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

1,1-Diboration paper accepted in Org. Lett.

Yang and Zhong-Qian’s paper describing the copper-catalyzed conversion of the terminal alkynes to stereodefined 1,1-diborylalkenes has been accepted in Org. Lett. and appears in final form online today. Mechanistically, the reaction involves a tandem sequence of dehydrogenative C(sp)–H borylation with HBdan followed by hydroboration with HBpin with copper playing a dual role as catalyst for both steps. Preparatively, the method enables one-step access to valuable alkyl- and aryl-substituted 1,1-diborylalkenes, which can then be further diversified through sequential cross-coupling. Congrats to postdoc Yang and undergrad co-author Zhong-Qian!

For a link to the paper, click here: https://pubs.acs.org/doi/full/10.1021/acs.orglett.0c01901

This work was first described in April in a pre-print that was deposited on ChemRxiv: https://chemrxiv.org/articles/Synthesis_of_Stereodefined_1_1-Diborylalkenes_via_Copper-Catalyzed_Diboration_of_Terminal_Alkynes/12133404

Alkene [3+2]-(Hetero)annulation Pre-print Online

We kick off the post-Father’s-Day workweek with a new pre-print on ChemRxiv describing the application of our lab’s strategy for directed nucleopalladation of alkenes to the synthesis of carbo- and heterocycles via [3+2]-(hetero)annulation. Though the mechanistic details are rather different, this reaction takes inspiration from the venerable Larock indole synthesis, enabling access to diverse indolines, 2,3-dihydrobenzofurans, and indanes from readily available starting materials. Working in close collaboration with Pfizer’s Oncology Medicinal Chemistry team and the Liu group at the University of Pittsburgh, we were able to examine a broad swath of a heterocyclic structural space relevant to drug discovery and to flesh out the reaction mechanism. Congrats to this fantastic team of coworkers: Hui-Qi, Pranali, and Hou-Xiang from our lab; Joyann, Shouliang, Michelle and Indra from Pfizer; and Ilia and Peng from Pitt. Special shout-out to our two undergraduate co-authors Pranali and Hou-Xiang!

For a link to the pre-print, click here: https://chemrxiv.org/articles/Anti-Selective_3_2_Hetero_annulation_of_Non-Conjugated_Alkenes_via_Directed_Nucleopalladation/12510038

The Engle Lab turns 5

Today we celebrate our 5 year Lab-iversary! Rather than our normal tradition of eating lunch and cake together, this year we celebrated social-distancing-style, with cupcakes and online games. Our first five years as a lab at Scripps have gone quickly, with plenty of highs, lows, and interesting discoveries along the way. Here’s to the next 5!

Alpha-Hydroarylation Paper Accepted in J. Am. Chem. Soc.

Our collaborative paper with Bristol-Myers Squibb on α-selective hydroarylation of acrylates and acrylamides has been accepted for publication in J. Am. Chem. Soc. Detailed mechanistic studies revealed that the reaction proceeds via a [Pd(Ar)(H)] intermediate, which undergoes migratory insertion to deliver the hydride group to the β-position, generating a [Pd(Ar)(enolate)]; C–C reductive elimination then furnishes the final product. The reaction is notable for its operational simplicity, mild reaction conditions, and widely available starting materials. Congrats to Engle lab authors Alena and John (now at BMS Process), as well as BMS collaborators Candice (Process Chemistry) and Emily (Discovery Chemistry) As a reminder, this manuscript first appeared as a ChemRxiv pre-print (click here).

For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/jacs.0c03040