Gram scale laboratory synthesis of TC AC 28, a high affinity BET bromodomain ligand

TC AC 28, 6-(1H-Indol-4-yl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-4-acetic acid methyl ester, has been synthesized on a near gram scale in seven steps with notable improvements in the reported poor yielding last 2 steps enabling this key chemical probe compound to be available for researchers

Toward control of gold cluster aggregation on TiO(2) via surface treatments

Published: October 1, 2015Well-defined Au–TiO₂ materials were synthesized by deposition of triphenylphosphine-protected Au₉ clusters on TiO₂ (Aeroxide P-25), pre-treated in eight different ways and subsequently exposed to two post-treatments. X-ray photoelectron spectroscopy and UV–vis diffuse reflectance spectroscopy studies showed that in most cases the PPh₃ ligand shell was removed upon deposition even before post-treatment, coinciding with some cluster aggregation. However, clusters deposited on TiO₂ treated using H₂SO₄ and H2O₂ showed remarkable resistance to aggregation, even after high-temperature calcination, while clusters on H₂-treated TiO₂ showed the greatest resistance to aggregation under ozonolysis.Jan-Yves Ruzicka, Faridah Abu Bakar, Christoffer Hoeck, Rohul Adnan, Campbell McNicoll, Tim Kemmitt, Bruce C. Cowie, Gregory F. Metha, Gunther G. Andersson, and Vladimir B. Golovk

Atom and step economical synthesis of acyclic quaternary centers via iridium-catalyzed hydroarylative cross-coupling of 1,1-disubstituted alkenes

Quaternary benzylic centers are accessed with high atom and step economy by Ir-catalyzed alkene hydroarylation. These studies provide unique examples of the use of non-polarized 1,1-disubstituted alkenes in branch selective Murai-type hydro(hetero)arylations. Detailed mechanistic studies have been undertaken, and these indicate that the first irreversible step is the demanding alkene carbometallation process. Structure-reactivity studies show that the efficiency of this is critically dependent on key structural features of the ligand. Computational studies have been undertaken to rationalize this experimental data, showing how more sterically demanding ligands reduce the reaction barrier via predistortion of the reacting intermediate. The key insight disclosed here will underpin the ongoing development of increasingly sophisticated branch selective Murai hydroarylations