Asymmetric Ru/Cinchonine Dual Catalysis for the One-Pot Synthesis of Optically Active Phthalides from Benzoic Acids and Acrylates

Abstract

Herein, we report the asymmetric Ru/cinchonine dual catalysis that provides straightforward access to enantioselective synthesis of C-3 substituted phthalides via tandem C–H activation/Michael addition cascade. The use of readily accessible and less expensive [RuCl2(p-cym)]2 and cinchonine catalyst for the one-pot assembly of chiral phthalides greatly overcomes the present trend of using highly sophisticated catalysts. The developed method provides access to both enantiomers of a product using pseudoenantiomeric cinchona alkaloids as catalysts streamlining the synthesis of phthalide in both the optically active forms.

Progress in Transition‐Metal‐Catalyzed Synthesis of Benzo‐Fused Oxygen‐ and Nitrogen Heterocyclic Compounds from Benzoic Acids

“…Lately, Dethe and coworkers reported asymmetric Rh(III)/cinchonine dual catalysis for the enantioselective synthesis of C‐3 substituted phthalides via tandem C−H activation/Michael addition cascade (Scheme 40). [47] The intermediate alkenylated acid was subjected to enantioselective intramolecular oxa‐Michael addition in the presence of cinchonine to yiald an enantioenriched phthalide derivative. The origin of stereoselectivity came from the more preferable chirality‐determining transition state of the cinchonine with carboxylate group via deprotonation of −CO 2 H group by quinuclidine nitrogen to form an ion‐pair, the hydroxy group of cinchonine activated the alkene via hydrogen bonding, which facilitated the attack of carboxylate on the Re‐face of the alkene thus generating the (R)‐enantiomer of the phthalide derivative.…”

Enantioselective C−H Bond Functionalization Involving Arene Ruthenium(II) Catalysis

“…Relay catalysis involves multiple catalytic cycles and the product of the first catalytic cycle enters the second catalytic cycle as a reactant. In 2022, Dethe and co-workers reported an asymmetric relay catalysis involving ruthenium-catalyzed CÀ H activation of benzoic acid (28) with acrylate (29). [28] As shown in Figure 4, the substrate firstly undergoes a ruthenium-catalyzed CÀ H olefination to generate the alkene product, which enters the second catalytic cycle of cinchonine-catalyzed enantioselective Michael addition.…”

“…In 2022, Dethe and co-workers reported an asymmetric relay catalysis involving ruthenium-catalyzed CÀ H activation of benzoic acid (28) with acrylate (29). [28] As shown in Figure 4, the substrate firstly undergoes a ruthenium-catalyzed CÀ H olefination to generate the alkene product, which enters the second catalytic cycle of cinchonine-catalyzed enantioselective Michael addition. By this strategy, various phthalides (30, 35 examples) were prepared in good to excellent yield (up to 95 %) with moderate to good enantiomeric excess (up to 94 %) (Scheme 14).…”

Ru(II)/Chiral Carboxylic Acid-Catalyzed Asymmetric [4 + 3] Annulation of Sulfoximines with α,β-Unsaturated Ketones

“…9 Nevertheless, the development of enantioselective versions of ruthenium(II)-catalyzed C−H activation has lagged far behind the same periodic palladium and rhodium. 4,10 Significant breakthroughs were achieved recently by taking advantage of the chiral transient directing group, 11 the chiral Ru(II) catalyst bearing the chiral η 6 -arene ligand, 12 the cooperative chiral amine ligand, 13 or the CCA ligand. 7,14 However, the development of efficient Ru(II)-catalyzed enantioselective C−H functionalizations is still in high demand, considering their specific features.…”

“…In the past decades, a great deal of attention have been paid for ruthenium­(II) catalysts in transition metal-catalyzed C–H activation owing to their cost efficiency and versatile reactivity . Nevertheless, the development of enantioselective versions of ruthenium­(II)-catalyzed C–H activation has lagged far behind the same periodic palladium and rhodium. , Significant breakthroughs were achieved recently by taking advantage of the chiral transient directing group, the chiral Ru­(II) catalyst bearing the chiral η 6 -arene ligand, the cooperative chiral amine ligand, or the CCA ligand. , However, the development of efficient Ru­(II)-catalyzed enantioselective C–H functionalizations is still in high demand, considering their specific features. Herein, we reported the Ru­(II)-catalyzed enantioselective [4 + 3] annulation of sulfoximines with α,β-unsaturated ketones (Scheme b) .…”