A new route for the efficient metalation of unfunctionalized aromatics

Abstract

The synthesis and isolation of a novel bimetallic species formed by reacting two equivalents of TMPLi with CuCl in the presence of Et₂O are reported. X-ray crystallography reveals the Et₂O-free tetranuclear aggregate (TMPCu)₂(TMPLi)₂ 1, which formally results from the catenation of dimers of TMPLi and TMPCu. NMR spectroscopy confirms that, upon dissolution in hydrocarbon media, the crystals fail to form a conventional Gilman cuprate dimer. Instead they exhibit a spectrum which is consistent with that recently proposed for an isomer of dimeric Gilman cuprate. Moreover, while pre-isolated Gilman cuprate is inert to benzene solvent, this new isomer smoothly affects aromatic deprotonation to give mainly Ph(TMP)₃Cu₂Li₂ 3, which is formally a heterodimer of Gilman cuprate TMPCu(μ-TMP)Li 2 and PhCu(μ-TMP)Li 4. Attempts to synthesise 3 through explicit combination of pre-isolated 2 and 4 were successful; additionally, this permitted the preparation of Ph(TMP)₃Cu₃Li 5 and Ph(TMP)₃CuLi₃ 7 when 4 was combined in 1 : 2 ratios with TMPCu or TMPLi, respectively. 5 was characterised as metallacyclic in the solid-state, its structural features resembling those in 3 but with reduced Li-π interactions. It also proved possible to perform Cu/Li exchange on 5 (using ^t BuOCu) to give a novel mixed organo(amido)copper species Ph(TMP)₃Cu₄ 6. Remarkably, the unprecedented reactivity of 1 towards benzene is reproduced by heating a 1 : 1 mixture of TMPLi and TMPCu in the same solvent; this gives predominantly 3. On the other hand, mixtures which are rich in either Cu or Li can lead to the selective in situ formation of 5 or 7. Though crystallographic data on 7 could not be obtained, DFT calculations accurately corroborated the observed structures of 3 and 5 and could be used to support 7 having the same structure type, albeit with enhanced Li-π interactions. This was consistent with NMR spectroscopic data. However, in contrast to 3 and 5, for which 2D NMR spectroscopy indicated only conformational changes, 7 was additionally found to exhibit fluxionality in a manner consistent with a dissociative process.

Fig. 1. Structure-types known for bis(TMP)cuprates. (a) Lipshutz-type cuprates (X = CN, L = THF, Et₂O, THP (THP = tetrahydropyran); X = halide, L = THF,,, L = Et₂O; X = SCN, L = THF, Et₂O, THP; X = OCN, L = THF36), (b) Gilman cuprate (TMP)₂CuLi, and (c) mixed TMPLi-TMPCu aggregate (M = Li, Cu).

Fig. 2. Thermal ellipsoid plot of 1 (30% probability). H-atoms and metal disorder omitted for clarity. Mean selected bond lengths (Å) and angles (°): N–Cu1 1.924, N–M2 1.978, N–Li3 2.065, N–M4 1.969, M–N–M 89.11, N–M–N 176.84.

Fig. 3. ⁷Li NMR spectra of 1 in C₆D₆, heated to 50 °C for 0–144 h. For details on minor, unlabelled peaks, see text.

Fig. 4. Thermal ellipsoid plot (30% probability) of 4₂. H-atoms omitted for clarity. Selected bond length (Å) and angles (°): Cu1–N1 1.892(2), Li1–N1 1.932(4), Cu1–C10 1.904(2), Li1–C10A 2.153(4); Cu1–N1–Li1 92.55(14), C10–Cu1–N1 178.71(8), Cu1–C10–Li1A 81.33(13), and N1–Li1–C10A 169.4(2).

Fig. 5. Thermal ellipsoid plot (30% probability) of 3. H-atoms omitted for clarity. Selected bond lengths (Å) and angles (°): Cu1–C28 1.895(2), Cu1–N1 1.907(2), Li2–N1 2.047(3), Li2–N2 2.022(3), Cu3–N2 1.913(2), Cu3–N3 1.915(2), Li4–N3 1.971(4), Li4–C28 2.348(4), Li4–C29 2.380(4), Li4–C33 2.431(4); C28–Cu1–N1 168.97(8), Cu1–N1–Li2 81.53(10), N1–Li2–N2 176.45(18), Li2–N2–Cu3 94.04(10), N2–Cu3–N3 177.11(7), and Cu3–N3–Li4 91.48(13).

Fig. 6. Thermal ellipsoid plot (30% probability) of 5. H-atoms and minor metal disorder omitted for clarity. Selected bond lengths (Å) and angles (°): Cu1–C28 1.915(4), Cu1–N1 1.934(3), Cu2–N1 1.933(3), Cu2–N2 1.916(3), Cu3–N2 1.940(3), Cu3–N3 1.918(3), Li4–N3 1.888(5), Li4–C28 2.204(5); C28–Cu1–N1 176.35(17), Cu1–N1–Cu2 86.40(13), N1–Cu2–N2 178.23(14), Cu2–N2–Cu3 91.31(13), N2–Cu3–N3 174.31(14), Li4–N3–Cu3 83.89(17), N3–Li4–C28 172.4(3), and Cu1–C28–Li4 81.85(17).

Scheme 1. Cu–Li exchange reactions leading to the formation of 6.

Fig. 7. Thermal ellipsoid plot (30% probability) of 6. Selected bond lengths (Å) and angles (°): Cu1–N1 1.948(3), N1–Cu2 1.934(4), Cu2–N2 1.929(3), N2–Cu3 1.939(4), Cu3–N3 1.921(4), N3–Cu4 1.948(4), Cu4–C28 1.992(4), C28–Cu1 1.971(4); C28–Cu1–N1 171.81(17), Cu1–N1–Cu2 84.97(14), N1–Cu2–N2 178.64(15), Cu2–N2–Cu3 89.16(14), N2–Cu3–N3 84.25(15), N3–Cu4–C28 167.12(17), and Cu4–C28–Cu1 75.45(15).

Fig. 8. ⁷Li NMR spectrum of 1 in C₆D₆, heated to 50 °C for 144 h. d₅-5 and d₅-7 can be identified as minor products.

Fig. 9. ⁷Li NMR spectra in C₆D₆ of reaction mixtures containing TMPCu and TMPLi in the ratios specified. Reaction mixtures were heated in C₆D₆ to 50 °C for ca. 24 h in a sealed NMR tube before data acquisition.

Scheme 2. Reactions explaining the production of 3, 5 and 7.

Fig. 10. Labelling scheme for 3 in solution, based upon the solid-state structure for the same compound.

Fig. 11. Selected NMR data for 3 in C₇D₈ at –10 °C. (a) ¹H,⁷Li-HOESY spectrum (τ = 0.05 s); (b) ¹H,¹H-NOESY spectrum (τ = 0.6 s).

Fig. 12. ¹H,¹H-NOESY spectrum of 3 in C₆D₆ at 25 °C; exchange correlations in blue (τ = 0.6 s).

Fig. 13. Labelling scheme for 5 in solution, based upon the solid-state structure for the same compound.

Fig. 14. Expansions of ¹H,¹H-NOESY spectra for 5 in (a) C₆D₆ at 25 °C, and (b) C₇D₈ at 80 °C; exchange correlations in blue (τ = 0.6 s).

Fig. 15. Labelling scheme for 7.

Fig. 16. ⁷Li,⁷Li-NOESY spectrum of 7 in C₇D₈, recorded at 25 °C; exchange correlations in blue (τ = 0.05 s). The shoulder at δ 2.23 ppm is TMPLi.

Fig. 17. ¹H,¹H-NOESY spectrum of 7 in C₆D₆, at 25 °C; exchange correlations in blue (τ = 0.6 s).

Scheme 3. Dissociative interchange of Li sites and amido ligands, mediated by the symmetrical amidolithium dimer (TMPLi)₂.