From 5-HMF to Novel Cyclopentenone-Based Aza Spirocycles: An Intramolecular Aza-Piancatelli Reaction in Action.

Abstract

With a double objective to upgrade biobased 5-HMF and to access to original spirocycles via an intramolecular aza-Piancatelli reaction, a multistep sequence was designed toward appropriate furylcarbinols. The impacts of both the nucleophiles, arylamines compared to alkoxyamines, and the length of the intramolecular tether were studied. After an in-depth evaluation of the different parameters, an extension of the scope provided a library of original azaspiro[4.5]non-8-en-7-ones and azaspiro[4.6]dec-3-en-2-ones whose skeletons have so far never been listed. The application of the aza-Piancatelli reaction associated with the use of biobased HMF in fine chemistry gives credit to the development of novative structures, as raised by the green chemistry community. Combining efforts in synthetic methodology with integration of biosourced platforms could open the way to new molecules exhibiting different properties from the ones raised from petrochemical sources.