Out in print now ! 🙌
Final version out today in @NatureSynthesis : nature.com/articles/s4416…View quoted post on X
David Cagan
@cagan_da
@NSF Postdoctoral Fellow in @BaranLabReads, @ScrippsResearch | PhD in Hadt Lab, @CaltechCCE | @theNASEM Ford & @NSF GRFP Fellow | Founder of Caltech Rising Tide
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Latest posts 5
Introducing kSAR: Conjugation kinetics was leveraged to identify key scaffolds for med chem ! Here we show the power of blending phys org with synthetic chemistry for medicinal applications
A Kinetics-first Approach Reveals Optimum Vinylaminopyrimidines for Cysteine-Based Antibody Conjugation – an exciting collaboration with @scrippsresearch colleagues @Dawson_Group and the Blackmond group along with BMS – appearing now in @ChemRxiv : chemrxiv.org/doi/abs/10.264…View quoted post on X
We asked ourselves, "What is the simplest way to make radicals from a diazene intermediate?" Turns out, you just need a little heat and a mild base. Radicals are seen even without a metal!
👋DRUG HUNTERS👋 N₂ extrusion from alkyl hydrazines delivers complex, medicinally relevant alkyl S(VI)-chemical space with exceptional chemoselectivity and operational simplicity.
Appearing today in @ChemRxiv: chemrxiv.org/doi/full/10.26…
Alkyl hydrazines (or their sulfonyl derivatives) serve as practical radical precursors readily prepared from ketones, alcohols, amines, and complex molecules. Simple thermal activation triggers clean N₂ extrusion to generate alkyl radicals that are captured by inexpensive SO₂ sources, delivering versatile sulfinates convertible in situ to sulfonyl fluorides or sulfinamides.
70+ examples, protecting-group-free late-stage functionalization of natural products and drugs (ticagrelor, erythromycin, spiramycin), 100-g scale with trivial work-up, and stereoretentive variants round out a unified platform that directly addresses the growing need for complex alkyl S(VI) motifs in medicinal chemistry. Detailed mechanistic studies, including temperature scanning calorimetry, radical clocks, and DFT calculations help to demystify the process.View quoted post on X
Closer inspection of the radical rebound PES predicts that the process is effectively *barrierless*. The geminate radical pair, Ni(I) + C*, recombines favorably. This happens so fast that we can even avoid cyclopropyl ring opening!
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We previously showed that hydrazides can make active Ni(I) species. Here we take that another step further, using hydrazines for cross-electrophile coupling via Ni(I)/Ni(III) cycles. Mechanism and safety considerations included!
Aryl Hydrazines: Convenient Homogenous Reductants for Cross-Coupling. A great collaboration with the Blackmond lab and Abbvie, appearing today in @ChemRxiv : chemrxiv.org/engage/chemrxi…View quoted post on X