On a whirlwind of a day, Andrew successfully defended his thesis over Zoom, dropped by campus for his champagne toast, and then hit the road for the transcontinental drive back to his hometown of Philadelphia. Starting next week, Andrew will begin his career as a consultant at Boston Consulting Group. We’re so grateful for your many contributions to the lab and proud of your accomplishments, Andrew. Good luck on this next adventure!
The final version of our manuscript describing the palladium-catlayzed enantioselective 1,2-arylfluorination of alkenes using a transient directing group (TDG) strategy is online today in J. Am. Chem. Soc. In the study we apply Design of Experiments (DoE) to optimize this challenging three-component coupling of alkenes, arylboronic acids, and [F+] electrophiles, which helps to account for the complex interactions between variables in this system. We further elucidate the reaction mechanism using reaction progress kinetic analysis (RPKA). In terms of preparative applications, the method proceeds in high ee and d.r., allowing formation of full substituted C(sp3)–Ar and C(sp3)–F centers. The transformation is the first time that 1,2-difunctionalization has been achieved using a TDG approach and as such represents an important milestone for our lab and for the field. Hats off to Zhonglin, Luke, Mingyu, Zi-Qi, Van, and Yang!
For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/jacs.1c03178
The work first appeared on ChemRxiv back in January. Check out the pre-print here: https://chemrxiv.org/articles/preprint/A_Transient_Directing_Group_Strategy_Enables_Enantioselective_Multicomponent_Organofluorine_Synthesis/13537283
With the lab fully vaccinated we were very happy to be able to give Dr. Van Tran a proper send off, including a Korean BBQ trip and a champagne toast. Best of luck in your next adventure as a process chemist at Gilead, Van! We miss you already.
In a pre-print appearing today on ChemRxiv, we provide a full account of our efforts to develop substrate-directed Markovnikov-selective hydroarylation/alkenylation of terminal alkenes with organoboronic acids under nickel(0) catalysis. In the paper, we tackle three important substrate classes, alkenyl sulfonamides, ketones, and amides, and discuss the systematic tuning of reaction conditions that is required to provide high yields in each case, reflecting subtle yet significant differences in coordination chemistry among the directing groups involved. Through a combination of isotope labeling, reaction kinetics, and density functional theory (DFT) calculations, we identified transmetalation as the turnover-limiting and selectivity-controlling step. Congrats to Zi-Qi, Omar, and Ruohan on this herculean effort.
For a link to the ChemRxiv pre-print, click here: https://chemrxiv.org/articles/preprint/Directed_Markovnikov_Hydroarylation_and_Hydroalkenylation_of_Alkenes_Under_Nickel_Catalysis/14639778
It has been a long time since we’ve been able to enjoy a group outing! This weekend, we did just that. We headed up to the Carlsbad Strawberry Company to get our fill of sunshine and fresh strawberries.
Congrats to G1 student Camille Rubel, who was awarded first place for her poster talk, “Stable Nickel Toolkit,” describing our lab’s work to develop convenient and bench-stable low-valent nickel complexes for use in catalysis to a diverse audience from the local San Diego community. The Scripps Research Community Symposium, which was held on Saturday, May 1st, invites the community — K-12 teachers, high school students, families with children, community college students, and more — to meet our scientists, hear from our graduate students, and interact with our science in fun and engaging ways.
https://education.scripps.edu/k-12-outreach/ca-outreach/scripps-research-symposium/
As part of the Organometallic Solutions to Challenges in Cross-Coupling special issue in Organometallics, our lab reports an usual rearrangement process triggered by addition of Pd(TFA)2 to alkenes containing a benzothiazole thioether (BT(S)) directing group. The transformations furnishes a structurally family of previously unknown tetrahydrothiophene-functionalized N,S-heterocyclic carbene palladium(II) complexes that are catalytically active in various C–C coupling reactions. Congrats to grad student Andrew, former high school intern Matt, as well as our treasured X-ray crystallography collaborators Milan and Arnie from UCSD.
For a link to the accepted manuscript, click here: https://pubs.acs.org/doi/10.1021/acs.organomet.1c00041
The work first appeared on ChemRxiv back in January. Check out the pre-print here: https://chemrxiv.org/articles/preprint/Ligand_Rearrangement_Leads_to_Tetrahydrothiophene-Functionalized_N_S-Heterocyclic_Carbene_Palladium_II_Complexes/13633301
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
Molecular Complexity through Catalysis 