Previous studies have shown that the critical transmetalation step in the Suzuki–Miyaura cross-coupling proceeds through a mechanism wherein an arylpalladium hydroxide complex reacts with an aryl boronic acid, termed the oxo-palladium pathway. Moreover, these same studies have established that the reaction between an aryl boronate and an arylpalladium halide complex (the boronate pathway) is prohibitively slow. Herein, studies on isolated intermediates, along with kinetic analysis, have demonstrated that the Suzuki–Miyaura reaction promoted by potassium trimethylsilanolate (TMSOK) proceeds through the boronate pathway, in contrast with other, established systems. Furthermore, an unprecedented, binuclear palladium­(I) complex containing a μ-phenyl bridging ligand was characterized by NMR spectroscopy, mass spectrometry, and computational methods. Density functional theory (DFT) calculations suggest that the binuclear complex exhibits an open-shell ground electronic state, and reaction kinetics implicate the complex in the catalytic cycle. These results expand the breadth of potential mechanisms by which the Suzuki–Miyaura reaction can occur, and the novel binuclear palladium complex discovered has broad implications for palladium-mediated cross-coupling reactions of aryl halides.

The sesquiterpene-tropolones belong to a distinctive structural class of meroterpene natural products with impressive biological activities, including anticancer, antifungal, antimalarial, and antibacterial. In this article, we describe a concise, modular, and cycloaddition-based approach to a series of sesquiterpene mono-and bistropolones, including (−)-epolone B, (+)-isoepolone B, (±)-dehydroxypycnidione, and (−)-10-epi-pycnidione. Alongside the development of a general strategy to access this unique family of metabolites were computational modeling studies that justified the diastereoselectivity observed during key cycloadditions. Ultimately, these studies prompted stereochemical reassignments of the pycnidione subclass and shed additional light on the biosynthesis of these remarkable natural products.

A dearomative 1,4-carboamination of arenes has been achieved using arenophile cycloaddition and subsequent palladium-catalyzed substitution with non-stabilized lithium enolates. This protocol delivers products with exclusive syn-1,4-selectivity and can be also conducted in an asymmetric fashion. The method allows rapid dearomative difunctionalization of simple aromatic compounds into functional small molecules amenable to further diversification.

The isomalabaricanes comprise a large family of marine triterpenoids with fascinating structures that have been shown to be selective and potent apoptosis inducers in certain cancer cell lines. In this article, we describe the successful total syntheses of the isomalabaricanes stelletin A, stelletin E, and rhabdastrellic acid A, as well as the development of a general strategy to access other natural products within this unique family. High-throughput experimentation and computational chemistry methods were used in this endeavor. A preliminary structure−activity relationship study of stelletin A revealed the trans-syn-trans core motif of the isomalabaricanes to be critical for their cytotoxic activity.