263768-79-2Relevant academic research and scientific papers
Iron(II)-Catalyzed Hydrogenation of Acetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism
Huber, Raffael,Passera, Alessandro,Mezzetti, Antonio
, p. 396 - 405 (2018)
We report here the tridentate, P-stereogenic, C2-symmetric PNP pincer ligand (SP,SP)-2,6-bis((cyclohexyl(methyl)phosphanyl)methyl)pyridine (1a) and its iron(II) complexes [FeBr2(CO)(1a)] (2a), [FeHBr(CO)(1a)] (3a), and [FeH2(CO)(1a)] (4a). In the presence of base, bromocarbonylhydride 3a catalyzes the hydrogenation of acetophenone to (S)-1-phenylethanol with 48% ee. The transition states of the enantiodetermining transfer of hydride from 3a to the carbonyl group of acetophenone were studied by density functional theory (DFT) with a full conformational analysis of the PNP ligand for the three different mechanistic models recently proposed for a related achiral catalyst. The DFT calculations show that the outer-sphere monohydride mechanism originally proposed by Milstein reproduces the experimentally observed sense of induction (S) and enantioselectivity, whereas the dihydride and inner-sphere pathways predict the formation of the R enantiomer.
P-Stereogenic PN(H)P Iron(II) Catalysts for the Asymmetric Hydrogenation of Ketones: The Importance of Non-Covalent Interactions in Rational Ligand Design by Computation
Huber, Raffael,Passera, Alessandro,Gubler, Erik,Mezzetti, Antonio
, p. 2900 - 2913 (2018/08/17)
The P-stereogenic PN(H)P pincer ligands (R(Me)PCH2CH2)2NH (R=Cy, (S,S)-1 a; R=tBu, (S,S)-1 b; R=Ph, (R,R)-1 c) and their iron(II) derivatives [FeBr2(CO)(PN(H)P)] (2 a–2 c) and [FeHBr(CO)(PN(H)P)] (3 a–3 c) were developed by DFT-driven ligand design. In a preliminary study, the P(Cy)Me-based pincer (S,S)-1 a and its Fe(II) complex 3 a were prepared, tested in the asymmetric transfer hydrogenation of acetophenone, and studied by Density Functional Theory (DFT). Based on the good agreement between the experimental and calculated enantioselectivity, rational design of the pincer by DFT was attempted, which suggested high enantioselectivity for the tert-butyl and phenyl analogues 3 b and 3 c. Therefore, a new synthetic protocol was developed for (R,R)-1 c using Buono's (S)-(1-(OH)Et)P(Me)Ph?BH3 as P-stereogenic synthon. Against the DFT prediction, 3 c gave 1-phenylethanol with 44% ee, which was reproduced by increasing the level of theory from DFT to post-Hartree-Fock M?ller-Plesset (MP2). This result can be explained by the overestimation of the enantiodeterming CH/π interaction by DFT, which reiterates the need for accurate energies in the assessment of small energy differences such as in asymmetric catalysis. (Figure presented.).
