Cycloisomerizations of 1,n-enynes catalyzed by electrophilic p-acid metal complexes provide a powerful method of carbon–carbon bond formation, and a unique platform for studying reactivity and mechanism.1  Our previous report on the total synthesis of (±)-gelsenicine took advantage of a cycloisomerization/rearrangement strategy to access the central bridging bicyclic structure of the compound.2  Continuing our interest in the…

Automated transiton state (TS) structure computations for a recently reported Pd-catalysed conjugated addition of arylboronic acids to 2-substituted chromones (Chem Sci, 2020, 11, 4602) reveal unexpected conformations of the key stereodifferentiating benzyl group on the pyridine-dihydroisoquinoline (PyDHIQ) ligand. Detailed analysis shows that stereoselectivity is determined primarily by favorable non-covalent contacts between this benzyl group…

Conventional cross-coupling reactions typically involve the union of a nucleophilic and electrophilic coupling partner. In contrast, reductive (or cross-electrophile) coupling has recently emerged as an alternative approach in which two electrophilic partners can be coupled together. However, achieving cross-selectivity is an ongoing challenge for it necessitates chemoselective activation of one electrophile over the other. Three recently…

Nucleophilic substitution reactions are at the heart of synthetic organic chemistry. While conventional strategies for conducting nucleophilic substitution reactions have been heavily studied, we hereby report the development of the novel photochemical approach to the induction of nucleophilic substitution reactions. This strategy employs a light-activated leaving group based on the 9-aryl-9-fluorene system. 9- fluorenol undergoes efficient…

Dithiodiketopiperazines or “DKP’s” is common motif that appears in various natural products. These natural products have been shown to display anti-viral or anti-tumor properties. Within the past two decades, an increasing number of natural products have been isolated containing a DKP core. Although synthetic strategy towards this core has been around since the 1960’s, there is still much innovation withing the area of DKP natural product total…

Antibody-drug conjugate (ADC) development has seen recent improvement through employment of targeted conjugate synthesis strategies. Methods that optimize delivery of antibodies, linkers, and conjugated drug compounds have emerged. Through these methods, higher drug conjugation density, increased linker stability, and lower unconjugated antibody concentrations can be achieved. Dual conjugation, a process by which two different conjugated drugs…