Bis(isonitrile) iron(II) complexes bearing a C2 -symmetric diamino (NH)2 P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %). The catalyst can be easily tuned by modifying the substituents of the isonitrile ligand.
A generalized
protocol for the synthesis of chiral (NH)2P2 macrocycles allows changing the linker between the
phosphines and gives access to a family of such ligands, as demonstrated
for the propane-1,3-diyl analogue. The corresponding complexes based
on earth-abundant and nontoxic iron were applied as catalysts in the
asymmetric transfer hydrogenation of polar double bonds. Thanks to
the ligand modularity and to the use of tunable isonitriles as ancillary
ligands, the catalyst system can be individually optimized for each
substrate to give high enantioselectivity (up to 99.9% conversion
and 99.6% ee, TOF up to >3950 h–1) for a broad
scope
of 26 substrates.
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 Møller‐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.magnified image
We report here the
tridentate, P-stereogenic, C
2-symmetric
PNP pincer ligand (S
P,S
P)-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.
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