Directed alkyne oxyhalogenation pre-print online

Over the years, we’ve found that translating lessons learned in alkene difunctionalization to alkyne substrates is not as straightforwards as it seems, owing to unique reactivity profiles of alkyl- versus alkenylpalladium species. In our most recent collaboration with the Shi group from Zhejiang University and the Lan group from Zhengzhou University, we show that use of the 2-(pyridin-2-yl)isopropyl (PIP) amide directing group enables regio- and stereoselective oxyhalogenation of alkynes. The alkenyl halide products can be readily diversified via cross-coupling to access an array of tetrasubstituted alkene products. Congrats to Mingyu, Juntao, and Raul (Scripps Research); Tao (Zhengzhou U), Yi and Ye-Qiang (Zhejiang U) for an excellent study.

For a link to the ChemRxiv pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/62a263752e62696e467d88b5

Enantioselective three-component 1,2-diarylation and -arylalkenylation of alkenes – Pre-print now online

After >3 years of work, we are happy to share a ChemRxiv pre-print today describing a solution to a longstanding problem, stereoinduction in intermolecular arylnickel migratory insertion into alkenes, which we investigated in the context of interest in catalytic 1,2-dicarbofunctionalization. We found that a sterically bulky, achiral sulfonamide directing group works in synergy with a specially tuned hemilabile ligand (Bn-biOX) to promote high enantioselectivity with a variety of arylboron and aryl iodide coupling partners. Through use of experimental and computational techniques, we elucidated the mechanism of this three-component catalytic coupling, which involves an enantiodetermining migratory insertion step, which is distinct from previous radical-based methods. It was a great collaborative effort between our lab (Omar, Taeho, Pranali, Camille, and Joe), the Liu lab at the University of Pittsburgh (Turki), the Scripps Automated Synthesis Facility (Brittany, Quynh, Emily, and Jason), and Bristol Myers Squibb (Steve). Congrats to everyone!

For a link to the pre-print in ChemRxiv, click here: https://chemrxiv.org/engage/chemrxiv/article-details/62b40edc0bbbc1d407726e34

International Precious Metals Institute Recognizes Alena

Congrats to rising G5 student Alena Vasquez who was awarded a 2022 IPMI Student Award by the International Precious Metals Institute, which was presented this week at the IPMI Conference in Orlando, FL. Alena was recognized for her pioneering work in developing a novel approach to palladium-catalyzed alkene hydrofunctionalization by harnessing trans-Pd(Ar)(H) intermediates. Along with Alena’s recognition, during the program Keary was acknowledged with the 2022 IPMI Advisor Award. Congrats!

For more about the IPMI Student Awards program, click here: https://www.ipmi.org/page/AwardPrograms

Welcome Gabby and Canyon!

Gabby, a rising Senior at CSU San Marcos, arrives for her summer internship in the Engle lab as part of the SURF program. She is excited to explore the world of transition metal catalysis with her mentor Alena! Canyon, a rising high school Senior from Ridgway Secondary School in Colorado, kicks off his summer research internship in the Engle lab with his mentor Johny! He’s wasted no time in getting his gloves dirty! We’re excited to teach them all about organometallics!

Transient Directing Group Strategy Expanded to Enantioselective Hydroalkenylation and Hydroalkynylation – Pre-Print Now Online

In a pre-print appearing online today in ChemRxiv we introduce new families of coupling partners and alkenyl aldehyde substrates into the dual catalytic platform using a transient directing group (TDG) as an organocatalyst together with palladium as the redox catalyst. Specifically, we show that under specifically tailored conditions, alkenyl and alkynyl bromides can engage in enantioselective reductive Heck hydrofunctionalization with ortho-alkenylbenzaldehydes, dienyl aldehydes, and non-conjugated aldehydes, establishing a new C(sp3)–C stereocenter at the δ position with respect to the aldehyde. Strategic use of Design of Experiment (DoE) again facilitated rapid reaction optimization due to the mechanistic complexity of this dual catalytic process. Congrats to the project team, Amit, Johny, and Luke, Quynh, and Jason! Well done all!

For a link to the pre-print in ChemRxiv, see: https://chemrxiv.org/engage/chemrxiv/article-details/62a521fa2e6269ab067ff2d9

Tandem Isomerization/Carbonylation Enabled by Low-Valent Tungsten Redox Catalysis – Paper In Press with Nature Chemistry

The final version of our study on site-selective W(0)/W(II)-catalyzed alkene isomerization/carbonylation appears this week in Nature Chemistry. In this method, we take advantage of the ability of tungsten to undergo changes between six- and seven-coordinate geometries during the W(0)/W(II) redox couple. In conjunction with a conformationally flexible bidentate directing auxiliary, selective isomerization to (and subsequent functionalization at) classically disfavored positions can be achieved. Congrats to project lead Tanner and visiting undergrad Ziyang (Nick); our collaborators at the University of Pittsburgh, Will, Yu, and Peng; our resident analytical wizard Jason from the Scripps ASF, and crystallographer extraordinaire Milan from UCSD.

For a link to the final version of the paper in Nature Chemistry, click here: https://www.nature.com/articles/s41557-022-00951-y

As a reminder, a pre-print of the paper was deposited in ChemRxiv back in April 2021: https://chemrxiv.org/engage/chemrxiv/article-details/60c757089abda23076f8e61a

(CAAC)Copper-catalyzed three-component carboboration of alkynes – Final version published in ACS Catalysis

The final version of our collaborative study with the Grotjahn lab at SDSU and the Bertrand lab at UCSD has been accepted for publication in ACS Catalysis and appears online this week. We find that under (CAAC)Cu catalysis (CAAC = cyclic (alkyl)(amino)carbene), three-component carboboration of terminal alkynes takes place to furnish branched alkenyl boron compounds with high levels of regioselectivity. Building on our prior findings, we show the CAAC ligands can override substrate control factors and dictate regioselectivity of borylcupration with various carbon electrophiles, including alkyl iodides and allyl alcohol derivatives. Congrats to the entire project team: Yang, Nana, Skyler, Mingyu, and Aaron from our lab; Sima and Doug from SDSU, and Rudy and Guy from UCSD.

For a link to the paper in ACS Catalysis, see: https://pubs.acs.org/doi/full/10.1021/acscatal.2c00614

As a reminder, a pre-print of the paper was deposited in ChemRxiv in February: https://chemrxiv.org/engage/chemrxiv/article-details/61f8b9da360c842812b1d6c2

Luke successfully defends his thesis

Congrats to Luke Oxtoby, who successfully defended his thesis this week, becoming the eighth Ph.D. graduate from the Engle lab. Luke’s research addressed an important problem by establishing the use of (co-catalytic) transient directing groups in palladium-catalyzed alkene functionalization. Next month, Luke will begin a position as a process chemist at Sterling Pharma Solutions in Germantown, Wisconsin. Congratulations Dr. Oxtoby!