Synthesis of Medium‐ and Large‐Ring Compounds Initiated by Photochemical Decarboxylation of ω‐Phthalimidoalkanoates

<jats:title>Abstract</jats:title><jats:p>The synthesis of a variety of hydroxylactams from ω‐phthalimidoalkanoates using a triplet‐sensitized photodecarboxylation reaction initiated by intramolecular photo electron transfer is described. Ring sizes available by this method span from 4 (benzazepine‐1,5‐dione <jats:bold>7</jats:bold>) to 26 (cyclodipeptide <jats:bold>26e</jats:bold>). Ground‐state template formation is proposed as the explanation for the high efficiency of this reaction and for the decrease in reactivity in the presence of organic bases instead of metal carbonates. The crucial step in this macrocyclization reaction seems to be the protonation of the intermediary ketyl radials (<jats:italic>Scheme 4</jats:italic>). Spacer groups investigated were alkyl chains (C<jats:sub>3</jats:sub>‐C<jats:sub>11</jats:sub>: <jats:bold>5c‐h, 11a, 12</jats:bold>), ether (<jats:bold>16, 18</jats:bold>), ester (<jats:bold>20, 22</jats:bold>), and amide (<jats:bold>26a‐f</jats:bold>) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products were observed, indicating the high preference for intra‐<jats:italic>vs.</jats:italic> intermolecular photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (<jats:italic>cf</jats:italic>, products <jats:bold>11</jats:bold> and <jats:bold>12</jats:bold>) in contrast to comparable singlet reactions. Except for the lactones <jats:bold>22</jats:bold>, all products were stable under the photolysis conditions. Prolonged irradiation of <jats:bold>22</jats:bold> led to the formation of the spiro compounds <jats:bold>23</jats:bold>, probably <jats:italic>via</jats:italic> an intermediary acyliminium betaine (<jats:italic>Scheme 8</jats:italic>). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glycine spacer (as in <jats:bold>27a</jats:bold> and <jats:bold>27b</jats:bold>), probably the consequence of a strong intramolecular H‐bond (<jats:italic>Scheme 10</jats:italic>).</jats:p>