Dynamic Trapping as a Selective Route to Renewable Phthalide from Biomass-Derived Furfuryl Alcohol

Angew Chem Int Ed Engl. 2020 Dec 21;59(52):23480-23484. doi: 10.1002/anie.202009001. Epub 2020 Oct 15.

Abstract

A novel route for the production of the versatile chemical building block phthalide from biorenewable furfuryl alcohol and acrylate esters is presented. Two challenges that limit sustainable aromatics production via Diels-Alder (DA) aromatisation-an unfavourable equilibrium position and undesired regioselectivity when using asymmetric addends-were addressed using a dynamic kinetic trapping strategy. Activated acrylates were used to speed up the forward and reverse DA reactions, allowing for one of the four DA adducts to undergo a selective intramolecular lactonisation reaction in the presence of a weak base. The adduct is removed from the equilibrium pool, pulling the system completely to the product with a fixed, desired regiochemistry. A single 1,2-regioisomeric lactone product was formed in up to 86 % yield and the acrylate activating agent liberated for reuse. The lactone was aromatised to give phthalide in almost quantitative yield in the presence of Ac2 O and a catalytic amount of strong acid, or in 79 % using only catalytic acid.

Keywords: Diels-Alder reactions; biomass; dehydration; lactonisation; sustainable chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / chemistry*
  • Biomass
  • Cycloaddition Reaction / methods*
  • Furans / chemistry*

Substances

  • Benzofurans
  • Furans
  • phthalide
  • furfuryl alcohol