Directed Cyclization Paper – Now In Press in Chem. Sci.

Xin, Zi-Qi, and Binh’s paper describing substrate-directed, palladium(II)-catalyzed intramolecular hydrofunctionalization has been accepted for publication in Chem. Sci. In this investigation we demonstrate that an bidentate AQ-amide directing group is able to promote otherwise disfavored ring-closure pathways, including those disfavored by Baldwin’s rules (e.g., 5-endotrig). This marks the culmination of a four-year journey initiated by former high-school intern Jessica (now at MIT) and her mentor John (now at Bristol Myers Squibb). Congratulations are in order for all co-authors for getting this to the finish line: Xin, Zi-Qi, John, Jessica, Van, Hui-Qi, Zhen, Zhonglin, and Kin from Scripps Research; Binh and Peng from University of Pittsburgh; and Rong (and Xin) from Nankai University Medical School.

For a link to the paper, click here: https://pubs.rsc.org/en/content/articlelanding/2020/sc/d0sc03409f#!divAbstract

This work was first described in April in a pre-print that was deposited on ChemRxivhttps://chemrxiv.org/articles/Controlling_Cyclization_Pathways_in_Palladium_II_-Catalyzed_Intramolecular_Alkene_Hydrofunctionalization_via_Substrate_Directivity/12090402/1

Regiodiverent Alkene Hydroarylation Paper Accepted in Angew. Chem. Int. Ed.

Our recent project in collaboration with the Liu lab from the University of Pittsburgh on the regiodivergent hydroarylation/-alkenylation of alkenyl carboxylic acids with organoboronic acids has been accepted in Angew. Chem. Int. Ed. and appears in final form online this week. Key to the success of this methodology is the discovery of a novel 4,4-dibenzyl-Pyrox ligand that grants access to the anti-Markovnikov product, overriding the inherent selectivity for the Markovnikov product under ligand-free conditions. Mechanistic studies point to a unique carboxylate-mediated concerted hydronickelation mechanism. Congrats to Engle lab members Zi-Qi, Ruohan, Van, and Yang; as well as a Liu lab member Yue.

For a link to the paper, click here: https://onlinelibrary.wiley.com/doi/10.1002/anie.202010840

This work was first described in July in a pre-print that was deposited on ChemRxiv: https://chemrxiv.org/articles/Ligand-Controlled_Regiodivergence_in_Nickel-Catalyzed_Hydroarylation_and_Hydroalkenylation_of_Alkenyl_Carboxylic_Acids/12650009

Facile Solid-State Decomposition of Sodium Alkoxide Salts – Pre-Print Now Online

NaOMe, NaOEt, and related bases are widely used in organic synthesis and are readily available in solid form as free-flowing white (or off-white) solids. During research into cross-coupling reactions, our lab in collaboration with Bristol Myers Squibb discovered that these bases undergo rapid decomposition under air through a complex sequence of events. Today we disclose a pre-print in ChemRxiv describing our efforts to understand this phenomenon. It turns out that this process is so pervasive that even “new” commercial lots of these bases can contain almost none of the desired material. This was a long and circuitous detective story that challenged us to use every analytical trick in the book, from Karl Fischer titration to solid state 23Na NMR.

Read the full story here: https://chemrxiv.org/articles/preprint/An_Under-Appreciated_Source_of_Reproducibility_Issues_in_Cross-Coupling_Solid-State_Decomposition_of_Primary_Sodium_Alkoxides_in_Air/12818234

BCB Hydroboration Pre-Print Online

The latest story from our ongoing collaboration with the Liu group at the University of Pittsburg and Pfizer, Inc. appears online today in pre-print form on ChemRxiv. The new method effect hydroboration of benzylidenecyclopropanes, -azetidines, -oxetanes, and other related substrates. Key to the success of the reaction was the discovery of a specially modified dppbz ligand for the copper catalyst, which promotes the reaction through T-shaped π-stacking and other non-covalent interactions with the substrate. Congrats to G3 student Taeho and our high-school intern Kane from the Engle lab, Tuğçe from the Liu lab, and Gary, Alex, Sajiv, Ryan, Ru and Indra from Pfizer!

Please click here for a link to the pre-print: https://chemrxiv.org/articles/preprint/Multifaceted_Substrate_Ligand_Interactions_Promote_the_Copper-Catalyzed_Hydroboration_of_Benzylidenecyclobutanes_and_Related_Compounds/12788390

2nd-Year Students Pass Qual Exams with Flying Colors

Congratulations to our Engle lab’s G2 students (Class of 2023), Taeho Kang, Zi-Qi Li, Luke Oxtoby, and Alena Vasquez, for passing their qual exams and advancing to candidacy. Despite the COVID-19 pandemic, lab shutdown, and challenging working circumstances, these four maintained a great attitude and mastered the art of giving a great scientific talk over zoom. Looking forward to seeing what this class has in store for the next three years!

2020 OM Bootcamp kicks off this week!

The 2020 Organometallics Bootcamp kicks off this week (Mon, 8 am PT), and for the first time it will be held entirely over zoom. We are opening it up to any interested undergraduate students (especially those from PUIs!) who may have missed out on summer research opportunities. Please email keary(at)scripps.edu for more info if you are interested in learning more and potentially participating. Hope to see you there!

Keary wins 2020 Amgen Young Investigator Award

Keary has been named as one of the five recipients of the 2020 Amgen Young Investigator Award, as selected by Amgen’s Therapeutic Discovery and Drug Substance Technologies Departments. Congratulations to Keary and the other awardees!

• Keary Engle, Ph.D., Scripps Research Institute
• Jean-Philippe Julien, Ph.D., University of Toronto
• Alison Narayan, Ph.D., University of Michigan
• Sergey Pronin, Ph.D., University of California Irvine.
• David Veesler, Ph.D., University of Washington

The five speakers will receive funding to support research from Amgen and will participate in a virtual Young Investigator Award Symposium this fall.

Regiodivergent hydroarylation pre-print

Team Nickel continues to be hard at work during this challenging summer, and today we report the latest chapter in our work towards diverse regiodivergent alkene functionalization in collaboration with Liu group at the University of Pittsburgh. Specifically, we discovered that a systematically tuned Pyrox ligand is able to overcome the inherent tendency of alkenyl carboxylic acids to react in an anti-Markovnikov fashion in nickel(0)-catalyzed hydroarylation and -alkenylation with oranoboronic acids, instead favoring formation of the anti-Markovnikov product. Great work by all of the authors—Zi-Qi, Ruohan, Van, and Yang from our group, and Yue from the Liu lab.

For a link to the pre-print, click here: https://chemrxiv.org/articles/preprint/Ligand-Controlled_Regiodivergence_in_Nickel-Catalyzed_Hydroarylation_and_Hydroalkenylation_of_Alkenyl_Carboxylic_Acids/12650009

Pre-print from team nickel describing versatile sulfonamide-directed 1,2-diarylation

Not even a pandemic can slow down Team Nickel, who report a versatile method to effect 1,2-diarylation of diverse alkenyl amine derivatives, including those bearing challenging 1,1- and 1,2-disubstitution patterns. Key to the success of this work was the discovery of sulfonamides as uniquely effective groups for directing the nickel catalysts and then subsequently activating the nitrogen atom for diverse N-functionalization reactions.

For a link to the pre-print, click here: https://chemrxiv.org/articles/Sulfonamide_Directivity_Enables_Ni-Catalyzed_1_2-Diarylation_of_Diverse_Alkenyl_Amines/12642803