Enantioselective alkylation of prochiral nucleophiles via a carbo-Wacker pathway

The third and final birthday preprint is now online in ChemRxiv. In this manuscript we report a previously unexplored mode of stereoinduction in Wacker type nucleopalladation—namely, desymmetrization of prochiral carbon-nucleophiles. The new method employs the dual action of palladium(II) to activate the alkene and a chiral phosphoric acid (CPA) to provide stereoinduction in the enantioselectivity-determining protodepalladation step. Congrats to the authors, Sri, Mingyu, Malkanthi, De-Wei, and Omar, as well as collaborators Jason Chen from the Automated Synthesis Facility at Scripps Research and Peng Liu from University of Pittsburg. Nice work! For a link to the manuscript, click here.

enantioselective

Ligand-Accelerated 1,2-Diarylation of Alkenes Directed by Simple Amides.

The second installment of the birthday preprint trilogy appears online today in ChemRxiv. This exciting contribution represents the culmination of a long and arduous research journey. By way of background, much of our lab’s work in alkene functionalization has strategically employed removable bi- and tridentate directing auxiliaries to control regioselectivity and stabilize key alkylmetal intermediates in catalysis. Achieving analogous reactivity with simple, monodentate functional groups has proven to be a significant challenge. In this manuscript, we report that electron-deficient olefin (EDO) ligands dramatically promote reactivity in directed 1,2-diarylation of simple alkenyl amides, offering a strong platform for future development of challenging alkene functionalization reactions of ubiquitous alkene starting materials. Congrats to the authors, Joe, Roman, Van, and Malkanthi, as well as our spectacular collaborators from BMS, Steve and Martin. Great work, team! For a link to the manuscript, click here.

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Umpolung Carboamination Preprint Online

The first of three birthday preprints is now online at ChemRxiv. The manuscript describes our adventures in using N–O electrophiles in nickel-catalyzed alkene functionalization, namely directed 1,2-carboamination of alkenyl carbonyl compounds. This work represents the first example of a three-component nickel-catalyzed reaction employing an N–O reagent. In terms of preparative utility, the transformation enables controlled formation of highly hindered C–N bonds, offering a potentially powerful platform for applications in medicinal chemistry. Congrats to the authors, Vincent (who performed the lion’s share of the work as his undergraduate project) and Joe (who was a great mentor throughout the process). Well done! For a link to the manuscript, click here.

carboamination

Protodepalladation Review Online

Several of the directed hydrofunctionalization reactions developed in our lab employ protodepalladation as one of the key steps. In this type of reaction, a C–Pd(II) bond is converted into a C–H bond and a free Pd(II) species under the action of a Brønsted acid. To shed light on this interesting and arguably underutilized elementary step, our former postdoc Miriam (now running an independent group at NUI Galway) has penned a Review article, which just appeared online today in Synthesis (click here). Congrats to Miriam on this contribution!

protodepalladation

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New Undergraduate Hanh Joins the Lab

Hanh (Hannah) Nguyen is the newest undergraduate member of the Engle Lab and is joining us from down the street at UCSD. She is working with Tanner (G2) on carbonylation chemistry and wasted no time setting up some high throughput screening in Scripps Automated Synthesis Facility in her first week. Welcome Hanh!