Phosphine-Catalyzed Diastereo- and Enantioselective Michael Addition of β-Carbonyl Esters to β-Trifluoromethyl and β-Ester Enones: Enhanced Reactivity by Inorganic Base

Abstract

A novel chiral biamide-phosphine multifunctional catalyst has been developed that mediates the asymmetric intermolecular Michael addition of β-carbonyl esters to β-trifluoromethyl enones and 3-aroyl acrylates in the presence of competing methyl acrylate and the inorganic base. This method provides a facile access to structurally diverse trifluoromethyl and quaternary stereogenic centers with excellent enantioselectivity (up to 99% ee) and good diastereoselectivity (up to 13:1 dr). The addition of the inorganic base (KPO) does not cause the background racemic reaction and enhances the reactivity by serving as a co-catalyst.

Lewis Acid-Catalyzed Rearrangement of Fluoroalkylated Propargylic Alcohols: An Alternative Approach to β-Fluoroalkyl-α,β-enones

“…1 Yellow oil; 1 The spectroscopic data were in good agreement with the literature data. 3 Colorless oil; 1 H NMR (CDCl3, 500 MHz)δ 8.09 (dd, J = 6.7, 2.0 Hz, 2H), 7.87 (dd, J = 6.5, The spectroscopic data were in good agreement with the literature data. 5 Colorless oil; 1 The spectroscopic data were in good agreement with the literature data.…”

Phosphine Organocatalysis

“…Zhang, Liu, and co-workers developed the asymmetric intermolecular Michael additions of β -carbonyl esters to β -trifluoromethyl enones and 3-aroyl acrylates, catalyzed by the multifunctional biamide-phosphine catalysts P2a and P2b in the presence of methyl acrylate and an inorganic base, K 3 PO 4 , which acted as a proton shuttle that enhanced the reactivity (Scheme 19). 81 With the use of 5 mol % of the catalyst in the presence of methyl acrylate (2 equiv) and K 3 PO 4 (30 mol %) in toluene at −20 °C, the Michael adducts were obtained in good to excellent yields (67–99%) with excellent enantioselectivities (84–99% ee). The Michael addition of β -ketoesters also occurred to give the products in moderate to good yields with excellent enantioselectivities (90–98% ee).…”

β‐Trifluoromethyl α,β‐unsaturated Ketones: Efficient Building Blocks for Diverse Trifluoromethylated Molecules

“…In 2017 Liu and Zhang, reported a synthesis of structurally diverse trifluoromethyl and quaternary stereogenic centers with the help of chiral biamidephosphine 60 catalysis. [44] It involved the asymmetric intramolecular Michael addition reaction of malonates 58 with β-trifluoromethyl enones 3 and 3-aroyl acrylates in the presence of competing methyl acrylate and K 3 PO 4 as inorganic base which act as a proton shuttle to enhance reactivity. This method gives facile access to structurally diverse trifluoromethyl and quaternary stereogenic centers 59 with excellent enantioselectivity (up to 99% ee) with malonates (Scheme 17).…”