Sulfonyl hydrazides as a general redox-neutral platform for radical cross-coupling
Sulfonyl hydrazides are stable and usually crystalline substances that can be accessed in a variety of ways, including transiently from hydrazones, to achieve a net reductive arylation of carbonyl compounds. We show their utility as versatile radical precursors, as exemplified with seven C-C bond-forming, redox-neutral cross-couplings with activated olefins, alkyl halides, redox-active esters, aryl halides, alkenyl halides, alkynyl halides, and a trifluoromethylating reagent, to forge C(sp<sup>3</sup>)-C(sp<sup>3</sup>), C(sp<sup>3</sup>)-C(sp<sup>2</sup>), and C(sp<sup>3</sup>)-C(sp) bonds. Exogenous redox (chemical, photo/electrochemical) additives are not necessary because these functional groups serve the dual role of radical precursor and electron donor. The homogeneous, water-compatible reaction conditions are operationally simple and contribute to streamlining synthesis and mild late-stage functionalization.
Authors
- Michael D. Mandler (ORCID: https://orcid.org/0000-0003-4681-7473)
- Maximilian D. Palkowitz (ORCID: https://orcid.org/0000-0002-3651-5175)
- Paul Richardson (ORCID: https://orcid.org/0000-0002-3700-8749)
- David S. Peters (ORCID: https://orcid.org/0000-0003-0942-4224)
- Jet Tsien (ORCID: https://orcid.org/0000-0002-2052-8051)
- Áron Péter (ORCID: https://orcid.org/0000-0003-2146-0607)
- Jiayan He
- Phil S. Baran (ORCID: https://orcid.org/0000-0001-9193-9053)
- Yu Kawamata (ORCID: https://orcid.org/0000-0002-5515-9612)
- David A. Cagan (ORCID: https://orcid.org/0000-0002-4719-2789)
- Martins S. Oderinde (ORCID: https://orcid.org/0000-0002-6858-321X)
- Benjamin Vokits
- Jiawei Sun
- Nicholas Raheja
- D.-G. Chen
- Haoxiang Zhang (ORCID: https://orcid.org/0009-0002-3107-8807)
Institutions
- Scripps Research Institute (US)
- Scripps Health (US)
- Scripps Institution of Oceanography (US)
- Bristol-Myers Squibb (Germany) (DE)
- Pfizer (United States) (US)
- Torrey Pines Institute For Molecular Studies (US)
- Bristol-Myers Squibb (United States) (US)
- Bristol-Myers Squibb (Sweden) (SE)
- Scripps (United States) (US)
Publication Details
- Journal
- Science
- Published
- 2025-03-06
- DOI
- https://doi.org/10.1126/science.adu6406
- Citations
- 28
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 26.21