Catalytic Asymmetric Addition of Meldrum’s Acid,Malononitrile, and 1,3‐Dicarbonyls to ortho‐Quinone Methides Generated In Situ Under Basic Conditions |
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Authors: | Lorenzo Caruana Martina Mondatori Vasco Corti Sara Morales Prof. Andrea Mazzanti Prof. Mariafrancesca Fochi Prof. Luca Bernardi |
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Affiliation: | 1. Department of Industrial Chemistry “Toso Montanari”, Alma Mater Studiorum‐University of Bologna, V. Risorgimento 4, 40136 Bologna (Italy);2. Department of Organic Chemistry, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid (Spain) |
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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. |
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Keywords: | asymmetric catalysis enantioselectivity organocatalysis quinone methides sulfones |
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