Prins-Peterson tandem reaction: direct diastereoselective synthesis of oxocines Davide Andrea Coppini, Juan Ignacio Padron Peña Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas (IPNA-CSIC), Spain Eight-membered cyclic ethers are biologically interesting and challenging organic compounds due to their presence in various bioactive natural products and their complex, macrocyclic structure complicating their synthesis. 1 These unsaturated eight-membered oxacycles (oxocines) have been synthesized exploiting various methodologies, such as RCM of olefins, 2 acetal-alkene cyclizations promoted by Lewis acids, 3 or Pd-catalyzed cyclizations. 4 Here, we present the Prins-Peterson tandem reaction as a direct alternative method. The reaction between tris -homoallyl alcohol and an aldehyde is catalyzed by Fe(III) salts and allows the formation of a Δ 4 -substituted oxocine. Preliminary tests during the optimization phase monitored by HPLC-MS also led to forming 2,3,5-trisubstituted tetrahydrofurans as the main byproduct.
Therefore, the reaction scope will be extended by using different aldehydes, silylated substituents, and more substituted starting alcohols; DFT calculations and mechanistic studies have been performed to elucidate the reaction mechanism and stereochemical outcome. References 1. C. Galli, L. Mandolini, European J. Org. Chem . 2000 , 2000 , 3117–3125. 2. Torres, A., Gutierrez, P., Alvarez-Manzaneda, R., Chahboun, R. & Alvarez-Manzaneda, E. Org. Biomol. Chem. 2016 , 14 , 9836−9845.
3. M. Bratz, W. H. Bullock, L. E. Overman, T. Takemoto, J. Am. Chem. Soc. 1995 , 117 , 5958–5966. 4. Yoshimitsu, Y.; Inuki, S.; Oishi, S.; Fujii, N.; Ohno, H. Org. Lett. 2013 , 15 (12), 3046–3049.
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