Iridium‐Catalyzed Highly Enantioselective Hydrogenation of Exocyclic α,β‐Unsaturated Carbonyl Compounds

Abstract

By using the iridium complex of a phosphine-oxazoline ligand with an axis-unfixed biphenyl backbone, a highly enantioselective hydrogenation of the C=C bond of exocyclic a,b-unsaturated carbonyl compounds to afford a-chiral cyclic ketones, lactones and lactams was developed.Keywords: asymmetric synthesis; cyclic carbonyl compounds; hydrogenation; iridium; oxazoline Cyclic carbonyl compounds with a-chiral carbon centers are an important group of compounds in organic synthesis and medicinal chemistry.[1] For the synthesis of these optically active compounds, enzyme-mediated reactions and chemical syntheses from optically active starting materials have usually been used. [2,3] However, most of the reported methods are limited in substrate scope, and high enantioselectivity has seldom been obtained. The most straightforward and simplest approach to these compounds would be asymmetric hydrogenation of cyclic a,b-unsaturated carbonyl compounds but much less efforts have been focused on this option. [4,5] In most recent years, iridium complexes with chiral phosphine-oxazoline ligands have attracted much attention because of their easy availability and high reactivity and enantioselectivity in the hydrogenation of unfunctionalized olefins [6] or olefin substrates with less strongly coordinating groups [7][8][9][10] . In this context, Zhou found that the C=C bond of an a,b-unsaturated carboxylic acid could be hydrogenated with high enantioselectivity by using an iridium spirophosphine-oxazoline (SIPHOX) complex; [8] Bolm and Hou found that the C=C bond of a,b-unsaturated ketones can be hydrogenated with high enantioselectivity by using an iridium phosphineoxazoline (PHOX) complex; [9] Hou further investigated the enantioselective hydrogenation of a,b-unsaturated amides by using an iridium complex derived from ferrocenylphosphine-oxazoline (Fc-PHOX).[10]However, there are few examples focused on the establishment of a-chiral carbon centers of cyclic carbonyl compounds, especially for lactones and lactams, via asymmetric hydrogenation. [4,9] Even in these limited examples, the asymmetric hydrogenation is strongly substrate dependent and there is no general solution for different kinds of cyclic substrates. Herein, we disclose our preliminary results of the highly enantioselective hydrogenation of exocyclic a,b-unsaturated carbonyl compounds by using an iridium complex with axis-unfixed biphenylphosphine-oxazoline ligands 1 (Scheme 1).Scheme 1. Complexation behavior of ligands 1a-f.

Asymmetric Hydrogenation of Olefins Using Chiral Crabtree-type Catalysts: Scope and Limitations

“…152 [Ir(cod)(70)][BAr F ], under 20 bar H 2 in toluene, reduced the unsaturated five-membered lactone S183 in 95% ee and the unsaturated sixmembered lactone S184 in 71% ee (Scheme 28).…”

Convenient synthesis of tropos phosphine-oxazoline ligands

“…This is the same for compounds 8 and ligands 3 (Table 1). When coordination of the ligands 3 with Pd or Ir ions, both of the two diastereomers of the ligands with different axial configurations afforded only the complexes with S axial configuration, and no complexes with R axial configuration were found [39][40][41]. a) The ratios of diastereomers were determined by 31 P NMR integration.…”

“…Taking account of the advantages of chiral P,N-chelating binaphthyl ligands 2 and the high utilization rate of tropos biphenyl ligand 1, we designed a novel kind of chiral phosphine-oxazoline ligands 3 with a tropos biphenyl backbone ( Figure 1). Those ligands showed excellent catalytic activity and enantioselectivity in Pd-catalyzed allylic alkylation and Ir-catalyzed hydrogenation [39][40][41]. Although one synthetic route of ligands 3 has been developed and reported in our previous papers [39,40], there are still some problems left to be solved.…”

Iridium‐Catalyzed Asymmetric Hydrogenation of α‐Alkylidene Succinimides

“…The catalytic activity of a series of (aS)-Ir/BiphPHOX catalysts was very high, and full conversion was observed within 10 minutes (entries 1-3). Furthermore, optimization of the hydrogen pressure and catalyst loading were investigated using CH 2 Cl 2 as the solvent (entries [9][10][11][12][13][14]. With an iPr substituent, the hydrogenation proceeded in quantitative yield with excellent enantioselectivity (99 % ee; entry 1).…”

“…[7] In particular, iridium complexes consisting of phosphine nitrogen ligands have attracted much attention because of their ready availability, high reactivity, and high enantioselectivity in asymmetric hydrogenation reactions. [11] Herein we report the first asymmetric hydrogenation of a-alkylidene succinimides catalyzed by (aS)-Ir/iPr-BiphPHOX for enantioselective synthesis of succinimide derivatives (Scheme 1).Hydrogenation reaction conditions were investigated as listed in Table 1. [11] Herein we report the first asymmetric hydrogenation of a-alkylidene succinimides catalyzed by (aS)-Ir/iPr-BiphPHOX for enantioselective synthesis of succinimide derivatives (Scheme 1).…”