Alkenyl Sulfonamide Diarylation – Now In Press

If you need something to “chew” on this Thanksgiving, look no further than our most recent collaborative paper severed by Team Nickel and Bristol Myers Squibb, accepted today for publication in ACS Catalysis. Led by second-year graduate student Omar Apolinar, the manuscript outlines the discovery and development of sulfonamides as uniquely effective nitrogen-based directing groups for the 1,2-diarylation of diverse alkenyl amine derivatives, including those with highly substituted alkenes and those where the alkene is remote from the sulfonamide. By taking advantage of the 4-cyanobenzenesulfonyl group, a close cousin of the venerable nosyl group, the sulfonamide can functional as a dual directing group and masked amine nucleophile, allowing for rapid modular synthesis of highly substituted amine products. Congrats to Omar, Van, Nana, and Joe from our lab and collaborator Mike Schmidt from BMS!

Click here for a link to the paper: https://pubs.acs.org/doi/10.1021/acscatal.0c03857

The work first appeared in pre-print form back in July: https://chemrxiv.org/articles/preprint/Sulfonamide_Directivity_Enables_Ni-Catalyzed_1_2-Diarylation_of_Diverse_Alkenyl_Amines/12642803/1

E/Z Isomerization Mechanistic Study Pre-Print Online

It has long been known that alkenes undergo isomerization—both positionally and stereochemically (E/Z)—in the presence of a palladium(II) catalyst, but the mechanistic details of this process have remained murky. In collaboration with the Blackmond lab at Scripps Research, we interrogated the mechanism of E/Z isomerization of alkenyl amides bearing an 8-aminoquinoline (AQ) directing group, which facilitates detection and characterization of otherwise short lived intermediates and suppresses positional isomerization. By leveraging a battery of techniques including in situ monitoring of intermediates, reaction kinetics, deuterium labeling, and DFT calculations, we were able to rule out several mechanistic hypotheses, with the pointing to a monometallic nucleopalladation mechanism. Congrats to Rei, Malkanthi, Mingyu, and high school intern Nhi on this work!

For a link, click here: https://chemrxiv.org/articles/preprint/Mechanistic_Studies_of_Pd_II_-Catalyzed_E_Z_Isomerization_of_Unactivated_Alkenes_Evidence_for_a_Monometallic_Nucleopalladation_Pathway/13194932

Former Postdoc De-Wei Gao Begins his Independent Academic Career

Congrats to former postdoc Dr. De-Wei Gao on his appointment as an Assistant Professor in the School of Physical Science and Technology at ShanghaiTech. De-Wei completed his Ph.D. at the Shanghai Institute of Organic Chemistry (SIOC) under the mentorship of Prof. Shu-Li You. He was a Postdoc in the Engle lab from 2016–2018, where he spearheaded our lab’s efforts in various aspects of copper catalysis. Since 2018, that time has been a Postdoc in the lab of Prof. Yi Tang at UCLA. Research in the Gao lab at ShanghaiTech will focus on selective synthesis of amino acids, peptides and proteins, the design of novel catalysts, and the development of biocompatible reactions.

To read more about the Gao group, click here: https://spst.shanghaitech.edu.cn/spst_en/2020/1010/c2939a56210/page.htm

BCB Hydroboration Paper Accepted in ACS Catalysis

Our latest collaboration with Pfizer, Inc. and the Liu group at the University of Pittsburgh describing the copper-catalyzed hydroboration of benzylidenecyclobutanes (BCBs) and related four-membered ring compounds has been accepted for publication in ACS Catalysis. Key to the success of this method was the identification of a modified 1,2-bis(diphenylphosphino)benzene (dppbz) ligand that enhances reactivity through π-stacking interactions with the substrate, as elucidated by density functional theory (DFT). Congrats to Taeho and Kane from our lab, ‪Tuğçe from the Liu lab at Pittsburgh, and Gary, Alex, Sajiv, Ryan, Ru, Scott, and Indra from Pfizer. Special props to high-school senior Kane for co-authoring his second paper!

For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/acscatal.0c03622

This work was first described back in August: https://chemrxiv.org/articles/preprint/Multifaceted_Substrate_Ligand_Interactions_Promote_the_Copper-Catalyzed_Hydroboration_of_Benzylidenecyclobutanes_and_Related_Compounds/12788390

COVID-19 Can’t Stop Us

Stop us from volunteering with the awesome middle school scientists at Barrio Logan College Institute that is!

We had the honor of leading bath bomb kinetics, where each student made a bath bomb with different amounts of ingredients and measured how that affected the rate of fizzing! With a little trial and error, these junior scientists were bath bomb pros in no time!

We adapted to social distancing requirements and delivered personalized science kits to each kid so they could do the experiment from home over Zoom at no cost!

This was our first virtual demo and it was a blast! We can’t wait for the next one.

Alkyne Cross-Coupling Pre-Print Now Online

In collaboration with Boehringer-Ingelheim (BI), we describe a method for palladium-catalyzed regio- and stereoselective cross-coupling of terminal alkynes with internal alkynes bearing various proximal directing groups. The transformation is enabled by a tailored P,N-ligand that was previously developed at BI for applications in asymmetric catalysis. Congrats to project lead, Mingyu, who started the project during an internship at BI, and to other co-workers from Scripps (Tianhua, Omar, and Rei) and BI (Carl, Bo, Dan, Olga, Chris, and Jeff)!

For a link to the pre-print, click here: https://chemrxiv.org/articles/preprint/Atom-Economical_Cross-Coupling_of_Internal_and_Terminal_Alkynes_to_Access_1_3-Enynes/13083419

Directed Cyclization Paper – Now In Press in Chem. Sci.

Xin, Zi-Qi, and Binh’s paper describing substrate-directed, palladium(II)-catalyzed intramolecular hydrofunctionalization has been accepted for publication in Chem. Sci. In this investigation we demonstrate that an bidentate AQ-amide directing group is able to promote otherwise disfavored ring-closure pathways, including those disfavored by Baldwin’s rules (e.g., 5-endotrig). This marks the culmination of a four-year journey initiated by former high-school intern Jessica (now at MIT) and her mentor John (now at Bristol Myers Squibb). Congratulations are in order for all co-authors for getting this to the finish line: Xin, Zi-Qi, John, Jessica, Van, Hui-Qi, Zhen, Zhonglin, and Kin from Scripps Research; Binh and Peng from University of Pittsburgh; and Rong (and Xin) from Nankai University Medical School.

For a link to the paper, click here: https://pubs.rsc.org/en/content/articlelanding/2020/sc/d0sc03409f#!divAbstract

This work was first described in April in a pre-print that was deposited on ChemRxivhttps://chemrxiv.org/articles/Controlling_Cyclization_Pathways_in_Palladium_II_-Catalyzed_Intramolecular_Alkene_Hydrofunctionalization_via_Substrate_Directivity/12090402/1

NEW POSTDOC DR. PHILLIPPA COOPER JOINS THE LAB

We are pleased to welcome our new postdoc Philippa to the team from the Bower lab at the University of Bristol, where she completed her Ph. D., developing iridium-catalyzed C-H functionalization reactions. Philippa has received Lindemann Trust Fellowship for her postdoctoral research in the Engle lab, and waited for so long to cross over the Atlantic Ocean in this pandemic situation. Welcome, Philippa!

Regiodiverent Alkene Hydroarylation Paper Accepted in Angew. Chem. Int. Ed.

Our recent project in collaboration with the Liu lab from the University of Pittsburgh on the regiodivergent hydroarylation/-alkenylation of alkenyl carboxylic acids with organoboronic acids has been accepted in Angew. Chem. Int. Ed. and appears in final form online this week. Key to the success of this methodology is the discovery of a novel 4,4-dibenzyl-Pyrox ligand that grants access to the anti-Markovnikov product, overriding the inherent selectivity for the Markovnikov product under ligand-free conditions. Mechanistic studies point to a unique carboxylate-mediated concerted hydronickelation mechanism. Congrats to Engle lab members Zi-Qi, Ruohan, Van, and Yang; as well as a Liu lab member Yue.

For a link to the paper, click here: https://onlinelibrary.wiley.com/doi/10.1002/anie.202010840

This work was first described in July in a pre-print that was deposited on ChemRxiv: https://chemrxiv.org/articles/Ligand-Controlled_Regiodivergence_in_Nickel-Catalyzed_Hydroarylation_and_Hydroalkenylation_of_Alkenyl_Carboxylic_Acids/12650009