The Piancatelli rearrangement of AMF (5-azidomethylfurfural) derivatives: a biobased opportunity for the synthesis of nitrogenous cyclopentenones

Abstract

In the field of renewable materials to substitute petroleum-based products, one of the main areas of research is the study and transformation of small molecules derived from biomass into high value-added compounds. In this context, we report the preparation of 4-(azidomethyl)-cyclopentenones starting from AMF (5-azidomethylfurfural) derivatives, directly obtained from the well-known biosourced renewable material CMF (5-chloromethylfurfural). The Piancatelli rearrangement of these AMF derivatives, catalyzed by Dy(OTf)₃ and under microwave activation, affords substituted cyclopentenones with two contiguous stereogenic centres, one of which is quaternary, exhibiting high diastereoselectivity. We were able to exploit the azidomethyl side chain to produce cyclopentenones with other nitrogenous functionalities, such as amine or triazole moieties. Moreover, these 4-(azidomethyl)-cyclopentenones exhibited desired cytotoxic activity against HCT116 and HL60 cancer cell lines with nanomolar IC₅₀ values.