Photodecarboxylative addition of carboxylates to phthalimides: a concise access to biologically active 3-(alkyl and aryl)methylene-1H-isoindolin-1-ones

A series of 3-(alkyl and aryl)methyleneisoindolin-1-one derivatives were synthesized in a simple two-step procedure using a recently established photodecarboxylative addition of carboxylates to phthalimides as the key-step. Subsequent acid-catalyzed dehydration and deprotection furnished the desired target compounds with high E-selectivity. The reaction sequence was applied to the synthesis of the known bioactive phenylethylene derivative, AKS-186. Different analogues, including heteroatom-containing isosteres were also synthesized using this approach.     

Photoinduced electron-transfer reactions with quinolinic and trimellitic acid imides: experiments and spin density calculations(1)

The regioselectivity of photoinduced electron-transfer (PET) reactions of unsymmetrical phthalimides is controlled by the spin density distribution of the intermediate radical anions. ROHF ab initio calculations were found to be most suitable for atomic spin density analysis. Intramolecular PET reactions of quinolinic acid imides were studied with the potassium butyrate and hexanoate 1a,b and a cysteine derivative 3. The photocyclizations products 2a,b and 4 were formed with moderate regioselectivities (68:32, 57:43, and 81:19) showing preferential ortho cyclization. The intermolecular reaction of potassium propionate and potassium isobutyrate with N-methylquinolinic acid imide (5) yielded as addition products the dihydropyrrolo[3,4-b]pyridines 6a,b with slight ortho regioselectivity (55:45). In contrast to these low regioselectivities, the PET reaction of potassium propionate with the methyl ester of N-methyltrimellitic acid imide (9) yielded solely the para addition product 10. Likewise, the intramolecular photoreaction of the cysteine derivative 7 gave a 75:25 (para/meta) mixture of regioisomeric cyclization products 8. The regioselectivity originates from donor-acceptor interactions prior to electron transfer and differences in spin densities in the corresponding imide radical anions. The results of DFT and ab initio calculations for the radical anions of the quinolinic acid imide (11(*)(-)) and the methyl ester of trimellitic acid imide (12(*)(-))( )()were in agreement with the latter assumption: spin densities in 11(*)(-) were higher for the imido ortho carbon atoms (indicating preferential ortho coupling); for 12(*)(-) the spin densities were higher for the imido para carbon atoms (indicating preferential para coupling). These correlations became more significant when the additional spin densities at the carbonyl oxygen and the adjacent carbon atoms were taken into account. The cyclization selectivities for 2, 4, and 8 deviate from the intermolecular examples probably because of ground-state and solvent effects.     

Benz[c]octalen

An expedient new synthesis of benzo[c]octalene starting from the Diels-Alder adduct of benzocyclobutadiene to 7,8-dimethylenecycloocta-1,3,5-triene is described. This octalene derivative, in solution, exists as an equilibrating mixture of the double bond isomers (2) and (3) whereas in its crystalline state only the isomer (2) is present.