Nickel-Catalyzed 1,2-Diarylation of Alkenyl Carboxylates – Now Accepted

For the past few years, our group has developed a toolkit of catalytic alkene 1,2-difunctionalization reactions using a substrate directivity strategy. Our early work employed bi- and tridentate auxiliaries for this purpose, which have proven to be highly effective and generally useful. Recently, in an exciting series of studies, we have found that simple functional groups are also capable of directing nickel-catalyzed 1,2-diarylation. In the present paper, as part of our ongoing collaboration with Bristol-Myers Squibb, Joe, Taeho, Van, Steve (from BMS Process Chemistry), Malkanthi, Tanner, and Kane describe the use of simple carboxylic acids as competent directing groups for alkene functionalization. After 1,2-diarylation, we can take advantage of classical and modern carboxylic acid functional group interconversions to access a myriad of 1,2,3-trifunctinoalized core structures. Nice work to all of the authors, and special congratulations to our former high school intern Kane, for publishing his first paper!

For a link to the paper, click here: https://onlinelibrary.wiley.com/doi/abs/10.1002/ange.201913062

BCP Hydroboration Paper – Now In Press

Our most recent collaboration with Pfizer and the Liu group at the University of Pittsburgh is now in press at ACS Catalysis. Methods to access small carbo- and heterocycles are of special importance in modern pre-clinical drug discovery and development owing the special properties of such motifs (conformationally restricted, low lipophilicity, etc.). In this project we developed a method to access substituted cyclopropyl boronic esters from benzylidene cyclopropanes (BCPs), which in turn can be made in a single step from benzaldehydes. While optimizing the reaction, we discovered an interesting effect of the ligand structure on pathway selectivity, and ultimately identified one ligand (BINAP) that could give almost exclusively ring-closed products, and another (dppe) that could give almost exclusively ring-opened products. To shed light on this phenomenon, our collaborators in the Liu group built a computational model that explains the observed reactivity trends. In terms of practical utility, we found the reaction to be compatible with a wide variety of azaheterocycles that are typically challenging to use in catalysis but are essential for medicinal chemists. Congratulation to all authors, particularly project co-leads Jose and Taeho.

For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/acscatal.9b03557

Directed Nickel-Catalyzed Oxidative Heck Coupling Enables by a Tailored H2 Acceptor

In collaboration with the Xue and Zhao groups from Nankai University, we describe a mechanistically unusual reaction to effect oxidative coupling of alkenes and arylboronic acids under nickel(0) catalysis, appearing today in a manuscript in Nature Communications. Previously, it has been shown that Ni(0) can oxidative add into alcohol O–H bonds to generate a catalytically active Ni(H)(OR), which is capable of mediating hydroarylation of alkenes. Based on careful tuning of the directing group, ligand, and hydrogen acceptor (an electron-poor alkene), we find that this pathway can be perturbed to instead give oxidative Heck products. The reaction is highly regioselective, even with challenging 1,2-disubstituted alkene substrates. Congrats to all of the authors.

For a link to the manuscript, click here: https://www.nature.com/articles/s41467-019-12949-1

Happy Halloween!

Our talented team of students carved some amazing pumpkins at the Engle Lab’s annual Halloween party! It was a spooky time spent playing video games and eating great food!

Congrats to the Class of 2019!

Huge congratulations to the Class of 2019! The Engle lab is incredibly proud of our recent, PhD, college, and high school graduates, who are moving on to incredible jobs, postdocs, and graduate/undergraduate programs around the world!

Graduate Students (PhD)

Dr. John Gurak, Jr.: Bristol-Myers Squibb Process Chemistry
Dr. Zhen Liu: Caltech (Postdoc, F. Arnold)

Undergrads/Visiting Undergrads

Omar Apolinar (CSUSM): Scripps Research (Ph.D. in Chemistry)
Tim Gallagher (Claremont McKenna): WWU Münster (Fulbright wtih F. Glorius)
Xiaohan Li (Nankai U): UCSB (Ph.D. in Chemistry)
Huiqi Ni (USTC): Scripps Research (Ph.D. in Chemistry)
Hanh Ngyuen (UCSD): Amgen Process Chemistry
Tianhua (Josh) Tang (Nankai U): U of Utah (Ph.D. in Chemistry)

High School Students

Nhi Ngyuen (San Marcos High Schooll): UC Berkeley
Matt Demer (San Diego Unified): UC Davis
Rohan Marsters (High Tech High International): AmeriCorps