Ru(II)–Pheox-Catalyzed Asymmetric Intramolecular Cyclopropanation of Electron-Deficient Olefins

Abstract

The first highly enantioselective intramolecular cyclopropanation of electron-deficient olefins, in the presence of Ru(II)--Pheox catalyst, is reported. The corresponding cyclopropane-fused γ-lactones were obtained in high yields (up to 99%) with excellent enantioselectivities (ee up to 99%). Moreover, this method enables efficient access to enantioenriched dicarbonyl cyclopropane derivatives, which are important intermediates for the synthesis of various bioactive compounds.

Computational chemical analysis of Ru(II)‐Pheox–catalyzed highly enantioselective intramolecular cyclopropanation reactions

“…Ru(II)‐Pheox–catalyzed intramolecular cyclopropanations of allyl diazoacetate derivatives (Table , entries 2‐5): These results were published in our previous report …”

“…In 2010, we developed a novel chiral complex, Ru(II)‐phenyloxazoline (Ru(II)‐Pheox) complex, which has a unique C 1 ‐symmetric structure (Figure ). Ru(II)‐Pheox can be easily synthesized from a commercially available benzoic acid derivative, an amino alcohol and a Ru source, and effectively promotes enantioselective intermolecular and intramolecular cyclopropanations with electron‐rich olefins, as well as electron‐deficient olefins, under mild reaction conditions.…”

Applications of Chiral Three-membered Rings for Total Synthesis: A Review

“…This mixture was further employed as key intermediate in the total synthesis of natural products, tremulenediol A and tremulenolide A [199], and to that of various cyclopropanederived peptidomimetics [200]. In 2015, Chanthamath and Iwasa reported the enantioselective intramolecular cyclopropanation of electron-deficient allylic diazoacetate 214, performed in the presence of ruthenium catalyst 215 that provided the corresponding diastereo-and enantiopure cyclopropane-fused g-lactone 216 in high yield (90%) [201]. The latter was employed as building block in the total syntheses of drug DCG-IV and natural product dysibetaine CPa (Scheme 82).…”

Synergistic NaBH4 Reduction/Cyclization of 2‐Aroylcyclopropane‐1‐carboxylates: Synthesis of 3‐Oxabicyclo[3.1.0]hexane Derivatives

“…The great pharmaceutical potential of this scaffold prompted us to search for new and efficient methods that would provide diversified structures in a minimum number of steps. As a result of their biological importance, many methods for the construction of 3‐oxabicyclo[3.1.0]hexanes have been developed 3‐Oxabicyclo[3.1.0]hexanes can be synthesized by various strategies, such as the Ireland–Claisen rearrangement procedure,, intramolecular cyclization reactions of aryldiazoacetates, Ru‐catalysed annulations, Pd‐promoted [2+1] cycloaddition reactions between dihydrofuran derivatives and alkynes, or Au‐catalysed cyclopropanation reactions of substituted (allyloxy)sulfonium ylides . Another interesting synthetic pathway, reported by Pathak and co‐worker, is based on the formation of single diastereomers of substituted 3‐oxabicyclo[3.1.0]hexanes through the reaction of the corresponding vinyl selenone with nitromethane, malononitrile, and dimethyl malonate in the presence of t BuOK in THF at room temperature .…”