Reaction Modes and Mechanism in Indolizine Photooxygenation Reactions

Photooxygenations of 1,2-, 1,3-, and 2,3-di- and 1,2,3-trisubstituted indolizines <b>1a</b>−<b>1f</b> under different reaction conditions in methanol and acetonitrile have been investigated to establish the general reaction pattern and mechanism in indolizine photooxygenation in view of the influence of the ring substituents and substitution pattern. Photooxygenations of 1-acyl-2-phenylindolizines <b>1a</b> and <b>1b </b>and 1,3-dibenzoyl-2-phenylindolizine (<b>1d</b>) are self-sensitized, while those of 1-(<i>p</i>-nitrobenzoyl)-2-phenylindolizine (<b>1c</b>) and 2-phenyl-3-(<i>p</i>-chlorobenzoyl)indolizine (<b>1e</b>) need to be sensitized by rose bengal (RB) or methylene blue (MB). These reactions proceed via a singlet oxygen mechanism yet follow different pathways in methanol and in acetonitrile, with peroxidic zwitterion <b>D</b> (in methanol) and dioxetane <b>E</b> across the indolizine C2−C3 bond (in acetonitrile) as the intervening intermediates. Methanol trapping of the peroxidic zwitterion results in C3−N bond cleavage and pyrrole ring opening to give the corresponding (<i>E</i>)- and (<i>Z</i>)-3-(2-pyridinyl)-3-benzoylpropenoic acid methyl esters (<b>2</b> and <b>3</b>) and 4-(2-pyridinyl)-3-phenyl-5-aryl-5-hydroxyfuran-2-one (<b>4</b>) as products in methanol, while O−O bond homolysis of the dioxetane furnishes 3-(2-pyridinyl)-3-benzoyl-2-phenyloxirane-2-carboxaldehyde (<b>6</b>) and 1-(6-methyl-2-pyridinyl)-2-phenylethanedione (<b>5</b>) as products in acetonitrile. 3-Benzoyl-1-indolizinecarboxylic acid methyl ester (<b>1f</b>) is unreactive toward singlet oxygen; however, it could be photooxygenated under electron transfer conditions with 9,10-dicyanoanthracene (DCA) as a sensitizer. This reaction takes place by the combination of the indolizine cation radical with the superoxide anion radical (or molecular oxygen) to give the pyridine ring oxidized methyl 3-benzoyl-5-methoxy-8-hydroxy-1-indolizinecarboxylate (<b>9f</b>), dimethyl 2-(2-pyridinyl)fumarate (<b>8f</b>), and dimethyl 2-(2-pyridinyl)maleate (<b>7f</b>) as products.