Full Account of Ni-Catalyzed Markovnikov Hydroarylation – Now In Press

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

W-Catalyzed Isomerization–Hydroborylation Pre-Print Posted

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

Ni-Catalyzed Alkenyl Ketone 1,2-Diarylation – Now In Press

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

C=C Bond (Hetero)annulation Review – Now Online

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

Cu(CAAC)-Catalyzed Alkyne Protoboration and -Silylation Paper – Now In Press

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

Luke wins the 2021 IPMI Johnson Matthey Student Award

Congratulations to rising G4 student Luke Oxtoby who has been awarded the 2021 International Precious Metals Institute Johnson Matthey Student Award in recognition of his graduate research, where he has achieve the first successful examples of enantioselective Heck-type alkene additions using a transient directing group strategy. Luke will travel to the IPMI annual conference in Reno, Nevada, in October, where he will present his research at a special awards session.

Welcome Yilin!

We have a new undergraduate intern Yilin, from UCSB. She has explored nickel-catalysis in aqueous micellar conditions as an undergraduate research assistant in Prof. Lipshutz’s group, and now she will be expanding her experience in nicekl catalysis, joining the Team Nickel under the mentorship of Ziqi.

The Engle Lab Turns 6

Time flies when you’re having fun, living through a pandemic, or both! The Engle lab celebrated six wonderful years at Scripps with an afternoon at the beach in Del Mar, where we enjoyed surfing, frisbee, and BBQ. The event doubled as a welcome party for our two newest members, José and Yilin. After more than a year of virtual social events, it was a special treat to gather together and celebrate this milestone.

Cross-metathesis route to alkenyl AQ amides

Over the years we’ve experienced first-hand the frustrations of resorting to circuitous synthetic routes to access substituted alkenyl AQ amide substrates, which serve as cornerstones of AQ-directed alkene functionalization chemistry. To address this Hui-Qi, Zi-Qi, and Van teamed up to develop a concise and modular method using cross-metathesis with the Grubbs 2nd generation catalyst. Remarkably the catalyst is impervious to the AQ group, allowing direct coupling of terminal alkenyl AQ amides with a variety of terminal alkenes. In one case, we shorten a four-step sequence to a single high-yielding step. This paper is part of a special issue in Tetrahedron celebrating Prof. Guangbin Dong’s 2021 Tetrahedron Young Investigator Award. Well done team!

For a link to the paper, click here: https://www.sciencedirect.com/science/article/abs/pii/S0040402021005019

Welcome José!

We have a summer visiting gradudate student José González from Gulías group at CIQUS-USC, Spain. He has been working on enantioselective Pd-catalyzed C-H activation at Gulías group. In the Engle lab, he is turning his attention to Ni-catalysis, collaborating with Taeho.