Ir-catalyzed asymmetric hydrogenation of β-keto esters with chiral ferrocenyl P,N,N-ligands

Abstract

The Ir-catalyzed asymmetric hydrogenation of b-keto esters with chiral ferrocenyl P,N,N-ligands has been developed. Under the optimized conditions, a wide range of b-keto esters were hydrogenated to afford the corresponding b-hydroxy esters in good to excellent enantioselectivities (up to 95% ee).

Iridium‐catalyzed asymmetric hydrogenation of β‐ketophosphonates with chiral ferrocenyl P,N,N‐ligands

“…Recently, our group developed an efficient Ir‐catalyzed AH of ketones and β‐ketoesters with novel chiral ferrocene‐based P,N,N‐ligands. [ 17 ] More importantly, with the chiral Ir/P,N,N ligand system, a series of α‐alkyl‐β‐aryl‐β‐ketoesters could be easily hydrogenated, and the corresponding chiral β‐hydroxyesters were obtained with excellent enantioselectivity and diastereoselectivity. [ 18 ] Encouraged by the previous results, we envisioned that this Ir/P,N,N ligand system should also be suitable for the AH of β‐ketophosphonates.…”

“…In contrast, ligand ( S c ,R p )‐ L6 with one chiral center showed disappointing reactivity (entry 6), which was similar as the AH of ketones and β‐ketoesters. [ 17,18 ] On the basis of above results, ( S c ,R p ,R c )‐ L3 was selected as the ligand for further optimization.…”

“…No reaction occurred when toluene, THF, Et 2 O, and CH 2 Cl 2 were used as solvents (entries 10–13). [ 17b,19 ] The results showed that the ee value was depended on the hydrogen pressure, higher hydrogen pressure decreased the enantioselectivity (entries 1 and 14–16). The conversions and enantioselectivities decreased when the catalyst loading was reduced to 0.1 mol% and less (entries 17–19).…”

Cinchona-Alkaloid-Derived NNP Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of β-Keto Ester

“…Colorless oil (181.6 mg, 57% yield, 97.0% ee), R isomer; [α] D 25 = +79.30 (c = 1.00 in CHCl 3 ) (lit. 15 [α] D 28 = −79.60 (c = 1.03 in CHCl 3 )). The ee was determined by HPLC (IA, isopropanol/hexane = 5/95; flow rate = 0.8 mL/min; 254 nm).…”

Indan-f-amphox: An Efficient PNN Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of β-Aryl β-Ketoesters

“…[ ] α ＋ 24.3 (c 0.9, MeOH). 1 Methyl (R)-3-(3-chlorophenyl)-3-hydroxypropanoate (4j): [22] Colorless oil, 41 mg, ＞99% conv., 95% yield, 91% ee. Methyl (R)-3-hydroxy-3-(o-tolyl)propanoate (4k): [23] Colorless oil, 38 mg, ＞99% conv., 98% yield, 95% ee.…”