Reaction Modes and Mechanism in Indolizine Photooxygenation Reactions

Photooxygenations of 1,2-, 1,3-, and 2,3-di- and 1,2,3-trisubstituted indolizines 1a−1f 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 1a and
1b and 1,3-dibenzoyl-2-phenylindolizine (1d) are self-sensitized, while those of 1-(p-nitrobenzoyl)-2-phenylindolizine (1c) and 2-phenyl-3-(p-chlorobenzoyl)indolizine (1e) 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 D (in
methanol) and dioxetane E 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 (E)- and (Z)-3-(2-pyridinyl)-3-benzoylpropenoic acid
methyl esters (2 and 3) and 4-(2-pyridinyl)-3-phenyl-5-aryl-5-hydroxyfuran-2-one (4) as products
in methanol, while O−O bond homolysis of the dioxetane furnishes 3-(2-pyridinyl)-3-benzoyl-2-phenyloxirane-2-carboxaldehyde (6) and 1-(6-methyl-2-pyridinyl)-2-phenylethanedione (5) as products in acetonitrile. 3-Benzoyl-1-indolizinecarboxylic acid methyl ester (1f) 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 (9f), dimethyl 2-(2-pyridinyl)fumarate (8f), and dimethyl 2-(2-pyridinyl)maleate (7f) as products.