Synthesis of medium- and large-ring compounds initiated by photochemical decarboxylation of omega-phthalimidoalkanoates

The synthesis of a variety of hydroxylactams item omega-phthalimidoalkanoates using a triplet-sensitized photodecarboxylation reaction initialed by intramolecular photo electron transfer is described. Ring sizes available by this method span from 4 (benzazepine-1.5-dione 7) to 6 (cyclodipeptide 26e). Ground-stale 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 (Scheme 4). Spacer groups investigated were alkyl chains (C-3-C-11: 5c-h, 11a, 12), ether (16, 18), ester (20, 22), and amide (26a-f) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products were observed, indicating the high preference for intra- vs. intermolrcular photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (cf. products 11 and 12) in contrast to comparable singlet reactions. Except for the lactones 22, all products were stable under the photolysis conditions. Prolonged irradiation of 22 led to the formation of the spiro compounds 23, probably via an intermediary acyliminium betaine (Scheme 8). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glycine spacer (as in 27a and 27b) probably the consequence of a strong intramolecular H-bond (Scheme 10).