Photochemistry of MTM- and MTE-esters of omega-phthalimido carboxylic acids: Macrocyclization versus deprotection

The photochemistry of five linear methylthiomethyl (MTM)-esters of omega -p hthalimido carboxylic acids Pht=N-(CH2)(n)COOCH2SCH3 1a-e (n = 1, 2, 3, 5, and 10), of the two methylthioethyl (MTE)esters Pht=N-(CH2)(n)COOCH2CH2SCH3 2a,b (n = 1, 2), and of the two methyl-substituted MTM/MTE esters 3a and 3 b was investigated. Two reaction channels were observed: (i) photocyclizati on to give medium-sized and macrocyclic rings, (ii) photochemical deprotect ion to give the free carboxylic acids. Photocyclization of Ib and Ic n = 2, 3) resulted in 4b,c in excellent yields whereas the substrates la and Id,e with shorter as well as longer spacer groups (n = i, 5, 10) gave preferent ially the deprotected products Ba,d,e. Subsequent photolysis afforded N-met hylphthalimide (6) from 5a. The MTE-esters 2a and 2b gave the macrocyclic l actones 7 and E-8. Thus, the competition between cyclization and deprotecti on strongly depended on the chain length of the hydrocarbon linker between phthalimido chromophore and ester group. To examine the influence of the po sition of the ester group in the linker chain the model substrates 3a and 3 b with identical number of atoms separating electron donor and acceptor gro up were investigated. The more flexible MTE-derivative 3b cyclized to give a 4:1 diastereoisomeric mixture of cis/trans-9b, whereas photolysis of the more reluctant MTM-ester 3a resulted in cis-ga only after prolonged irradia tion. These results show that MTM can function as a photolabile protecting group whereas MTE cannot be removed photochemically. The distance dependenc e of the secondary reaction steps indicates that the primary electron trans fer is not necessarily induced starting from close contact geometries.