Impact of N-Aryl- and NHC Core-Substituents on the Coupling of Alkylzinc Nucleophiles: Is Bigger always Better?

Bulky Pd-N-heterocyclic carbene (NHC) catalysts (e. g., N-(di-2,6-(3-pentyl)phenyl), IPent) have been shown to have significantly higher reactivity in a wide variety of cross-coupling applications (i.

Salt to Taste: The Critical Roles Played by Inorganic Salts in Organozinc Formation and in the Negishi Reaction.

The first cross-coupling of organozinc nucleophiles with aryl halides was reported in 1977 by Negishi. Unknown to all at the time was the importance of salt additives that were often present as a byproduct from the organozinc preparation. For decades, these salt additives were overlooked until 2006 when it was discovered that two different, yet effective methods for preparing organozinc solutions (i.

A Path to More Sustainable Catalysis: The Critical Role of LiBr in Avoiding Catalyst Death and its Impact on Cross-Coupling.

The role that LiBr plays in the lifetime of Pd-NHC complexes has been investigated. A bromide ion is proposed to coordinate to Pd thereby preventing beta hydride elimination (BHE) (to form NHC-H ) of the reductive elimination (RE) intermediate that normally completes with the desired cross-coupling catalytic cycle. Coordinating groups, such as anilines, are able to bind suitably well to Pd to prevent this pathway from occurring, thus reducing the need for the added salt.

Discovery of an antivirulence compound that reverses β-lactam resistance in MRSA.

Staphylococcus aureus is the leading cause of infections worldwide, and methicillin-resistant strains (MRSA) are emerging. New strategies are urgently needed to overcome this threat. Using a cell-based screen of ~45,000 diverse synthetic compounds, we discovered a potent bioactive, MAC-545496, that reverses β-lactam resistance in the community-acquired MRSA USA300 strain.

The Role of LiBr and ZnBr on the Cross-Coupling of Aryl Bromides with Bu Zn or BuZnBr.

The impact of LiBr and ZnBr salts on the Negishi coupling of alkylZnBr and dialkylzinc nucleophiles with both electron-rich and -poor aryl electrophiles has been examined. Focusing only on the more difficult coupling of deactivated (electron-rich) oxidative addition partners, LiBr promotes coupling with BuZnBr, but does not have such an effect with Bu Zn. The presence of exogenous ZnBr shuts down the coupling of both BuZnBr and Bu Zn, which has been shown before with alkyl electrophiles.