Phthalimide linkers

Wang linker, mimic 297 Wang resin, phthalimide library synthesis 103... 

Sulfur can also act as an electron donor towards the phthalimide group competing with the carboxylate ion. Therefore, in bifunctional compounds incorporating the two electron donors (carboxylate and thioether groups), the connecting linker and the solvent is crucial for the result of the reaction (Scheme 9.6) [8],... 

Under acetone-sensitized conditions, an intermolecular electron transfer from the sulfur to triplet acetone has been postulated in thioalkyl-N-substituted phthalimides. Proton transfer from the terminal a-position of the sulfur, followed by C—C bond formation, efficiently leads to macrocyclization with long and flexible chains as linkers (Scheme 9.7) [9]. 

The preparation of a phthalimide-containing resin to be used under Mitsunobu conditions means that primary amines can be generated cleanly after cleavage by hydrazinolysis.30 With this goal in mind, the resin linker 57 was obtained in > 90% yield via the synthesis outlined below. An example of the resin in use is shown with M-benzyladenosine 58, where the less hindered hydroxyl group was successfully converted to the amine 59 in 85%. 

In addition to alkenes and acetylenes, carbonyl-containing compounds also participate in [2+2] cycloaddition reactions with indoles. The first example of oxetane formation via the photoreaction of indoles with a carbonyl group (a type of Patemo-Biichi reaction) was reported by Machida and coworkers [34, 35] (Scheme 16), who carried out the intramolecular cyclization of iV-acetylindole with phthalimide tethered with appropriate linkers 67a-d. Interestingly, only the... 

Esters in the linker group between the phthalimide and the indole moieties 72a, b were also tolerated, resulting in the formation of large macrocycles 73a, b, including a 22-membered ring 73b (Scheme 18). 

STR) that led to the identification of the alkyne linker as the key motif responsible for serious neurological and cardiovascular liabilities in a class of acetyl-CoA carboxylase 2 (ACC2) inhibitors. To study this toxicity, the alkyne derivatives were prepared by first employing the Sonogashira reaction conditions shown below, followed by deprotection of the phthalimide group. 

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