摘要：Jiawei Sun,JiayanHe, Jet Tsien,HaoxiangZhang, David A. Cagan, Benjamin P. Vokits, David S. Peters, Martins S.Oderinde, Michael D.

转自：康龙化成

Sulfonyl Hydrazides as a General Redox-neutral Platform for Radical Cross-coupling

Jiawei Sun, Jiayan He, Jet Tsien, Haoxiang Zhang, David A. Cagan, Benjamin P. Vokits, David S. Peters, Martins S. Oderinde, Michael D. Mandler, Paul Richardson, Doris Chen, Maximilian D. Palkowitz, Nicholas Raheja, Yu Kawamata, and Phil S. Baran*

Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA, USA;

Discovery and Development Sciences, Bristol Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, USA;

Discovery and Development Sciences, Bristol Myers Squibb, 10300 Campus Point Drive, San Diego, CA, USA;

Synthesis & Enabling Technologies, Discovery and Development Sciences, Bristol Myers Squibb, Princeton, New Jersey, USA;

Medicinal Chemistry Department, Pfizer Inc., 10770 Science Center Drive, San Diego, California, USA;

Discovery and Development Sciences, Bristol Myers Squibb, 250 Water Street, Cambridge, Massachusetts, USA.

—Science2025, 10.1126/science.adu6406

KEYWORDS: Ni catalysis, radical cross-coupling, Giese addition, trifluoromethylation (反应类型), Sulfonyl hydrazides, Alkenes halideAryl halide, Aryl triflate (原料), C(sp3)- C(sp3), C(sp3)- C(sp2), C(sp3)- C(sp) (成键类型)

ABSTRACT: 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. Here we disclose their utility as versatile radical precursors as exemplified with seven C-C bond forming, redox-neutral cross-couplings with activated olefins,lalkyl halides, redox active esters, aryl halides, alkenyl halides, alkynyl halides, and a trifluoromethylatingreagent to forge C(sp)-C(sp), C(sp3)-C(sp2), and C(sp)-C(sp) bonds. Exogenous redox (chemical, photo/electrochemical) additives are not necessary as 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.

Background

Selected Substate Scope

Proposed Mechanism

Prof. Phil S. Baran and co-workerdescribed radical cross-coupling chemistry that has had a profound impact on the practice of organic synthesis and has enabled simplifying radical retrosynthetic disconnections that did not exist a decade ago. Despite great strides in this field, the use of exogenous catalysts, stoichiometric reductants/oxidants, and photo/electrochemical setups diminishes its practical utility compared to conventiomal, redox-neutral C-C bond forming cross-couplings such as the venerable Suzuki reaction. The fundamental advance of this disclosure is the discovery that sulfonyl hydrazides can serve not only as versatile radical progenitors but serve us their own electron donors, driven by the loss of N2, to facilitate a metal mediated catalytic cycle thereby obviating the need tor external redox stimuli. From a practical perspective, sulfonyl hydrazides are generally stable, crystalline substances that do not need to be purified by chromatography and can often be used in crude form. Curiously, these groups are not very polar and are well-behaved on silica gel. Catalysis is demonstrated with Ni, but the same principle should be applicable tox many other organometallic systems. In fact, preliminary experiments suggest that other metals such as Cu, Co, Pd, and Fe, can provide varying levels of product in C(sp3)-C(sp2) coupling. Because easily prepared sulfonyl hydrazides divorce redox chemistry from radical cross-couplings, reaction setup is dramatically simplified (arguably as simple as a classic Suzuki coupling). It is likely that these C- C bond forming reactions will find application in nearly all branches of chemical synthesis.

来源：新浪财经