Carboxylate-Assisted Ruthenium-Catalyzed Direct C-H Bond Functionalizations
by Lianhui Wang
Date of Examination:2014-02-26
Date of issue:2014-03-03
Advisor:Prof. Dr. Lutz Ackermann
Referee:Prof. Dr. Lutz Ackermann
Referee:Prof. Dr. Dietmar Stalke
Persistent Address:
http://dx.doi.org/10.53846/goediss-4397
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Abstract
English
Ruthenium-catalyzed direct C–H bond functionalizations was shown to be an attractive approach for the development of sustainable chemical processes. The significant rate acceleration of cycloruthenations by carboxylates has provided the bases for various catalyzed C–H bond functionalizations. In a first project, ruthenium(II)-catalyzed oxidative annulations were realized in an aerobic fashion with cocatalytic amounts of Cu(OAc)2·H2O under an atmosphere of ambient air. Pleasingly, the C–H/N–H bond functionalization occurred with unparalleled selectivities and ample scope to deliver indole 207 and pyrrole derivatives 209. While reactions with CuBr2 as the co-oxidant did not furnish the desired products, cocatalytic amounts of metal acetates restored the catalytic efficacy, thus providing strong evidence for carboxylate-assisted aerobic oxidations. Furthermore, the highly selective conversion of unsymmetrical alkynes 38 constituted a strong testament to the unique features of chemoselective ruthenium catalysts.This efficient ruthenium(II) catalyst also enabled broadly applicable oxidative alkyne annulations with electron-rich enamines 210 to provide diversely decorated pyrroles 211, even with air as the ideal oxidant. We were delighted to observe that numerous useful electrophilic functional groups were well tolerated, including ester, vinyl, bromo, cyano, and nitro substituents. Notably, oxidative annulations of unsymmetrical alkynes 38 occurred with synthetically useful levels of regiocontrol.Along with the rapid development of the oxidative annulations, challenging oxidative olefinations with electron-rich anilides 212 as well as electron-deficient benzamides 214 were elaborated with [RuCl2(p-cymene)]2, KPF6 and Cu(OAc)2·H2O as the catalytic system. Remarkably, this protocol proved to be most effective with water as the reaction medium and provided an expedient access to differently decorated arenes 213 and 215. Furthermore, we were pleased to observe that this ruthenium-catalyzed oxidative C–H alkenylations proceeded smoothly even on a large scale.A catalytic system comprising of [RuCl2(PPh3)3], AgOTf and rac-BINAP enabled step-economical additions of C(sp3)–H bonds (216) onto unactivated alkenes 111 with ample scope under comparably mild reaction conditions. Furthermore, the pyridyl directing group was efficiently removed to furnish (NH)-free pyrrolidines 218.Finally, [Ru3(CO)12] and AgO2C(1-Ad) enabled the first ruthenium-catalyzed intermolecular ortho-selective halogenations of benzamides 219 via C−H activation. Thereby, brominations and iodinations of electron-rich and electron-deficient benzamides were achieved in a highly selective fashion as well as with excellent functional group tolerance. Preliminary mechanistic studies provided evidence for a reversible C−H metalation event in this process.
Keywords: catalysis + ruthenium + carboxylate + C-Hactivation