Regioselective and Enantioselective Intermolecular Buchner Ring Expansions in Flow

The first example of a regioselective and enantioselective intermolecular Buchner ring expansion is reported using continuous flow. The practicality and scope of the reaction are greatly improved under flow conditions. Reactions of ethyl diazoacetate with symmetric and nonsymmetric arenes afford cycloheptatrienes in good yield and excellent regioselectivity. The first example of an asymmetric intermolecular Buchner reaction is demonstrated with disubstituted diazo esters in good to excellent enantioselectivity. The asymmetric reactions proceed with absolute regioselectivity to afford cycloheptatrienes with an all-carbon quaternary center

Synthesis of Azaphilone-Based Chemical Libraries

The synthesis of azaphilone scaffolds that have been further diversified by cross coupling acylation and amine addition is reported. Methodology development also led to novel modifications including C5 acetoxylation and condensations producing isoquinolin-6­(7H) structures. Overall, the library synthesis afforded three azaphilone sublibraries, including vinylogous pyridones which project diversity elements in four sectors of the azaphilone core

Redesign of a Pyrylium Photoredox Catalyst and Its Application to the Generation of Carbonyl Ylides

We report the exploration into photoredox generation of carbonyl ylides from benzylic epoxides using newly designed 4-mesityl-2,6-diphenylpyrylium tetrafluoroborate (MDPT) and 4-mesityl-2,6-di-<i>p</i>-tolylpyrylium tetrafluoroborate (MD­(<i>p</i>-tolyl)­PT) catalysts. These catalysts are excited at visible wavelengths, are highly robust, and exhibit some of the highest oxidation potentials reported. Their utility was demonstrated in the mild and efficient generation of carbonyl ylides from benzylic epoxides that otherwise could not be carried out by current common photoredox catalysts

Synthesis and Reactivity of Bicyclo[3.2.1]octanoid-Derived Cyclopropanes

Photochemical oxa-di-π-methane rearrangement of bicyclo[3.2.1]­octanoid scaffolds affords multifunctional, donor–acceptor cyclopropanes. A related photochemical reaction of an iminium ether substrate uncovered an unprecedented aza-di-π-methane rearrangement of a β,γ-unsaturated iminium. Donor–acceptor cyclopropanes have been evaluated as substrates for reactions generating several new chemotypes

Multidimensional Reaction Screening for Photochemical Transformations as a Tool for Discovering New Chemotypes

We have developed an automated photochemical microfluidics platform that integrates a 1 kW high-pressure Hg vapor lamp and allows for analytical pulse flow or preparative continuous flow reactions. Herein, we will discuss the use of this platform toward the discovery of new chemotypes through multidimensional reaction screening. We will highlight the ability to discretely control wavelengths with optical filters, allowing for control of reaction outcomes

Development of a Potent and Selective HDAC8 Inhibitor

A novel, isoform-selective inhibitor of histone deacetylase 8 (HDAC8) has been discovered by the repurposing of a diverse compound collection. Medicinal chemistry optimization led to the identification of a highly potent (0.8 nM) and selective inhibitor of HDAC8