Electrochemical Oxidation of Δ9-Tetrahydrocannabinol at Nanomolar Concentrations.

With increasing marijuana legalization, there is a growing need for technology that can determine if an individual is impaired due to recent marijuana usage. The electrochemical oxidation of Δ9-THC to form its corresponding quinones can be used as a framework to develop an electrochemical sensor for Δ9-THC. This study describes an electrochemical oxidation of Δ9-THC that uses a copper anode, a platinum cathode, and an atmosphere of oxygen. The oxidation is feasible at nanomolar concentrations, which approaches the reactivity that is necessary for developing a real-world marijuana breathalyzer. Moreover, we show that vaporized Δ9-THC can be captured directly in an electrolyte medium and subjected to electrochemical oxidation, thus paving the way for use in future technology development.

Total Synthesis of Phenanthroindolizidines Using Strained Azacyclic Alkynes.

We report a concise approach to phenanthroindolizidine alkaloids, wherein strained azacyclic alkynes are intercepted in Pd-catalyzed annulations. Two types of strained intermediates were evaluated: a functionalized piperidyne and a new strained intermediate, an indolizidyne. We show that each can be employed, ultimately allowing access to three natural products: tylophorine, tylocrebine, and isotylocrebine. These efforts demonstrate the successful merger of strained azacyclic alkyne chemistry with transition-metal catalysis for the construction of complex heterocycles.

Merging Metals and Strained Intermediates.

Strained intermediates such as cyclic alkynes and allenes are most commonly utilized in nucleophilic additions and cycloadditions, but have seen increased use in a third area of reactivity: metal-mediated transformations. The merger of strained intermediates and metal catalysis has enabled rapid access to complex, polycyclic systems. Following a discussion of relevant landmark studies involving metals and strained intermediates, this article highlights recent advances in transition metal-mediated transformations from our laboratory. Specifically, this includes the use of arynes in the synthesis of decorated organometallic complexes, and the utilization of cyclic allenes to access enantioenriched heterocycles. Moreover, the broad applicability of such transformations, and exciting future areas of research are discussed.

π-Extension of heterocycles via a Pd-catalyzed heterocyclic aryne annulation: π-extended donors for TADF emitters.

We report the annulation of heterocyclic building blocks to access π-extended polycyclic aromatic hydrocarbons (PAHs). The method involves the trapping of short-lived hetarynes with catalytically-generated biaryl palladium intermediates and allows for the concise appendage of three or more fused aromatic rings about a central heterocyclic building block. Our studies focus on annulating the indole and carbazole heterocycles through the use of indolyne and carbazolyne chemistry, respectively, the latter of which required the synthesis of a new carbazolyne precursor. Notably, these represent rare examples of transition metal-catalyzed reactions of N-containing hetarynes. We demonstrate the utility of our methodology in the synthesis of heterocyclic π-extended PAHs, which were then applied as ligands in two-coordinate metal complexes. As a result of these studies, we identified a new thermally-activated delayed fluorescence (TADF) emitter that displays up to 81% photoluminescence efficiency, along with insight into structure-property relationships. These studies underscore the utility of heterocyclic strained intermediates in the synthesis and study of organic materials.

A platform for on-the-complex annulation reactions with transient aryne intermediates.

Organometallic complexes are ubiquitous in chemistry and biology. Whereas their preparation has historically relied on ligand synthesis followed by coordination to metal centers, the ability to efficiently diversify their structures remains a synthetic challenge. A promising yet underdeveloped strategy involves the direct manipulation of ligands that are already bound to a metal center, also known as chemistry-on-the-complex. Herein, we introduce a versatile platform for on-the-complex annulation reactions using transient aryne intermediates. In one variant, organometallic complexes undergo transition metal-catalyzed annulations with in situ generated arynes to form up to six new carbon-carbon bonds. In the other variant, an organometallic complex bearing a free aryne is generated and intercepted in cycloaddition reactions to access unique scaffolds. Our studies, centered around privileged polypyridyl metal complexes, provide an effective strategy to annulate organometallic complexes and access complex metal-ligand scaffolds, while furthering the synthetic utility of strained intermediates in chemical synthesis.