Photo-induced oxidant-free oxidative C–H/N–H cross-coupling between arenes and azoles

Abstract

Direct cross-coupling between simple arenes and heterocyclic amines under mild conditions is undoubtedly important for C–N bonds construction. Selective C(sp2)-H amination is more valuable. Herein we show a selective C(sp2)-H amination of arenes (alkyl-substituted benzenes, biphenyl and anisole derivatives) accompanied by hydrogen evolution by using heterocyclic azoles as nitrogen sources. The reaction is selective for C(sp2)-H bonds, providing a mild route to N-arylazoles. The KIE (kinetic isotope effect) experiment reveals the cleavage of C–H bond is not involved in the rate-determining step. Kinetic studies indicate the first-order behaviour with respect to the arene component. It is interesting that this system works without the need for any sacrificial oxidant and is highly selective for C(sp2)-H activation, whereas C(sp3)-H bonds are unaffected. This study may have significant implications for the functionalization of methylarenes which are sensitive to oxidative conditions.

Electrophotocatalysis with a Trisaminocyclopropenium Radical Dication

“…which can oxidize benzene (4)via SET to produce the radical cation 45 with concomitant direct regeneration of 1.N ucleophilic trapping of 45 by pyrazole 5 followed by deprotonation leads to the radical 46.Further oxidation of this radical by 2 or directly at the anode,f ollowed by re-aromatization via loss of aproton then reveals the coupled product 6.Although this rationale is in line with previous reports of this type of arene-azole coupling, [16,17,27] it is plausible that in some cases, the pyrazole substrates,rather than the arenes,undergo initial oxidation, given the higher oxidation potentials of many of the arenes in our study.W eview this as aless likely possibility because the arene is used in vast excess,the chemistry works even with strongly deactivated pyrazoles (for example, 5), we have observed small amounts of oligomeric products arising from benzene oxidation, and the attempted reaction of pyrazole by itself resulted in no conversion. However,t he mechanistic possibilities for this reaction are clearly complex, and further study is warranted.…”

“…[23] With an oxidation potential of 2.48 V( vs.S CE), the controlled functionalization of benzene presents am ajor challenge for both electrochemistry [24] and photochemistry. [25,26] Previous instances of this type of coupling reaction by Nicewicz, [23] Lei, [27] as well as Grätzel and Hu [16] have been conducted with more easily oxidized arenes using the 9-mesityl-10-methylacridinium photocatalyst;however,the oxidative functionalization of benzene remains ac hallenge.W ef ound that, using ac ell voltage of 1.5 V(E anode = 1.4 V) [28] and irradiation with a23W compact fluorescent light (CFL) in acetonitrile with acetic acid, [29] 8mol %T AC 1 catalyzed the oxidative coupling of benzene (4)a nd pyrazole (5)t of urnish product 6 cleanly in 65 %y ield (Figure 2A). Thec ounterelectrode product, hydrogen gas,could be seen as bubbles formed at the cathode.…”

A Catalyst‐Free Amination of Functional Organolithium Reagents by Flow Chemistry

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Reported is the electrophilic amination of functional organolithium intermediates with well-designed aminating reagents under mild reaction conditions using flowm icroreactors.T he aminating reagents were optimizedt oa chieve efficient CÀNbond formation without using any catalyst. Recently,C À Ha mination reactions based on electrochemical [5] and photoredox methods [6] have also been reported.Electrophilic amination of carbanions (typically,o rganometallic compounds) [7] serves as an alternative tool, which is based on an umpolung strategy. Based on stopped-flowNMR analysis,the reaction time for the preparation of the aminating reagent was quickly optimized without the necessity of work-up.Integrated one-flowsynthesis consisting of the generation of an aryllithium, the preparation of an aminating reagent, and their combined reaction was successfully achieved to give the desired amine within 5minutes of total reaction time.

Synthetic methodologies for the formation of carbon-nitrogen bonds have become the important subject in organic synthesis.

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Late‐Stage Functionalization of Arylacetic Acids by Photoredox‐Catalyzed Decarboxylative Carbon–Heteroatom Bond Formation

“…[15] During our study on photoredox-catalyzed carbon-nitrogen (CÀN) bond formation, [16] we discovered that our photocatalytic systemsc ould be applicable to the decarboxylative functionalizationo fa rylacetic acids ( Figure 1B). [17] Herein, we report CÀ Na nd CÀOb ond formation throughp hotoredox-catalyzed decarboxylation of arylacetic acids. The reaction shows good functional group compatibility without pre-activation of the nitrogen-or oxygen-based coupling partner.…”