Congratulations to rising 4th year graduate student Zi-Qi Li, who has been selected for a prestigious 2021–2022 Bristol Myers Squibb Graduate Fellowship in recognition of her research on palladium- and nickel-catalyzed alkene functionalization. Zi-Qi will present her research along other graduate fellows at BMS in the spring. Way to go, Zi-Qi!

For the past 5+ years, simple alkenyl alcohol substates have been on our wish list of “ideal” substrates for directed three-component alkene difunctionalization. However, extensive efforts within our lab and by others have proven that these starting materials are especially challenging due to a number of competitive side reactions that can arise (cyclization, alcohol oxidation, alkylmetal chain-walking, etc.). In an exciting study appearing online today in J. Am. Chem. Soc., Taeho and Nana together with Bristol Myers Squibb collaborators Peter, Klement, and Hao, have demonstrated a creative approach to integrate alkenyl alcohols into three-component carboamination that hinges on judicious tuning of the leaving group on the nitrogen electrophile. By carefully modulating the LUMO energy of this reaction partner, high pathway selectivity for the desired three-component coupling can be achieved across a broad array of substrates. Congrats to the team on this awesome advance!

For a link to the published manuscript in J. Am. Chem. Soc., click here: https://pubs.acs.org/doi/10.1021/jacs.1c07112.

As a reminder, a pre-print of this paper was published back in March: https://chemrxiv.org/engage/chemrxiv/article-details/60c7562e567dfebe64ec63f7

The Engle Lab is thrilled to announce that we have received an NSF CAREER award to support ongoing research in the area of Pd(II)-catalyzed C(alkenyl)–H activation. This research project will allow us to determine the catalyst properties that drive selectivity for C(alkenyl)–H activation or nucleopalladation from common Pd(II)–π-alkene intermediates, towards our long term goal of developing a toolkit for universal alkene functionalization. The grant will also support ongoing outreach activities to communicate organometallic chemistry principles to diverse audiences and provide state-of-the-art training experiences to undergraduates and high school interns. We are grateful to the National Science Foundation for supporting this project, which will run for the next five years.

For more about the CAREER program, click here: https://www.nsf.gov/funding/pgm_summ.jsp?pims_id=503214

To kick off the academic year, we welcome new members Dr. Amit Simlandy, Shenghua Yang, and Juntao Sun to the Engle lab!

Dr. Simlandy is here for his second postdoc; his first was with Prof. Kevin Brown at Indiana where he became the carboboration master. We are so happy to have him.

Shenghua is a Scripps veteran who did his undergraduate work in the Baran lab. We are glad we could convince him to move downstairs to join us.

After a tumultuous odyssey across land and sea, Juntao finally arrived in La Jolla to begin his PhD. His track record in the Engle lab shows that he will be publishing in no time.

Congrats to Dr. Malkanthi Karunananda, who was selected for a 2021 Cottrell Postdoctoral Fellowship from Research Corporation for Science Advancement with support from the National Science Foundation. The fellowship will support Malkanthi as she pursues computational studies of alkene functionalization reactions using a transient directing group strategy in collaboration with Prof. Ken Houk at UCLA. As part of the fellowship, Malkanthi will also co-teach a primer in computational chemistry for organic chemists. Congrats on this recognition, Malkanthi!

For more information about the program, click here: https://rescorp.org/cottrell-scholars/cottrell-fellowships

For a link to the award announcement, click here: https://rescorp.org/news/2021/09/rcsa-nsf-support-14-postdocs-in-2nd-year-of-cottrell-fellowships

While alkene hydroarylation methods have advanced rapidly over the past few years, Markovnikov-selective methods remain rare. Last year, we reported Ni-catalyzed hydroarylation of alkenyl carboxylic acid substrates with arylboronic acids, where the Markovnikov or anti-Markovnikov product could be accessed by changing the ligand environment around the metal center. In an Edge Article appearing online today in Chemical Science, we report a full account of our efforts to expand the substrate scope and elucidate the mechanism of the Markovnikov-selective (“ligand-free”) version of this method. Effective reaction conditions for alkenyl sulfonamides, ketones, and amides were identified, and detailed mechanistic studies suggested that the turnover-limiting and regiodetermining step is arylboronic acid transmetalation. Bravo to Zi-Qi, Omar, and Ruohan on this tour de force.

Click here for a link to the article in Chemical Science: https://pubs.rsc.org/en/content/articlelanding/2021/sc/d1sc03121j#!divAbstract

As a reminder, a pre-print of this article appeared back in May: https://chemrxiv.org/engage/chemrxiv/article-details/60c7592dbb8c1a05f33dcb81

Team Tungsten strikes again—with their latest pre-print appearing online today in ChemRxiv. This manuscript describes use of W(0) to catalyze site-selective isomerization–hydroboration of simple alkenyl amides. Conceptually, this work shows that native carbonyl groups can facilitate controlled alkene isomerization to otherwise disfavored positions, allowing for selective functionalization at classically inaccessible sites. Additionally, not only does this report mark the first use of W to catalyst a hydroboration reaction, it also demonstrates that W exhibits unique regioselectivity that complements that of existing methods with Rh and Ir. Congrats to the team, G4 student Tanner, visiting grad student Raul, and postdoc Phillippa. This study was performed in collaboration with Raul’s home lab, that of Prof. Rubén Martin at ICIQ in Tarragona, Spain.

For a link to the pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/60e77eb2551cb06ecbadb7a4

The latest paper from Team Nickel is now in press in Organic Letters. In this project, former visiting student Roman teamed up with current graduate student Omar to expand carbonyl-directed alkene 1,2-diarylation (previously demonstrated with amides and carboxylates) to even more challenging alkenyl ketones. Suppressing unwanted alkene isomerization proved to be challenging due to the acidity of the α-C–H bonds, requiring exhaustive (and exhausting!) reaction optimization. We performed a series of mechanistic experiments which collectively support L-type carbonyl coordination, and we compared the efficiency of these reaction conditions to those from related methods across three different substrate families to better understand the similarities and differences. Congrats to the whole team, which (in addition to Roman and Omar) includes Joe, Malkanthi, Zi-Qi, Van, and our BMS collaborator Steve.

For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/acs.orglett.1c01447,

As a reminder, an earlier version of this manuscript appeared as a pre-print back in March: https://chemrxiv.org/engage/chemrxiv/article-details/60c755b19abda2146bf8e413

Hui-Qi and Phillippa’s Feature Article reviewing recent advances in Pd-catalyzed (hetero)annulation of C=C bonds with ambiphilic aryl halides has just been accepted for publication and appears online today in Chem. Commun. The article summarizes exciting advances in this field during the past 15 years, and highlights outstanding challenges that once solved will push the utility of this chemistry to even greater heights. Well done, Hui-Qi and Phillippa, and thanks to the Chem. Commun. editors for the invitation!

For a link to the article, click here: https://pubs.rsc.org/en/content/articlelanding/2021/cc/d1cc02836g#!divAbstract

In a paper appearing today online in Angewandte Chemie International Edition, we show the unique selectivity of Cu(CAAC) (CAAC = cyclic(alkyl)(amino)carbene) catalyst in mediating boryl and silyl additions to terminal alkynes. Through careful ligand optimization, we show how high Markovnikov selectivity can be maintained across different alkyne substrates and boryl/silyl coupling partners. This collaborative project brought together chemists from three different institutions in America’s Finest City: the Grotjahn lab at San Diego State University, the Bertrand lab at UC San Diego, and the Engle Lab at Scripps Research. Well done to the entire project team!

For a link to the paper, click here: https://onlinelibrary.wiley.com/doi/10.1002/anie.202106107

The work first appeared in ChemRxiv back in April. Check out the pre-print here: https://chemrxiv.org/engage/chemrxiv/article-details/60c75776f96a0044cb288c84