Ir/Thioether–Carbene, −Phosphinite, and −Phosphite Complexes for Asymmetric Hydrogenation. A Case for Comparison

Abstract

We studied for the first time the potential of novel and simple Ir/thioether-NHC complexes in the asymmetric hydrogenation of unfunctionalized olefins and cyclic β-enamides. For comparison, we prepared and applied the analogues thioether–phosphinite/phosphite complexes. We found that the efficiency of the new Ir/thioether-NHC catalyst precursors varies with the type of olefin. Thus, while the Ir/thioether-NHC catalyst precursors provided lower catalytic performance than their related Ir/thioether-P complexes in the hydrogenation of olefins lacking a coordinating group, the catalysts had similar good performance for the reduction of functionalized olefins (e.g., tri- and disubstituted enol phosphonate derivatives). Catalytic results together with the studies of the reactivity toward H2 indicated that the thioether-carbene design favors the formation of inactive trinuclear species, which are responsible for the low activities obtained with these carbene-type catalysts. Nevertheless, this catalyst deactivation can be avoided by using functionalized olefins such as enol phosphonates. We also report the discovery of simple-to-synthesize Ir/thioether-P catalysts containing a simple backbone that gave high enantioselectivities for some trisubstituted olefins, some challenging 1,1′-disubstituted olefins, and cyclic β-enamides.

Recent advances in the metal-catalyzed asymmetric alkene hydrogenation of cyclic conjugated carbonyl compounds

“…A large portion of catalyst communicated for the hydrogenation of 6-membered analogous were well-performing and good to highly stereoselective. Yuan & Zhang 57 (Ir/BiphPHOX L1c , 68% ee), Pàmies & Diéguez (Ir/thioether-carbene, -phosphinite, and -phosphite L36–37 , 72 Ir/phosphite-sulfoximine 17 L9 , Ir/phosphite-oxazoline 15 a L6 , 28% ee, 97% ee, 99% ee, >99% ee, respectively), Alberico & Pàmies & Diéguez 18 (Ir/phosphite-selenoether L10a , 94% ee), Margalef & Pericàs & Diéguez 19 (Ir/phosphinite-thioether L11a , up to 98% ee), Besora & Diéguez 52 (Ir/phosphite-thioether L31 , up to >99% ee), Verdaguer & Besora & Diéguez 12 (Ir/MaxPHOX L3 , up to 98% ee), Manoury & Diéguez 21 (Ir/phosphine-thioether L38 , 84% ee), and Lv 16 (Rh/ZhaoPhos L8 , up to 99% ee) contributed in this regard and prepared the desired chiral lactones by catalytic asymmetric hydrogenation.…”

Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation

“…Diéguez and co-workers also reported the iridium-catalyzed AH of cyclic enamides S95 and S96 in excellent enantioselectivities employing a phosphite-oxazoline ligand ( L47 , Scheme ). , The same group further extended this methodology using other modular ligands. − Overall, these protocols allowed an efficient route to the asymmetric synthesis of 2-aminotetralines and 3-aminochromanes, key structural units in many biologically active agents such as rotigotine, terutroban, and nepicastat (Figure ). , …”

Recent Progress in Developing Thioether-Containing Ligands for Catalysis Applications

“…Pàmies, Diéguez, and co-workers developed chiral Ir/thioether-NHC Y complexes with a six-membered (κ 2 - C , S )-chelate and applied them to asymmetric hydrogenation reactions. 62 Cyclic β-enamides and tri- and disubstituted olefin substrates possessing a good coordination group (enol phosphonate) were totally reduced to give 55 – 57 with promising ees ranging from 72 to 91% (Scheme 28 ). However, the high steric constraints imposed by the thioether-carbene backbone are not favorable when considering a more sterically hindered substrate, thus leading to poor asymmetric induction.…”