Electrochemical C−H/N−H Activation by Water‐Tolerant Cobalt Catalysis at Room Temperature

Abstract

Electrochemistry enabled C À H/N À Hf unctionalizations at room temperature by external oxidant-free cobalt catalysis.Thus,the sustainable cobalt electrocatalysis manifold proceeds with excellent levels of chemoselectivity and positional selectivity,a nd with ample scope,t hus allowing electrochemical C À Ha ctivation under exceedingly mild reaction conditions at room temperature in water.Notably,CÀHactivation has emerged as an increasingly potent platform for molecular syntheses, [1] with transformative applications to natural product chemistry, [2] pharmaceutical industries, [3] and material sciences, [4] among others.While C À Ht ransformations have thus far largely exploited the noble transition metals palladium, iridium, ruthenium, and rhodium, recent focus has shifted towards earth-abundant, inexpensive,a nd less toxic 3d base metals. [5] Particularly, versatile cobalt catalysis has proven powerful for the functionalization of otherwise inert CÀHb onds, [6] thus enabling inter alia step-economical heterocycle syntheses by C À H/N À Hf unctionalizations. [7] Despite indisputable advances,t hese C À H/N À Halkyne annulations were as of yet strongly limited to high reaction temperatures and/or stoichiometric amounts of toxic metals as the sacrificial oxidants. [6,8] In sharp contrast, we have now unraveled the power of electrochemical [9] CÀ H [10] activation [11] to enable the first cobalt-catalyzed C À H/N À Ha lkyne annulation at ambient temperature,o nw hich we report herein. Salient features of our approach comprise 1) unprecedented electrochemical CÀH/NÀHa ctivation/ annulations,2 )isoquinolone syntheses without toxic sacrificial metal oxidants,3)fully H 2 O-tolerant electrochemical CÀ Hactivation, and 4) cobalt-catalyzed CÀHfunctionalizations, under ambient conditions,e nabled by sustainable electricity (Figure 1). In contrast to avery recent C À Hoxygenation that was restricted to the use of an access of 240 equivalents of the alcohol substrate, [12] the electrochemical CÀH/NÀHfunctionalization is operative with close to equimolar quantities in an atom-economical fashion.We initiated our studies by exploring reaction conditions for the envisioned electrochemical C À H/N À Hf unctionalization of the benzamide 1a in as imple undivided cell with ap latinum plate cathode and ar eticulated vitreous carbon (RVC) anode (Table 1a nd see Table S-1 in the Supporting Information). [13] Thus,t he desired isoquinolone 3aa was Table 1: Optimization of the electrochemical CÀH/NÀHa lkyne annulation. Entry [TM] Solvent Base Yield [%] [a] Reaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), [Co] (20 mol %), base (2.0 equiv), and solvent (10 mL) at 23 8 8Cand 4mAfor 16 husing an RVC anode, Pt-plate cathode, undivided cell. [b] Oxygenation product also formed in 17 %. [c] [TM] (10 mol %). [d] 60 8 8C, 8h.[e] No electricity. acac = acetylacetonoate, DMSO = dimethylsulfoxide, Piv = pivaloyl.Figure 1. Electrochemical cobalt-catalyzed CÀH/NÀHfunctionalization at room temperature.

C–H Activation: Toward Sustainability and Applications

“…The applicability of Co, Ni, and Cu electrochemistry to C–H functionalization has been demonstrated extensively by Ackermann since 2017. 90 , 134 − 139 In a recent protocol, a challenging C–C/C–N bond formation with a potentially sensitive allene was accomplished under mild conditions in the biosolvent glycerol using simple Co(OAc) 2 salt ( Scheme 34 A). 140 Furthermore, electricity generated in house from wind and solar energy was exploited.…”

Chemodivergent Nickel(0)-Catalyzed Arene C–F Activation with Alkynes: Unprecedented C–F/C–H Double Insertion

“…Alkyne insertion reactions have emerged as a powerful tool for the formation of cyclic compounds. Thus, several protocols through transition metal-catalyzed C-H activation have been established with alkynes to form isoquinolones [24][25][26][27][28] or indoles. [29][30][31][32] The use of alkyne as a coupling partner can also lead to the direct formation of polysubstituted arenes.…”

Observations of Electron-driven Evaporation in a Flare Precursor

“…Chromospheric evaporation can be detected in multi-wavelengths, ranging from HXR (Liu et al 2006;Ning 2011;Zhang & Ji 2013) through EUV/UV (Czaykowska 1999;Li et al 2015a;Tian & Chen 2018) to microwave (Aschwanden & Benz 1995;Ning et al 2009) channels. In HXR or EUV imaging observations, the material movement from double footpoints to loop top along the flare loops is considered to be the HXR/EUV signature of chromospheric evaporation (Ning & Cao 2010;Ning & Cao 2011;Zhang & Ji 2013;Li et al 2017a).…”