Enantioselective Synthesis of Chromanones via a Peptidic Phosphane Catalyzed Rauhut–Currier Reaction

Abstract

The enantioselective intramolecular Rauhut-Currier reaction has been developed using a bifunctional dipeptidic phosphane catalyst, providing a direct access to biologically active α-methylene-δ-valerolactones in high yields and enantiomeric excesses. The novel catalyst is accessible in only four steps from commercial sources and exhibits unusual binding selectivities for a small molecule, suggesting the possibility for long-range interactions between the catalyst and the substrate.

Phosphine Organocatalysis

“…In 2015, Grossmann, Spring, and co-workers studied the synthesis of α -methylidene- δ -lactones through RC cyclization of chalcone derivatives (Scheme 35). 120 Using the valine-derived phosphine P5 or the phenylalanine-isoleucine-derived phosphine Boc-FIP P9 as the chiral catalyst, chalcone derivatives presenting various substituents underwent the cyclizations to furnish chromanones in moderate to excellent yields and with moderate to excellent enantioselectivities. Shortly thereafter, the Albrecht group reported a similar synthesis of α -methylidene- δ -lactones using a phosphine-catalyzed intramolecular RC reaction (Scheme 36).…”

The Intramolecular Rauhut−Currier Reaction between Nitroalkenes and Acrylates: An Approach to 3‐Methylene‐3,4‐Dihydrocoumarin Scaffold

“…Among the numerous 3,4‐dihydrocoumarin derivatives, 3‐methylene‐3,4‐dihydrocoumarins was recently proved to have a broad spectrum of biological activities, such as anticancer and antimicrobial activity . However, up to date, only a few examples deal with the construction of 3‐methylene‐3,4‐dihydrocoumarin scaffold, including the synthesis of 3‐methylene‐3,4‐dihydrocoumarins starting from 3‐methoxy‐2‐diethoxyphosphorylacrylate via a Friedel‐Crafts alkylation, Michael addition and Horner‐Wadsworth‐Emmons reaction sequences, 12c,13 the asymmetric construction of 3‐methylene‐3,4‐dihydrocoumarin skeleton via an intramolecular vinylogous R−C reaction of para ‐quinone methides under the catalysis of a chiral amine‐phosphine as well as the enantioselective synthesis of 3‐methylene‐3,4‐dihydrocoumarin derivatives through a polyfunctional dipeptidic phosphine catalyzed intramolecular R−C reaction of chalcones . Therefore, the development of novel efficient protocol for the synthesis of such a skeleton, employing readily available starting materials and reagents under mild reaction conditions, is still a formidable challenge and in great demand.…”

Theoretical study on the reaction mechanisms and stereoselectivities of DABCO‐catalyzed Rauhut–Currier/cyclization reaction of methyl acrylate with 2‐benzoyl‐3‐phenyl‐acrylonitrile

“…The cross coupling versions of the RC reaction have also been documented . In recent years, the RC reaction has been developed for synthetic applications to make new molecules for natural product and organic synthesis …”