Ketone Asymmetric Hydrogenation Catalyzed by P-NH-P′ Pincer Iron Catalysts: An Experimental and Computational Study

Abstract

Always cite the published version, so the author(s) will receive recognition through services that track citation counts, e.g. Scopus. If you need to cite the page number of the author manuscript from TSpace because you cannot access the published version, then cite the TSpace version in addition to the published version using the permanent URI (handle) found on the record page.ABSTRACT: Our group previously reported the development of iron carbonyl catalysts bearing chiral tridentate P-N-P' ligands for the asymmetric hydrogenation of prochiral ketones in THF. An NMR study into the activation process identified the amine hydride alkoxide complexes Fe(P-NH-P')(CO)(H)(OR 1 ) with R 1 = Me, tBu or tAmyl and P-NH-P' = PPh2CH2CH2NHCH2CH2PiPr2 or (S,S)-PPh2CHPhCHMeNHCH2CH2PCy2. These still required treatment with excess KOtBu and H2(g) to be catalytically active in THF. Both experimental methods and Density Functional Theory (DFT) calculations were used to show that this treatment leads to the formation of a hydride amide complex Fe(P-N-P')(CO)(H) which reacts with dihydrogen to form cis and trans dihydride complexes Fe(P-NH-P')(CO)(H)2, identified by NMR spectroscopy. In the presence of KOtBu, NaOtBu or KOtBu/2,2,2-cryptand and H2(g), these species are active for the catalytic hydrogenation of acetophenone, while in the absence of H2(g), inactive Fe(0) complexes are formed. Ketone hydrogenation is proposed to occur in an outer sphere stepwise process and this enantio-determining step has been modeled by DFT. The calculations suggest that the energy barriers for either hydride attack on the ketone, or dihydrogen splitting either to the nitrogen of the amide complex in the inner coordination sphere or to the oxygen of an alkoxide group in the outer sphere are similar and that either hydride transfer or dihydrogen splitting could determine the turn-over frequency depending of the nature of the ketone.

Enantioselective Hydrogenation of Activated Aryl Imines Catalyzed by an Iron(II) P-NH-P′ Complex

“…34 In the previous studies of FeH2(CO)(P-NH-P') complexes, the enantiodetermining step in the AH of ketones was proposed on the basis of density functional calculations (DFT) to be hydride transfer to the ketone which is hydrogen-bonded to the NH of the P-NH-P' ligand ( Figure 1, TS B ). 33,35 Similarly, The N-H proton is commonly proposed to interact with the imine nitrogen and act as proton donor to unactivated imines. [36][37][38] However the nitrogen of these activated imines are sterically hindered and not basic.…”

Iron Dihydride Complexes: Synthesis, Reactivity, and Catalytic Applications

“…Because hydride is a strong trans ‐influencing group, many of the pincer trans ‐dihydride complexes were thought to be hydridic enough to transfer H − to polar double bonds, as confirmed by DFT studies ,,,,. The reactivity for some of these dihydrides towards C=O and C≡N bonds has been probed experimentally (Figure ).…”

“…The two hydride ligands were found to be trans to each other except in the case of ( iPr PN H P)FeH 2 (CO) where the cis isomer was also observed as the minor product . A cis and trans mixture of dihydride complexes was also obtained by the Morris group in their study of non‐symmetrical pincer systems (eqs 24 and 25) . In this case, direct hydrogenolysis of the methoxide complexes failed to produce the dihydride complexes; however, they were formed when an external base KO( t ‐Bu) was employed.…”

“…Extensive catalyst screening suggested that one of the phosphorus donors needed to have alkyl groups unless the chelating ring system was expanded from 5,5 to 5,6, in which case a lower TOF was obtained (800 h −1 for reducing acetophenone) . A detailed mechanistic study showed that dihydrides generated from the hydridoalkoxide complexes, KO( t ‐Bu), and H 2 (Figure , eqs 24 and 25) had very similar catalytic activity, suggesting that these dihydrides were key catalytic intermediates …”

Multi‐Step Reactions Involving Iron‐Catalysed Reduction and Hydrogen Borrowing Reactions

“…Morris reported a huge variety of chiral pincer PNP iron complexes (e.g. 3 ) able to perform hydrogenation of ketones with high ee and notably TOF up to 1980 h –1 . The best activities in enantioselective reduction were obtained using an in situ iron catalyst from a macrocyclic tetraaminodiphosphane ligand 4 and Fe 3 (CO) 12 with ee up to 99 % and TOF up to 3500 h –1 .…”