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

In the field of renewable material 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 added-value 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, with high diastereoselectivities. We were able to exploit the azidomethyl side chain to produce cyclopentenones with other nitrogenous functionalities, such as amine or triazole moities. Moreover, these 4-(azidomethyl)-cyclopentenones exhibited relevant cytotoxic activities against HCT116 and HL60 cancer cell lines with nanomolar IC50 values.