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.