Potassium tert-Amylate: A Cautionary Tale.

Potassium tert-amylate ( t-AmylOK) is a well-known, commercially available base and generally regarded as a more solvent-soluble form of potassium tert-butoxide ( t-BuOK). However, despite the structural similarity between the tert-butyl and amyl moieties, potassium tert-amylate in toluene can undergo distinct physical property changes in the presence of protic solvents that warrant further consideration. This is particularly surprising given that t-AmylOH is a byproduct of deprotonation with t-AmylOK, as well as the fact that its structurally similar relative, t-BuOK, is commercially available in t-BuOH.

Kinetic Modeling of the Nickel-Catalyzed Esterification of Amides.

Nickel-catalyzed coupling reactions provide exciting tools in chemical synthesis. However, most methodologies in this area require high catalyst loadings, which commonly range from 10-20 mol % nickel. Through an academic-industrial collaboration, we demonstrate that kinetic modeling can be used strategically to overcome this problem, specifically within the context of the Ni-catalyzed conversion of amides to esters.

Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A.

We describe here N-phenylpyrrolidine-based inhibitors of HCV NS5A with excellent potency, metabolic stability, and pharmacokinetics. Compounds with 2S,5S stereochemistry at the pyrrolidine ring provided improved genotype 1 (GT1) potency compared to the 2R,5R analogues. Furthermore, the attachment of substituents at the 4-position of the central N-phenyl group resulted in compounds with improved potency.

The palladium-catalyzed aerobic kinetic resolution of secondary alcohols: reaction development, scope, and applications.

The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions.

Heterogeneous reductive isomerization reaction using catalytic Pd/C and H2.

[reaction: see text] A highly selective catalytic reductive isomerization reaction is described. The extremely mild and neutral reaction conditions (10% Pd/C, H2, and MeOH at 0 degrees C) tolerate a wide range of functional groups and generally result in excellent yields. Mechanistic studies suggest that this reaction does not proceed via a stepwise reduction/elimination sequence or a pi-allylpalladium intermediate.

Development of an enantiodivergent strategy for the total synthesis of (+)- and (-)-dragmacidin f from a single enantiomer of quinic Acid.

An enantiodivergent strategy for the total chemical synthesis of both (+)- and (-)-dragmacidin F beginning from a single enantiomer of quinic acid has been developed and successfully implemented. Although unique, the synthetic routes to these antipodes share a number of key features, including novel reductive isomerization reactions, Pd(II)-mediated oxidative carbocyclization reactions, halogen-selective Suzuki couplings, and high-yielding late-stage Neber rearrangements.

The total synthesis of (+)-dragmacidin F.

The first total synthesis of (+)-dragmacidin F has been accomplished, establishing the absolute configuration of this biologically important, antiviral marine alkaloid. The convergent route described features a palladium-mediated oxidative pyrrole carbocylization reaction to construct the [3.3.