SYNTHESIS OF MEDIUM-RING AND LARGE-RING COMPOUNDS INITIATED BY PHOTOCHEMICAL DECARBOXYLATION OF OMEGA-PHTHALIMIDOALKANOATES

The synthesis of a variety of hydroxylactams item omega-phthalimidoalk anoates using a triplet-sensitized photodecarboxylation reaction initi aled by intramolecular photo electron transfer is described. Ring size s available by this method span from 4 (benzazepine-1.5-dione 7) to 6 (cyclodipeptide 26e). Ground-stale template formation is proposed as t he explanation For the high efficiency of this reaction and for the de crease 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). Sp acer groups investigated were alkyl chains (C-3-C-11: 5c-h, 11a, 12), ether (16, 18), eater (20, 22), and amide (26a-f) linkages. Within the detection limits, no dimeric (= decarboxylative coupling) products we re observed, indicating the high preference for intra- vs. intermolrcu lar photoelectron transfer. The C,C radical combination step proceeds with low stereoselectivity (cf. products 11 and 12) in contrast to com parable singlet reactions. Except for the lactones 22, all products we re stable under the photolysis conditions. Prolonged irradiation of 22 led to the formation of the spiro compounds 23, probably via an inter mediary acyliminium betaine (Scheme 8). One serious limitation of the decarboxylative macrocyclization is its incompatibility with the glyci ne spacer (as in 27a and 27b) probably the consequence of a strong int ramolecular H-bond (Scheme 10).