One‐Pot Synthesis of Indolizines Using TBHP as the Methylene Source Under Metal‐Free Condition

• Published in: European journal of organic chemistry Vol. 2020; no. 2; pp. 262 - 266
• Main Authors: Zhang, Qianwei, Ablajan, Keyume, Wang, Bin, Ma, Huifang, Guo, Zhongqi
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 16.01.2020; Wiley Subscription Services, Inc
• Subjects: Aromatic compounds; Butyl hydroperoxide; Cascade chemical reactions; Chemical synthesis; Chemistry; Chemistry, Organic; Cycloaddition; Heterocycles; Ketones; Metal‐free; Methylene; Methylene source; Multicomponent reactions; Oxidizing agents; Physical Sciences; Science & Technology; Heterocycles; Metal-free; H BOND; CATALYZED ANNULATION; DIAZO-COMPOUNDS; ALKENES; Cycloaddition; CINNAMIC-ACIDS; Methylene source; Multicomponent reactions; SUBSTITUTED INDOLIZINES; PYRIDINIUM YLIDES; C-C BOND; ALKYLATION-PEROXIDATION
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201901803

An I2/tert‐butyl hydroperoxide (TBHP)‐mediated [2+1+1+1] cycloadditions/oxidative aromatization reactions for the synthesis of indolizines using the one‐pot cascade process have been developed. A variety of aryl methyl ketones react with pyridine/isoquinoline and TBHP in the transition‐metal‐free reaction. This method utilizes readily available starting materials and TBHP acted in this reaction not only as oxidant and radical initiator but also as a methylene source, therefore providing a novel method of atom economy for the synthesis of indolizines. A novel and simple direct construction of indolizines have been accomplished under metal‐free conditions using the one‐pot cascade process. This new protocol utilizes unfunctionalized starting materials, simple procedures, and successfully introduces the methylene source from TBHP into the indolines.