Uncatalyzed solventless Diels–Alder reaction of 2-amino-3-nitroacrylate: synthesis of new epimeric 2-amino-3-nitro-norbornene- and norbornane-2-carboxylic acids

• Published in: Tetrahedron 2006-02, Vol.62 (6), p.1288-1294
• Main Authors: Caputo, Francesco, Clerici, Francesca, Gelmi, Maria Luisa, Nava, Donatella, Pellegrino, Sara
• Format: Article
• Language: English
• Subjects: 2-Amino-3-nitro-norbornane-2-carboxylic acids; 2-Amino-3-nitro-norbornene-2-carboxylic acids; Diels–Alder; Epimerization
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2005.10.056

A highly diastereoselective Diels–Alder reaction between cyclopentadiene and ethyl ( Z)-2- N-Boc-amino-3-nitroacrylate in neat conditions affords the ethyl 2- t-butoxycarbonylamino-3- endo-nitro-bicyclo[2.2.1]hept-5-ene-2- exo-carboxylate: a new constrained carbocyclic amino acid. Catalytic hydrogenation of this cycloadduct gave the corresponding reduced norbornane derivative. A preliminary investigation into the chemistry of these two amino acids was performed. In particular, the epimerization to their corresponding 3- exo-nitro compounds by treatment both with acid and base was studied. From this study, valuable information on the endo/ exo process at the C-3 carbon atom, as well as on the stability of the different stereomers, was obtained. The stability is closely related to the presence or the absence of the double bond in the ring and to the substitution pattern. Finally, deprotection of the amino acid function has been performed. Graphical Abstract