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Acetylides from Alkyl Propiolates as Building Blocks for C3 Homologation


  • This research was supported by the Spanish Ministerio de Educación y Ciencia, the European Regional Development Fund (CTQ2005-09074-C02-02) and the Spanish MSC ISCIII (RETICS RD06/0020/1046), CSIC (Proyecto Intramural Especial 200719), and the Fundación Instituto Canario de Investigación del Cáncer (FICI-G.I.N°08/2007). S.L.-T. thanks MEC for a FPU grant, F.C.-A. thanks CSIC for a JAE predoc grant. We thank Dr. Tomás Martín and Dr. Pedro de Armas for helpful discussions and critical reading of this manuscript.


Three that matter: Metal acetylides from alkyl propiolates allow C3 homologations with transference of their versatile reactivity profile to products that can then react without further elaboration. Metal-free acetylides, which are generated by the action of a good nucleophile on the alkyl propiolate, react with suitable electrophiles through different domino reactions to generate skeletal diversity.

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Alkyl propiolates are reagents with a versatile reactivity profile that entirely remains in the C3-homologated product for further elaboration. To be effective, this C3 homologation requires suitable methods for the generation of the acetylide anion that are compatible with both the conjugated ester and the electrophilic partner. Recent advances include catalytic procedures for the in situ generation of these acetylides in the presence of suitable electrophiles. Whereas the organometallic methods have brought stereoselectivity to these reactions, the organocatalytic methods laid the ground for new efficient domino processes that generate complexity.