title: Catalytic asymmetric addition of Meldrum's acid, malononitrile, and 1,3-dicarbonyls to ortho-quinone methides generated in situ under basic conditions.
abstract: A new approach to the utilization of highly reactive and unstable ortho-quinone methides (o-QMs) in catalytic asymmetric settings is presented. The enantioselective reactions are catalysed by bifunctional organocatalysts, and the o-QM intermediates are formed in situ from 2-sulfonylalkyl phenols through base-promoted elimination of sulfinic acid. The use of mild Brønsted basic conditions for transiently generating o-QMs in catalytic asymmetric processes is unprecedented, and allows engaging productively in the reactions nucleophiles such as Meldrum's acid, malononitrile and 1,3-dicarbonyls. The catalytic transformations give new and general entries to 3,4-dihydrocoumarins, 4H-chromenes and xanthenones. These frameworks are recurring structures in natural product and medicinal chemistry, as testified by the formal syntheses of (R)-tolterodine and (S)-4-methoxydalbergione from the catalytic adducts.
authors.affiliation: Department of Industrial Chemistry "Toso Montanari", Alma Mater Studiorum-University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy).
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Caruana
authors.forename: Martina
authors.initials: M
authors.lastname: Mondatori
authors.forename: Vasco
authors.initials: V
authors.lastname: Corti
authors.forename: Sara
authors.initials: S
authors.lastname: Morales
authors.forename: Andrea
authors.initials: A
authors.lastname: Mazzanti
authors.forename: Mariafrancesca
authors.initials: M
authors.lastname: Fochi
authors.forename: Luca
authors.initials: L
authors.lastname: Bernardi
keywords: asymmetric catalysis; enantioselectivity; organocatalysis; quinone methides; sulfones