Metal-free and benign approach for the synthesis of dihydro-5′: H-spiro[benzo [c] chromene-8,4′-oxazole]-5′,6(7 H)-dione scaffolds as masked amino acids

Abstract

An eco-friendly, straightforward, and three-component condensation/cascade reaction of 4-hydroxycoumarins and (Z)-azlactones to construct diversified dihydro-5′H-spiro[benzo[c]chromene-8,4′-oxazole]-5′,6(7H)-diones as new masked amino acid derivatives has been developed with high to excellent yields and regio- A nd diastereoselectivity. This metal-free reaction proceeds via a one-pot cascade Michael addition/lactonization/decarboxylation reaction utilizing reusable propylene carbonate as a green solvent. The scale-up examination was also performed, showing high atom economy under the reaction conditions. Moreover, the mechanism of the reaction was further investigated using isotope-labeling, LC-MS monitoring, and TLC-MALDI-MS. © 2019 The Royal Society of Chemistry.