Migratory Insertion Strategies for Dearomatization

Abstract

Development of strategies for molecule functionalization by dearomatization has surged in the last two decades. The benefits of overcoming the resonance stabilization energy outweigh the cost; diverse compounds could be accessed in a short number of steps. One approach that has been of interest in recent years is the dearomatization of indoles and other (hetero)aromatic compounds by migratory insertion. The chiral σ-bond palladium intermediate could be reduced or trapped by a second functionalization. In this short review we will summarize the recently discovered reactions from our group and others in this field of metal-catalyzed dearomatizations by migratory insertion.1 Introduction2 Monofunctionalizations: Heck and Reductive Heck Reactions2.1 N-Tethered Heterocycles2.2 Non-N-tethered Heterocycles2.3 Non-heterocycles3 Dearomative Difunctionalizations: Interrupted Heck Reaction3.1 N-Tethered Heterocycles3.2 Non-N-tethered Heterocycles4 Conclusion

Pd‐Catalyzed Intermolecular Dearomative Heck Reaction of Indole Derivatives

“…Over the past decade, Pd‐catalyzed Heck reaction has been applied in the dearomatization of indoles. In this regard, several elegant intramolecular dearomative Heck reactions of indoles have been developed . However, to date, the reported works are mainly limited to intramolecular reactions, which proceed via β‐hydride elimination or trapping by an additional nucleophile (Scheme (a)).…”

Pd‐Catalyzed Dearomatization of Indole Derivatives via Intermolecular Heck Reactions†

“…In this regard, dearomatization of indole derivatives has been widely recognized as a straightforward approach to access diverse indolines . Over the past decades, transition‐metal‐catalyzed Heck reactions have been applied in the dearomatization of indoles, as exemplified by the elegant contributions from the groups of Yao and Wu, Jia, Lautens, Jing and Liang, Zhou, and Wu (Scheme 1(a)). Notably, Kitamura and Fukuyama completed the total synthesis of (+)‐hinckdentine A with the dearomative Heck reaction as a key step .…”

Sequential Insertion of Alkynes, Alkenes, and CO into the Pd–C Bond of ortho-Palladated Primary Phenethylamines: from η3-Allyl Complexes and Enlarged Palladacycles to Functionalized Arylalkylamines

“…Palladium is one of the most versatile transition metals in organic synthesis, given its well-known ability to catalyze the formation of C–C and C–heteroatom bonds. , Nevertheless, the extraordinarily high variability of applications of palladium relies just on a few elementary steps inherent to its reactivity, and among them, the migratory insertion reaction of an unsaturated ligand into a Pd–C bond stands out. − Thus, a myriad of methods to functionalize alkenes, , alkynes, or allenes through Pd catalysis have been reported so far.…”