Ligand and solvent control of selectivity in the C–H activation of a pyridylimine-substituted 1-naphthalene; a combined synthetic and computational study

Abstract

The pyridylimine-substituted 1-naphthalenes, 2-(1-C₁₀H₇)-6-{CRN(2,6-i-Pr₂C₆H₃)}C₅H₃N (R = Me HL_Me, H HL_H), react with Na₂[PdCl₄] in acetic acid at elevated temperature to afford either ortho-C–H_naphthyl activated (L_Me)PdCl (2_ortho) or the unactivated adduct (HL_H)PdCl₂ (1b). Alternatively, 1b and its ketimine analogue (HL_Me)PdCl₂ (1a), can be prepared by treating (MeCN)₂PdCl₂ with either HL_Me or HL_H in chloroform at room temperature. Regio-selective ortho-C–H activation to form 2_ortho can also be initiated by the thermolysis of 1a in acetic acid, while no reaction occurs under similar conditions with 1b. Interestingly, the C–H activation of HL_Me to give 2_ortho is found to be reversible with 100% deuteration of the peri-site occurring on reacting Na₂[PdCl₄] with HL_Me in acetic acid-d₄. By contrast, heating 1a in toluene gives a 55 : 45 mixture of 2_ortho and its peri-activated isomer 2_peri. Pure 2_peri can, however, be obtained either from (L_Me)PdOAc (3_peri) by OAc/Cl exchange or by the sequential reactions of 1a with firstly silver acetate then with aqueous sodium chloride. Intriguingly, a peri to ortho interconversion occurs on heating 2_peri in acetic acid to give 2_ortho. DFT calculations have been used to investigate the C–H activation steps and it is found that in acetic acid ortho-C–H activation is kinetically and thermodynamically favoured but peri-CH activation is kinetically accessible (ΔΔG^‡ = 2.4 kcal mol⁻¹). By contrast in toluene, the reaction appears to be irreversible with the difference in barrier height for ortho- and peri-C–H activation being very small within the error of the method (ΔΔG^‡ = 0.7 kcal mol⁻¹), findings that are in agreement with the empirically observed product distribution for 2_ortho and 2_peri. Single crystal X-ray structures are reported for 1a, 1b, 2_ortho and 2_peri.