Directing Group Flexibility Unlocks Hindered Alkene Substrates – Pre-Print Now Online

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

Catalytic Cyclopropanation of Olefins with Alkyl Sulfonyl Fluorides – Paper Now In Press

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

Debuting Nickel Bis(Duroquinone) – New Pre-print Online

Today we disclose the latest chapter in our longstanding collaboration with Bristol Myers Squibb on air-stable nickel(0) complexes, reporting the synthesis, characterization, and reactivity of Ni(DQ)2, a homoleptic Ni(0)–olefin complex with exceptional stability. Congrats to the entire project team from Scripps (Wen-Ji, Shirley, Shenghua, and Camille), Bristol Myers Scripps (Nana and Steve), the Lin lab at Cornell (Zhipeng), and the Crystallography Facility at UCSD (Jake and Milan).

For a link to the ChemRxiv pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/69150940a10c9f5ca1fc53c1

Engle Lab Preps for Discovery Day at Fleet Science

Members of the Engle lab took took to local TV this week to promote Scripps Research Discovery Day at Fleet Science Center. On Sunday, November 9, from 10 AM–3 PM, more than 50 graduate students and postdocs will guide the community through interactive experiences in neuroscience, chemistry, immunology and more, offering an opportunity to get a sneak peak of life as a researcher and the tools behind the scientific breakthroughs that are underway. Way to go, Madison, Wen-Ji, and Keary!

Learn more: scripps.edu/fleet or fleetscience.org/events/genius-house

Unique Chiral Styrene Derivatives Accessed via Dual Catalysis – Manuscript in Press in JACS

Appearing this week in J. Am. Chem. Soc., we describe a special class of substituted styrenes that exhibit equivalent atrop- and positional isomerism. In other words, inversion about the hindered C(aryl)–C(alkenyl) bond is equivalent to relocating the olefin to adjacent position. These unique molecules can be conveniently accessed via Mizoroki–Heck 1,3-homodiarylation under co-catalysis by palladium and an amino acid transient directing group (TDG), with density functional theory (DFT) calculations shedding light on how the amino acid controls multiple layers of selectivity in this cascade process. Congrats to the entire collaborative team: Amit, Yiyao, Wen-Ji, and Madeline from Scripps Research; and Turki from the Liu lab at the University of Pittsburgh!

For a link to the paper in J. Am. Chem. Soc., click here: https://pubs.acs.org/doi/full/10.1021/jacs.5c10118

As a reminder, we first deposited a pre-print on ChemRxiv back in May; click here for a link: https://chemrxiv.org/engage/chemrxiv/article-details/6835b62d1a8f9bdab53f41a4

Pumpkin Carving 2025

The Engle lab celebrated Halloween 2025 in style with our traditional pumpkin party, featuring spooky stylings, devilish deserts, and creepy carvings. One pumpkin and one child ended up mummified by the end of the evening! Happy Halloween!

New pre-print reveals new approach to unique polymers through three-component cross-coupling

Our lab, together with collaborators at Bristol Myers Squibb, University of Pittsburgh, and Georgia Tech, has developed a new nickel-catalyzed 1,2-alkylarylation of 1,5-cyclooctadiene (COD) that enables access to previously inaccessible cyclooctene monomers bearing C(sp³) and C(sp²) substituents. This method employs alkyl-9-BBN reagents as effective transmetalating partners, maintaining a two-electron redox manifold and avoiding radical pathways incompatible with 1,5-cyclooctadiene. The resulting monomers undergo ring-opening metathesis polymerization (ROMP) to afford new polymers with tunable properties dictated by the alkyl and aryl coupling partners. DFT studies reveal that the enhanced reactivity of alkyl-9-BBN arises from destabilization of the pre-transmetalation complex, distinguishing it from less reactive alkylboronic esters. Congrats to the entire team: Anne, Aimee, and Camille from Scripps Research; Shijia from the Liu lab at the University of Pittsburgh; and Ethan from the Gutekunst lab at Georgia Tech; and Steve from BMS.

For a link to the pre-print in ChemRxiv, click here: https://chemrxiv.org/engage/chemrxiv/article-details/68e901addfd0d042d1dace4c

Chris joins the lab as a postdoctoral fellow

The Engle lab is pleased to welcome Dr. Chris Rybak, who joins Scripps Research after completing a stellar Ph.D. at Purdue University. As a member of Prof. Chris Uyeda’s lab at Purdue, Chris’s dissertation research focused on dinickel catalytic approaches to azoarenes. A lifelong midwesterner, Chris will soak in San Diego sunshine while exploring new areas of the d-block for catalytic method discovery. Welcome Dr. Rybak!

Jeffrey completes his summer internship

This week marked the completion of Jeffrey Zhang’s summer internship, and we are sad to see him go! During his three months in the Engle lab, Jeffrey made important contributions to a new project in nickel-catalysis under the mentorship of Sourav. Out of the lab, Jeffrey kept his tennis game sharp on the weekends and traveled around the West Coast to soak in the sights and scenery. Congrats on all of your accomplishments, Jeffrey! We can’t wait to follow your career back at Cambridge and beyond!