Enantioselective Synthesis of Functionalized 4-Aryl Hydrocoumarins and 4-Aryl Hydroquinolin-2-ones via Intramolecular Vinylogous Rauhut–Currier Reaction of para-Quinone Methides

Abstract

A novel strategy for the asymmetric construction of functionalized 4-aryl-3,4-dihydrocoumarins and 4-aryl-3,4-dihydroquinolin-2-ones via an intramolecular vinylogous Rauhut-Currier reaction of para-quinone methides (p-QMs) under the bifunctional catalysis of chiral amine-phosphine is described. This intramolecular mode for the catalytic enantioselective 1,6-conjugate addition of p-QMs has been explored for the first time, delivering two types of synthetically important heterocycles in high yields and enantioselectivites.

Phosphine Organocatalysis

“…In 2017, the Fan group described a chiral phosphine P10 -catalyzed intramolecular vinylogous RC reaction of para -quinone methides ( p -QMs) for the construction of functionalized 4-aryl-3,4-dihydrocoumarins and 4-aryl-3,4-dihydroquinolin-2-ones (Scheme 37). 122 Various p -QM esters presenting electronically different substituents on the aromatic ring underwent the reaction in dichloromethane at 15 °C to afford 4-aryl hydrocoumarins in high yields (89–99%) and with moderate to excellent enantioselectivities (50–99% ee). The enantioselectivities decreased for substrates having substituents at the 5-position, due to a steric effect.…”

Organocatalytic Enantioselective Cross‐Vinylogous Rauhut–Currier Reaction of Methyl Coumalate with Enals

“…In addition, the development of vinylogous RC reactions employing activated dienes would be also very interesting as the products contain additional functionality. Recently, the groups of Zhang, Zhao, and Fan have reported the asymmetric cross‐vinylogous RC reactions, using para ‐quinone methides as the electrophilic partner, by 1,6‐addition. By contrast, the alternative asymmetric vinylogous process, using an activated diene as the nucleophilic partner, has not been achieved.…”

Recent Advances in the Catalytic Enantioselective Reactions of para‐Quinone Methides

“…As showni nS cheme 21, Fan and co-workersa ccomplished a key asymmetric vinylogous Rauhut-Currier reaction of p-QMs for the synthesis of chiral-functionalized coumarins (X = O) and quinolinones (X = NTs, NMe;T s= para-methylphenylsulfonyl). [26] Undert he bifunctionalc atalysis of chiral amine-phosphine C19 with al oading of 10 mol %, the intramolecular vinylogous Rauhut-Currier reaction of p-QMs 67 afforded ar ange of syntheticallyu seful,o ptically active 4-aryl-3,4-dihydrocoumarins and 4-aryl-3,4-dihydroquinolin-2-ones in highy ields and with excellent enantioselectivities.H owever, p-QMst hat contained sterically bulky substituents at the 3-positiong ave lower ee values, owing to steric hindrance. Mechanistically,i nitial nucleophilic attack of the 1,2-amine-phosphine catalyst on the acrylate moiety of the p-QM providedazwitterionic intermediate that was stabilized by ah ydrogen-bondingi nteraction.…”

“…As shown in Scheme , Fan and co‐workers accomplished a key asymmetric vinylogous Rauhut–Currier reaction of p ‐QMs for the synthesis of chiral‐functionalized coumarins (X=O) and quinolinones (X=NTs, NMe; Ts= para ‐methylphenylsulfonyl) . Under the bifunctional catalysis of chiral amine–phosphine C19 with a loading of 10 mol %, the intramolecular vinylogous Rauhut–Currier reaction of p ‐QMs 67 afforded a range of synthetically useful, optically active 4‐aryl‐3,4‐dihydrocoumarins and 4‐aryl‐3,4‐dihydroquinolin‐2‐ones in high yields and with excellent enantioselectivities.…”