In our latest pre-print, we explore the origins of diminished reactivity of α,α-gem-disubstituted alkenyl amides through a combination of kinetics, organometallic synthesis, and density functional theory, allowing us to pinpoint the rigidity of our standard 8-aminoquinoline amide directing group as problematic in a key step in the catalytic cycle. Switching to a simple flexible directing group leads to >115x rate acceleration and dramatic expansion of substrate scope. The work was made possible through a multi-institutional team from Scripps Research (Engle and Blackmond labs), the University of Pittsburgh (Liu lab), Bristol Myers Squibb, Enamine! Congrats to the project co-leads, Al, Gift, and Shijia—as well as the entire team.

For a link to the pre-print in ChemRxiv, click here: https://chemrxiv.org/engage/chemrxiv/article-details/69368ccda10c9f5ca1daf3bf

The final peer-reviewed version of our collaborative study on palladium(II)-catalyzed olefin cyclopropanation with alkyl–SO₂F compounds appears this week in Nature Synthesis. Largely unexplored in catalysis, alkyl–SO₂F compounds are an intriguing class of ambiphiles that can engage in nucleophilic reactivity upon deprotonation and electrophilic reactivity owing the the presence of the -SO₂F leaving group. As we discovered in this study, these properties enable alkyl–SO₂F to promote cyclopropanation through a unique mechanism that grants access to challenging substitution patterns and stereochemical outcomes. Congrats to the entire team of colleagues from Scripps Research, University of Pittsburgh, Enamine, and Pfizer!

For a link to the paper in Nature Synthesis, click here: https://www.nature.com/articles/s44160-025-00925-1.

As a reminder, we first deposited a pre-print on ChemRxiv back in November, 2024: https://chemrxiv.org/engage/chemrxiv/article-details/672b9b3cf9980725cf547804