Congrats to Van Tran, Ph.D., who successfully defended her thesis earlier today, become the fifth Ph.D. graduate from the group (and second to defend online). Van has made pioneering contributions in diverse areas, including developing a new approach to C(sp3)–C and C(sp3)–heteroatom bond cleavage under palladium catalysis, demonstrating the power of nickel for catalyzing conjunctive cross-coupling reactions with alkenes, and inventing a series of a new low-valent nickel pre-catalysts. Congrats on all of your success, Van! Best of luck in your next adventure as as a process chemist at Gilead.
In collaboration with the labs of Profs. Guy Bertrand (UC San Diego) and Doug Grotjahn (San Diego State), we have discovered that that cyclic (amino)(alkyl)carbene (CAAC) ligands, which have been extensively developed in the Bertrand lab over the past several years, when coordinated with copper yield catalysts with unique selectivity in classical copper–boryl alkyne addition reactions. Specifically, we developed highly general Markovnikov-selective protoboration and -silylation protocol of terminal alkynes that is agnostic to the electronic properties of both the alkyne substrate and the boryl/silyl nucleophile. This represents first report from a powerful new collaboration between three groups across three institutions in San Diego. Congrats to the entire authorship team: Yang, Aaron, and Keary (Scripps); Sima (SDSU/UCSD); Doug (SDSU); and Glen, Rudy, and Guy (UCSD).
For a link to the pre-print, click here: https://chemrxiv.org/articles/preprint/Cyclic_Alkyl_Amino_Carbene_Ligands_Enable_Cu-Catalyzed_Markovnikov_Protoboration_and_Protosilylation_of_Terminal_Alkynes_A_Versatile_Portal_to_Functionalized_Alkenes/14368607
Turning to a new part of the periodic table this week, we describe our first foray into the use of W(0)/W(II) catalysis for migratory alkene functionalization. By taking advantage of the ability of tungsten to toggle between six- and seven-coordinate geometries upon oxidative addition, we are able to isomerize an alkene to a classically disfavored position through a metallacycle contraction process, where it is primed for carbonylative functionalization. Bravo to Tanner and Zi-Yang (Nick) from our group; our computational collaborators Will and Yu from the Liu group at the University of Pittsburgh; and X-ray crystallographer extraordinaire Milan from UCSD.
For a link to the ChemRxiv pre-print, click here: https://chemrxiv.org/articles/preprint/Low-Valent_Tungsten_Redox_Catalysis_Enables_Controlled_Isomerization_and_Carbonylative_Functionalization_of_Alkenes/14362238
After wrapping up his Ph.D. earlier this month, Dr. Mingyu Liu departs San Diego to begin his postdoc with Prof. Tim Swager at MIT, where he will take on new challenges in organic materials, chemical sensing, and membrane design. We sent Mingyu off in style with a socially distanced gathering at a local park, and Hermione was happy to be able to reunite with one of her best friends. Best of luck on your new adventure Mingyu!
The E/Z isomerization of internal alkenes under palladium catalysis is a fundamental reaction that has been known for >50 years. The mechanism remains poorly understood, particularly in the case of non-conjugated alkene substates and palladium(II) carboxylate catalysts (e.g., Pd(OAc)2). To clarify this mechanistic puzzle, Rei (a joint student with the Blackmond lab), Malkanthi, Mingyu, and Nhi (a former high school intern), combined insights from reaction kinetics, in situ NMR, isotope labeling experiments, and computation. The data ruled out several other mechanistic hypotheses proposed in the literature and pointed to a monometallic nucleopalladation pathway. Check out the accepted paper in ACS Catalysis. Congrats to the whole team!
For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/acscatal.1c00783
The work first appeared back in November. Check out the pre-print 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
In a breakthrough report that pushes the frontier of practical utility in nickel-catalyzed alkene functionalization, Taeho, Nana, and collaborators at Bristol Myers Squibb have discovered a method to carry out selective 1,2-carboamination of free alkenyl alcohols with aryl/alkenylboronic acids and nitrogen electrophiles. Key to the success of this transformations is the careful design of the activating group for the N–O electrophile, which promotes the desired three-component process and suppresses side reactions. The reaction enables rapid synthesis of alkyl-amine-containing bioactive small molecules and late-stage modification of natural products. Bravo on this one, folks!
For a link to pre-print, click here: https://chemrxiv.org/articles/preprint/Nickel-Catalyzed_1_2-Carboamination_of_Alkenyl_Alcohols/14195426
The final, peer-reviewed version of our study in collaboration with the process chemistry team at Boehringer-Ingelheim on alkyne cross-coupling to access 1,3-enynes appears this week in J. Am. Chem. Soc. The high regio- and stereoselectivity of this reaction stems from the use of a hindered P,N-ligand previously developed at BI, which Mingyu and the BI team identified during his summer internship in Ridgefield, CT. Hats off to the entire project team: Mingyu, Tianhua (Josh), Omar, and Rei from Scripps Research; and Carl, Bo, Dan, Olga, Chris, and Jinhua (Jeff) from BI. Not a bad way to follow up your successful thesis defense from last week, Dr. Liu!
For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/jacs.0c12565
This work first appeared as a pre-print back in October: https://chemrxiv.org/articles/preprint/Atom-Economical_Cross-Coupling_of_Internal_and_Terminal_Alkynes_to_Access_1_3-Enynes/13083419
Mingyu becomes the first member of the Engle lab to defend his these virtually, passing with flying colors! Congratulations Dr. Liu! 🎉 🎊 🎓 🥂 Though our normal tradition is to celebrate in the Beckman atrium with champagne, this time a virtual toast had to do. Special should out to Prof. Vy Dong from UC Irvine for serving as external examiner. Congrats on all of your accomplishments, and thanks for your myriad contributions to the group over the past 5 years, Mingyu!
The latest work from Team Nickel and the Bristol Myers Squibb collaboration is now online as a pre-print in ChemRxiv. The paper describes extension of carbonyl-directed nickel-catalyzed alkene 1,2-diarylation to alkenyl ketone substrates, which are challenging owing to the weaker Lewis basicity of the ketone lone pair as well as the increased susceptibility to unwanted isomerization. We also conducted a comparative study of the different reaction conditions that have been published for this family of transformations in order to identify key similarities and differences. Hats off the fantastic team led by visiting student Roman (now a Ph.D. student with Frank Glorius at WWU Münster) and second-year grad student Omar. Also contributing were Joe, Malkanthi, Zi-Qi, and Van, as well as Steve from BMS Process. Awesome stuff, team!
For a link to the pre-print, click here: https://chemrxiv.org/articles/preprint/Nickel-Catalyzed_1_2-Diarylation_of_Alkenyl_Ketones_A_Comparative_Study_of_Carbonyl-Directed_Reaction_Systems/14150174
We did something a little different from chemistry… With the help of the talented middle schoolers at Barrio Logan College Institute, we built ROBOTS! It was so fun to work with these students and ensure all have access to science, even in a pandemic. We provided curated science kits to each student and led small groups over zoom. Thanks BLCI for spending your workshop night with us!