Mechanistic studies of a palladium-catalyzed regioselective aryl C-H functionalization of 2-pyrrole phenyl iodide with norbornene are presented. Kinetic and spectroscopic analyses together with crystallographic data provide evidence for intermediates in a proposed stepwise mechanism. On the basis of the mechanistic studies, the origin of the regioselectivity is due to a ligand exchange between I(-) and HO(-) on the norbornyl palladium complex. These mechanistic studies also implicate that either alkoxide or water is responsible for the formation of the palladacycle, but a reversible ring-opening-ring-closing process of the palladacycle with HX can retard the rate of reaction of a key intermediate. The significant aspects of the proposed mechanism are discussed in detail.

Identification of new reactions expands our knowledge of chemical reactivity and enables new synthetic applications. Accelerating the pace of this discovery process remains challenging. We describe a highly effective and simple platform for screening a large number of potential chemical reactions in order to discover and optimize previously unknown catalytic transformations thereby revealing new chemical reactivity. Our strategy is based on labeling one of the reactants with a polyaromatic chemical tag, which selectively undergoes photoionization-desorption process upon laser irradiation without the assistance of an external matrix and enables rapid mass spectrometric detection of any products originating from such labeled reactants in complex reaction mixtures without any chromatographic separation. This method was successfully employed for high-throughput discovery and subsequent optimization of two previously unknown benzannulation reactions.

This contribution reviews a family of reactions devised in our laboratory that effect the oxidative conversion of phenols into 4-amido-dienones. A salient feature of this chemistry is the use of hypervalent iodine reagents, especially diacetoxyiodobenzene (DIB), as uniquely capable oxidants in the context of the new transformation. The advent of this methodology has created new opportunities in alkaloid synthesis. Our efforts toward FR-901483, TAN-1251C, cylindricine C, and other nitrogenous natural products illustrate some applications in that domain.

A highly efficient water-accelerated palladium-catalyzed reaction of gem-dibromoolefins with a boronic acid via a tandem Suzuki-Miyaura coupling and direct arylation is reported. A wide range of aryl, alkenyl, and alkyl boronic acids, as well as a variety of substitution patterns on the phenyl ring, are tolerated. Additionally, mechanistic studies were conducted to ascertain the order of the couplings as well as the role(s) of water. Results from this study indicate that the major pathway is a Suzuki-Miyaura coupling/direct arylation sequence and that water accelerates the Pd(0) formation and Suzuki-Miyaura coupling.

Shall we dance? Within the proposed mechanism for the palladium-catalyzed title reaction, the strained alkene norbornene (or norbornadiene) enters and exits the catalytic cycle in a catalytic "square dance", acting as both a promoter and a coupling partner in the formation of four carbon-carbon bonds, two of them by challenging C--H activation processes.