Synthesis of Non-symmetrical Dispiro-1,2,4,5-Tetraoxanes and Dispiro-1,2,4-Trioxanes Catalyzed by Silica Sulfuric Acid

• Published in: Journal of organic chemistry Vol. 86; no. 15; pp. 10608 - 10620
• Main Authors: Amado, Patrícia S. M, Frija, Luís M. T, Coelho, Jaime A. S, O’Neill, Paul M, Cristiano, Maria L. S
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.08.2021; Amer Chemical Soc
• Subjects: catalysts; Chemistry; Chemistry, Organic; organic chemistry; Physical Sciences; Science & Technology; silica; sulfuric acid; GEM-DIHYDROPEROXIDES; TETRAOXANES; ENDOPEROXIDE; ARTEMISININ RESISTANCE; PLASMODIUM-FALCIPARUM; ARTEMETHER-LUMEFANTRINE; HYDROPEROXYSILYLATION; MALARIA; IDENTIFICATION; EFFICIENT
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/acs.joc.1c01258

A novel protocol for the preparation of non-symmetrical 1,2,4,5-tetraoxanes and 1,2,4-trioxanes, promoted by the heterogeneous silica sulfuric acid (SSA) catalyst, is reported. Different ketones react under mild conditions with gem-dihydroperoxides or peroxysilyl alcohols/β-hydroperoxy alcohols to generate the corresponding endoperoxides in good yields. Our mechanistic proposal, assisted by molecular orbital calculations, at the ωB97XD/def2-TZVPP/PCM­(DCM)//B3LYP/6-31G­(d) level of theory, enhances the role of SSA in the cyclocondensation step. This novel procedure differs from previously reported methods by using readily available and inexpensive reagents, with recyclable properties, thereby establishing a valid alternative approach for the synthesis of new biologically active endoperoxides.