FULL PAPER DOI: 10.1002/ejoc.201301774 [8+2] Formal Cycloaddition Reactions of Tropones with Azlactones under Brønsted Acid Catalysis and Synthesis of α-(2-Tropyl), α-Alkyl α-Amino Acids Francisco Esteban, [a] Ricardo Alfaro, [a] Francisco Yuste, [a] Alejandro Parra, [a] José Luis García Ruano,* [a] and José Alemán* [a] Keywords: Amino acids / Tropones / Cycloaddition / Brønsted acids catalysis / Heterocycles The reaction of tropones with azlactones catalyzed by Brønsted acids affords a variety of dihydro-2H-cyclohepta- [b]furan derivatives, corresponding to a formal [8+2] cycload- dition process. They can easily be opened by nucleophiles to Introduction The nonbenzenoid aromatic structure of tropones and troponoids has attracted the attention of chemists in the last decades from a theoretical and synthetic point of view. [1] These structures have been found and used in the total synthesis of natural products, [2] and their behavior in cycloaddition reactions has been widely studied as an ido- neous π system for the investigation of the competition be- tween different types of reactions. [3] Other aspects concern- ing their reactivity, such as nucleophilic additions, have also been studied, [4] and most of them have involved 1,8- Scheme 1. Different reactivities of tropone derivatives. [a] Departmento de Química Orgánica (módulo 1), Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain E-mail: jose.aleman@uam.es www.uam.es/JLGR Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.201301774. Eur. J. Org. Chem. 2014, 1395–1400 © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1395 afford a new type of α,α-disubstituted α-amino acid (or pept- ide) containing seven-membered rings at the quaternary po- sition. addition processes (Scheme 1, equation a). One of the most interesting reactions of the tropones occurs with reagents that simultaneously contain nucleophilic and electrophilic centers. They are tandem processes involving an initial nu- cleophilic attack at C-2 of the tropone ring (1,8-addition) followed by an intramolecular reaction of the resulting enolate with the electrophilic center of the reagent (Scheme 1, equation b). Precursors of different 1,3-dipoles have been used in these reactions to afford bicyclic struc- tures that formally correspond to [8+2] [5] and [6+3] [6] cyclo- additions processes, [7] but the use of azlactones in this type of reaction has never been explored. At this point, we hypothesized about the reactions of tropones with azlactones because they are stable com- pounds that exhibit dual electrophilic (carbonylic carbon atom) and nucleophilic (C-2 or C-4) behavior. The C-4