A First Example of Cobalt‐Catalyzed Remote CH Functionalization of 8‐Aminoquinolines Operating through a Single Electron Transfer Mechanism

Abstract

Thed evelopment of new C À Hf unctionalization protocols based on inexpensive cobalt catalysts is currently attracting significant interest. Functionalized 8-aminoquinoline compounds are high-potential building blocks in organic chemistry andpharmaceutical compoundsa nd new facile routes for their preparation would be highly valuable.R ecently, copper has been applied as catalyst for the functionalization of 8-aminoquinoline compoundsa nd found to operate through as ingle electron transfer (SET) mechanism, although requiring elevated reaction temperatures.H erein, we described the first example of ac obalt-catalyzed remote C À Hf unctionalization of 8-aminoquinoline compoundso perating through aS ET mechanism, exemplified using ap ractical and mild nitration protocol. Ther eactionu ses inexpensive cobaltn itrate hexahydrate [Co(NO 3 ) 2 ·6 H 2 O] as catalyst and tert-butyl nitrite (TBN) as nitro source. This methodology offers the basis for the facile preparationo fm any newf unctionalized 8-aminoquinoline derivatives. Scheme 4. Proposed mechanism for the nitration reaction at C-5. Scheme 5. (a) Competition reactions performed to investigate relative reactivity of substrates 17 and 19.Y ields calculated from 1 HNMR spectra of the crude reaction mixture using 1,3,5-trimethoxybenzene as internal standarda nd are based on conversion of corresponding substrate. Reaction conditions: substrate( 0.5 mmol;0 .25 mmol of each substrate), Co(NO 3 ) 2 ·6 H 2 O( 29.1 mg, 0.1 mmol, 20 mol%),T BN (267 mL, 90%, 4.0 equiv., 2.0 mmol), acetic acid (3.5 mL), room temperature, 18 h. (b) Summary of kinetic isotopeexperiment(KIE);for further details see the Supporting Information. 1686 asc.wiley-vch.de

tert‐Butyl Nitrite (TBN), a Multitasking Reagent in Organic Synthesis

“…Herein, TBN acts as a nitro source. The use of inexpensive cobalt catalyst and easily prepared starting material are the main advantages of this reaction . Similarly, Hajra et al.…”

“…The use of inexpensive cobaltc atalyst and easily prepared starting material are the main advantages of this reaction. [100] Similarly,H ajra et al developed a methodf or the regioselective C-7 nitration of 8-aminoquinoline amide (93)u nder am etal-free condition. The control experiment suggests that the reaction proceeds via ar adical pathway (Scheme 68).…”

Cu–Catalyzed C5 Nitration of Indolines under Mild Conditions

“…tert ‐Butyl nitrite is deemed as a non‐metal green nitro surrogate which has been widely used in various nitrations without the generation of metal contaminants under mild conditions . However, the tert ‐butyl nitrite‐mediated C(sp 2 )—H nitration generally leads to the mixtures of ortho and para ‐substituted products, even in the presence of copper or cobalt catalyst (Scheme , b). To achieve highly regioselective nitration with tert ‐butyl nitrite, the novel palladium catalyst are require .…”

Direct Functionalization of C−H Bonds by Iron, Nickel, and Cobalt Catalysis

“…Remarkable is also the example of Whiteoak and Ribas, where they report a nitration reaction. Interestingly, nitration takes place within the quinoline ring, so in this specific example it is the directing group which gets functionalized, and not the attached aromatic ring (not shown) …”

“…Interestingly,n itration takes place within the quinoline ring, so in this specific example it is the directing group which gets functionalized, andn ot the attacheda romatic ring (not shown). [112] Another bidentate directing group was applied by Niu and Song (158,S cheme 30), initially in an alkoxylation reactiont owards 159. [113] The reactionc onditions are quite similar to the ones reportedb yD augulis.…”