Single Boryl Isomerization in Silyl-Bridged Photochromic Diboryl Dyes

Silyl-bridged dimers of a ppy-BMes2 (ppy = 2-phenylpyridine, Mes = mesityl) photochrome were found to undergo photochromic switching involving a single boryl unit only. A through-space intramolecular energy transfer was found to be responsible for the single-chromophore isomerization phenomenon and fluorescence quenching. Steric congestion in the diboryl molecules was found to have an impact on photoisomerization quantum efficiency

Single Boryl Isomerization in Silyl-Bridged Photochromic Diboryl Dyes

Silyl-bridged dimers of a ppy-BMes2 (ppy = 2-phenylpyridine, Mes = mesityl) photochrome were found to undergo photochromic switching involving a single boryl unit only. A through-space intramolecular energy transfer was found to be responsible for the single-chromophore isomerization phenomenon and fluorescence quenching. Steric congestion in the diboryl molecules was found to have an impact on photoisomerization quantum efficiency

Catalytic Hydroacylation as an Approach to Homoaldol Products

A method has been developed for the intermolecular hydroacylation of homoallyl alcohols with salicylaldehydes to furnish homoaldol products in 50–98% yields. The method also applies to the hydroacylation of 2-hydroxystyrenes. This work highlights the use of hydroacylation as a unified approach to both aldol and homoaldol products

Directed C–H Bond Oxidation of (+)-Pleuromutilin

Antibiotics derived from the diterpene fungal metabolite (+)-pleuromutilin (1) are useful agents for the treatment Gram-positive infections in humans and farm animals. Pleuromutilins elicit slow rates of resistance development and minimal cross-resistance with existing antibiotics. Despite efforts aimed at producing new derivatives by semisynthesis, modification of the tricyclic core is underexplored, in part due to a limited number of functional group handles. Herein, we report methods to selectively functionalize the methyl groups of (+)-pleuromutilin (1) by hydroxyl-directed iridium-catalyzed C–H silylation, followed by Tamao–Fleming oxidation. These reactions provided access to C16, C17, and C18 monooxidized products, as well as C15/C16 and C17/C18 dioxidized products. Four new functionalized derivatives were prepared from the protected C17 oxidation product. C6 carboxylic acid, aldehyde, and normethyl derivatives were prepared from the C16 oxidation product. Many of these sequences were executed on gram scales. The efficiency and practicality of these routes provides an easy method to rapidly interrogate structure–activity relationships that were previously beyond reach. This study will inform the design of fully synthetic approaches to novel pleuromutilins and underscores the power of the hydroxyl-directed iridium-catalyzed C–H silylation reaction

Directed C–H Bond Oxidation of (+)-Pleuromutilin

Antibiotics derived from the diterpene fungal metabolite (+)-pleuromutilin (<b>1</b>) are useful agents for the treatment Gram-positive infections in humans and farm animals. Pleuromutilins elicit slow rates of resistance development and minimal cross-resistance with existing antibiotics. Despite efforts aimed at producing new derivatives by semisynthesis, modification of the tricyclic core is underexplored, in part due to a limited number of functional group handles. Herein, we report methods to selectively functionalize the methyl groups of (+)-pleuromutilin (<b>1</b>) by hydroxyl-directed iridium-catalyzed C–H silylation, followed by Tamao–Fleming oxidation. These reactions provided access to C16, C17, and C18 monooxidized products, as well as C15/C16 and C17/C18 dioxidized products. Four new functionalized derivatives were prepared from the protected C17 oxidation product. C6 carboxylic acid, aldehyde, and normethyl derivatives were prepared from the C16 oxidation product. Many of these sequences were executed on gram scales. The efficiency and practicality of these routes provides an easy method to rapidly interrogate structure–activity relationships that were previously beyond reach. This study will inform the design of fully synthetic approaches to novel pleuromutilins and underscores the power of the hydroxyl-directed iridium-catalyzed C–H silylation reaction

Directed C–H Bond Oxidation of (+)-Pleuromutilin

Antibiotics derived from the diterpene fungal metabolite (+)-pleuromutilin (<b>1</b>) are useful agents for the treatment Gram-positive infections in humans and farm animals. Pleuromutilins elicit slow rates of resistance development and minimal cross-resistance with existing antibiotics. Despite efforts aimed at producing new derivatives by semisynthesis, modification of the tricyclic core is underexplored, in part due to a limited number of functional group handles. Herein, we report methods to selectively functionalize the methyl groups of (+)-pleuromutilin (<b>1</b>) by hydroxyl-directed iridium-catalyzed C–H silylation, followed by Tamao–Fleming oxidation. These reactions provided access to C16, C17, and C18 monooxidized products, as well as C15/C16 and C17/C18 dioxidized products. Four new functionalized derivatives were prepared from the protected C17 oxidation product. C6 carboxylic acid, aldehyde, and normethyl derivatives were prepared from the C16 oxidation product. Many of these sequences were executed on gram scales. The efficiency and practicality of these routes provides an easy method to rapidly interrogate structure–activity relationships that were previously beyond reach. This study will inform the design of fully synthetic approaches to novel pleuromutilins and underscores the power of the hydroxyl-directed iridium-catalyzed C–H silylation reaction