Hydroamination as a route to nitrogen-containing oligomers

Abstract

Hydroamination of H₂NC₆H₄-p-C≡CPh (1) with 10 mol% Ti(NR₂)₄ (R = Me and Et) at 70 °C for 3.5 days affords oligomers (2) ((2a) R = Me and (2b) R = Et), characterized by NMR, IR, and UV/Vis spectroscopy, and by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry and gel permeation chromatography (GPC). These data indicate 10 to 15 repeat units in the chain. Model reactions, performed using phenylacetylene or diphenylacetylene and aniline or 2,6-diisopropylaniline, generated a variety of enamines and imines (compounds (3)–(11)), three of which were characterized by X-ray crystallography. Evidence suggests the hydroamination oligomerization follows the widely accepted [2 + 2] cycloaddition mechanism, although chain capping with NR₂ (R = Me and Et) appears to occur via alkyne insertion in a Ti–N σ-bond.

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Introduction

Hydroamination of carbon–carbon multiple bonds represents an atom-economical methodology for the synthesis of amines.^1–7 Though thermodynamically favourable,^8,9 the direct reaction is plagued by a high activation energy barrier. As a result, a variety of hetero- and homogeneous catalysts have been reported to carry out catalytic hydroamination.^1,8,10,11 These catalysts include acids^11,12 and bases,^11,13 heavier group 2 complexes,^14–18 lanthanides and actinides,⁵ several group 4 metal species,^2–4,6,7 other early transition metals such as vanadium¹⁹ and tantalum,²⁰ late transition metals (Ru, Rh, Pd, Pt, Ag, and Au),^8,10 and heavy metals including mercury and thallium.⁸

The most well-studied catalysts are the group 4 transition metal compounds,⁷ as they are inexpensive, nontoxic, and commercially available or easily synthesized. Bergman and coworkers were first to describe the mechanism of group 4 metal-mediated hydroamination of an alkyne (Scheme 1).^21–23 This widely accepted mechanism involves the generation of a group 4 metal imide, which undergoes [2 + 2] cycloaddition with an alkyne affording an azametallacyclobutene. Subsequent reaction of this species with amine generates an (amido)(enamido)metal species which releases enamine and regenerates the metal-imide species.

Scheme 1 Hydroamination of an alkyne using a group 4 catalyst via a [2 + 2] cycloaddition pathway.

Recently, some exceptions to this mechanism have been uncovered. For example, cationic^24,25 and neutral^26,27 group 4 complexes have been shown to catalyze intramolecular hydroamination cyclization of alkenes^24–27 or alkynes²⁷via a M–N σ-bond insertion mechanism. This pathway is analogous to that proposed by Marks et al.²⁸ for group 3 transition metal and lanthanide catalysts (Scheme 2),⁵ and involves intramolecular insertion of a pendant alkene or alkyne into a M–N σ-bond. Reaction with additional amine releases enamine and regenerates the active metal amide catalyst. Interestingly, performing lanthanide-catalyzed olefin polymerization in the presence of certain bulky secondary amines affords amine-capped polyolefin.²⁹

Scheme 2 Hydroamination cyclization of an aminoalkene or aminoalkyne using a lanthanide catalyst via a σ-bond insertion pathway.

In addition to mechanistic studies, many researchers have focused on applications in total synthesis,³⁰ enantioselective catalysis,^24,31,32 or the development of new or improved catalysts.^{2,4,6,24,25,33} Our goal is to employ hydroamination as a route to new oligomers and polymers. We rationalized that for a step-growth polymerization process, a maximal degree of polymerization necessitates precise control over the stoichiometry as expressed in the Carothers equation.³⁴ Thus, bifunctional monomers were targeted, containing primary amine and alkyne moieties where the molecular geometry precludes intramolecular reaction. Herein, we report the catalytic hydroamination of such substrates as a route to oligomers, as well as the small molecule model studies designed to probe the structure of the oligomer and aspects of the oligomerization mechanism.

Experimental section

General considerations

All manipulations of air- and/or water-sensitive compounds were carried out under an atmosphere of dry oxygen-free nitrogen using standard Schlenk techniques or a Vacuum Atmospheres inert atmosphere glove box. ¹H and ¹³C{¹H} NMR spectra were acquired on a Bruker Avance 300 MHz spectrometer, a Bruker Avance 400 MHz spectrometer, a Bruker SpectroSpin 500 MHz spectrometer, a Varian Mercury 300 MHz spectrometer, or a Varian Mercury 400 MHz spectrometer. All NMR spectra were recorded in C₆D₆ at 25 °C, and ¹H and ¹³C resonances were referenced to the solvent resonance. ¹H–¹³C HSQC and HMBC experiments were carried out to aid in peak assignments. Infrared spectra were recorded using a Perkin-Elmer Spectrum One FT-IR spectrometer at 25 °C, either as a Nujol mull or deposited onto the NaCl plate from a CH₂Cl₂ or C₆D₆ solution. Elemental analyses were performed using a Perkin-Elmer 2400 C/H/N analyzer. UV/Vis spectra were acquired on a double-beam Lambda 12 UV-Visible spectrometer, using the solvent as the external standard. Mass spectra were recorded with a VG 70-250S mass spectrometer in positive ion electron impact (EI) mode.

For gel permeation chromatography (GPC) analysis, samples were dissolved in THF (ca. 1–2 mg mL⁻¹). Absolute polymer molecular weights were determined using a Waters GPC equipped with a refractive index detector, a laser light scattering detector, and a viscometer. Relative polymer molecular weights were determined using a Waters liquid chromatograph equipped with a differential refractometer. Polystyrene standards were purchased from Polymer Laboratories, with molecular weights varying between 580 and 283 300 g mol⁻¹. MALDI-TOF mass spectra were acquired using a Waters Micromass MALDI micro MX with the following conditions: positive polarity mode, reflectron flight path, 12 kV flight tube voltage, 10 Hz laser firing rate, 10 shots per spectrum, pulse 1950 V, detector 2350 V. The instrument was calibrated using polyethyleneglycol (PEG). Matrices were prepared using 6 mg of α-cyano-4-hydroxycinnamic acid (CHCA) in 1 mL of a 6 : 3 : 1 mixture of CH₃CN : CH₃OH : H₂O plus one drop of CF₃COOH. Analyte solutions consisted of 3–5 mg of oligomer in 1 mL of CH₂Cl₂. Samples were prepared using the layer method:³⁵ 1 µL of matrix was spotted onto the sample plate under an atmosphere of air, allowed to dry, then 1 µL of analyte was spotted onto the sample plate under an inert atmosphere,³⁶ and the plate was allowed to dry again.

Anhydrous solvents were purchased from Aldrich and purified using Grubbs' column systems manufactured by Innovative Technology.³⁷ C₆D₆ was purchased from Cambridge Isotopes Laboratories, vacuum distilled from Na/benzophenone, and freeze–pump–thaw degassed (×3). Unless otherwise noted, starting materials were purchased from Aldrich and used as received. Diethylamine and triethylamine were degassed by sonication; aniline, 2,6-diisopropylaniline and N-methylamine were degassed by sparging with N₂. Hyflo Super Cel® (Celite) was dried in a vacuum oven for at least 12 h prior to use. Molecular sieves (4 Å) were dried at 100 °C under vacuum. Phenylacetylene was vacuum-distilled from CaH₂ and stored in the dark at −35 °C. trans-Pd(PPh₃)₂Cl₂, Ti(NMe₂)₄ and Ti(NEt₂)₄ were purchased from the Strem Chemical Co. Compound (1) has been previously reported.³⁸

Synthesis of H₂NC₆H₄-p-C≡CPh (1)

To a NEt₃ solution (50 mL) of 4-iodoaniline (2.190 g, 10.00 mmol) were added trans-Pd(PPh₃)₂Cl₂ (70 mg, 0.010 mmol, 0.010 equiv.) and CuI (19 mg, 0.10 mmol, 0.010 equiv.). The brown mixture was stirred and freshly distilled HC≡CPh (1.175 g, 11.50 mmol, 1.15 equiv.) was added. The mixture turned red-orange in colour and was stirred overnight at room temperature. The solvent was removed in vacuo, and the residue extracted with Et₂O and filtered through Celite. Removal of Et₂O in vacuo resulted in a brown oil, which was then extracted with a 3 : 1 solution of CH₂Cl₂ : hexanes, filtered, and the solvent evaporated to give a brown solid. Yield: 1.785 g (92%). ¹H NMR: 7.54 (m, 2H, o-C₆H₅), 7.40 (m, 2H, m-C₆H₄), 7.01–6.98 (m, 3H, m- and p-C₆H₅), 6.11 (m, 2H, o-C₆H₄), 2.73 (br s, 2H, NH₂). ¹³C{¹H} NMR: 147.4 (ipso-CN), 133.3 (ArH), 131.8 (ArH), 128.6 (ArH), 127.7 (ArH), 124.9 (quat-Ar), 114.7 (ArH), 112.9 (quat-Ar), 91.3 (C≡C), 88.1 (C≡C). EI-MS (m/z): 193.1 (100%) ([M]⁺). HRMS: C₁₄H₁₁N mass 193.0892, calcd mass 193.0891. FT-IR (from C₆D₆ soln, cm⁻¹): ν(N–H) 3475, 3380 (med., sharp), ν(C≡C) 2211 (med., sharp). UV/Vis (CH₃CN, ca. 10⁻⁵ M): λ_max = 311 nm. Anal. Calcd for C₁₄H₁₁N: C, 87.01; H, 5.74; N, 7.25. Found: C, 86.88; H, 5.92; N, 6.82%.

Synthesis of H₂N{[–C₆H₄-p-CH=CPhNH–]_x/[–C₆H₄-p-CH₂CPh=N–]_y}_nC₆H₄CH=CHNR₂(2)

Compound (1) (640 mg, 3.31 mmol), Ti(NR₂)₄ (R = Me, Et, 0.33 mmol, 0.10 equiv.), and 40 mL toluene were placed in a 100 mL bomb to give a brown mixture. After heating at 70 °C for 3.5 d, the mixture was evacuated to about 5–10 mL, then precipitated into a vortex of 75 mL hexanes. The solid brown precipitate was isolated on a frit.

Using Ti(NMe₂)₄ as the precatalyst, yield of (2a): 229 mg (36%). ¹H NMR: 8.0–6.3 (br, 15H, ArH), 6.1 (d, 1.3H, =CH, ³J_H–H = 8 Hz), 3.8 (br, 1H, CH₂), 2.8 (br, 1.1H, NH), 1.7 (br, 1.1H, N(CH₃)₂). The integration data suggest that the ratio of enamine : imine is ca. 2.7 : 1, and that the ratio of enamine + imine : NMe₂ end group is ca. 10 : 1. ¹³C{¹H} NMR (partial): 167.4 (C=N), 138.7 (Ar), 133.3 (Ar), 132.9 (Ar), 131.9 (Ar), 131.8 (Ar), 128.9 (Ar), 128.6 (Ar), 128.2 (Ar), 124.8 (Ar), 101.7 (=CH), 48.8 (N(CH₃)₂), 36.0 (CH₂). FT-IR (from CH₂Cl₂ soln, cm⁻¹): ν(N–H) 3384 (weak), no peaks detected from 2700 to 1650, ν(C=N) 1620 (med., sharp), ν(Ph) 1592 (strong, sharp), ν(Ph) 1515 (med., sharp). UV/Vis (CH₃CN, ca. 10⁻⁵ M): λ_max = 311 nm. For GPC analysis, oligomer (2a) was placed in THF under air and filtered to remove insoluble particulates prior to acquiring GPC data. Since (2a) is partly soluble in THF, some of the sample was removed upon filtration. GPC (versus polystyrene standards): M_n 730, M_w 1540. GPC (laser light scattering detection): M_n 1230, M_w 1680. MALDI-TOF MS: highest molecular weight species 2944 = 15 × (193) + 45 m/z.

Using Ti(NEt₂)₄ as the precatalyst, yield of (2b): 494 mg (77%). ¹H NMR: 8.0–6.2 (br, 15H, ArH), 6.1 (d, 1H, =CH, ³J_H–H = 8 Hz), 3.8 (br, 1H, CH₂), 3.0 (q, 0.5H, N(CH₂CH₃)₂), 2.8 (br, 1H, NH), 1.0–0.8 (m, 0.8H, N(CH₂CH₃)₂). The integration data suggest that the ratio of enamine : imine is ca. 2 : 1, and that the ratio of enamine + imine : NEt₂ end group is ca. 12 : 1. ¹³C{¹H} NMR (partial): 165.0 (C=N), 133.3 (Ar), 131.9 (Ar), 131.8 (Ar), 128.9 (Ar), 128.6 (Ar), 126.5 (Ar), 101.7 (=CH), 44.7 (N(CH₂CH₃)₂), 31.5 (CH₂), 21.8 (N(CH₂CH₃)₂). FT-IR (from CH₂Cl₂ soln, cm⁻¹): ν(N–H) 3384 (weak), ν(C=N) 1620 (weak), ν(Ph) 1592 (weak), ν(Ph) 1515 (weak). MALDI-TOF MS: highest molecular weight species 2005 = 10 × (193) + 73 m/z.

Synthesis of PhCH=CPh(NHPh) (3), PhCH₂CPh(=NPh) (4), PhCH=CPh(NH(C₆H₃iPr₂)) (5), and PhCH₂CPh(=N(C₆H₃iPr₂)) (6)

These reactions were carried out under identical conditions. Diphenylacetylene (891 mg, 5.00 mmol) and Ti(NMe₂)₄ (112 mg, 0.500 mmol) were combined in a 50 mL bomb which was wrapped in aluminium foil. Freshly degassed aniline (0.46 mL, 0.47 mg, 5.0 mmol, for compounds (3) and (4)) or 2,6-diisopropylaniline (0.94 mL, 0.88 g, 5.0 mmol, for compounds (5) and (6)) was added via syringe. The reaction mixture was heated at 70 °C for 65 h, and volatile materials were removed in vacuo to afford a brown oil.

For (3) and (4),²⁰ C₂₀H₁₇N. The ratio of (3) : (4) is 47 : 53. X-Ray quality crystals of (4) were obtained from the reaction mixture. ¹H NMR: (3): 7.61–7.55 (m, C₆H₅), 7.17–7.12 (m, C₆H₅), 6.88–6.82 (m, C₆H₅), 6.69–6.65 (m, C₆H₅), 6.34 (s, C₆H₅), 5.61 (s, =CHPh), 5.09 (s, NH); (4): 8.27–8.20 (m, C₆H₅), 7.73–7.67 (m, C₆H₅), 7.21–7.16 (m, C₆H₅), 3.83 (s, CH₂). EI-MS (m/z): 271.1 (2%) ([M]⁺), 180.1 (17%) ([M]⁺ − CH₂Ph), 178.1 (100%) (PhC≡CPh). HRMS: C₂₀H₁₇N mass 271.1366, calcd mass 271.1361. FT-IR (mixture of (3) and (4), deposited from C₆D₆ soln, cm⁻¹): ν(N–H) 3392 (med., broad), ν(C=N) 1626 (strong, sharp), ν(C=C) 1600 (strong, sharp).

For (5)³⁹ and (6), C₂₆H₂₉N. The ratio of (5) : (6) is 5: 95. X-Ray quality crystals of (6) grew from the reaction mixture. ¹H NMR: (5): 7.53–7.51 (m, ArH), 7.1–6.9 (m, ArH), 5.30 (s, =CHPh), 4.38 (br s, NH), 3.39 (septet, CH(CH₃)₂), 1.45 (d, CH(CH₃)_a(CH₃)_b), 1.30 (d, CH(CH₃)_a(CH₃)_b); (6): 8.07–8.05 (m, C₆H₅), 7.20–7.12 (m, NC₆H₃ and C₆H₅), 6.91–6.81 (m, C₆H₅), 3.86 (s, CH₂), 2.88 (septet, CH(CH₃)₂), 1.21 (d, CH(CH₃)_a(CH₃)_b), 1.10 (d, CH(CH₃)_a(CH₃)_b). ¹³C{¹H} NMR: (6) (partial): 165 (C=N), 135 (N-ipso-C), 131.6 (ArH), 130.1 (ArH), 128.9 (ArH), 128.3 (ArH), 128.0 (ArH), 126.1 (ArH), 123.8 (ArH), 123.0 (ArH), 36.4 (CH₂), 28.5 (CH(CH₃)₂), 23.6 (CH(CH₃)_a(CH₃)_b), 21.8 (CH(CH₃)_a(CH₃)_b). EI-MS (m/z): 355.2 (7%) ([M]⁺); 264.2 (100%) ([M]⁺ − CH₂Ph), 178.1 (82%) (PhC≡CPh). HRMS: C₂₆H₂₉N mass 355.2307, calcd mass 355.2300. FT-IR (mixture of (5) and (6), deposited from C₆D₆ soln, cm⁻¹): ν(N–H) 3399 (weak), ν(C=N) 1627 (med., sharp), ν(C=C) 1600 (med., sharp). FT-IR ((6) deposited from C₆D₆ soln, cm⁻¹): ν(C=N) 1627 cm⁻¹ (strong, sharp).

Synthesis of CH₂=C(Ph)(NHPh) (7m), CHPh=CH(NHPh) (7am), CH₃C(Ph)(=NPh) (8m), PhCH₂CH(=NPh) (8am), (PhCH=CH)₂(NPh) (9), CH₂=C(Ph)(NH(C₆H₃iPr₂)) (10m), CHPh=CH(NH(C₆H₃iPr₂)) (10am), CH₃C(Ph)(=N(C₆H₃iPr₂)) (11m), and PhCH₂CH(=N(C₆H₃iPr₂)) (11am)

These reactions were carried out under identical conditions. Phenylacetylene (511 mg, 5.00 mmol) and Ti(NMe₂)₄ (112 mg, 0.500 mmol) were combined in a 50 mL bomb which was wrapped in aluminium foil. Freshly degassed aniline (0.46 mL, 0.47 mg, 5.0 mmol, for compounds (7), (8), and (9)) or 2,6-diisopropylaniline (0.94 mL, 0.88 g, 5.0 mmol, for compounds (10) and (11)) was added via syringe. The reaction mixture was heated at 70 °C for 60 h, and volatile materials were removed in vacuo to afford a brown oil.

For (7), (8),⁴⁰ and (9). X-Ray quality crystals of (9) were obtained from the reaction mixture. The ratio of (7m) : (7am) : (8m) : (8am) : (9) is ca. 2 : 48 : 11 : 15 : 24. ¹H NMR (partial): 6.50 (dd, ³J_H–H = 14 Hz, ³J_H–H = 7 Hz, =CHNH, (7am)), 5.47 (d, ³J_H–H = 14 Hz, =CHPh, (7am)), 4.49 (d, ²J_H–H = 2 Hz, =CH_aH_b, (7m)), 3.46 (d, ³J_H–H = 8 Hz, CH₂, (8am)), 2.88 (s, CH₃, (8m)). EI-MS for mixture of products (m/z): 297.2 (2%) ([(9)]⁺); 195.1 (92%) ([(7) and/or (8)]⁺), 147.1 (9%) ([H₂C=C(Ph)(NMe₂) or PhCH=CH(NMe₂)]⁺). FT-IR (mixture of (7), (8), and (9), deposited from C₆D₆ soln, cm⁻¹): ν(N–H) 3401 (med., broad), ν(C=N) 1634 (v strong, sharp), ν(C=C) 1595 (v strong, sharp), ν(C–N) 1275 (med., sharp). For crystals of (9): ¹H NMR: 7.28–7.25 (m, 4H, CC₆H₅), 7.03–6.99 (m, 4H, CC₆H₅), 7.01–6.95 (m, 2H, m-NC₆H₅), 6.72–6.69 (d, 2H, PhC(H)=C(H)N, ³J_H–H = 12 Hz), 6.25–6.20 (m, 2H, CC₆H₅), 6.21–6.18 (m, 2H, o-NC₆H₅), 5.75 (d, 2H, PhC(H)=C(H)N, ³J_H–H = 12 Hz). ¹³C{¹H} NMR (partial): 142.2 (ipso-NC₆H₅), 131.6 (m-NC₆H₅), 130.8 (CC₆H₅), 129.7 (CC₆H₅), 128.9 (p-NC₆H₅), 127.8 (CC₆H₅), 126.4 (CC₆H₅), 126.0 (CC₆H₅), 124.0 (CC₆H₅), 120.5 (PhC(H)=C(H)N), 118.6 (ipso-CC₆H₅), 114.3 (o-NC₆H₅), 105.2 (PhC(H)=C(H)N). EI-MS (m/z): 297.2 (22%) ([M]⁺), 295.1 (100%) ([M]⁺ − 2H). HRMS: C₂₂H₁₉N mass 297.1513, calcd mass 297.1517. FT-IR (deposited from C₆D₆ soln): ν(C=C) 1594 cm⁻¹ (strong, sharp), ν(C–N) 1275 cm⁻¹ (strong, sharp). UV/Vis (CH₃CN, ca. 10⁻⁵ M): λ_max = 357 nm. Anal. Calcd for C₂₂H₁₉N: C, 87.85; H, 6.44; N, 4.71. Found: C, 88.46; H, 6.48; N, 5.27%.

For (10) and (11). The ratio of (10m) : (10am)³⁹ : (11m) : (11am)³⁹ is 3 : 11 : 40 : 46. ¹H NMR (partial): 7.41 (t, ³J_H–H = 5 Hz, CHN, (11am)), 6.65 (dd, ³J_H–H = 14 Hz, ³J_H–H = 7 Hz, =CHNH, (10am)), 5.36 (d, ²J_H–H = 2 Hz, =CH_aH_b, (10m)), 5.19 (d, ³J_H–H = 14 Hz, =CHPh, (10am)), 4.38 (d, ²J_H–H = 2 Hz, =CH_aH_b, (10m)), 4.16 (br, NH, (10am)), 3.51 (d, ³J_H–H = 5 Hz, CH₂, (11am)), 2.35 (s, CH₃, (11m)). EI-MS (m/z): 279.2 (3%) ([M]⁺), 264.2 (5%) ([M]⁺ − Me), 188.1 (19%) ([M]⁺ − CH₂Ph), 177.2 (29%) (2,6-diisopropylaniline), 162.1 (100%) (2,6-diisopropylaniline − Me). HRMS: C₂₀H₂₅N mass 279.1981, calcd mass 279.1987. FT-IR (mixture of (10m), (10am), (11m), and (11am), deposited from C₆D₆ soln, cm⁻¹): ν(N–H) 3401 (weak), ν(C=N) 1620 (strong, sharp), ν(C–N) 1264 (med., sharp).

X-Ray data collection and reduction

Crystals were manipulated and suspended in Paratone or mounted in capillaries in a glove box, thus maintaining a dry, O₂-free environment for each crystal. Diffraction experiments were performed on a Siemens SMART System CCD diffractometer. The data (4.5° < 2θ < 45–50.0°) were collected in a hemisphere of data in 1329 frames with 10 second exposure times. The observed extinctions were consistent with the space groups in each case. A measure of decay was obtained by re-collecting the first 50 frames of each dataset. The intensities of reflections within these frames showed no statistically significant change over the duration of the data collections. The data were processed using the SAINT and SHELXTL processing packages. An empirical absorption correction based on redundant data was applied to each dataset. Subsequent solution and refinement were performed using the SHELXTL solution package.

Structure solution and refinement

Non-hydrogen atomic scattering factors were taken from the literature tabulations.⁴¹ The atom positions were determined using direct methods employing the SHELXTL direct methods routine. The refinements were carried out by using full-matrix least squares techniques on F, minimizing the function ω (F_o − F_c)² where the weight ω is defined as 4F_o²/2σ (F_o²) and F_o and F_c are the observed and calculated structure factor amplitudes, respectively. In the final cycles of each refinement, all non-hydrogen atoms were assigned anisotropic temperature factors in the absence of disorder or insufficient data. In the latter cases atoms were treated isotropically. For compounds (4) and (6), the H atoms on C(2) were located and refined. All other C–H atom positions were calculated and allowed to ride on the carbon to which they are bonded assuming a C–H bond length of 0.95 Å. H-Atom temperature factors were fixed at 1.10 times the isotropic temperature factor of the C-atom to which they are bonded, and the H-atom contributions were calculated, but not refined. The locations of the largest peaks in the final difference Fourier map calculation as well as the magnitude of the residual electron densities in each case were of no chemical significance. Crystallographic parameters for compounds (4), (6), and (9) are given in Table 1.

Table 1 Crystallographic Data

	(4)	(6)	(9)
a Data collected with Mo Kα radiation (λ = 0.71069 Å). R = Σ(Fo − Fc)/ΣFo. b R w={Σ[w(Fo^2 − Fc^2)^2]/Σ[w(Fo)^2]}^½.
Formula	C20H17N	C26H29N	C22H19N
Formula weight	271.35	355.50	297.38
Crystal system	Monoclinic	Monoclinic	Orthorhombic
Space group	P21/n	P21/c	Pbca
a/Å	5.5976(11)	11.2839(5)	16.1137(8)
b/Å	8.3168(6)	11.8464(5)	8.8958(4)
c/Å	31.769(3)	15.6094(7)	22.9830(12)
α/deg
β/deg	92.784(4)	94.908(2)
γ/deg
V/Å^3	1477.2(2)	2078.91(16)	3294.5(3)
Z	4	4	8
Temp./°C	−100	−100	−100
d(calc)/g cm^−1	1.220	1.136	1.199
Abs coeff., µ/cm^−1	0.070	0.065	0.0418
Data collected	9575	44 347	11 649
Data Fo^2 > 3σ(Fo^2)	2584	6382	2900
Variables	198	252	208
R	0.0410	0.0461	0.0566
R w	0.1009	0.1320	0.1711
GOF	1.029	1.032	1.040

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Results and discussion

Hydroamination oligomerization

Reaction of monomer (1) with 0.10 equiv. of Ti(NMe₂)₄ at 70 °C in toluene for ca. 80–90 h resulted in hydroamination oligomerization to give (2a) (Scheme 3). Oligomer (2a) was isolated in 36% yield upon precipitation into a vortex of hexanes. Solubility of low molecular weight species in hexanes may account for the low yield. The broad peaks in the ¹H NMR spectrum of (2a) are indicative of an oligomer. Signals attributed to enamine CH and imine CH₂ moieties are observed at 6.1 and 3.8 ppm, respectively, in a ratio of ca. 2.7 : 1. The corresponding peaks in the ¹³C NMR spectrum are observed at 167 (C=N), 101 (PhCH), and 36 ppm (CH₂), assigned by HSQC and HMBC experiments. The IR spectrum of oligomer (2a) shows the absence of peaks between 2700 and 1650 cm⁻¹ consistent with the loss of C≡C fragments. The peaks at 3384 and 1620 cm⁻¹ are attributed to the N–H stretch of a secondary amine and the C=N stretch of an imine moiety, respectively.^42,43 The UV/Vis spectrum of oligomer (2a) is very similar to that of monomer (1), suggesting minimal conjugation along the oligomer chain. Relative to polystyrene standards, GPC data for (2a) indicate M_n = 730 and M_w = 1540, corresponding to a number-average degree of polymerization (DP_n) of 4. Using laser light scattering detection, GPC data indicate a higher DP_n of 6 (M_n = 1230 and M_w = 1680).

Scheme 3 Hydroamination oligomerization of compound (1) to synthesize oligomers (2).

According to the Carothers equation, the degree of polymerization depends on the stoichiometry of the functional groups and on the extent of the reaction. Since monomer (1) provides exact stoichiometry, the low degree of polymerization is likely to result from an incomplete reaction. However, it should be noted that the molecular weight values may be underestimated since GPC data were acquired under air in THF. Samples of (2a) were not completely soluble in THF and were filtered to remove insoluble material (possibly including higher molecular weight oligomers) prior to GPC analysis. Moreover, the residual water present in air may hydrolyze the backbone,⁴³ leading to chain degradation. However, attempts at reducing the water-sensitive imine and enamine fragments of the oligomer backbone were inconclusive.

Literature precedent suggests that the mechanism of hydroamination for this group 4 catalyst follows a [2 + 2] cycloaddition pathway (Scheme 1).^2–4,6,7,44 This mechanism accounts for chain growth because the hydroamination product after each turnover contains a primary amine functionality which can form a new titanium–imide species. However, this mechanism does not account for the observation of the major set of peaks in the MALDI-TOF mass spectrum of (2a) (Fig. 1), located at 193n + 45 m/z. While 193n corresponds to an integral number (n) of monomer units (mass = 193 Daltons), 45 corresponds to HNMe₂, could result from insertion of alkyne into the Ti–NMe₂ bond of the catalyst followed by protonolysis. Catalysis performed using Ti(NEt₂)₄ resulted in oligomer (2b), with peaks at 193n + 73 m/z in the MALDI-TOF mass spectrum. NMR data for oligomers (2a) and (2b) show resonances corresponding to the NR₂ fragment and end group analysis by ¹H NMR indicates approximately 10–12 repeat units in the chains. The incorporation of one secondary amine fragment is suggestive of a σ-bond insertion mechanism (Scheme 2).

Fig. 1 MALDI-TOF mass spectrum of (2a). Major peaks are located at 193n + 45 m/z, where 193 Daltons is the mass of the monomer, n is an integer, and 45 Daltons corresponds to addition of HNMe₂.

Model compounds for hydroamination oligomerization

To glean information regarding the mechanism of hydroamination, model reactions were performed using diphenylacetylene or phenylacetylene and aniline, 2,6-diisopropylaniline, N-methylaniline or diethylamine. No reaction was observed for either alkyne with N-methylaniline or diethylamine in the presence of Ti(NMe₂)₄ at 70 °C for 3–4 days. This lack of reactivity using a secondary amine is inconsistent with a mechanism that relies solely on σ-bond insertion, implying that the [2 + 2] cycloaddition mechanism is likely operative for the growth of the oligomer chain using this titanium(IV) catalyst.

In the hydroamination reactions of diphenylacetylene with aniline or 2,6-diisopropylaniline (Scheme 4), a mixture of enamine (PhCH=CPh(NHAr), (3) Ar = Ph or (5) Ar = C₆H₃iPr₂) and imine (PhCH₂CPh(=NAr), (4) Ar = Ph or (6) Ar = C₆H₃iPr₂) was formed (Scheme 3). The relative ratios of (3) : (4) and (5) : (6) are 47 : 53 and 5 : 95, respectively. The preferential formation of imines stands in contrast to several literature reports.^21,39,45,46 Imines (4) and (6) were characterized by single-crystal X-ray diffraction studies (Fig. 2) and the hydrogen atoms on C(2) were unambiguously located and refined. Upon heating imine (6) to 70 °C for 4 days, with or without catalytic Ti(NMe₂)₄, no conversion to enamine (5) was detected by ¹H NMR spectroscopy.

Scheme 4 Synthesis of model compounds (3)–(8), (10) and (11).

Fig. 2 ORTEP drawings of (4) and (6), with ellipsoids drawn at the 50% probability level. All hydrogen atoms except those on C2 have been omitted for clarity. Selected bond lengths (Å) and angles (°) for (4): N(1)–C(1) 1.282(2), N(1)–C(3) 1.423(2), C(1)–C(2) 1.517(2), C(1)–C(9) 1.500(2), C(2)–C(15) 1.514(2), C(1)–C(2)–C(15) 114.3(1), C(2)–C(1)–N(1) 124.2(1), C(2)–C(1)–C(9) 118.6(1), N(1)–C(1)–C(9) 117.2(1), C(1)–N(1)–C(3) 120.9(1); (6): N(1)–C(1) 1.279(1), N(1)–C(3) 1.420(1), C(1)–C(2) 1.512(1), C(1)–C(21) 1.494(1), C(2)–C(15) 1.523(1), C(1)–C(2)–C(15) 115.81(8), C(2)–C(1)–N(1) 124.16(9), C(2)–C(1)–C(21) 116.86(8), N(1)–C(1)–C(21) 116.86(8), C(1)–N(1)–C(3) 124.43(8).

Reactions using phenylacetylene and aniline or 2,6-diisopropylaniline (Scheme 4) afforded imines and enamines, which exhibited Markovnikov (M) or anti-Markovnikov (AM) regiochemistry.¹⁰ In general, the regiochemistry depends not only on the catalyst,^{39,45,47–52} but also on the amine^49,50,52 and alkyne^{10,39,45,47,48,52} substrates. In the reaction of aniline and phenylacetylene, the ¹H NMR and mass spectral data revealed a mixture of products, including CH₂=C(Ph)(NHPh) (7m), CHPh=CH(NHPh) (7am), CH₃C(Ph)(=NPh) (8m), PhCH₂CH(=NPh) (8am) and the unexpected product (PhCH=CH)₂(NPh) (9). The ratio of these products in the reaction mixture was ca. 2 : 48 : 11 : 15 : 24. In the mass spectrum, H₂C=C(NMe₂)(Ph) (or its anti-Markovnikov regioisomer CHPh=CH(NMe₂)) was also observed, as per literature precedent.⁴⁰ Signals in the ¹H NMR derived from the isomers of (7) and (8) were assigned on the basis of literature comparisons.^39,40

Crystals of (9) were obtained from the reaction mixture, and their formulation was confirmed by two-dimensional NMR experiments and single crystal X-ray diffraction (Fig. 3). The bond distances and angles in (9) are typical of enamines.^53,54 The N-atom is planar while the C₃NC₃ backbone is also very nearly planar. This planarity suggests donation of the N-lone pair into the extended π-system. This view is supported by λ_max = 357 nm in the UV/Vis spectrum of (9), which is red-shifted dramatically from that of aniline (λ_max = 230 nm). The formation of compound (9) most likely results from the reaction of (7am) or (8am) with an additional equivalent of phenylacetylene. The presence of compound (9) and H₂C=C(NMe₂)(Ph) or CHPh=CH(NMe₂) implicates the insertion of phenylacetylene into a Ti–N σ-bond.

Fig. 3 ORTEP drawing of (9), with ellipsoids drawn at the 50% probability level. All hydrogen atoms have been omitted for clarity. Selected bond lengths (Å) and angles (°) for (9): N(1)–C(5) 1.506(4), N(1)–C(2) 1.393(3), N(1)–C(3) 1.415(3), C(1)–C(2) 1.357(3), C(3)–C(4) 1.346(3), C(1)–C(11) 1.423(3), C(4)–C(17) 1.436(3), C(2)–N(1)–C(5) 120.9(2), C(3)–N(1)–C(5) 119.9(2), C(2)–N(1)–C(3) 119.2(2), N(1)–C(2)–C(1) 126.3(3), N(1)–C(3)–C(4) 125.5(3), C(2)–C(1)–C(11) 125.0(2), C(3)–C(4)–C(17) 126.7(2).

The related reactions employing 2,6-diisopropylaniline yielded CH₂=C(Ph)(NHAr) (10m), CHPh=CH(NHAr) (10am), CH₃C(Ph)(=NAr) (11m) and PhCH₂CH(=NAr) (11am) (where Ar = C₆H₃iPr₂), as judged by ¹H NMR and mass spectral data.³⁹ The product distribution of (10m) : (10am) : (11m) : (11am) was determined to be 3 : 11 : 40 : 46. In this case, no 2 : 1 addition product analogous to (9) was formed.

Conclusions

Oligomer (2), formed by hydroamination, contains up to 15 repeat units in the chain, capped by one molecule of dialkylamine which originates from the Ti(NR₂)₄ (R = Me and Et) catalyst. Model reactions yielding (3)–(11) suggest that oligomer (2) contains both imine and enamine moieties, with minimal regioselectivity. These model systems also suggest that propagation is dominated by the [2 + 2] cycloaddition mechanism, while the incorporation of a terminal secondary amine group proceeds via insertion of alkyne into Ti–N σ-bonds.

Acknowledgements

We thank Prof. Mark Nitz and Dr Richard Jagt for their help with MALDI-TOF mass spectrometry, and Prof. Derek P. Gates and Dr Kevin J. T. Noonan for their assistance with GPC measurements. Financial support from NSERC of Canada is gratefully acknowledged. DWS is grateful for the award of a Canada Research Chair and a Killam Research Fellowship.

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Footnote

† Electronic supplementary information (ESI) available: IR spectra, UV/Vis spectra, and MALDI-TOF mass spectra. CCDC reference numbers 761296–761298. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c0py00120a

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