Hydrogen Bond Controlled Anti-Aza-Michael Addition: Diastereoselective Synthesis of Cyclobutene-Containing Amino Acid Derivatives
The chemical reactivity encoded in a highly substituted cyclobutane platform, which contains the (E,E)-dimethyl 2,2'-(cyclobutane-1,2-diylidene)diacetate structural motif, has been explored. The cyclobutane platform features a C2 axis of symmetry as well as a dense and interconnected ring funct...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/132392 |
| Acceso en línea: | http://hdl.handle.net/10261/132392 |
| Access Level: | acceso abierto |
| Palabra clave: | Hydrogen bonds Diastereoselectivity Sigmatropic rearrangement Michael addition Amino acids |
| Sumario: | The chemical reactivity encoded in a highly substituted cyclobutane platform, which contains the (E,E)-dimethyl 2,2'-(cyclobutane-1,2-diylidene)diacetate structural motif, has been explored. The cyclobutane platform features a C2 axis of symmetry as well as a dense and interconnected ring functionalization pattern that is defined by two allylic/benzylic stereogenic oxygen-containing quaternary centers with a 1,2-trans configuration and two exocyclic acrylate chains. The reactivity profile of the cyclobutane platform is defined by two important kinetic barriers (steric strain and antiaromaticity) and two structure-biased chemical processes: (1) the thermally-driven [3,3] sigmatropic rearrangement between one of the two equivalent aryloates and the corresponding allylic acrylate chain and (2) the allylic nucleophilic substitution (SN2' reaction) that involves a tertiary aryloate and its exocyclic double bond (anti-Michael addition). The reaction of platform 3a with secondary amines delivered the corresponding cyclobutene amino acid derivatives 15a¿15f in excellent yields (up to ¿95¿%) and high diastereoselectivities (up to 99:1). Computational studies are described to rationalize the observed diastereoselectivity. |
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