Dynamic Trapping as A Selective Route to Renewable Phthalide from Bio-based Furfuryl Alcohol.

A novel route for the production of the versatile chemical building block phthalide from bio-renewable furfuryl alcohol and acrylate esters is presented. Two challenges that generally limit sustainable aromatics production via Diels-Alder (DA) aromatization, i.e. an unfavorable equilibrium position and undesired regioselectivity when using asymmetric addends, have been addressed by using a dynamic kinetic trapping strategy. Our strategy involves the use of activated acrylates to speed up both the forward and reverse DA reactions, allowing for one of the four DA adducts to undergo a selective intramolecular lactonization reaction in the presence of a weak base. This way, the adduct is removed from the equilibrium pool, pulling the system completely to the product with the now fixed, desired regiochemistry. A single 1,2-regioisomeric lactone product is now formed in up to 86% yield and the acrylate activating agent liberated for reuse. The lactone could be aromatized to give phthalide in almost quantitative yield in the presence of Ac 2 O and a catalytic amount of strong acid or in 79% using only catalytic acid.