Stephane Caron

A practical, efficient, and rapid method for the oxidation of electron deficient pyridines using trifluoroacetic anhydride and hydrogen peroxide–urea complex

Abstract A general method for the oxidation of electron-poor pyridines to their N-oxides using UHP and TFAA in either CH2Cl2 or CH3CN was developed. The methodology proved to tolerate a number of functional groups and substitution patterns and proceeded on notoriously difficult to oxidize substrates.

Preparation and Utility of Trihaloethyl Imidates: Useful Reagents for the Synthesis of Amidines

2,2,2-Trifluoro- and trichloroethyl imidates, which are easily prepared by reaction of a nitrile and a trihaloethanol in the presence of HCl, have proven to be excellent reagents for the preparation of amidines under mild reaction conditions. Depending on the nature of the amine nucleophile, the imidates can react either as the free-base or the hydrochloride salt in a telescoped process. In several cases, the p-bromobenzoate salt of the desired product was directly isolated from the reaction mixture.

New ligands for nickel catalysis from diverse pharmaceutical heterocycle libraries

Ligands are essential for controlling the reactivity and selectivity of transition metal-catalyzed reactions. Access to large phosphine ligand libraries has become an essential tool for the application of metal-catalyzed reactions industrially, but these existing libraries are not well suited to new catalytic methods based on non-precious metals (i.e., Ni, Cu, Fe). The development of the requisite nitrogen- and oxygen-based ligand libraries lags far behind phosphines and the development of new libraries is anticipated to be time consuming. Here we show that this process can be dramatically accelerated by mining a typical pharmaceutical compound library that is rich in heterocycles for new ligands. Using this approach, we were able to screen a structurally diverse set of compounds with minimal synthetic effort and identify several new ligand classes for nickel-catalyzed cross-electrophile coupling. These new ligands gave improved yields for challenging cross-couplings of pharmaceutically relevant substrates compared to previously published ligands.

Pharmaceutical Process Chemistry: Evolution of a Contemporary Data-Rich Laboratory Environment

Over the past 20 years, the industrial laboratory environment has gone through a major transformation in the industrial process chemistry setting. In order to discover and develop robust and efficient syntheses and processes for a pharmaceutical portfolio with growing synthetic complexity and increased regulatory expectations, the round-bottom flask and other conventional equipment familiar to a traditional organic chemistry laboratory are being replaced. The new process chemistry laboratory fosters multidisciplinary collaborations by providing a suite of tools capable of delivering deeper process understanding through mechanistic insights and detailed kinetics translating to greater predictability at scale. This transformation is essential to the field of organic synthesis in order to promote excellence in quality, safety, speed, and cost efficiency in synthesis.

Synthesis of the kappa-agonist CJ-15,161 via a palladium-catalyzed cross-coupling reaction

Syntheses of CJ-15,161 (1) involving intermolecular N-arylation of an appropriately functionalized diamine, obtained from the precursor alpha-amino acids or, more conveniently, from the corresponding 1,2-amino alcohols via 1,2,3-oxathiazolidine-2,2-dioxide 22, are reported.