Rare-earth metal diisopropylamide-catalyzed intramolecular hydroamination

Abstract

Rare-earth metal diisopropylamide complexes LiLn(NiPr₂)₄(THF) (Ln = Sc, Y, La), [LiY(NiPr₂)₄]_n, NaLn(NiPr₂)₄(THF) (Ln = Sc, Y), Sc(NiPr₂)₃(THF) and Ce(NiPr₂)₄ were screened as catalysts for the intramolecular hydroamination/cyclization (IHC) of 1-amino-2,2-dimethyl-4-pentene, 1-amino-2,2-diphenyl-4-pentene, and 1-amino-2,2-diphenyl-5-hexene at ambient and moderately increased temperature of 60 °C in C₆D₆. The lithium ate complexes displayed the most efficient precatalysts with high conversion rates at 60 °C for the phenyl-substituted substrates and Ln = Y and La, affording turnover frequencies N_t as high as 164 h⁻¹. The catalytic activity could be increased by employing THF-free complex [LiY(NiPr₂)₄]_n (N_t = 45.8 h⁻¹ at 26 °C; 34.1 h⁻¹ for LiY(NiPr₂)₄(THF)). In situ generation of putative LiY(NiPr₂)₄(THF) from YCl₃(THF)_3.3 and four equivalents of LiNiPr₂ (LDA) in C₆D₆ generated a catalyst revealing N_t comparable to pre-isolated crystallized LiY(NiPr₂)₄(THF) but yielding even higher substrate conversion. The IHC reactions were also examined for rare-earth metal bis(trimethylsilyl)amide catalysts Ln[N(SiMe₃)₂]₃ (Ln = Sc, Y, La) as well as for LDA using the same reaction conditions, revealing overall superior activity of the silylamide derivatives but poor performance of LDA compared to the rare-earth metal diisopropylamide complexes LiLn(NiPr₂)₄(THF). Cyclization of 1-amino-2,2-diphenyl-5-hexene to the 6-membered heterocycle 2-methyl-4,4-diphenylpiperidine by lanthanum derivative LiLa(NiPr₂)₄(THF) was accompanied by a competitive isomerization reaction affording max. 20% of 1-amino-2,2-diphenyl-4-hexene after 2 h at 60 °C. Crystalline tetravalent Ce(NiPr₂)₄ showed a better IHC performance than crystalline trivalent Sc(NiPr₂)₃(THF) as preliminary examined for 1-amino-2,2-diphenyl-4-pentene at 26 °C (N_t = 5.6 and 0.9 h⁻¹, respectively), but cyclization came to a halt after 2 h, probably due to decomposition of the catalyst.