Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling

We report the development of a new class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in the remote desymmetrization of diarylmethanes via copper-catalyzed Ullman cross-coupling. Through design of these peptides, high levels of enantioinduction and good isolated yields were achieved in the long-range asymmetric cross-coupling (up to 93:7 er and 76% yield) between aryl bromides and malonates. Our mechanistic studies suggest that distal stereocontrol is achieved through a Cs-bridged interaction between the Lewis-basic <i>C</i>-terminal carboxylate of the peptides with the distal arene of the substrate

Aminocarbonylation of Aryl Tosylates to Carboxamides

The palladium - catalyzed aminocarbonylation of aryl tosylates with amines is reported. Suitable conditions were identified by high throughput reaction screening and then further optimized. The substrate scope of the reaction with respect to the aryl tosylate component and the amine component are reported. Competitive aminolysis of the aryl tosylates to afford the amine toluenesulfonamides and the phenol was not observed

Ir-Catalyzed Borylation as an Efficient Route to a Nicotine Hapten

The process development of a nicotine analog or hapten (<b>1</b>) for conjugation to a protein as an antigen is described. The original process in early development used an Ir-catalyzed borylation reaction to enable rapid derivatization of nicotine with the desired regiocontrol. While the process was very efficient, it required chromatography to meet purity targets. A related process was later developed that possessed crystalline intermediates to better control levels of process-related impurities and heavy metals in <b>1</b>. This control strategy for <b>1</b> was essential due to the strict purity requirements for conjugation of <b>1</b> when forming an antigen. In addition, the Ir-catalyzed borylation was studied to enable robust manufacture via this methodology which led to an efficient process for the preparation of <b>1</b>

Synthesis of Filibuvir. Part II. Second-Generation Synthesis of a 6,6-Disubstituted 2<i>H</i>‑Pyranone via Dieckmann Cyclization of a β‑Acetoxy Ester

This paper describes an improved sequence for the conversion of an oxazolidinone (<b>3</b>) to a β-keto lactone (<b>5</b>). The primary drivers behind this change were the modest and variable yields observed in the intramolecular cyclization to generate the β-keto lactone. Changing the cyclization substrate from oxazolidinone to alkyl ester offered a significantly improved cyclization, as well as improvements in the alkyne hydrogenation. Selection of the optimal substrates for methanolysis and intermediate salt formation are also described