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.

已知mer型trans-[Fe-(P-N-P′)-(CO)2Br]­BF4复合物为酮和亚胺不对称直接加氢的预催化剂。通过使用相关的配体骨架，我们成功合成并测试了系列三种新型预催化剂[Fe-(PCy2CH2CHNCH-(R)-CH2PPh2)-(CO)2Br]­BF4，其手性来源于(S)-氨基醇的苯基、苄基和异丙基取代基(R)，从而得到了活性较高且选择性的系统。对于乙酰苯酮还原为(S)-1-苯基乙醇，在50°C和5-25 atm的氢气压力下，可获得高达920 h–1的转换频率和高达74%的对映选择性。然而，我们发现将这些大的取代基R置于氮原子旁边会降低催化活性。为进一步扩展配体结构，我们以对二苯基膦基苯甲醛和膦胺PPh2CHR1CHR2NH2（R1 = H, Ph, CH2Ph, iPr，R2 = H或R1 = Me, Ph，R2 = Ph）以及它们相应的[Fe-(P-N-P′)-(NCMe)3]­[BF4]2和[Fe-(P-NH-P′)-(NCMe)3]­[BF4]2复合物为起点，开发了六种P-N-P和五种P-NH-P′系统，这些复合物均不具有催化活性。最终，我们合成了一种新的非手性铁复合物mer,cis-Fe-(PPh2(o-C6H4)-CHNCH2CH2PPh2)-(CO)-Br2，该复合物对乙酰苯酮的直接加氢具有活性，在50°C和25 atm的氢气压力下，转换频率可达800 h–1。