U-57930 C

C,C-Palladacycles are an important class of organometallic compounds in which palladium is σ-bonded to two carbon atoms. They have three notable features that make them attractive in organic synthesis and organometallic chemistry: (1) C,C-Palladacycles are reactive intermediates that can be accessed via Pd(0)-catalyzed C-H activation of organic halides. Compared to Pd(II)-catalyzed heteroatom-directed C-H activation, C-H activation catalyzed by Pd(0) has some distinct advantages. In this type of catalytic reaction, the halo groups of readily available organic halides act as traceless directing groups. Furthermore, this strategy avoids the use of stoichiometric external oxidants. (2) C,C-Palladacycles have differentiated reactivities from common open-chain Pd(II) species. In particular, C,C-palladacycles have high reactivity toward electrophiles including alkyl halides. This unique reactivity can be utilized to develop novel reactions. (3) C,C-Palladacycles have two C-Pd bonds, providing a unique platform for developing novel reactions.Although a number of reactions of C,C-palladacycles had been developed prior to our work, the scope was largely limited to intramolecular cyclization reactions. Although Catellani reactions are intermolecular reactions of C,C-palladacycles, only one of the C-Pd bonds is functionalized. Our laboratory has sought to develop intermolecular difunctionalization reactions of C,C-palladacycles that exploit their unique reactivity and open new possibilities in organic synthesis. Aiming to develop synthetically useful reactions, we primarily focus on ring-forming reactions. In this Account, we summarize our laboratory's efforts to exploit intermolecular difunctionalization reactions of C,C-palladacycles that are obtained through Pd(0)-catalyzed C-H activation. We have developed a wide array of new reactions that represent facile and efficient methods for the synthesis of cyclic organic compounds, including functional materials and drug molecules. A range of C,C-palladacycles have been studied, including C(aryl),C(aryl)-palladacycles from 2-halobiaryls, C(aryl),C(alkyl)-palladacycles from ortho-iodo-tert-butylbenzenes or ortho-iodoanisole derivatives, and those obtained by cascade reactions. C,C-Palladacycles have been found to react with a variety of oxidants to furnish Pd(IV) intermediates, such as alkyl halides, aryl halides, diazo compounds, and N,N-di-tert-butyldiaziridinone, ultimately affording various cyclic structures, including 5-10-membered rings, carbo- and azacycles, spirocycles, and fused rings. Furthermore, novel reactivity of C,C-palladacycles has been discovered. For example, we found that C,C-palladacycles have unusually high reactivity toward disilanes, which can be leveraged to disilylate a variety of C,C-palladacycles with very high efficiency. These results should provide inspiration to develop other C-Si bond-forming reactions in the future. We hope that this Account will stimulate further research into the rich chemistry of C,C-palladacycles, in particular reactions that find practical applications in the synthesis of bioactive and functional molecules and those that advance the state of the art in C-H functionalization.

A healthy corneal endothelium is required for corneal clarity. Both the glaucoma disease state and its various forms of treatment can have adverse effects on the corneal endothelium. Both the presence of glaucoma and the magnitude of intraocular pressure elevation are related to endothelial cell loss (ECL). Topical medical therapy, laser procedures, and both traditional surgeries-trabeculectomy and tube-shunts-and newer minimally invasive glaucoma surgeries have variable effects on ECL. This review will summarize the reported effects of glaucoma and its treatment on ECL. Concerns for corneal endothelial cell health should be part of the decision-making process when planning glaucoma therapy for lowering intraocular pressure, with added caution in case of planned device implantation in eyes with preexisting ECL and low endothelial cell density at high risk for corneal endothelial decompensation.

Cytochrome P450 enzymes (CYPs) catalyze a series of C-H and C=C oxygenation reactions, including hydroxylation, epoxidation, and ketonization. They are attractive biocatalysts because of their ability to selectively introduce oxygen into inert molecules under mild conditions. This review provides a comprehensive overview of the C-H and C=C oxygenation reactions catalyzed by CYPs and the various strategies for achieving higher selectivity and enzymatic activity. Furthermore, we discuss the application of C-H and C=C oxygenation catalyzed by CYPs to obtain the desired chemicals or pharmaceutical intermediates in practical production. The rapid development of protein engineering for CYPs provides excellent biocatalysts for selective C-H and C=C oxygenation reactions, thereby promoting the development of environmentally friendly and sustainable production processes.