Synthesis of Iron P‑N-P′ and P‑NH-P′ Asymmetric Hydrogenation Catalysts

Complexes of the type mer,trans-[Fe­(P-N-P′)­(CO)₂Br]­BF₄ are known to be precatalysts for the asymmetric direct hydrogenation of ketones and imines. Employing related ligand scaffolds, we successfully generated and tested the series of three new precatalysts [Fe­(PCy₂CH₂CHNCH­(R)­CH₂PPh₂)­(CO)₂Br]­BF₄ with chirality derived from (S)-amino alcohols with phenyl, benzyl, and isopropyl substituents (R), yielding fairly active and selective systems. For the reduction of acetophenone to (S)-1-phenylethanol turnover frequencies up to 920 h^–1 and up to 74% enantiomeric excess at 50 °C and 5–25 atm of H₂ were obtained. We found, however, that placing these large groups R next to nitrogen was found to be deleterious to catalytic activity. Extending the scope of the ligand structure, we then developed a series of six P-N-P and five P-NH-P′ systems starting with o-diphenylphosphinobenzaldehyde and the phosphine-amines PPh₂CHR¹CHR²NH₂ (R¹ = H, Ph, CH₂Ph, iPr with R² = H or R¹ = Me, Ph with R² = Ph) as well as their corresponding [Fe­(P-N-P′)­(NCMe)₃]­[BF₄]₂ and [Fe­(P-NH-P′)­(NCMe)₃]­[BF₄]₂ complexes, which were not catalytically active. Finally, we made the new achiral iron complex mer,cis-Fe­(PPh₂(o-C₆H₄)­CHNCH₂CH₂PPh₂)­(CO)­Br₂, which was active for the direct hydrogenation of acetophenone, achieving turnover frequencies of 800 h^–1 at 50 °C and 25 atm of H₂.