Huaze (Eric) wrapped up his summer internship in the Engle lab this week and will be returning to Atlanta to begin his senior year at Emory University. During his time in the group, Eric collaborated closely with Yiyao on projects in copper catalysis. His enthusiasm, curiosity, and hard work made a strong impression on the lab, and we are grateful for his contributions this summer. We wish Eric all the best as he finishes his undergraduate studies and look forward to following his future successes in grad school and beyond!

The 8-aminoquinoline (AQ) directing group has been central to our research on Pd(II)-catalyzed alkene and alkyne functionalization, yet despite its widespread use in the field, the structural basis of its exceptional performance had never been examined in detail. In a new paper published in Tetrahedron Letters as part of a special issue honoring Pep Cornella’s TYIA Award, Al provides a concrete, quantitative answer to this long-standing question.

Through a survey of over 200 crystal structures in the Cambridge Structural Database combined with DFT calculations, Al shows that AQ is conformationally pre-organized: its fused quinoline scaffold locks the two donor nitrogens in a planar, chelation-ready geometry (φ ≈ 0°) at essentially zero energetic cost. Flexible C(sp³)-linked auxiliaries such as PM, PIP, and PDE, by contrast, rest predominantly in an anti conformation and must reorganize to bind—paying 0.6–2.5 kcal/mol to reach the chelation geometry. NBO analysis reveals the electronic origin of AQ’s rigidity: the amide nitrogen lone pair simultaneously delocalizes into both the quinoline π-system and the carbonyl π*, and rotation disrupts both pathways at once.

Interestingly, this pre-organization does not necessarily make AQ a faster-coordinating substrate—the flexible PM auxiliary actually binds Pd more rapidly. Rather, pre-organization governs which directing group wins the catalyst under competition. These findings recast conformational pre-organization from a qualitative descriptor into a quantitative design principle for the development of removable bidentate auxiliaries. Congratulations to Al on a beautifully executed study!

Read the paper in Tetrahedron Letters: https://doi.org/10.1016/j.tetlet.2026.156231

This week marked the conclusion of Zoe’s summer “Pinternship”, a research internship initiative of the Pinhead Institute based in Telluride, Colorado. During her time with us, Zoe worked closely with Madison on catalytic alkyne functionalization, tackling real synthetic chemistry challenges with impressive focus and adaptability. She will be heading home to begin her senior year at Ouray High School — and to prepare for what promises to be a very busy ice climbing season. As a member of Team USA, Zoe is one of the top young ice climbers in the country, and her tenacity on the wall was clearly on display in the lab as well. We have loved having Zoe with us this summer and can’t wait to see what she accomplishes both in and out of the lab. Best of luck, Zoe!

We are delighted to share our new review article in Chemical Reviews in collaboration with the laboratory of Prof. Bing-Feng Shi at Zhejiang University! Enantioselective C–H functionalization has emerged as a next-generation synthetic paradigm—enabling direct modification of otherwise inert C–H bonds to build molecular complexity efficiently and with high stereochemical control. While precious metals have historically dominated this field, earth-abundant 3d transition metals (cobalt, nickel, iron, copper) are increasingly at the forefront, offering compelling advantages in cost, sustainability, and distinctive reactivity profiles.

In this review, we join forces with the Shi lab to survey the rapid progress in 3d metal-catalyzed asymmetric C–H functionalization through March 2025—covering both inner-sphere and outer-sphere mechanisms, chiral ligand design, mechanistic insights, and synthetic applications, as well as the key challenges and opportunities that remain.

Congratulations to co-authors Pu-Fan Qian, Jia-Heng Hu, Yan-Xuan Wu, and our undergrad intern Yuan Xu, who joined us in La Jolla for the summer, on this tremendous effort, and thank you to Prof. Shi and the entire Zhejiang University team for such a wonderful collaboration!

📄 Read the full review in Chemical Reviews: https://pubs.acs.org/doi/10.1021/acs.chemrev.6c00255

Congrats to fifth-year graduate student Shenghua Yang, who successfully defended his dissertation today. Shenghua’s Ph.D. research focused on expanding the design and strategic application of bisphosphine ligands in homogeneous cataylsis. In particular, Shenghua’s research culminated in the design of a new family of wide-bite-angle chiral bisphosphines with superb performance in asymmeytic C–C coupling reactions. Later this summer, Shenghua will move north for a postdoc position at the Molecular Foundry of Lawrence Berkeley National Laboratory.

In our earlier work on Pd(II)-catalyzed cyclopropanation of alkenyl amides with nitroalkanes, we noticed an intriguing byproduct that had gone unaccounted for. When we revisited the reaction and subjected this material to X-ray crystallography, it turned out to be an isoxazoline N-oxide—a member of a versatile yet underexplored class of heterocycles. Recognizing the opportunity, we set out to develop conditions that would favor formation of this product selectively. We are pleased to share the results of those efforts in Organic Letters!

By switching precatalyst, base, and solvent, Yiyao, Hui-Qi, Lan, Yilin, and Shenghua were able to redirect the reaction pathway and access intricately functionalized isoxazoline N-oxides in a single step from simple alkenyl amides and nitroalkanes via Pd(II)/Pd(IV) catalysis. The method delivers products with high diastereoselectivity and the N-oxide scaffolds proved to be versatile intermediates — amenable to reduction, auxiliary removal, and 1,3-dipolar cycloaddition for downstream access to diverse nitrogen-containing frameworks. Congratulations to all co-authors and our collaborators Nick Scherschel and Prof. Davin Piercey at the Purdue Energetics Research Center!

Read the paper in Organic Letters: https://pubs.acs.org/doi/10.1021/acs.orglett.6c01696

The peer-reviewed version of Nana and Aimee’s study on shelf-stable bis(perfluoroaryl)nickel(II) complexes is now published in Organometallics! In this work, the team introduces two new bench-stable Ni(II) precatalysts, Ni(C₆F₅)₂(NCPh)₂ and [NBu₄]₂[{Ni(C₆F₅)₂(μ-OH)₂}₂], that combine exceptional stability and broad solubility with operational simplicity. Upon activation, the complexes cleanly release inert decafluorobiphenyl as the only byproduct. Catalytic competence was demonstrated across Suzuki–Miyaura coupling, Buchwald–Hartwig amination, Miyaura borylation, and alkene difunctionalization. Congratulations to all co-authors and our collaborators in the Figueroa lab at UC San Diego and at Bristol Myers Squibb!

📄 Read the paper in Organometallics: https://pubs.acs.org/doi/10.1021/acs.organomet.6c00134

🧪 Original preprint on ChemRxiv: https://chemrxiv.org/doi/full/10.26434/chemrxiv.15000413/v1

We are delighted to share our new review article, “Catalytic Functionalization of Unactivated π-Bonds Enabled by Bidentate Directing Auxiliaries,” now published in Angewandte Chemie International Edition!

A defining theme of our group’s research over the past decade has been the use of bidentate directing auxiliaries to enable new catalytic functionalization reactions of π-bonds and to facilitate mechanistic elucidation. It has been gratifying to watch this approach gain widespread adoption across the synthetic community.

In this review, we join forces with the laboratory of Prof. Taeho Kang at Korea University to take stock of where the field stands — covering key developments in hydrofunctionalization, difunctionalization, and C–H activation across palladium, nickel, copper, and other transition-metal catalysts, and discussing the outstanding challenges and opportunities that will shape the next chapter of this chemistry.

Congratulations to all of the student coauthors: Seunghyeon Cho (Korea University), Al Vicente Riano D. Lisboa (Scripps Research), and Juntao Sun (Scripps Research). Thank you to Prof. Kang and the whole team for such a wonderful collaboration!

📄 Read the review in Angewandte Chemie International Edition: https://onlinelibrary.wiley.com/doi/10.1002/anie.4046829

Congratulations to Engle lab member Juntao Sun, who successfully defended his Ph.D. dissertation at Scripps Research this month. Juntao began his formal education at Nankai University, and first came to our group as an undergraduate intern in the summer of 2019, working under the mentorship of Dr. Mingyu Liu. We were then fortunate to recruit him into the Scripps Research Ph.D. program in 2021, making him the third former undergraduate intern in our group to go on to earn a doctoral degree here.

In his thesis research, Juntao developed new strategies for selective generation and functionalization of alkenylmetal intermediates, including unlocking copper(II) as a potent π-Lewis acid for alkyne functionalization. Juntao will now put this expertise to excellent use as part of the high-throughput experimentation team at Incyte, in Wilmington, Delaware. Congratulations, Dr. Sun — and thank you for everything you’ve brought to our lab!

We’re excited to share our solution to a longstanding challenge in asymmetric catalysis: the enantioselective anti-Michael addition of diverse (hetero)aryl groups to unsaturated carbonyl compounds. As every organic chemistry student learns, organometallic additions to Michael acceptors take place almost universally at the β-carbon. Our new Pd-catalyzed reaction overrides this intrinsic selectivity through a unique trans-Pd(Ar)(H) mechanism, delivering aryl groups directly to the α-position with up to 99% ee across a broad substrate scope. The key to unlocking this reactivity is (S,S)-(R,R)-PhTRAP, a chiral trans-spanning bisphosphine whose unusually wide bite angle simultaneously suppresses competing hydrodehalogenation and creates a well-defined chiral environment for stereoselection. DFT calculations, reaction kinetics, and organometallic experiments work together to reveal the multi-faceted role of this ligand throughout the catalytic cycle. Congratulations to the whole team, particularly Shenghua Yang, Alena Vasquez, Binh Mai, and Turki Alturaifi, and thank you to our collaborators at the University of Pittsburgh and Bristol Myers Squibb!

🧪 Check out the pre-print in ChemRxiv: https://chemrxiv.org/doi/full/10.26434/chemrxiv.15002500/v1