Annulating Ambiphile Mapping Paper – Now In Press

The final peer-reviewed version of our collaborative paper with Pfizer mapping reactivity trends in the Pd(II)/Pd(IV) catalytic annulation of alkenyl amides appears online today in Angewandte Chemie International Edition. In the paper, we describe protocols for synthesizing a diverse array 5-, 6-, and 7-membered carbon/heterocycles of ambiphilic organohalides and show how changing the structure of the nucleophile and electrophile influences reactivity. Congrats to Hui-Qi, Philliipaa, and Pranali from the Scripps Research and Shouliang, Fen, Neal, Joyann, Michelle, and Indra from Pfizer Oncology Medicinal Chemistry for another great collaboration!

Click here for a link to the article in Angewandte Chemie International Edition: https://onlinelibrary.wiley.com/doi/10.1002/anie.202114346

As a reminder, a pre-print of the paper first appeared in ChemRxiv back in October: https://chemrxiv.org/engage/chemrxiv/article-details/6172bcd10c0480fd773f44a4

2021 ENGLE LAB HOLIDAY PARTY

It’s that time of year again🥳! This year, we were able to hold our traditional Engle group holiday party in-person. We shared delicious food, exchanged gifts through a white elephant game (fun!), and enjoyed the nice chilly December weather of San Diego. Tints of red and green color piqued our holiday excitement. From our lab to yours, we wish everyone a joyous holiday season and a most prosperous and healthy New Year!

Latest Pre-Print Unveils Free-Amine-Directed Carboamination of Alkenes

Diamines are a family of valuable compounds with diverse functions. In many cases, they are not trivial to prepare, particularly when the two nitrogen atoms contain different substituents. In a new study that appears this week on ChemRxiv, our lab in collaboration with scientists from Bristol Myers Squibb (BMS) developed a reaction where a free amine can direct regioselective 1,2-carboamination of an unactivated alkene, representing the first time that an unprotected amine has been used to direct three-component alkene difunctionalization. Key to the successful development of this method was judicious tuning of the leaving group on the N–O electrophile such that it possess well-matched reactivity for the corresponding alkyl nickelacycle intermediate. Congrats to Taeo, José, and Zi-Qi, and thanks to our collaborators from BMS, Klement and Peter, for a great collaboration.

For a link to the pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/61b14f9a7ada95b46a6e62ee

Three-Component syn-Carbosulfenylation of Alkene Through Reagent Design – Pre-Print Now Online

We’ve recently started exploring foreign parts of the periodic table, and turned our attention to sulfur. Organosulfur compounds are useful in various settings, and three-component couplings represent a fast, efficient, and modular way to synthesize such compounds. Classical carbosulfenylation (the addition of a carbon and a sulfur(II) group across an alkene) proceed via a reactive thiiranium intermediate that is then opened in an SN2 fashion, with limitations arising from the electrophilic nature of the sulfenyl transfer groups typically employed. We envisioned an alternative organometallic approach relying on three-component catalytic coupling of organoboron nucleophiles, sulfenyl electrophiles, and unactivated alkenes. This novel transformation was enabled by the discovery of a new family of N–S electrophiles that possess perfectly balanced reactivity, which could be understood through computational studies. Hats off to the team, graduate student co-authors Zi-Qi and Taeho, and former SURF intern Yilin, who has since returned to UCSB to finish her senior year of college.

For a link to the pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/61a7d3e0f35d4ca9794de71d

New book chapter reviews difunctionalization of unsaturated organics

In a new book chapter that appears online this week, Luke, Alena, Taeho, and Zi-Qi review the broad field of metal-mediated difunctionalization of unsaturated organic compounds (i.e., those containing a carbon–carbon π-bond). The chapter is part of the forthcoming book Comprehensive Organometallic Chemistry IV edited by Prof. Ian Tonks.

Click here for a link to the article: https://www.sciencedirect.com/science/article/pii/B9780128202067000962

Keary is selected for 2021 ChemComm Emerging Investigator Lectureship

This week Keary was selected together with Prof. Thomas Bennett (Cambridge) to receive the 2021 ChemComm Emerging Investigator Lectureship. The award recognizes scientists in the early stages of their independent academic careers who have made exceptional contributions to the field of chemistry. As part of the award, in 2022 Keary will give a series of lectures in both in-person and virtual format . Congrats to Keary and the entire Engle lab past and present for contributing the science being recognized!

For more information, click here: https://blogs.rsc.org/cc/2020/11/16/chemcomm-emerging-investigator-lectureship-2021-nominations-now-open/

WELCOME NEW STUDENTS AND POSTDOC

We are excited to have three new members in the group. They are all coming from different stage of their education and adding more diversity to the lab. First, we are delighted to have our new postdoc Skyler. Skyler joined our group right after finishing his Ph. D. in organic chemistry with prof. Sarah Reisman at Caltech, and he has the freshest Ph. D. Diploma in the group. Palladium team is welcoming their new undergraduate crew Jeremy. Finally, we are happy to welcome our new highschool student Anna to the team Nickel.

Ready for your Trick-or-treating bag – Two review articles now in press

Trick, treat, or review? Just in time for Halloween 🎃 , we close out the month of October with two new review articles appearing online from the group. In the first article, which is in press in Tetrahedron, Mingyu and Juntao survey different strategies from the recent literature for generation and functionalization of C(alkenyl)–Pd intermediates in catalysis. These types of reactions constitute an increasingly versatile toolkit for accessing highly substituted alkenes in organic synthesis. This article is part of a special collection celebrating our colleague Prof. Dale Boger’s 2020 Tetrahedron Prize.

Click here for a link to the article in Tetrahedron: https://www.sciencedirect.com/science/article/pii/S0040402021007985

The second review article appears in Chemical Review and offers a comprehensive overview of the area of metal-catalyzed, coordination-assisted C(sp3)–H activation reactions up to March 2020, when not-so-coincidentally the COVID-19 pandemic lockdown first started. It’s been a long journey since—over 100 pages and over 500 references—but we’re pleased to be able to share the fruits of our labor with the community. This review was written by Andrew and Camille in collaboration with Bin from Prof. Bing-Feng Shi’s group at Zhejiang University. Congrats to all of the authors of both articles!

Click here for a link to the article in Chemical Reviews: https://pubs.acs.org/doi/10.1021/acs.chemrev.1c00519https://pubs.acs.org/doi/10.1021/acs.chemrev.1c00519

Ambiphile Mapping in the Palladium(II/IV) anti-Annulation of alkenes – Pre-print Online

We are happy to share our most recent work with collaborators from Pfizer Oncology Medicinal Chemistry, appearing today as a pre-print in ChemRxiv, where we describe a versatile approach to carbo- and heterocycle synthesis from unactivated alkenes and ambiphilic organohalides. Under Pd(II)/Pd(IV) catalysis, the Wacker-type mechanism leads to net anti addition, which is distinct from classical Larock-type couplings. In this study, we systematically map structure–reactivity trends of the ambiphile, leading to unprecedented breath of reaction partners that can be employed. Congrats to everyone at Scripps (Hui-Qi, Phillippa, and Pranali), and Pfizer (Shouliang, Fen, Neal, Joyann, Michelle, and Indra) for a great team effort!

For a link to the pre-print, click here: https://chemrxiv.org/engage/chemrxiv/article-details/6172bcd10c0480fd773f44a4