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

Complexes of the type <i>mer</i>,<i>trans</i>-[Fe­(P-N-P′)­(CO)<sub>2</sub>Br]­BF<sub>4</sub> 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(PCy<sub>2</sub>CH<sub>2</sub>CHNCH­(R)­CH<sub>2</sub>PPh<sub>2</sub>)­(CO)<sub>2</sub>Br]­BF<sub>4</sub> with chirality derived from (<i>S</i>)-amino alcohols with phenyl, benzyl, and isopropyl substituents (R), yielding fairly active and selective systems. For the reduction of acetophenone to (<i>S</i>)-1-phenylethanol turnover frequencies up to 920 h<sup>–1</sup> and up to 74% enantiomeric excess at 50 °C and 5–25 atm of H<sub>2</sub> 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 <i>o</i>-diphenylphosphinobenzaldehyde and the phosphine-amines PPh<sub>2</sub>CHR<sup>1</sup>CHR<sup>2</sup>NH<sub>2</sub> (R<sup>1</sup> = H, Ph, CH<sub>2</sub>Ph, iPr with R<sup>2</sup> = H or R<sup>1</sup> = Me, Ph with R<sup>2</sup> = Ph) as well as their corresponding [Fe­(P-N-P′)­(NCMe)<sub>3</sub>]­[BF<sub>4</sub>]<sub>2</sub> and [Fe­(P-NH-P′)­(NCMe)<sub>3</sub>]­[BF<sub>4</sub>]<sub>2</sub> complexes, which were not catalytically active. Finally, we made the new achiral iron complex <i>mer</i>,<i>cis</i>-Fe­(PPh<sub>2</sub>(<i>o</i>-C<sub>6</sub>H<sub>4</sub>)­CHNCH<sub>2</sub>CH<sub>2</sub>PPh<sub>2</sub>)­(CO)­Br<sub>2</sub>, which was active for the direct hydrogenation of acetophenone, achieving turnover frequencies of 800 h<sup>–1</sup> at 50 °C and 25 atm of H<sub>2</sub>.