliminocarbamoyl intermediate (VI). The reductive elimination of ketimine–amidine (3) leads to the Pd(0) complex closing cycle-B.

Computational Studies on Palladium(0)–Phosphine Complexes

The goal of the computational studies is to establish a relationship between the ligand electronic effects of palladium(0)–phosphine complexes and their catalytic activity. The electronic effects n class="Chemical">are addressed by quantum chemical descriptors, such as NPA charges and critical points within the framework of the Quantum theory of atoms in molecules (QTAIM) methodology.

The catalytic conversions, CO frequencies, and the electron density in the ring critical points (RCPs) are compiled in Table . The structures of the 14-electron n class="Chemical">Pd(0)–diphosphine complexes are depicted in Figure . The experimental conversion showed a notable difference depending on the various bidentate ligands. The lowest catalytic activity (55%) was obtained in the case of the dppe-ligand and the highest one (> 99%) was found for the xantphos-containing complex. These values show a reasonable correlation with the chelate angles and NPA charges of the palladium center. Not surprisingly, the bite angle increases with the increasing ring size from dppe to xantphos. Apart from the ring size, spanned by diphosphines and palladium, the difference in the structures of the Pd-complexes lies in the flexibility of the chelating ring as dppf[19] and xantphos[20] show much higher rigidity in comparison to dppe[21] and dppp.[22]

Table 3

Conversions, Pd NPA charges, and Electron Densities at the RCP for the Corresponding Complexes

ligand	conv. (%)	QPd	ρ(RCP)
dppe (4)	55	–0.004	0.0211
dppp (5)	60	–0.082	0.0119
dppf (6)	90	–0.139	0.0089
xantphos (7)	>99	–0.126	0.0131/0.0137a (0.0152)

The values belong to the two rings separated by bond path. The density at the bond critical point on the Pd and O bond path is given in parenthesis.

Figure 2

Computed structures of dppe–, dppp–, dppf–, and xantphos–Pd(0) complexes. Bond lengths are given in Å. NPA charges are written in gray. Bond angles (P–Pd–P) are written in blue.

Computed structures of dppe–, n class="Chemical">dppp–, dppf–, and xantphos–Pd(0) complexes. Bond lengths are given in Å. NPA charges are written in gray. Bond angles (P–Pd–P) are written in blue.

The values belong to the two rings separated by bond path. The density at the bond critical point on the n class="Chemical">Pd and O bond path is given in parenthesis.

To shed light on the charge density distribution in n class="Chemical">Pd(dppe) and Pd(xantphos) QTAIM calculations have been performed. Figure shows the contour maps of the Laplacian of the electron density (∇2ρ) as well as the bond paths of Pd(dppe) (a) and Pd(xantphos) (b) complexes. The Pd(xantphos) complex reveals a notable difference from the rest of the complexes as it has two ring critical points (RCPs), separated by a bond path connecting the Pd center and the oxygen. The ring critical point is the point within a ring where the electron density reaches its minimum. The presence of the bond path suggests a weak Pd–O interaction, however, the large distance between palladium and oxygen excludes the possibility for a covalent Pd–O bond.

Figure 3

Contour-line diagrams of the Laplacian of the electron density (∇2ρ(r)) for Pd(dppe) (a) and Pd(xantphos) (b).

Contour-line diagrams of the Laplacian of the electron density (∇2ρ(r)) for Pd(n class="Chemical">dppe) (a) and Pd(xantphos) (b).

Conclusions

Palladium-catalyzed aminoimidoylation was cn class="Chemical">arried out using para-substituted aryl halides as substrates. The single and double insertion of tert-butyl isocyanide resulted in the formation of amidines and ketimine–amidines, respectively. All iodobenzenes except for the 4-hydroxy- and 4-carboxy-iodobenzene can be practically fully converted, enabling the isolation of both types of products, i.e., the reaction tolerates a wide range of substituents. Bromobenzene resulted in moderate yield toward mainly the formation of the single insertion product. No catalytic conversion was achieved with chlorobenzene. By carrying out the reaction under optimized conditions isolated yields of practical importance can be obtained. A catalytic reaction applicable for the synthesis of amidines, and especially, ketimine–amidines of synthetic importance was developed. The ketimine–amidine derivative was synthesized with 100% chemoselectivity starting from iodobenzene as the substrate. The reaction conversion was found to be higher for catalysts possessing more basic diphosphines as reflected in the partial charge of the palladium center according to natural bond orbital (NBO) calculations. Among monotertiary phosphines the more basic P(tBu)3 and PCy3 resulted in moderate catalytic activity and selectivity, whereas in the presence of triphenylphosphine no conversion was achieved.

Experimental Section

General Procedures

NMR spectra (n class="Chemical">1H and 13C NMR) were recorded in CDCl3 using a Bruker Avance III 500 spectrometer at 500 and 125.7 MHz, respectively. Chemical shifts δ are reported in ppm relative to CHCl3 (7.26 and 77.00 ppm for 1H and 13C, respectively). Hewlett Packard 5830A gas chromatograph fitted with a capillary column coated with OV-1 (injector temp. 250 °C; oven: starting temp. 50 °C (hold-time 1 min), heating rate 15 °C min–1, final temp. 320 °C (hold-time 11 min); detector temp. 280 °C; carrier gas: helium (rate: 1 mL min–1)) as well as Agilent LC/MSD Trap XCT Plus (electrospray ionizer, eluent: methanol (0.2 v/v % acetic acid)) were used routinely for the immediate analysis of the reaction mixtures. An IMPACT 400 spectrometer (Nicolet) applying a DTGS detector in the region of 400–4000 cm–1 was used to record Fourier-transform infrared spectra in KBr pellets (mass of the samples: ca. 0.5 mg) with a resolution of 4 cm–1.

Imidoylation Experiments

In a typical experiment, a solution of PdCl2 (8.8 mg, 0.05 mmol), n class="Chemical">dppf (27.5 mg, 0.05 mmol), and 1 mmol iodo substrate (1a–1q) was dissolved in 10 mL of toluene under argon. tert-Butyl isocyanide (170 μL, 1.5 mmol) and piperidine (495 μL, 5 mmol) were added to the homogeneous yellow solution. The reaction was conducted for 72 h at 105 °C. Some metallic palladium was formed at the end of the reaction which was filtered off. (A sample of this solution was immediately analyzed by GC–MS.) The mixture was then concentrated and evaporated to dryness. The residue was dissolved in chloroform (20 mL) and washed three times with water (20 mL). The organic phase was thoroughly washed with brine (20 mL), dried over Na2SO4, and concentrated to a dark brown viscous material or yellow thick oil. Chromatography on alumina (activated, neutral) with chloroform/ethyl-acetate (was used from rate 9.5:0.5 to 6:4) yielded the desired compounds as yellow/gray/brown solids or highly viscous materials.

Characterization of the Products

(Z)-N-tert-Butyl-1-phenyl-1-(piperidin-1-yl)methanimine (2a)

δH (500 MHz, CDCl3) 7.66 (t, 6.48 Hz, n class="Chemical">1H, 4-Ph); 7.58 (t, 6.58 Hz, 2H, 3,5-Ph); 7.42 (d, 6.19 Hz, 2H, 2,6-Ph); 4.16 (br.s, 2H, CH2); 3.08 (br.s, 2H, CH2); 1.91 (br.s, 2H, CH2); 1.71 (br.s, 2H, CH2); 1.52 (br.s, 2H, CH2); 1.27 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 163.4; 132.5; 129.5; 129.4 (double intensity); 128.8 (double intensity); 58.0; 51.5; 50.9; 31.1 (triple intensity); 26.3; 26.2; 23.3. IR (KBr, (cm–1)): 1608 (CNN). MS m/z (rel. int. %): 244 (30), 187 (38), 104 (100), 84 (90), 57 (27); [found: C, 78.45; H, 9.28; N, 11.34; C16H24N2 requires C, 78.64; H, 9.90; N, 11.46%]; Rf (10:90 EtOAc/CHCl3): 0.34; yield: 18 mg (62%) brown highly viscous material,

(1Z,2Z)-N1,N2-di(tert-Butyl)-1-phenyl-2-(piperidin-1-yl)ethane-1,2-diimine (3a)

δH (500 MHz, CDCl3) 7.82 (br.s, n class="Chemical">2H, 2,6-Ph); 7.39 (br.s, 3H, 3,5-Ph); 3.55–3.04 (m, 4H, CH2); 1.59 (br.s, 4H, CH2); 1.50 (br.s, 2H, CH2); 1.41 (s, 9H, NC(CH3)3); 1.10 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 157.3; 150.4; 139.6; 132.3; 129.6; 128.5; 128.2; 127.6; 58.0; 53.4; 45.8; 31.5 (triple intensity); 29.6 (triple intensity); 26.0; 25.1. IR (KBr, (cm–1)): 1615 (CNN, CNC). MS m/z (rel. int. %): 327 (2), 270 (5), 244 (7), 214 (5), 167 (10), 160 (10), 111 (100), 103 (35), 57 (40); [found: C, 76.40; H, 9.71; N, 12.32; C21H33N3 requires C, 77.01; H, 10.16; N, 12.83%]; Rf (5:95 EtOAc/CHCl3): 0.80; yield: 174 mg (68%) dark brown powder, mp 55–56 °C.

4-[(1Z,2Z)-N-tert-Butyl-2-(tert-butylimino)-2-(piperidin-1-yl)ethanimidoyl]aniline (3b)

δH (500 MHz, CDCl3) 7.58 (br.s, n class="Chemical">2H, 3,5-Ph); 6.67 (d, 8.24 Hz, 2H, 2,6-Ph); 3.08 (m, 4H, 2 × CH2); 1.60 (br.s, 2H, CH2); 1.52 (m, 4H, 2 × CH2); 1.37 (s, 9H, NC(CH3)3); 1.21 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 156.2; 148.6; 130.0; 128.9 (double intensity); 114.4 (double intensity); 112.4; 57.9; 49.5; 46.2; 31.0; 29.7; 25.5; 24.6. IR (KBr, (cm–1)): 1600 (CNN, CNC). MS m/z (rel. int. %): 342 (>1), 286 (3), 259 (5), 175 (27), 119 (100), 111 (72), 84 (10), 57 (15). [found: C, 70.72; H, 8.77; N, 14.61; C21H34N4 requires C, 73.64; H, 10.01; N, 16.36%]; Rf (30:70 EtOAc/CHCl3): 0.22; yield: 29 mg (25%) brown highly viscous material.

(1Z,2Z)-1-(4-Methoxyphenyl)-N1,N2-di(tert-butyl)-2-(piperidin-1-yl)ethane-1,2-diimine (3d)

δH (500 MHz, CDCl3) 7.72 (br.s, n class="Chemical">2H, 3,5-Ph); 6.96 (d, 6.83 Hz, 2H, 2,6-Ph); 3.87 (s, 3H, OCH3); 3.54 (m, 4H, 2 × CH2); 1.64 (m, 6H, 3 × CH2); 1.39 (s, 9H, NC(CH3)3); 1.29 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 163.7; 162.8; 162.0; 130.7; 128.8; 121.2; 114.8; 58.9; 57.7; 55.5; 31.2; 30.4; 29.5; 26.3; 23.8. IR (KBr, (cm–1)): 1603 (CNN, CNC). MS m/z (rel. int. %): 357 (<1), 300 (5), 274 (5), 244 (6), 217 (3), 190 (28), 167 (12), 134 (99), 111 (100), 84 (5), 57 (22); [found: C, 72.86; H, 9.53; N, 10.95; C22H35N3O requires C, 73.91; H, 9.87; N, 11.75%]; Rf (10:90 EtOAc/CHCl3): 0.62; yield: 116 mg (68%) dark brown highly viscous material.

(Z)-1-(4-tert-Butylphenyl)-N-tert-butyl-1-(piperidin-1-yl)methanimine (2e)

δH (500 MHz, CDCl3) 7.57 (d, 8.26 Hz, n class="Chemical">2H; 3,5-Ph); 7.34 (d, 8.05 Hz, 2H, 2,6-Ph); 4.2 (s, 2H, CH2); 3.1 (s, 2H, CH2); 1.93 (s, 2H, CH2); 1.73 (s, 2H, CH2); 1.55 (s, 2H, CH2); 1.40 (s, 9H, NC(CH3)3); 1.29 (s, 9H, C(CH3)3). δC (125.7 MHz, CDCl3) 156.5; 131.2; 128.7; 126.2; 57.9; 51.6; 50.9; 35.2; 31.1; 26.4; 26.2; 23.4. IR (KBr, (cm–1)): 1607 (CNN). MS m/z (rel. int. %): 300 (29), 285 (25), 243 (29), 160 (100), 84 (95), 57 (17); [found: C, 78.98; H, 10.08; N, 8.76; C20H32N2 requires C, 79.94; H, 10.73; N, 9.32%]; Rf (15:85 EtOAc/CHCl3): 0.32; yield: 28 mg (51%) dark brown solid, mp 147–148 °C.

(1Z,2Z)-N1,N2-di(tert-Butyl)-1-(piperidin-1-yl)-2-[4-tert-butylphenyl]ethane-1,2-diimine (3e)

δH (500 MHz, CDCl3) 7.70 (d, 7.23 Hz, n class="Chemical">2H; 3,5-Ph); 7.39 (d, 7.58 Hz, 2H, 2,6-Ph); 3.46 (br.s, 4H, 2 × CH2); 1.81 (br.s, 2H, CH2); 1.50 (br.s, 4H, 2 × CH2); 1.40 (s, 9H, NC(CH3)3); 1.35 (s, 9H, C(CH3)3); 1.08 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 157.1; 150.6; 136.9; 127.3; 126.8; 126.2; 125.0; 60.2; 57.8; 53.4; 34.7; 31.5; 31.2; 29.6; 25.9. IR (KBr, (cm–1)): 1614 (CNN, CNC). MS m/z (rel. int. %): 383 (<1), 326 (3), 300 (5), 216 (18), 160 (82), 111 (100), 57 (24); [found: C, 77.73; H, 9.69; N, 10.53; C25H41N3 requires C, 78.27; H, 10.77; N, 10.95%]; Rf (5:95 EtOAc/CHCl3): 0.54; yield: 141 mg (73%) dark brown highly viscous material.

(Z)-N-tert-Butyl-1-(4-methylphenyl)-1-(piperidin-1-yl)methanimine (2f)

δH (500 MHz, CDCl3) 7.68 (br.s, n class="Chemical">2H, 3,5-Ph); 7.26 (d, 7.16 Hz, 2H, 2,6-Ph); 3.58 (m, 4H, 2 × CH2); 2.43 (s, 3H, Ar-CH3); 1.41 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 130.0; 129.7 (double intensity); 128.9; 127.1 (double intensity); 126.9; 59.2; 49.8; 30.2; 29.5 (triple intensity); 26.0; 21.4. IR (KBr, (cm–1)): 1614 (CNC). MS m/z (rel. int. %): 285 (<1), 259 (23), 201 (25), 118 (100), 84 (72), 57 (15); [found: C, 78.55; H, 9.43; N, 10.72; C17H26N2 requires C, 77.37; H, 10.33; N, 12.30%]; Rf (20:80 EtOAc/CHCl3): 0.51; yield: 94 mg (61%) light brown powder, mp 67–68 °C.

(1Z,2Z)-N1,N2-di(tert-Butyl)-1-(4-methylphenyl)-2-(piperidin-1-yl)ethane-1,2-diimine (3f)

δH (500 MHz, CDCl3) 7.71 (d, 6.86 Hz, n class="Chemical">2H, 3,5-Ph); 7.18 (d, 6.75 Hz, 2,6-Ph); 3.53 (m, 4H, 2 × CH2); 2.39 (s, 3H, Ar-CH3); 1.69 (br.s, 2H, CH2); 1.57 (br.s, 4H, 2 × CH2); 1.40 (s, 9H, NC(CH3)3); 1.01 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 157.1; 150.6; 139.6; 137.1; 128.9; 127.6; 57.8; 53.3; 31.5; 30.9; 29.6; 25.9; 25.1; 21.3. IR (KBr, (cm–1)): 1617 (CNN, CNC). MS m/z (rel. int. %): 341 (<1), 284 (5), 258 (13), 174 (23), 111 (100), 84 (3), 57 (17); [found: C, 77.13; H, 9.70; N, 11.84; C22H35N3 requires C, 77.37; H, 10.33; N, 12.30%]; Rf (5:95 EtOAc/CHCl3) 0.65; yield: 100 mg (77%) brown solid, mp 72–73 °C.

(Z)-N-tert-Butyl-1-(piperidin-1-yl)-1-[4-(propan-2-yl)phenyl]methanimine (2g)

δH (500 MHz, CDCl3) 7.43 (br.s, n class="Chemical">2H, 3,5-Ph); 7.33 (br.s, 2H, 2,6-Ph); 4.16 (br.s, 1H, CH2); 3.48 (m, 2H, CH2); 3.10 (br.s, 1H, CH2); 3.03 (sep, 7.08 Hz, 1H, CH); 1.92 (br.s, 2H, CH2); 1.73 (br.s, 2H, CH2); 1.54 (br.s, 2H, CH2); 1.32 (d, 6.01 Hz, 6H, 2 × CH3); 1.28 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 163.7; 154.1; 131.7; 131.3; 128.9; 128.3; 128.2; 127.4; 57.8; 50.9; 34.2; 31.1; 26.3; 23.7; 23.4. IR (KBr, (cm–1)): 1608 (CNN). MS m/z (rel. int. %): 286 (31), 270 (28), 229 (30), 146 (100), 84 (90), 57 (18); [found: C, 78.43; H, 9.63; N, 9.16; C19H30N2 requires C, 79.66; H, 10.56; N, 9.78%]; Rf (20:80 EtOAc/CHCl3): 0.35; yield: 21 mg (56%) dark brown highly viscous material.

(1Z,2Z)-N1,N2-di(tert-Butyl)-1-(piperidin-1-yl)-2-[4-(propan-2-yl)phenyl]ethane-1,2-diimine (3g)

δH (500 MHz, CDCl3) 7.66 (br.s, n class="Chemical">2H, 3,5-Ph); 7.27 (d, 8.12 Hz, 2H, 2,6-Ph); 3.57 (br.s, 2H, CH2); 3.15 (m, 2H, CH2); 2.94 (sep, 6.93 Hz, 1H, CH); 1.92 (br.s, 2H, CH2); 1.62 (br.s, 4H, 2 × CH2); 1.37 (s, 18H, 2 × NC(CH3)3); 1.24 (d, 6.82 Hz, 6H, 2 × CH3). δC (125.7 MHz, CDCl3) 163.6; 154.0; 152.6; 137.1; 134.5; 128.8; 127.1; 127.0; 59.1; 50.5; 33.9; 30.3; 29.4; 26.0; 23.7. IR (KBr, (cm–1)): 1611 (CNN, CNC). MS m/z (rel. int. %): 369 (<1), 354 (<1), 312 (3), 286 (5), 202 (20), 146 (77), 111 (100), 84 (7), 57 (23); [found: C, 77.60; H, 9.71; N, 10.72; C24H39N3 requires C, 77.99; H, 10.64; N, 11.34%]; Rf (10:90 EtOAc/CHCl3): 0.58; yield: 88 mg (48%) dark brown solid, mp 85–86 °C.

(1Z,2Z)-1-([1,1′-Biphenyl]-4-yl)-N1,N2-di(tert-butyl)-2-(piperidin-1-yl)ethane-1,2-diimine (3h)

δH (500 MHz, CDCl3) 7.87 (br.s, n class="Chemical">2H, Ph); 7.72 (br.s, 1H, Ph); 7.65 (d, 7.31 Hz, 2H, Ph); 7.63 (br.s, 2H, Ph); 7.48 (m, 2H, Ph); 3.53 (m, 2H, CH2); 3.22 (br.s, 2H, CH2); 1.53 (m, 6H, 3 × CH2); 1.43 (s, 9H, NC(CH3)3); 1.11 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 168.1; 147.4; 135.3; 129.0; 128.9; 128.3; 127.8; 127.4; 127.1; 60.1; 51.2; 31.6; 30.0; 29.6; 26.0; 22.7. IR (KBr, (cm–1)): 1612 (CNN, CNC). MS m/z (rel. int. %): 403 (>1), 347 (3); 320 (5), 236 (15), 180 (66), 152 (7), 111 (100), 84 (5), 57 (22); [found: C, 79.52; H, 9.08; N, 9.91; C27H37N3 requires C, 80.35; H, 9.24; N, 10.41%]; Rf (15:85 EtOAc/CHCl3) 0.43; yield: 45 mg (49%) ocher brown solid, mp 68–69 °C.

(Z)-N-tert-Butyl-1-(4-fluorophenyl)-1-(piperidin-1-yl)methanimine (2i)

δH (500 MHz, CDCl3) 7.52 (dd, 6.88 Hz, 4.94 Hz (19F, n class="Chemical">1H), 2H, 3,5-Ph); 7.311 (dd, 8.23 Hz, 7.26 Hz (19F, 1H), 2H, 2,6-Ph); 3.61 (br.s, 4H, 2 × CH2); 1.77 (br.s, 2H, CH2); 1.64 (m, 4H, 2 × CH2); 1.31 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 165.7; 162.6 ((19F, 13C) 413.7 Hz); 131.5 ((19F, 13C) 9.1 Hz); 117.0 ((19F, 13C) 22.9 Hz); 106.7; 57.9; 51.2; 31.4; 26.2; 23.2. IR (KBr, (cm–1)): 1607 (CNN), 1227 (CF). MS m/z (rel. int. %): 262 (23), 247 (20), 205 (27), 122 (100), 84 (95), 57 (38); [found: C, 72.46; H, 8.24; N, 9.94; C16H23N2F requires C, 73.25; H, 8.84; N, 10.68%]; Rf (40:60 EtOAc/CHCl3): 0.41; yield: 43 mg (46%) red brown highly viscous material.

(1Z,2Z)-1-(4-Fluorophenyl)-N1,N2-di(tert-butyl)-2-(piperidin-1-yl)ethane-1,2-diimine (3i)

δH (500 MHz, CDCl3) 7.81 (dd, 7.11 Hz, 6.05 Hz (19F, n class="Chemical">1H), 2H, 3,5-Ph); 7.07 (dd, 8.21 Hz, 8.21 Hz (19F, 1H), 2H, 2,6-Ph); 3.50 (br.s, 4H, 2 × CH2); 1.74 (br.s, 2H, CH2); 1.58 (br.s, 4H, 2 × CH2); 1.40 (s, 9H, NC(CH3)3); 1.09 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 164.8; 162.8; 156.0 ((19F, 13C) 759.3 Hz); 135.8; 129.5 ((19F, 13C) 8.2 Hz), 115.1 ((19F, 13C) 21.1 Hz); 58.0; 53.3; 31.5; 29.6; 25.9; 25.1. IR (KBr, (cm–1)): 1614 (CNN, CNC), 1229 (CF). MS m/z (rel. int. %): 345 (<1), 288 (4), 262 (7), 178 (12), 111 (100), 84 (5), 57 (35); [found: C, 72.40; H, 8.92; N, 11.39; C21H32N3F requires C, 73.00; H, 9.34; N, 12.16%]; Rf (20:80 EtOAc/CHCl3): 0.58; yield: 157 mg (72%) dark brown solid, mp 65–66 °C.

(1Z,2Z)-1-(4-Chlorophenyl)-N1,N2-di(tert-butyl)-2-(piperidin-1-yl)ethane-1,2-diimine (3j)

δH (500 MHz, CDCl3) 7.75 (d, 7.23 Hz, n class="Chemical">2H; 3,5-Ph); 7.35 (d, 7.54 Hz, 2H, 2,6-Ph); 3.30 (br.s, 4H, 2 × CH2); 1.56 (br.s, 4H, 2 × CH2); 1.45 (br.s, 2H, CH2); 1.40 (s, 9H, NC(CH3)3); 1.08 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 156.2; 149.7; 138.1; 135.6; 128.9; 128.7; 128.4; 128.2; 58.1; 53.3; 44.9; 31.5 (triple intensity); 29.5 (triple intensity); 26.9; 25.9. IR (KBr, (cm–1)): 1615 (CNN, CNC), 768 (CCl). MS m/z (rel. int. %): 363/361 (<1), 306/304 (4), 280/278 (5), 196/194 (8), 167 (12), 140/138 (10), 111 (100), 84 (4), 57 (32); [found: C, 68.95; H, 8.27; N, 10.83; C21H32N3Cl requires C, 69.68; H, 8.91; N, 11.61%]; Rf (10:90 EtOAc/CHCl3): 0.62; yield: 45 mg (62%) olive brown solid, mp 69–70 °C.

(Z)-1-(4-Bromophenyl)-N-tert-butyl-1-(piperidin-1-yl)methanimine (2k)

δH (500 MHz, CDCl3) 7.75 (d, 7.79 Hz, n class="Chemical">2H, 3,5-Ph); 7.33 (d, 7.89 Hz, 2H, 2,6-Ph); 4.19 (br.s, 2H, CH2); 3.09 (br.s, 2H, CH2); 1.93 (br.s, 2H, CH2); 1.74 (br.s, 2H, CH2); 1.54 (br.s, 2H, CH2); 1.31 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 162.4; 132.9 (double intensity); 131.3; 130.3 (double intensity); 128.2; 58.03; 51.9; 51.0; 31.2 (triple intensity); 26.2; 23.2. IR (KBr, (cm–1)): 1610 (CNN). MS m/z (rel. int. %): 324/322 (13), 309/307 (10), 267/265 (19), 184/182 (44), 84 (100), 57 (38); [found: C, 58.70; H, 6.61; N, 7.78; C16H23N2Br requires C, 59.45; H, 7.17; N, 8.67%]; Rf (30:70 EtOAc/CHCl3): 0.64; yield: 45 mg (54%) dark gray solid, mp 70–71 °C.

(1Z,2Z)-1-(4-Bromophenyl)-N1,N2-di(tert-butyl)-2-(piperidin-1-yl)ethane-1,2-diimine (3k)

δH (500 MHz, CDCl3) 7.69 (br.s, n class="Chemical">2H; 3,5-Ph); 7.52 (br.s, 2H, 2,6-Ph); 3.29 (br.s, 4H, 2 × CH2); 1.58 (br.s, 2H, CH2); 1.50 (br.s, 4H, 2 × CH2); 1.40 (s, 9H, NC(CH3)3); 1.08 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 156.3; 149.7; 138.6; 131.3 (double intensity); 129.2 (double intensity); 124.2; 58.1; 53.4; 53.3; 31.5; 29.5; 26.0; 25.1. IR (KBr, (cm–1)): 1616 (CNN, CNC). MS m/z (rel. int. %): 407/405 (<1), 350/348 (2), 324/322 (3), 240/238 (5), 167 (13), 111 (100), 57 (33). Rf (10:90 EtOAc/CHCl3) 0.45; yield: 156 mg (73%) medium brown solid, mp 81–82 °C.

Methyl 4-[(Z)-(tert-butylimino)(piperidin-1-yl)methyl]benzoate (2l)

δH (500 MHz, CDCl3) 8.25 (d, 7.07 Hz, n class="Chemical">2H, 3,5-Ph); 7.54 (d, 7.06 Hz, 2H, 2,6-Ph); 4.21 (br.s, 2H, CH2); 4.01 (s, 3H, COOCH3); 3.06 (br.s 2H, CH2); 1.92 (br.s, 2H, CH2); 1.52 (br.s, 4H, 2 × CH2); 1.29 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 165.4; 162.3; 133.8; 131.6; 131.3; 130.4; 129.0; 128.3; 58.0; 52.8; 51.0; 31.1; 26.2; 23.2. IR (KBr, (cm–1)): 1724 (CO), 1609 (CNN), 1281 (COCH3). MS m/z (rel. int. %): 302 (20), 287 (20), 245 (22), 218 (5), 162 (90), 84 (100), 57 (35); [found: C, 70.78; H, 8.50; N, 8.68; C18H26N2O2 requires C, 71.49; H, 8.67; N, 9.26%]; Rf (35:65 EtOAc/CHCl3): 0.31; yield: 33 mg (42%) brown highly viscous material.

Methyl 4-[(1Z,2Z)-N-tert-Butyl-2-(methylimino)-2-(piperidin-1-yl)ethanimidoyl]benzoate (3l)

δH (500 MHz, CDCl3) 8.05 (d, 8.49 Hz, n class="Chemical">2H, 3,5-Ph); 7.89 (d, 8.24 Hz, 2H, 2,6-Ph); 3.95 (s, 3H, COOCH3); 3.51 (br. s, 4H, 2 × CH2); 1.69 (br. s, 2H, CH2); 1.58 (br. s, 4H, 2 × CH2); 1.41 (s, 9H, NC(CH3)3); 1.07 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 166.9; 156.7; 149.7; 143.5; 130.9; 129.5 (double intensity); 127.5 (double intensity); 58.4; 53.3; 52.2; 31.6 (triple intensity); 29.7; 29.5 (triple intensity); 25.9; 25.1. IR (KBr, (cm–1)): 1728 (CO), 1621 (CNN, CNC), 1279 (COCH3). MS m/z (rel. int. %): 385 (3), 328 (5), 302 (5), 246 (4), 218 (6), 162 (17), 111 (100), 84 (5), 57 (31); [found: C, 71.68; H, 8.84; N, 10.71; C23H35N3O2 requires C, 71.65; H, 9.15; N, 10.90%]; Rf (10:90 EtOAc/CHCl3): 0.49; yield: 94 mg (45%) dark brown highly viscous material.

1-{4-[(Z)-(tert-Butylimino)(piperidin-1-yl)methyl]phenyl}ethane-1-one (2n)

δH (500 MHz, CDCl3) 7.98 (br.s, n class="Chemical">2H, 3,5-Ph); 7.38 (br.s, 2H, 2,6-Ph); 3.13 (br.s, 4H, 2 × CH2); 2.66 (s, 3H, C(O)CH3); 1.60 (br.s, 2H, CH2), 1.49 (br.s, 4H, 2 × CH2); 1.04 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 197.4; 156.4; 137.1; 129.2 (double intensity); 127.9 (double intensity); 53.2; 46.8; 32.5; 29.7; 26.6; 26.0; 24.8. IR (KBr, (cm–1)): 1681 (COCH3), 1618 (CNN). MS m/z (rel. int. %): 286 (30), 271 (26), 229 (33), 146 (100), 103 (21), 84 (95), 57 (42); [found: C, 75.31; H, 8.48; N, 9.15; C18H26N2O requires C, 75.48; H, 9.15; N, 9.78%]; Rf (20:80 EtOAc/CHCl3): 0.46; yield: 75 mg (64%) pale yellow solid, mp 84–85 °C.

1-{4-[(1Z,2Z)-N-tert-Butyl-2-(tert-butylimino)-2-(piperidin-1-yl)ethanimidoyl]phenyl}ethan-1-one (3n)

δH (500 MHz, CDCl3) 7.98 (d, 8.13 Hz, n class="Chemical">2H, 3,5-Ph); 7.92 (d, 7.98 Hz, 2H, 2,6-Ph); 3.51(m, 4H, 2 × CH2); 2.65 (s, 3H, COCH3); 1.67 (br.s, 2H, CH2); 1.58 (br.s, 4H, 2 × CH2). δC (125.7 MHz, CDCl3) 197.9; 156.6; 149.6; 143.6; 137.7; 128.3 (double intensity); 127.7 (double intensity); 58.5; 53.3; 31.6 (triple intensity); 30.9; 29.5 (triple intensity); 26.7; 26.0; 25.1. IR (KBr, (cm–1)): 1686 (COCH3), 1618 (CNN, CNC). MS m/z (rel. int. %): 369 (<1), 313 (3), 286 (5), 230 (3), 202 (5), 172 (13), 146 (15), 111 (100), 84 (5), 57 (33); [found: C, 73.93; H, 8.78; N, 10.74; C23H35N3O requires C, 74.75; H, 9.55; N, 11.37%]; Rf (10:90 EtOAc/CHCl3): 0.66; yield: 132 mg (66%) golden yellow solid, mp 102–103 °C.

(Z)-N-tert-Butyl-1-(piperidin-1-yl)-1-[4-(trifluoromethyl)phenyl]methanimine (2o)

δH (500 MHz, CDCl3) 7.64 (br.s, n class="Chemical">2H; 3,5-Ph); 7.38 (br.s, 2H, 2,6-Ph); 3.12 (br.s, 4H, 2 × CH2); 1.60 (br.s, 2H, CH2); 1.48 (br.s, 4H, 2 × CH2); 1.01 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 156.0; 142.3; 129.2 (double intensity); 124.8 (double intensity); 46.5; 32.6; 31.4; 29.0; 28.8; 26.0; 25.0. IR (KBr, (cm–1)): 1610 (CNN), 1325 (CF3). MS m/z (rel. int. %): 312 (29), 297 (25), 255 (35), 172 (94), 145 (12), 84 (100), 57 (41); [found: C, 64.57; H, 7.01; N, 9.08; C17H23N2F3 requires C, 65.36; H, 7.42; N, 8.97%]; Rf (30:70 EtOAc/CHCl3): 0.42; yield: 102 mg (68%) pale brown solid, mp 65–66 °C.

(1Z,2Z)-N1,N2-di(tert-Butyl)-1-(piperidin-1-yl)-2-[4-(trifluoromethyl)phenyl]ethane-1,2-diimine (3o)

δH (500 MHz, CDCl3) 7.94 (d, 8.26 Hz, n class="Chemical">2H, 3,5-Ph); 7.65 (d, 8.30 Hz, 2H, 2,6-Ph); 3.51 (br.s, 4H, 2 × CH2); 1.61 (br.s, 4H, 2 × CH2); 1.59 (br.s, 2H, CH2); 1.41 (s, 9H, NC(CH3)3); 1.08 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 156.2; 149.5; 142.7; 131.4; 127.8 (double intensity); 125.1 (double intensity); 123.1; 58.4; 53.3; 31.6 (triple intensity); 29.6; 29.5 (triple intensity); 25.9; 25.1. IR (KBr, (cm–1)): 1617 (CNN, CNC), 1325 (CF3). MS m/z (rel. int. %): 395 (<1), 338 (3), 312 (3), 256 (5), 228 (3), 167 (15), 111 (100), 84 (4), 57 (45); [found: C, 66.53; H, 7.86; N, 10.08; C22H32N3F3 requires C, 66.53; H, 7.86; N, 10.08%]; Rf (15:85 EtOAc/CHCl3): 0.55; yield: 142 mg (72%) medium brown solid, mp 74–75 °C.

4-[(Z)-(tert-Butylimino)(piperidin-1-yl)methyl]benzonitrile (2p)

δH (500 MHz, CDCl3) 7.68 (d, 7.55 Hz, n class="Chemical">2H, 3,5-Ph); 7.37 (d, 7.45 Hz, 2H; 2,6-Ph); 3.12 (br.s, 4H, 2 × CH2); 1.60 (m, 2H, CH2); 1.48 (m, 4H, 2 × CH2); 1.00 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 155.5; 143.3; 131.7 (double intensity); 129.6 (double intensity); 118.4; 112.3; 46.7; 32.6; 29.8; 25.9 (triple intensity); 24.9. IR (KBr, (cm–1)): 2229 (ArCN), 1599 (CNN). MS m/z (rel. int. %): 269 (24), 254 (21), 212 (32), 129 (79), 102 (10), 84 (100), 57 (38); [found: C, 75.23; H, 8.16; N, 15.43; C17H23N3 requires C, 75.80; H, 8.61; N, 15.60%]; Rf (25:75 EtOAc/CHCl3): 0.38; yield: 93 mg (73%) ocher brown solid, mp 101–102 °C.

4-[(1Z,2Z)-N-tert-Butyl-2-(tert-butylylimino)-2-(piperidin-1-yl)ethanimidoyl]benzonitrile (3p)

δH (500 MHz, CDCl3) 7.94 (d, 8.32 Hz, n class="Chemical">2H; 3,5-Ph); 7.68 (d, 8.47 Hz, 2H, 2,6-Ph); 3.45 (br.s, 4H, 2 × CH2); 1.63 (br.s, 2H, CH2); 1.55 (br.s, 4H, 2 × CH2); 1.41 (s, 9H, NC(CH3)3); 1.07 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 156.0; 149.0; 143.4; 132.1 (double intensity); 128.1 (double intensity); 118.8; 113.0; 58.7; 53.4; 31.6; 29.4; 25.9; 25.0; 24.5. IR (KBr, (cm–1)): 2225 (ArCN), 1613 (CNN, CNC). MS m/z (rel. int. %): 295 (3), 269 (5), 239 (3), 213 (5), 167 (11), 137 (2), 111 (100), 84 (5), 57 (20); [found: C, 74.49; H, 8.76; N, 15.33; C22H32N4 requires C, 74.96; H, 9.15; N, 15.89%]; Rf (10:90 EtOAc/CHCl3): 0.64; yield: 130 mg (78%) beige solid, mp 104–105 °C.

(1Z,2Z)-N1,N2-di(tert-Butyl)-1-(4-nitrophenyl)-2-(piperidin-1-yl)ethane-1,2-diimine (3q)

δH (500 MHz, CDCl3) 8.24 (d, 9.05 Hz, n class="Chemical">2H, 3,5-Ph); 8.01 (d, 8.73 Hz, 2H, 2,6-Ph); 3.55 (br.s, 4H, 2 × CH2); 1.60 (br.s, 6H, 3 × CH2); 1.42 (s, 9H, NC(CH3)3); 1.08 (s, 9H, NC(CH3)3). δC (125.7 MHz, CDCl3) 155.8; 148.9; 148.5; 144.9; 128.4 (double intensity); 123.5 (double intensity); 58.9; 53.4; 31.6 (triple intensity); 29.4 (triple intensity); 25.9; 25.0. IR (KBr, (cm–1)): 1612 (CNN, CNC), 1520 (ArNO2), 1344 (ArNO2). MS m/z (rel. int. %): 372 (<1), 316 (3), 289 (5), 233 (7), 167 (12), 111 (100), 84 (5), 57 (31); [found: C, 67.05; H, 8.25; N, 14.63; C21H32N4O2 requires C, 67.71; H, 8.66; N, 15.04%]; Rf (10:90 EtOAc/CHCl3): 0.57; yield: 88 mg (48%) ocher yellow solid, mp 110–111 °C.

Computational Details

All the structures were optimized without symmetry constraints with tight convergence criteria using the program ORCA 4.0.1[23] with the exchange and correlation functionals developed by Grimme[24] containing the D3 empirical dispersion correction with Becke and Johnson damping.[25] Vibrational analyses made sure that all the structures were genuine minima. For the palladium atom, the def2-TZVP basis set[26] was employed with the respective pseudopotentials.[26] For the other atoms, the def2-SVP basis set[26] was used. n class="Chemical">Natural bond orbital (NBO) analyses have been performed by the GENNBO 5.0 program.[27] Quantum theory of atoms in molecules (QTAIM) analyses of the wave function[28] were carried out with the AIMAll software.[29]