Photochemistry of N-phthaloylcysteine derivatives: Multiplicity-directed regioselective CH activation

The photochemistry of the methyl esters of N-phthaloylcysteine derivatives 1b-5b was studied. The results are remarkable, because they prove a pronounced, multiplicity-controlled regioselectivity of the initial CH activation step. From substrates 1b-4b the benzazepine-1,5-dione 6 was produced exclusively by the singlet path. The formation of compound 6 is initiated by a gamma-H abstraction; this was demonstrated by deuterium labeling experiments. The penicillamine derivative 5b was unreactive in the singlet manifold. From substrates 1b-3b and 5b the thiazinoisoindoles 7-9 and 11 were produced exclusively by the triplet path. The sterically hindered S-isopropylcysteine derivative 4b also furnished this product type (10) as a proportion of the products in the singlet manifold. These annulation products result from a primary photoinduced electron-transfer (PET) step followed by heterolytic epsilon-H activation. The mechanistic scenario was elucidated by quenching and sensitization experiments. An interplay of CH activation steps and electron back-transfer is probably responsible for this type of spin selectivity.