In a breakthrough report that pushes the frontier of practical utility in nickel-catalyzed alkene functionalization, Taeho, Nana, and collaborators at Bristol Myers Squibb have discovered a method to carry out selective 1,2-carboamination of free alkenyl alcohols with aryl/alkenylboronic acids and nitrogen electrophiles. Key to the success of this transformations is the careful design of the activating group for the N–O electrophile, which promotes the desired three-component process and suppresses side reactions. The reaction enables rapid synthesis of alkyl-amine-containing bioactive small molecules and late-stage modification of natural products. Bravo on this one, folks!

For a link to pre-print, click here: https://chemrxiv.org/articles/preprint/Nickel-Catalyzed_1_2-Carboamination_of_Alkenyl_Alcohols/14195426

The final, peer-reviewed version of our study in collaboration with the process chemistry team at Boehringer-Ingelheim on alkyne cross-coupling to access 1,3-enynes appears this week in J. Am. Chem. Soc. The high regio- and stereoselectivity of this reaction stems from the use of a hindered P,N-ligand previously developed at BI, which Mingyu and the BI team identified during his summer internship in Ridgefield, CT. Hats off to the entire project team: Mingyu, Tianhua (Josh), Omar, and Rei from Scripps Research; and Carl, Bo, Dan, Olga, Chris, and Jinhua (Jeff) from BI. Not a bad way to follow up your successful thesis defense from last week, Dr. Liu!

For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/jacs.0c12565

This work first appeared as a pre-print back in October: https://chemrxiv.org/articles/preprint/Atom-Economical_Cross-Coupling_of_Internal_and_Terminal_Alkynes_to_Access_1_3-Enynes/13083419

Mingyu becomes the first member of the Engle lab to defend his these virtually, passing with flying colors! Congratulations Dr. Liu! 🎉 🎊 🎓 🥂 Though our normal tradition is to celebrate in the Beckman atrium with champagne, this time a virtual toast had to do. Special should out to Prof. Vy Dong from UC Irvine for serving as external examiner. Congrats on all of your accomplishments, and thanks for your myriad contributions to the group over the past 5 years, Mingyu!

The latest work from Team Nickel and the Bristol Myers Squibb collaboration is now online as a pre-print in ChemRxiv. The paper describes extension of carbonyl-directed nickel-catalyzed alkene 1,2-diarylation to alkenyl ketone substrates, which are challenging owing to the weaker Lewis basicity of the ketone lone pair as well as the increased susceptibility to unwanted isomerization. We also conducted a comparative study of the different reaction conditions that have been published for this family of transformations in order to identify key similarities and differences. Hats off the fantastic team led by visiting student Roman (now a Ph.D. student with Frank Glorius at WWU Münster) and second-year grad student Omar. Also contributing were Joe, Malkanthi, Zi-Qi, and Van, as well as Steve from BMS Process. Awesome stuff, team!

For a link to the pre-print, click here: https://chemrxiv.org/articles/preprint/Nickel-Catalyzed_1_2-Diarylation_of_Alkenyl_Ketones_A_Comparative_Study_of_Carbonyl-Directed_Reaction_Systems/14150174

We did something a little different from chemistry… With the help of the talented middle schoolers at Barrio Logan College Institute, we built ROBOTS! It was so fun to work with these students and ensure all have access to science, even in a pandemic. We provided curated science kits to each student and led small groups over zoom. Thanks BLCI for spending your workshop night with us!

After three hugely successful years in the Engle lab, Dr. Yang Gao departs this week to begin a position in Discovery Chemistry at Corteva in Indianapolis, IN. In the Engle lab, Yang led our research program in copper catalysis and collaborated with both the Liu lab at the University of Pittsburgh and the Bertrand lab at UCSD. His love for copper chemistry runs so deep that it was only fitting that he and his wife named their new German shepherd puppy “Copper.” In addition to educating everyone in the lab about mechanistic organometallic chemistry, Yang managed to also teach the Scripps community some new moves on the hardwood as well. Best of luck on your new adventure, Yang!

Welcome to all prospective graduate students who are visiting us virtually this week and two weeks from now. Everyone at Scripps Research wishes that we could be with you in person to share our exciting science (and temperate weather) with you. To give everyone a flavor for life in the Engle lab, we put together a virtual tour. Props to Camille, Nana, and all of the featured lab members!

Keeping with lab tradition during recruitment season, Hermione features prominently!

Today in ChemRxiv we report an unusual and surprising organometallic rearrangement triggered by addition of Pd(TFA)₂ to at alkenyl benzothiazole thioether (BT(S)). This story started two years ago. While wrapping up an in-depth study of the BT(S) directing group and its various uses in palladium(II) catalysis (ACS Catal. 2019, 9, 7626), Andrew treated a standard substrate with Pd(TFA)₂. Rather than forming the PdX₂(substrate)₂ complex like we was with other Pd(II) salts, Andrew obtained an unusual structure where the organic ligand had undergone significant rearrangement and was now coordinated as a bidentate N,S-heterocyclic-carbene–tetrahydrothiophene—shout out to UCSD Crystallography for elucidating the structure! Andrew then teamed up with a high school intern, Matt Demer (now at UC Davis), and continued close collaboration with crystallographers Milan and Arnie from UCSD to understand the scope, limitations, and mechanism of this process. Bravo, Andrew and team!

For a link to the pre-print, click here: https://chemrxiv.org/articles/preprint/Ligand_Rearrangement_Leads_to_Tetrahydrothiophene-Functionalized_N_S-Heterocyclic_Carbene_Palladium_II_Complexes/13633301

Since our lab’s first paper establishing a transient directing group strategy for asymmetric Heck-type hydroarylation went online in 2019, we’ve been hard at work trying to extend this approach to three-component 1,2-difunctionalization. At long last we’ve succeeded, and we are thrilled to report the fruits of our labor: a remarkably versatile 1,2-arylfluorination reaction that can form fully substituted C(sp³)–Ar and C(sp³)–F stereo centers in up to >99% ee. Pivotal to the success of the project was use of design of experiments (DoE) to facilitate rapid optimization of reaction conditions and reaction progress kinetic analysis (RPKA) to elucidate the reaction mechanism. Hats off to Zhonglin, Luke, Mingyu, Zi-Qi, Van, and Yang on the landmark achievement!

For a link, click here: https://chemrxiv.org/articles/preprint/A_Transient_Directing_Group_Strategy_Enables_Enantioselective_Multicomponent_Organofluorine_Synthesis/13537283

The holiday paper flurry continues! ❄️⛄️🥶 This time it’s Team Nickel, who together with collaborators at Bristol Myers Squibb describe the use of Ni(COD)(DMFU) as a well-defined, all-in-one precatalyst for alkene diarylation. This lovely red free-flowing solid can be conveniently prepared in high yield from Ni(COD)₂ and is indefinitely thermally stable as long as handled in an inert-atmosphere glovebox. Congrats to the Scripps team, Nana, Van, and Omar, as well as BMS team, Steve and Martin. Here’s to another great year to come in the Scripps–BMS collaboration!

For a link to the paper, click here: https://www.thieme-connect.com/products/ejournals/abstract/10.1055/a-1344-6040