Title : Domino annulations based on chromonyl-norbornyl-palladacycle intermediate
Abstract:
The close relationships between biological activity, molecular complexity, and structural diversity stimulate synthetic chemists and pharmaceutical chemists to develop novel strategies to access significant structures inspired from natural products or bioactive molecules. Chromone has particularly emerged as a privileged unit owning to its wide distribution in drugs and natural products. Therefore, exploring novel approaches for the construction of diverse chromone derivatives has been the focus of intensive efforts, and numerous significant advances have been made in the field of catalysis. Transition metal-catalyzed domino reaction has been proven as an effective approach to assemble complex molecules by forging two or more new chemical bonds from readily available substrates in one single operation. In this context, the Catellani-type annulation cooperatively catalyzed by palladium and norbornene (NBE), which was originally discovered by Lautens in 2000 and further developed by the groups of Catellani, Malacria, Liang, Luan, Zhou, et al., represents a powerful tool for the construction of complex arenes. It is notable that an aryl-NBE-palladacycle (ANP) generated via successive oxidative addition of palladium(0) into the aryl-iodide, syn-migratory insertion into NBE and C(sp2)−H activation was a key intermediate for these transformations. Given that the importance of chromone scaffold in medicinal chemistry, we recently found that the chromonyl-norbornyl-palladacycle (CNP) intermediate derived from 3-iodochromone, norbornene, and Pd(0) catalyst was an active Pd(II) species, which could further react with different kinds of electrophilic reagent, such as α-bromoacetophenones, benzyl bromides, cyclopropenones, aziridines, dimethyl squarate and o-bromobenzoic acid, to construct various chromone-containing polycyclic compounds, wherein the corresponding [2+3+1], [2+2+1] and [2+2+2] domino annulations were involved.
Audience Takeaway Notes:
- We revealed some highlights, including: 1) the 2,2-bifunctionalization of NBE was firstly realized in palladium catalyzed [2+3+1] annulation; 2) the carbonylation with cyclopropenones as the sole CO surrogate can be firstly realized through a palladium-catalyzed [2+2+1] annulation; 3) the aziridine was firstly employed as a vinylidene unit in a unique manner by cleavage of two C−N bonds via palladium-catalyzed [2+2+1] annulation; 4) dimethyl squarate was firstly utilized as solid C1 source in the [2+2+1] annulation. The novel characteristics of substrates will provide inspirations for organic chemists to design other reactions.
- We developed the novel [2+m+n] domino annulations based on the CNP intermediate to synthesis of various chromone-containing polycyclic compounds, which will be interested from pharmaceutical chemists.
- These findings open a new venue for the properties of NBE, the synthesis of polycyclics as well as will be of interest to a broad audience — in addition to organic/organometallic chemists who can appreciate the conceptually novel nature of these reports, we anticipate that the chemical transformation based on chromone will be of use to researchers working on drug discovery and chemical biology.
