1,1-Diboration paper accepted in Org. Lett.

Yang and Zhong-Qian’s paper describing the copper-catalyzed conversion of the terminal alkynes to stereodefined 1,1-diborylalkenes has been accepted in Org. Lett. and appears in final form online today. Mechanistically, the reaction involves a tandem sequence of dehydrogenative C(sp)–H borylation with HBdan followed by hydroboration with HBpin with copper playing a dual role as catalyst for both steps. Preparatively, the method enables one-step access to valuable alkyl- and aryl-substituted 1,1-diborylalkenes, which can then be further diversified through sequential cross-coupling. Congrats to postdoc Yang and undergrad co-author Zhong-Qian!

For a link to the paper, click here: https://pubs.acs.org/doi/full/10.1021/acs.orglett.0c01901

This work was first described in April in a pre-print that was deposited on ChemRxiv: https://chemrxiv.org/articles/Synthesis_of_Stereodefined_1_1-Diborylalkenes_via_Copper-Catalyzed_Diboration_of_Terminal_Alkynes/12133404

Alkene [3+2]-(Hetero)annulation Pre-print Online

We kick off the post-Father’s-Day workweek with a new pre-print on ChemRxiv describing the application of our lab’s strategy for directed nucleopalladation of alkenes to the synthesis of carbo- and heterocycles via [3+2]-(hetero)annulation. Though the mechanistic details are rather different, this reaction takes inspiration from the venerable Larock indole synthesis, enabling access to diverse indolines, 2,3-dihydrobenzofurans, and indanes from readily available starting materials. Working in close collaboration with Pfizer’s Oncology Medicinal Chemistry team and the Liu group at the University of Pittsburgh, we were able to examine a broad swath of a heterocyclic structural space relevant to drug discovery and to flesh out the reaction mechanism. Congrats to this fantastic team of coworkers: Hui-Qi, Pranali, and Hou-Xiang from our lab; Joyann, Shouliang, Michelle and Indra from Pfizer; and Ilia and Peng from Pitt. Special shout-out to our two undergraduate co-authors Pranali and Hou-Xiang!

For a link to the pre-print, click here: https://chemrxiv.org/articles/Anti-Selective_3_2_Hetero_annulation_of_Non-Conjugated_Alkenes_via_Directed_Nucleopalladation/12510038

The Engle Lab turns 5

Today we celebrate our 5 year Lab-iversary! Rather than our normal tradition of eating lunch and cake together, this year we celebrated social-distancing-style, with cupcakes and online games. Our first five years as a lab at Scripps have gone quickly, with plenty of highs, lows, and interesting discoveries along the way. Here’s to the next 5!

Alpha-Hydroarylation Paper Accepted in J. Am. Chem. Soc.

Our collaborative paper with Bristol-Myers Squibb on α-selective hydroarylation of acrylates and acrylamides has been accepted for publication in J. Am. Chem. Soc. Detailed mechanistic studies revealed that the reaction proceeds via a [Pd(Ar)(H)] intermediate, which undergoes migratory insertion to deliver the hydride group to the β-position, generating a [Pd(Ar)(enolate)]; C–C reductive elimination then furnishes the final product. The reaction is notable for its operational simplicity, mild reaction conditions, and widely available starting materials. Congrats to Engle lab authors Alena and John (now at BMS Process), as well as BMS collaborators Candice (Process Chemistry) and Emily (Discovery Chemistry) As a reminder, this manuscript first appeared as a ChemRxiv pre-print (click here).

For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/jacs.0c03040

Congrats to the Class of 2020!

Huge congratulations to the Class of 2020! The Engle lab is incredibly proud of our recent, PhD, visiting PhD, and college students who are moving on to incredible jobs, postdocs, and graduate programs around the world!

Graduate Students (PhD)

Dr. Joseph Derosa: Caltech (Postdoc, J. Peters)

Visiting Graduate Students (PhD)

Dr. Xin Wang (Nankai University Medical School)

Undergrads/Visiting Undergrads

Jiahao Chen (Fudan U): Fudan University (Ph.D. in Chemistry)
Ryan Helsel (UCSD): UCSB (M.A. in Chemistry / Teacher Education)
Hou-Xiang Lu (Tsinghua U): Tsinghua University (Ph.D. in Chemistry)
Tian-Zhang Qiao (Nankai U): Cornell U (Ph.D. in Chemistry)
Zi-Yang (Nick) Qin (USTC): Caltech (Ph.D. in Chemistry)
Juntao Sun (Nankai U): Scripps Research (Ph.D. in Chemistry)
Zhong-Qian Wu (Tsinghua U): UChicago (Ph.D. in Chemistry)

We are also excited that two 2019 graduates will be pursuing their Ph.D. degrees next year:

Hanh Ngyuen (UCSD): UC Irvine (Ph.D. in Chemistry)
Tim Gallagher (Claremont McKenna): Scripps Research (Ph.D. in Chemistry)

1,1-diborylation pre-print online

Appearing today in a pre-print on ChemRxiv, Yang and Zhong-Qiang describe a copper-catalyzed tandem process for preparing differentially protected E-configured 1,1-diboryl alkenes from terminal alkynes. Mechanistically the reaction proceeds through the intermediacy of an alkynyl–Bdan intermediate which undergoes in situ hydroboration. Special congrats to undergrad co-author, Zhong-Qian, who is headed to UChicago to start his Ph.D.

For a link to the pre-print, click here: https://chemrxiv.org/articles/Synthesis_of_Stereodefined_1_1-Diborylalkenes_via_Copper-Catalyzed_Diboration_of_Terminal_Alkynes/12133404

directed cyclization pre-print online

Appearing today as a pre-print in ChemRxiv we describe a series of Pd(II)-catalyzed intramolecular alkene hydrofunctionalization reactions, where we take advantage of a proximal directing group to recruit the metal catalyst and promote otherwise disfavored rings closures. This work was part of a fun collaboration with the Liu group at the University of Pittsburgh and the Xiang group at Nankai University Medical School. Congrats to the three project leads: Xin (a visiting PhD student from Nankai University who spent one year in our lab in La Jolla, Zi-Qi (a second-year PhD student at Scripps Research), and Binh (a postdoc at the University of Pittsburgh). Props to the rest of the team, especially former high-school intern Jessica Xu, who carried out critical proof-of-concept studies in the summer of 2016 and is now an undergraduate student at MIT. Way to go, team!

For a link to the pre-print, click here: https://chemrxiv.org/articles/Controlling_Cyclization_Pathways_in_Palladium_II_-Catalyzed_Intramolecular_Alkene_Hydrofunctionalization_via_Substrate_Directivity/12090402

Keary selected as 2020 ONR Young Investigator

The Engle lab is excited and honored to be selected for the 2020 Office of Naval Research Young Investigator program. This award through the Advanced Energetic Materials program will support a project titled, “Selective Alkene Functionalization as a Platform for Energetic Materials Development“. We are looking forward to applying our experience in catalytic alkene functionalization to streamline the discovery and development of new energetics — should be a blast 😉

For a full list of 2020 awardees, click here: https://www.onr.navy.mil/Education-Outreach/Sponsored-Research/YIP/2020-young-investigators