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 γ‐H ion; 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 ϵ‐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. Pronounced, multiplicity‐controlled regioselectivity of the initial C‐H activation step was observed in the photochemical reaction of the methyl esters of N‐phthaloylcysteine derivatives 1: the benzazepine‐ 1,5‐dione product was produced exclusively by the singlet path and thiazinoisoindoles exclusively by the triplet path. The mechanistic scenarios were elucidated by quenching and sensitization experiments.