Free-Amine-Directed 1,2-Carboamination of Alkenes – Now In Press

The final version of our paper on free-amine-directed 1,2-carboamination of alkenes under nickel catalysis is available online today in ACS Catalysis. In this manuscript, we describe how careful tuning of the reactivity of the nitrogen electrophile through modification of the leaving group allows for the first example of three-component 1,2-difunctionalization of alkene with a free amine directing group. The reaction proceeds with a broad scope of organoboron coupling partners, cyclic and acyclic amine electrophiles, and primary and secondary alkenyl amine substrates. Congrats to Taeho, José, and Zi-Qi, as well as our collaborators Klement and Peter from discovery chemistry at Bristol Myers Squibb.

For a link to the paper, click here: https://pubs.acs.org/doi/full/10.1021/acscatal.2c00373

As a reminder, a pre-print of the paper first appeared in ChemRxiv back in December 2021: https://chemrxiv.org/engage/chemrxiv/article-details/61b14f9a7ada95b46a6e62ee

C(alkenyl)–H Activation Enabled by a Transient Directing Group – Pre-Print Now Online

We continue our investigations into dual catalytic alkene functionalization promoted by a metal and a transient directing group (TDG). We previously described methods for Heck-type hydroarylation and 1,2-arylfluorination. In this ChemRxiv pre-print we show that it is instead possible to achieve C(alkenyl)–H activation from a common Pd(II)–alkene olefin intermediate, as promoted by a tailored carboxylate additive. This mode of reactivity can be leveraged in the oxidative cross-coupling of two alkenes to yield 1,3-diene products, including axially chiral 3-aryl-1,3-dienes. Congrats to the entire project team: Mingyu, Juntao, Hui-Qi, and Raúl from our lab; and Tuğçe from the Liu group the University of Pittsburgh.

Nana departs for BMS

Congrats to Dr. Nana Kim, who completes her postdoc this week. During her time in the Engle lab, Nana spearheaded new directions in nickel pre-catalyst development, including the identification of Ni(COD)(DMFU) as a potent precatalyst for alkene diarylation and development of a versatile bench-stable Ni(0) precatalyst for a variety of important catalytic reactions. Nana will soon start her career as a process chemist at Bristol Myers Squibb in New Brunswick, NJ. We wish you the best of luck in your new adventure, Nana!

Tanner successfully defends his Ph.D. Thesis

Congrats to the Engle lab’s newest doctor, Tanner C. Jankins, Ph.D.! In Tanner’s Ph.D. research, he spearheaded a new research directing focused on W(0)/W(II) redox catalysis, where non-classical seven coordinate geometries at W(II) can be exploited to enable facile alkene isomerization–functionalization processes. Outside of the lab, Tanner served as Engle group chef, the Scripps resident extreme sports instructor, and organometallics grad course TA. Congratulation on all of your success Tanner! Tanner will soon start his postdoc in the lab of Prof. Bill Morandi at ETH Zürich.

new bench-stable Ni(0) pre-catalyst toolkit – pre-print now online.

In collaboration with chemistry from Cornell University, Bristol Myers Squibb, and UC San Diego, today we report the culmination of a multi-year effort to identify new bench-stable Ni(0) precatalysts with coordination properties that complement Ni(COD)(DQ) (COD = 1,5-cyclcooctadiene, DQ = duroquinone) in terms of reactivity and stability. After surveying upwards of 100 ligands, we identified 10 18-electron complexes of the type Ni(COD)(L), where L = quinone, cyclopentadienone, thiphene-S-oxide, of fulvene) that are remarkable air-stable in solid and solution state. We characterized this family of complexes using NMR, X-ray crystallography, IR, NBO analysis, CV, and TGA, and showed how their kinetic behavior varies when used as pre-catalysts in a variety of Ni-catalyzed reactions from the literature. Congrats to the whole team, especially project leads Van and Nana!

For a link to the ChemRxiv pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/62034cfce0f52929aeac5fd0

Regioselective (CAAC)Cu-Catalyzed Carboboration of Alkynes – Pre-Print Online

The latest results from our collaboration on (CAAC)Cu catalysis (CAAC = cyclic(alkyl)(amino)carbene) with the Grotjahn lab (SDSU) and Betrand lab (UCSD) are described in a pre-print appearing today in ChemRxiv. Building on our previous discovery that strong σ-donating CAAC ligands can effectively quench the Lewis acidity of boryl ligand on the Cu center and promote regioselective boryl transfer to the internal (α) position (Angew. Chem. Int. Ed. 2021, 60, 19871) in protoboration, in the current study we extend this concept to a number of C(sp3) electrophiles. This protocol allows for expedient and selective assembly of alkenylboron products that are versatile building blocks in synthesis. Hats off to the tri-institutional team: Yang, Nana, Sima, Mingyu, Aaron, Doug, Guy, Rudy, and Keary!

For a link to the ChemRxiv pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/61f8b9da360c842812b1d6c2

Alena wins 2022 WCC Merck Research Award

Congratulations to G4 student Alena Vasquez for winning the 2022 Women Chemist Committee (WCC) Merck Research Award, presented by the American Chemical Society. Alena was selected as one of 8 award recipients nationwide from a highly competitive pool of 3rd and 4th year Ph.D. students in the fields of Organic, Chemical Biology, Analytical, Computational or Structural Chemistry, and related disciplines. As part of the award, Alena will present at the the WCC/Merck Research Symposium held in August at the 262nd ACS National Meeting in Chicago, IL.

Catalytic Coupling of Nitroalkanes and Alkenes – Pre-Print Now Online

In a paper appearing this morning in ChemRxiv, we report the Pd(II)-catalyzed coupling of nitroalkanes and alkenes using a directed carbopalladation strategy. The combined use of PdI2 as precatalyst and HFIP as solvent proved to be uniquely effective in activating nitroalkane pronucleophiles. This finding can be leveraged in chemorthogonal activation of bis-nucleophilic coupling partners under different conditions. The resulting C(sp3)-NO2 group in the product is a versatile functional handle that can be converted into myriad useful functional groups, granting access to product structures that are otherwise difficult to prepare. Bravo to the team: Amit, Warabhorn (Por), Hui-Qi, and John!

For a link to the ChemRxiv pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/61f56e5c71868defd0c2a7d5

Annulating Ambiphile Mapping Paper – Now In Press

The final peer-reviewed version of our collaborative paper with Pfizer mapping reactivity trends in the Pd(II)/Pd(IV) catalytic annulation of alkenyl amides appears online today in Angewandte Chemie International Edition. In the paper, we describe protocols for synthesizing a diverse array 5-, 6-, and 7-membered carbon/heterocycles of ambiphilic organohalides and show how changing the structure of the nucleophile and electrophile influences reactivity. Congrats to Hui-Qi, Philliipaa, and Pranali from the Scripps Research and Shouliang, Fen, Neal, Joyann, Michelle, and Indra from Pfizer Oncology Medicinal Chemistry for another great collaboration!

Click here for a link to the article in Angewandte Chemie International Edition: https://onlinelibrary.wiley.com/doi/10.1002/anie.202114346

As a reminder, a pre-print of the paper first appeared in ChemRxiv back in October: https://chemrxiv.org/engage/chemrxiv/article-details/6172bcd10c0480fd773f44a4

2021 ENGLE LAB HOLIDAY PARTY

It’s that time of year again🥳! This year, we were able to hold our traditional Engle group holiday party in-person. We shared delicious food, exchanged gifts through a white elephant game (fun!), and enjoyed the nice chilly December weather of San Diego. Tints of red and green color piqued our holiday excitement. From our lab to yours, we wish everyone a joyous holiday season and a most prosperous and healthy New Year!