Synthesis of Naphthalimides through Tandem Pd(II)-Catalyzed C(sp³)–H Oxidation and Diels–Alder Reaction Using a Transient Directing Group Strategy

Abstract

Naphthalimides have found extensive applications in materials science and pharmaceuticals. It is still highly desirable to develop efficient methods for the synthesis of naphthalimides with structural diversity. In this work, we developed a new approach for the synthesis of naphthalimides via a tandem reaction of o-methylbenzaldehydes and maleimides. The tandem reaction involves Pd­(II)-catalyzed benzylic C­(sp3)–H oxidation using an amino acid as the transient directing group and Diels–Alder reaction. The subsequent dehydration forms naphthalimides. The reaction introduces the imide moiety and constructs a benzene ring simultaneously, allowing for easy access to a range of naphthalimides with a variety of substituents.

Palladium-Catalyzed [3 + 2] Annulation of ortho-Substituted Iodoarenes with Maleimides via a Consecutive Double Heck-type Strategy

“… − Due to their significant biological properties and pharmaceutical importance, some notable strategies have been established for attaining such heterocyclic frameworks; for instance, transition metal-catalyzed annulations effectively accomplish such heterotricyclic systems. − Despite the aforementioned notable strategies, there is still enough scope to develop efficient synthetic methodologies to accomplish such heterocyclic products. Mainly, maleimide and its derivatives are highly affordable and simple starting materials; therefore, in recent years, chemists have employed maleimides as leading coupling partners under induced catalytic transformations. − Especially, maleimide-based transition metal-catalyzed C–H activations to construct polycyclic molecules have been developed. − On the other hand, Pd-catalyzed activation of aryl halides and their eventual Heck couplings with olefins were found as one of the promising tools for constructing polycyclic molecules, − which can be extended to maleimides to get polycyclic compounds. However, unfortunately, under basic Pd(0) catalysis, maleimides are susceptible to hydrolysis of imide bonds because of the reaction’s basic pH, which drastically limits the use of maleimides from usual olefin coupling partners .…”