π-Extension of heterocycles 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.

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.

Total Synthesis as a Vehicle for Collaboration.

"Collaboration" is not the first word most would associate with the field of total synthesis. In fact, the spirit of total synthesis is all-too-often reputed as being more competitive, rather than collaborative, sometimes even within individual laboratories. However, recent studies in total synthesis have inspired a number of collaborative efforts that strategically blend synthetic methodology, biocatalysis, biosynthesis, computational chemistry, and drug discovery with complex molecule synthesis.

Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space.

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays.

Enantioselective Total Syntheses of Methanoquinolizidine-Containing Akuammiline Alkaloids and Related Studies.

The akuammiline alkaloids are a structurally diverse class of bioactive natural products isolated from plants found in various parts of the world. A particularly challenging subset of akuammiline alkaloids are those that contain a methanoquinolizidine core. We describe a synthetic approach to these compounds that has enabled the first total syntheses of (+)-strictamine, (-)-2( S)-cathafoline, (+)-akuammiline, and (-)-Ψ-akuammigine.

Pardon the Interruption: A Modification of Fischer's Venerable Reaction for the Synthesis of Heterocycles and Natural Products.

This account provides an overview of our laboratory's studies of an unusual variant of the Fischer indolization reaction. We describe the discovery of the so-called 'interrupted Fischer indolization' and the development of the reaction from a methodological standpoint. In addition, our efforts to evaluate and apply this methodology in the context of akuammiline alkaloid total synthesis are discussed.