摘要：Áron Péter,1†Jiawei Sun,1†Jiayan He,1§JetTsien,1§Haoxiang Zhang,1§BenjaminP. Vokits,2David S. Peters,3Michael D. Mandler,4Maximili

转自：康龙化成

A General Redox-Neutral Platformfor Radical Cross-Coupling

Áron Péter,1†Jiawei Sun,1† Jiayan He,1§ JetTsien,1§ Haoxiang Zhang,1§ BenjaminP. Vokits,2 David S. Peters,3 Michael D. Mandler,4 Maximilian D. Palkowitz,5 Yu Kawamata,1 Phil S. Baran*1

1Departmentof Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA,92037, United States.

2 BristolMyers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey08534, United States

3 SmallMolecule Drug Discovery, Bristol Myers Squibb Research & Early Development,10300 Campus Point Drive, 92121 San Diego, CA, United States.

4 SmallMolecule Drug Discovery, Bristol Myers Squibb Research & Early Development,Route 206 & Province Line Road, Princeton, NJ 08543 USA

5 SmallMolecule Drug Discovery, Bristol Myers Squibb, 250 Water Street, Cambridge,Massachusetts 02141, United States

Recommended by Murong Xu_MC3

KEYWORDS: Redox-neutralreactions (反应类型),Reductivearylation (反应类型),Sulfonylhydrazides (原料), C(sp2)-C(sp3), C(sp3)-C(sp3),C(sp3)-C(sp) (成键类型)

ABSTRACT: Sulfonylhydrazides are disclosed as versatile radical precursors as exemplified withseven new C–C bond forming, redox-neutral cross-couplings with: (1) activatedolefins, (2) alkyl halides, (3) redox active esters, (4) aryl halides, (5)alkenyl halides, (6) alkynyl halides, and (7) a trifluoromethylating reagent to forge C(sp3)-C(sp3),C(sp3)-C(sp2),and C(sp3)-C(sp) bonds. Sulfonyl hydrazides are stableand usually crystalline substances that can be accessed in a variety of waysincluding transiently from hydrazones toachieve a netreductive arylationof carbonyl compounds.Exogenous redox (chemical, photo/electrochemical) additives are not necessaryas these functional groups serve the dual role of radical precursor andelectron donor. The operational simplicity (homogeneous, water tolerant,dump-and-stir) and practicality of the method are demonstrated as well asapplications to streamlining synthesis and mild late-stage functionalization.

(A)Common radical cross coupling precursors; (B) alkyl diazenes aspotential leads for redox-neutral crosscoupling; (C)realization of broadly general redox-neutral cross coupling using sulfonylhydrazide precursors

Sevennew classes of redox-neutral reactions with sulfonyl hydrazides (selectedexamples): (A)Giese addition and cross coupling with alkyl halides and RAEs; and (C)Trifluoromethylation with Grushin'sreagent

Sevennew classes of redox-neutral reactions with sulfonyl hydrazides: (B)cross-coupling with C(sp2) and C(sp) halides to create aryl-, alkenyl-, and alkynylalkyl linkages;

A one-pot protocol for sulfonyl hydrazidecouplings with aryl halides via hydrazones through in situ reduction with aninexpensive silane (selected)

Seemingly trivial hydroxyethylation ofan aryl chloride can now be accomplished with ease

Prof.Phil S. Baran etalhavedisclosed the discovery that sulfonyl hydrazides canserve not only as versatile radical progenitors but serve as their own electrondonors, driven by the loss of N2, to facilitate a metal mediated catalyticcycle thereby obviating the need for external redox stimuli. From a practicalperspective, sulfonyl hydrazides aregenerally stable, crystalline substances that do not need to be purified bychromatography and can often be used in crude form. Catalysis is demonstratedwith Ni, but the same principle should be applicable to many otherorganometallic systems. In fact, preliminary experiments suggest that othermetals such as Cu, Co, Pd, andFe, can provide varying levels of product in C(sp3)-C(sp2) coupling. This studyoutlines the invention of seven new transformations, but a vast array of newreactions is now conceivable. Since easily prepared sulfonyl hydrazides divorceredox chemistry from radical cross-couplings, reaction setup is dramaticallysimplified (arguably as simple as a classic Suzuki coupling). Future studieswill include applications to tertiary radical coupling, interfacing sulfonylhydrazides with other organometallic reaction modes, further extending thescope to C–heteroatom bond cross coupling, and a deeper mechanistic inquiry. Itis likely that these new C–C bond forming reactions will find application innearly all branches of chemical synthesis when targeting novel materials,chemical biology probes, nucleic acids, peptides, sugars, natural products,agrochemicals, and medicines.

来源：新浪财经