Copper-mediated oxidative [3 + 2]-annulation of nitroalkenes and pyridinium ylides: general access to functionalized indolizines and efficient synthesis of 1-fluoroindolizines?

Organic & Biomolecular Chemistry Pub Date: 2019-01-16 DOI: 10.1039/C8OB03126F

Abstract

A general method for the synthesis of substituted indolizines by copper(II) acetate-promoted oxidative [3 + 2]-annulation of α-fluoronitroalkenes with in situ generated pyridinium ylides was developed. Application of the copper(II) acetate–2,6-lutidine system provides efficient access to various 1-fluoroindolizines in up to 81% yield. Both electron-rich and electron-deficient nitroalkenes as well as different pyridinium and isoquinolinium salts can be involved in the reaction. Moreover, it was found that copper-mediated annulation is applicable for other α-substituted (alkyl, chloro, and ester) nitroalkenes giving rise to the corresponding indolizines. First synthesis of monofluorinated [3,2,2]cyclazines was demonstrated via oxidative annulation of 3-unsubstituted fluoroindolizines with diethyl acetylene dicarboxylate.

Graphical abstract: Copper-mediated oxidative [3 + 2]-annulation of nitroalkenes and pyridinium ylides: general access to functionalized indolizines and efficient synthesis of 1-fluoroindolizines
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