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

Facile Solid-State Decomposition of Sodium Alkoxide Salts – Pre-Print Now Online

NaOMe, NaOEt, and related bases are widely used in organic synthesis and are readily available in solid form as free-flowing white (or off-white) solids. During research into cross-coupling reactions, our lab in collaboration with Bristol Myers Squibb discovered that these bases undergo rapid decomposition under air through a complex sequence of events. Today we disclose a pre-print in ChemRxiv describing our efforts to understand this phenomenon. It turns out that this process is so pervasive that even “new” commercial lots of these bases can contain almost none of the desired material. This was a long and circuitous detective story that challenged us to use every analytical trick in the book, from Karl Fischer titration to solid state 23Na NMR.

Read the full story here: https://chemrxiv.org/articles/preprint/An_Under-Appreciated_Source_of_Reproducibility_Issues_in_Cross-Coupling_Solid-State_Decomposition_of_Primary_Sodium_Alkoxides_in_Air/12818234

BCB Hydroboration Pre-Print Online

The latest story from our ongoing collaboration with the Liu group at the University of Pittsburg and Pfizer, Inc. appears online today in pre-print form on ChemRxiv. The new method effect hydroboration of benzylidenecyclopropanes, -azetidines, -oxetanes, and other related substrates. Key to the success of the reaction was the discovery of a specially modified dppbz ligand for the copper catalyst, which promotes the reaction through T-shaped π-stacking and other non-covalent interactions with the substrate. Congrats to G3 student Taeho and our high-school intern Kane from the Engle lab, Tuğçe from the Liu lab, and Gary, Alex, Sajiv, Ryan, Ru and Indra from Pfizer!

Please click here for a link to the pre-print: https://chemrxiv.org/articles/preprint/Multifaceted_Substrate_Ligand_Interactions_Promote_the_Copper-Catalyzed_Hydroboration_of_Benzylidenecyclobutanes_and_Related_Compounds/12788390

2nd-Year Students Pass Qual Exams with Flying Colors

Congratulations to our Engle lab’s G2 students (Class of 2023), Taeho Kang, Zi-Qi Li, Luke Oxtoby, and Alena Vasquez, for passing their qual exams and advancing to candidacy. Despite the COVID-19 pandemic, lab shutdown, and challenging working circumstances, these four maintained a great attitude and mastered the art of giving a great scientific talk over zoom. Looking forward to seeing what this class has in store for the next three years!