Congratulations to Zhen, who has been selected as a Finalist for the 2019 Reaxys PhD Prize! Zhen was acknowledged for his 2016 J. Am. Chem. Soc. publication, “β,γ-Vicinal Dicarbofunctionalization of Alkenyl Carbonyl Compounds via Directed Nucleopalladation.” The 45 Finalists, selected from 360 nominations, are invited to a the Reaxys PhD Prize Symposium, which takes place in Amsterdam on Oct 3 and 4, 2019.
For the past four years, a major focus of our research has been developing substrate-directed Heck- and Wacker-type alkene hydrofunctionalization and 1,2-difunctionalization reactions. In particular, we’ve previously found that alkenyl amides containing removable bi- and tridentate directing groups are highly effective substrates, owing to the ability of the directing group to facilitate regioselective addition of the first reaction partner and then subsequently form a stabilized palladacycle that can be intercepted with a proton, nucleophile, or electrophile. Based on these results, we became interested in identifying news weakly coordinating directing groups that can enable regioselective addition of a nucleophile and then allow a site-selective β-H elimination.
In a manuscript appearing online today in ACS Catalysis, we describe the discovery and development of the benzothiazole thioether, (BT)S, directing group for oxidative Heck and C–H activation reactions (click here). In a colossal 15-page-long (!!!) paper covering reaction development, mechanistic studies, and applications in total synthesis, Andrew, Kin, and Malkanthi, demonstrate the unique coordination properties of (BT)S and showcase its synthetic versatility . Congrats to the three Engle lab authors listed above, and huge thanks to our tireless collaborator Jason from the Scripps Research Automated Synthesis Facility for guidance on high-throughput experimentation, design of experiments, and kinetics! In case anyone missed it, a pre-print of this work was published on ChemRxiv back in early April (click here).
Two senior undergraduates from Tsinghua University, Houxian and Zhongqian, started their internships with Zhen and Yang, respectively. They’re already doing great work using the glove box and running reactions. Summer time in the Engle lab is going to be a blast.
Appearing online today in ChemRxiv is a pre-print describing a collaboration with Pfizer’s Oncology Medicinal Chemistry group and with Prof. Peng Liu’s computational organic chemistry lab. With Pfizer, we continue to work together develop new catalytic methods to access strained carbo- and heterocycles. With the Liu group, we team up to study mechanism and ligand effects in catalytic alkene addition chemistry. In the latest story to emerge from these efforts, we report that benzylidene cyclopropanes (BCPs), which can be prepared from benzaldehydes in a single step by Wittig olefination, can undergo pathway-selective hydroboration under the action of a copper-bisphosphine catalyst. Depending on the structure of the phosphine ligand, two divergent product outcomes can be obtained, with the cyclopropane opening via β-carbon elimination or remaining intact. Though Lewis basic heterocycles often inhibit catalysis with late transition metals, this is not the case here, as the tolerance for a wide variety of pyridines, quinolines, etc., is generally excellent. This is makes it well-suited for use in pre-clinical drug discovery and development. Thanks to our collaborators at Pfizer for helping us develop and field-test this method, and to our collaborators in the Liu lab for invaluable insight regarding the role of the ligand in dictating pathway selectivity. For a link to the pre-print, click here.)
High school intern, Kane, begins working with mentor Taeho! He’s wasted no time in getting his gloves dirty and running columns and prep TLCs. We’re excited to teach him all about organometallics!
Our review on palladium(0)-catalyzed reductive Heck coupling of alkenes appears online today in the new Cell Press journal, Trends in Chemistry. Reductive Heck hydroarylation is a rapidly technology that has already found utility in complex molecule synthesis and offers exciting prospects in pharmaceutical development. In 1990 Sandro Cacchi wrote a comprehensive review on this topic (click here), but much has happened in the last 30 years, and as our group has become increasingly interested in this topic, we thought it was time to summarize the state of play to stimulate further interest in this important area. Congrats to Luke and John, and special thanks to Steve and Martin from Bristol-Myers Squibb for their involvement throughout the process, and especially for offering insight into opportunities of reductive Heck coupling in the pharmaceutical industry. For a link to the review article click here.
(not pictured: John)
Congrats to UC LEADS Scholar Hanh Nguyen has completed her BS in Molecular Synthesis at UCSD and is now off to Thousand Oaks, CA, where she will work as a Process Chemist at Amgen, prior to applying to graduate school to pursue her Ph.D. Hanh is a first-generation college graduate, who previously studied at Santa Ana College prior to transferring to UCSD. In addition to working in the Engle lab under the mentorship of Tanner, Hanh also previously carried out research with Prof. T. Don Tilley at UC Berkeley and Prof. Emmanuel Theodorakis at UCSD. Thanks for your hard work during the past year, and best of luck in your next adventure, Hanh!