Fast and scalable continuous flow synthesis of butenolides and coumarins

Ferreira, Lucas Coral, de Souza Galaverna, Renan, McBride, Tom, Costa e Silva, Rodrigo, Browne, Duncan L. ORCID: https://orcid.org/0000-0002-8604-229X and Pastre, Julio Cezar 2025. Fast and scalable continuous flow synthesis of butenolides and coumarins. Reaction Chemistry and Engineering 10.1039/d4re00567h

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Abstract

Herein, we present a versatile and efficient continuous flow protocol for the synthesis of structurally diverse butenolides and coumarins through the in situ generation of acylketenes via the retro hetero-Diels–Alder reaction of dioxinones with α-hydroxy-ketones and salicylaldehydes, respectively. This protocol enabled the synthesis of 5 examples of butenolides with yields ranging from 30 to 91% and 16 examples of coumarins with yields ranging from 30 to 99%. The versatility and practicality of the protocol were demonstrated by the gram-scale synthesis of a biologically relevant γ-spiro butenolide core, as well as the production of benzo-coumarins. Modern medicinal chemistry demands both scalability and the ability to synthesize structurally diverse compounds in a single synthetic platform, and our methodology effectively addresses these challenges in a fast and safer manner.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Chemistry
Publisher:	Royal Society of Chemistry
Date of First Compliant Deposit:	20 March 2025
Date of Acceptance:	7 February 2025
Last Modified:	20 Mar 2025 10:49
URI:	https://orca.cardiff.ac.uk/id/eprint/176466

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