Redox-Paired Alkene Difunctionalization Paper – Now Online in JACS

The final version of our redox-paired alkene difunctionalization paper appears online today in J. Am. Chem. Soc. In this study, we outline a novel redox paradigm for alkene difunctionalization in which an oxidative difunctionalization process is coupled to a reductive difunctionalization process without any additional terminal oxidants or reductants. The unique mechanism of this reaction involves a PdII/PdIV/PdII/PdIV catalytic cycle, as elucidated through experiment and computations. Congrats to the entire project team, and thanks to our collaborators Prof. Ken Houk from UCLA and Prof. Peng Liu from the University of Pittsburgh.

For a link to the paper in J. Am. Chem. Soc., click here:

As a reminder, a pre-print of this work was deposited at the end of 2022:

Latest Pre-Print Describes a Unique Sigma-Bond Annulation Process

The newest method to emerge from the group builds on our interest in developing catalytic strong activation reactions via β-X elimination. We have previously demonstrated that PdII(π-olefin) intermediates generated in this manner can be engaged in nucleopalladation / protodepalladation sequences to effect functional group metathesis of an outgoing C(sp3)–X (X = C, N, O, F, etc.) for a new C(sp3)–C or C(sp3)–N. In our newest pre-print, Hui-Qi, Jing-Chen, and collaborators from Pfizer extend the reach of this approach, demonstrating annulation of transiently generated PdII(π-olefin) intermediates via β-X elimination. In terms of synthetic planning, the reaction allows conversion of simply aliphatic alcohol, amine, and thiol compounds into valuable heterocyclic products. Especially exciting applications are in amino acid upgrading and heterocycle transfiguration. Congrats to the team!

For a link to the pre-print in ChemRxiv, click here:

New visiting student Xiaowei joins the lab!

We have a new undergraduate intern Xiaowei Chen visiting from Rice University. Xiaowei previously worked in the group of Prof. Julian West on ligand-to-metal charge transfer photocatalysis. She joins the lab as an AYRIU scholar and will be working with Anne to explore nickel catalysis. Welcome to the group, Xiaowei!

Asymmetric Reductive Heck Hydroalkenylation and Hydroalkynylation – Now In Press in Angewandte Chemie

Appearing online today in Angewandte Chemie International Edition, we describe the most recent findings from our program in dual catalytic enantioselective alkene functionalization via a transient directing group strategy. Specifically, we developed a method for hydroalkenylation and hydroalkynylation of alkenyl aldehydes that is enabled by reversible condensation of tert-leucine. Together with the lab of Prof. Peng Liu at the University of Pittsburgh, we applied density functional theory to elucidate the structural features of the amino acid co-catalyst that lead to high catalytic efficiency and high enantioselectivity. Congrats to the entire project team!

For a link to the paper, click here:

As a reminder, a pre-print of this work in summer 2022:

Electrochemical Synthesis of Ni(0) – Pre-Print Now Online

Traditional syntheses of low-valent nickel complexes, such as the archetypal Ni(0) species, Ni(COD)2, require the use stoichiometric quantities of pyrophoric organometallic reductants, such as DIBAL–H, which pose operational and safety complications. In our most recent study, we report a convenient, green, and scalable electroreductive route to Ni(COD)2 as well as other useful low-valent nickel species, including the air-stable Ni(0) precatalyst, Ni(COD)(DQ), that avoids stoichiometric reductants altogether. The method can conveniently performed using the standardized IKA ElectraSyn 2.0 or alternatively in a recirculating flow setup. Congrats to the entire collaborative team: Camille (Engle lab, Scripps Research & Vantourout lab, University of Lyon; Yilin (Engle lab, Scripps Research), Tamara and Gabriele (Baran lab, Scripps Research); Greg and Steve (Bristol Myers Squibb); and Xiangyu (Lin lab, Cornell).

For a link to the pre-print in ChemRxiv, click here:

New Palladium-Catalyzed Cyclopropanation Method – Pre-Print Now Online

In our latest research publication, Hui-Qi, Por, and collaborators from the Piercey lab at Purdue University and Pfizer, Inc. report a new method for olefin cyclopropanation under Pd(II)/Pd(IV) catalysis. Compared to previous methods, the reaction can directly employ C–H pronucleophiles, such as 1,3-diketones, without the need for activation as a diazo or other carbenoid progenitor. Additionally, with internal alkenes, the reaction provides unusual anti-selective addition due to the underlying directed carbopalladation mechanism. Congrats to the entire team on this collaborative effort.

For a link to the pre-print in ChemRxiv, click here:

Ziqi and Taeho successfully defended their PhDs!

Congrats to the Engle Lab’s newest doctors Ziqi Li and Taeho Kang!

Ziqi’s Ph.D. focused on the development of a series of regio- and enantioselective hydroarylation reactions. Additionally, she pioneered the development of a collection of reagents and ligand-enabled carbosulfenylation reactions.  Ziqi will soon follow in the footsteps of Keary and other Engle Lab alumni starting her postdoc at Caltech. There, she will pursue research in the lab of Prof. Frances Arnold.

Taeho’s Ph.D. work spanned across various research fields in nickel, copper, and palladium chemistry. In particular, his research focused on nickel-catalyzed 1,2-difunctionalization reactions directed by native functional groups such as free alcohols, amines, and carboxylic acids. Taeho will start a position as a joint postdoc in the labs of Prof. Geoffrey Coates and Prof. Yadong Wang at Cornell University. 

Earth-Abundant Metal Catalysis Review – Now Online in Org. Process Res. Dev.

Together with Prof. Paul Chirik at Princeton and Drs. Eric Simmons and Steve Wisniewski from Bristol Myers Squibb, Keary authored a Perspective in Org. Process Res. Dev. on the importance of academia–industry collaboration in advancing the state of the art in base metal catalysis. The article outlines the various factors that motivate research in base metal catalysis within the pharmaceutical industry and discusses how these challenges can spur innovations reaction, catalyst, and ligand development, such as in the case of our collaborative work on bench-stable Ni(0) pre-catalysts.

For a link to the article, click here:

New Computational Collaboration – Online Today in J. Am. Chem. Soc.

Today we are pleased to announce publication of a collaborative study with Prof. Yu Lan’s group at Zhengzhou University elucidating the mechanism of nickel-catalyzed conjunctive cross-coupling reactions of alkenes, aryl iodides, and organozinc reagents, which reveals a previously under-appreciated role of the organozinc reagent as a Z-type ligand that facilitates reductive elimination. This revised mechanistic model explains how this type of conjunctive cross-coupling can proceed under such mild conditions without specialized ligand, despite involving a typically challenging C(sp3)–C(sp3) reductive elimination event. Congrats to the entire project team!

For a link to the paper in J. Am. Chem. Soc., click here:

Kinetic Alkene Isomerization via Tungsten Catalysis – Pre-Print Online

In our newest pre-print posted online today, we continue our explorations of reactions enabled by the W0/WII redox manifold and report the discovery of a mild method for selectively isomerizing γ,δ-unsaturated amides into their β,γ-unsaturated counterparts without “over-isomerization” into conjugation. By controlling the ligand environment around the metal center, stereoselectivity can be controlled to favor either the (Z)- or the (E)-isomer. Though organometallic synthesis, we were able to shed light on some details of the reaction mechanism, highlighted by synthesis of a stable WII(π-Allyl)(OAc) complex that can converted in situ to a WII(π-allyl)(H) species, thereby intercepting a proposed intermediate in the catalytic cycle. Congrats to Tanner, Camile, and Raul!

For a link to the pre-print in ChemRxiv, click here: