Skeletal editing by iron-catalyzed carbene insertion of trichloromethanes Direct interchange between five- and six-membered nitrogen heterocycles by skeletal editing is valuable in drug discovery. Specifically, inserting a c…

Back in 2019 I wrote my first grant, for the ACS PRF, in which I proposed carbon insertion into LSD (truly a pipe dream at the time). After teaming up with @nagiblab.bsky.social and @deolsonlab.bsky.social, the dream is finally a reality!

www.sciencedirect.com/science/arti...

Break Stuff

open.spotify.com/track/5cZqsj... this song goes triple platinum in my lab room

Mechanisms and Synthetic Applications of Cyclic, Nonstabilized Isodiazenes: Nitrogen-Atom Insertion into Pyrrolidines and Related Rearrangements Reactive intermediates that can promote nonintuitive bond disconnections underpin advancements in skeletal editing methodologies. Accordingly, a detailed understanding of their reactivity and its underlying mechanisms is central to progress in this space. Herein, we catalog and study the reactivity of nonstabilized cyclic isodiazene intermediates generated via the reaction of cyclic secondary amines with an anomeric amide reagent. Depending on the amine structure, distinct and predictable product classes can be accessed: cyclic hydrazones are formed from pyrrolidines, N-amino indoles from indolines, orthoquinodimethane intermediates from isoindolines, cyclopropanes from azetidines, and cyclic tetrazines from piperidines. Mechanistic experiments and density functional theory calculations suggest that many of these transformations proceed through an azomethine imine intermediate. In most cases, this reactive species subsequently rearranges to a cyclic hydrazone by an unusual self-catalysis mechanism proceeding through a dimeric tetrazine. This oxidative nitrogen insertion was leveraged in several subsequent synthetic applications. Redox diversification of the cyclic hydrazones enables access to pyridazines and cyclic hydrazines, including the synthesis of an orthogonally protected l-piperazic acid from the readily available chiral pool l-prolinol.

A work many years in the making out today in @jacs.acspublications.org, where we try to make sense of the structure-reactivity patterns of isodiazenes that refuse to participate in nitrogen deletion:

The pyrrolidine rearrangement was particularly useful for pyridazine and piperazic acid synthesis:

Carbon-Atom Scavengers Enable Divergent, Selective Carbon Deletion of Azaarenes Divergent synthesis is a powerful strategy that provides simultaneous access to multiple derivatives of a given substrate. However, the emerging developments in skeletal editing have largely delivered...

Our latest is a serendipitously discovered pair of reactions that can pull either the C2 or C3 carbon out of quinolines by choice of an amine scavenger. A deep mechanistic dive took us some surprising places, in @chemiejisoo.bsky.social's latest.

pubs.acs.org/doi/full/10....

We're thrilled to share Associate Professor Mark Levin has been named a recipient of the 2025 National Brown Investigator Award. This award provides up to $2 million over five years and supports fundamental science discoveries in chemistry and physics. physicalsciences.uchicago.edu/news/article...

News story from UChicago:
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