Electrocatalytic C–H phosphorylation through nickel(III/IV/II) catalysis

•Electro-oxidative C–H phosphorylation of arenes and alkenes•Chemical oxidants are not required in an undivided cell setup•Sustainable 3d nickela-electrocatalysis with H2 as the only byproduct•Mechanistic insights by NMR spectroscopy, X-ray analysis, mass spectrometry, CV Phosphorus-containing molecules play a pivotal role numerous applied areas have transformative applications molecular syntheses medicinal chemistry, well crop-protection agents pharmaceutical industries. As consequence, there is continued strong demand for resource-economical strategies their assembly. Although direct methods C–H/C–P functionalizations particularly attractive, thus far they largely relied on precious-transition-metal catalysts toxic or expensive chemical oxidants, jeopardizing overall efficiency. In sharp contrast, we herein disclose sustainable strategy resource-efficient access to plethora aryl alkenyl phosphonates phosphines means electro-oxidative nickela-electrocatalysis. Key our success were detailed spectroscopic computational mechanistic into nickel(III/IV) manifold through oxidation-induced reductive elimination. was achieved Earth-abundant nickel waste-free electricity redox surrogate. The robust nickela-electrooxidative activation arenes, heteroarenes, olefins diverse phosphonating reagents successfully delivered arylphosphonates, phenylphosphine oxides, diazaphospholidine oxides relevance bioactive compounds materials. guanidine-assisted electrooxidative C–P formation avoided hydrogen sole byproduct. Catalytically relevant nickel(II) nickel(III) intermediates isolated fully characterized diffraction analysis. complexes observed operando high-resolution electrospray ionization spectrometry (HR-ESI-MS) monitoring. Cyclic voltammetry analysis density functional theory (DFT) calculations provided evidence nickel(III/IV/II) manifold. Arylphosphonates widely utilized structural motifs agrochemical industries,1Baguley T.D. Xu H.-C. Chatterjee M. 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Eur. 24: 19166-19170Crossref (67) alkoxylation,49Zhang Struwe Hu Nickela-electrocatalyzed alkoxylation secondary alcohols: elimination nickel(III).Angew. 59: 3178-3183Crossref (49) became attracted considerably more cost-efficient equivalent, results which summarized 1C). features comprise (1) phosphorylation, (2) absence byproduct, (3) unmasked within operationally simple setup, (4) isolation catalytically competent activated nickelacycles, (5) cyclic (CV), functinal calculations, electrospray-ionization supporting mechanism. We initiated studies probing reaction conditions benzamide 1a 2a non-sequential manner S1). After considerable experimentation (Tables 1 S1–S6), desired product 3 high yields base 1,1,3,3-tetramethylguanidine (TMG) additive Ni(DME)Cl2 when graphite felt (GF) anode (Ni) foam cathode used (Table 1, entries 1–6). found be advantageous formation, whereas other additives (such di-tBubpy) inhibited 5–9). Control experiments verified base, Ni catalyst, 10–12). complexes, instance, Ni(cod)2, NiI2, NiCl2, well, albeit slightly reduced efficacy entry 13; Table S4). It noteworthy proved effective electrocatalyzed than metals, cobalt, copper, manganese, iron. adding protocol reflects robustness over 5d palladium, ruthenium, iridium, 14–20; S6).Table 1Optimization phosphorylationEntryBaseAdditive[TM]3aReaction conditions: (0.25 mmol), (0.50 [TM] (10 mol %), (20 (1.0 equiv), TBAI (0.125 DMA (3.0 mL), CCE = 8.0 mA, 12 h, N2, GF cathode, yield.1NaO2CAd(4-CF3C6H4)3PNi(DME)Cl262%2NaOAc(4-CF3C6H4)3PNi(DME)Cl2(35%)bYields determined 1H 1,3,5-(MeO)3C6H3 internal standard.3DBU(4-CF3C6H4)3PNi(DME)Cl2(51%)bYields standard.4DBN(4-CF3C6H4)3PNi(DME)Cl2(60%)bYields standard.5TMG(4-CF3C6H4)3PNi(DME)Cl272% (74%)bYields standard.6TMG[3,5-(CF3)2C6H3]3PNi(DME)Cl273% standard.7TMGXphosNi(DME)Cl267%8TMG–Ni(DME)Cl245% (50%)bYields standard.9TMGdi-tBubpyNi(DME)Cl2–10–[3,5-(CF3)2C6H3]3PNi(DME)Cl2–11TMG[3,5-(CF3)2C6H3]3P−–12TMG[3,5-(CF3)2C6H3]3PNi(DME)Cl2–cWithout current.13TMG[3,5-(CF3)2C6H3]3PNi(cod)266%14TMG[3,5-(CF3)2C6H3]3PCu(OAc)2·H2O(<5%)bYields standard.15TMG[3,5-(CF3)2C6H3]3PCo(OAc)2·4H2O(<5%)bYields standard.16TMG[3,5-(CF3)2C6H3]3PMn(OAc)2(8%)bYields standard.17TMG[3,5-(CF3)2C6H3]3PFe(acac)3(<5%)bYields standard.18TMG[3,5-(CF3)2C6H3]3PPdCl2–19TMG[3,5-(CF3)2C6H3]3P[Cp∗RhCl2]2–d[TM] (5.0 %). DMA, N,N-dimethylacetamide; DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene; DBN, 1,5-diazabicyclo[4.3.0]non-5-ene; TMG, tetramethylguanidine; di-tBubpy, 4,4′-di-tert-butyl-2,2′-dipyridyl.20TMG[3,5-(CF3)2C6H3]3P[Cp∗IrCl2]2–d[TM] 4,4′-di-tert-butyl-2,2′-dipyridyl.a Reaction yield.b Yields standard.c Without current.d 4,4′-di-tert-butyl-2,2′-dipyridyl. Open table tab With optimized electrocatalytic hand, influence N-substitution pattern nickela-electrocatalyzed investigated 2, 3–8; S7). line studies,49Zhang electron nitrogen atoms quinoline moiety influences 3–8). Other N,N- N,O-bidentate groups failed facilitate Subsequently, probed versatility nickela-electrochemical differently functionalized heteroarenes 9–27). Thus, diversely decorated substrates bearing valuable groups, halos, esters, amines, tolerated (14–16). position control regime demonstrated meta-substituent (19–21). limited but hereoarenes likewise phosphorylated products 24 25 even shorter time. Remarkably, aminoquinoline monodentate pyridine resulted selective amide-guided 26. Benzamide protected amino furnish peptide 27 notable racemization (Figures S68 S69). scaled up loss efficiency (17, 1.31 g). reflected alkenes 1′ 3, 28–36). Hence, cyclohexene reacted efficiently phosphorylating reagents, including thereby furnishing 28–30 improved 32. Furthermore, acyclic olefinic carboxamides, α- α,β-substituted acrylic acids, afforded corresponding 34 35 partial isomerization S22 S23), diene under otherwise identical S7, 36). Moreover, highlighted range electronically sterically different phosphonates, 2 4, 37–48). 41 derived natural d-menthol obtained yield. Bulky six- seven-membered (42–44) tolerated. delight, mono- dialkylphosphine also amenable arylphosphonates 45 46. diarylphosphine converted triphenylphosphine 47, could ligands.50Li Lu L.-Q. Das Pisiewicz Junge Beller Highly chemoselective metal-free reduction phosphines.J. 134: 18325-18329Crossref (165) electron-deficient, encumbered diaminophosphine 48, compound potentially flame retardant epoxy resins.51Li Cao Yao Reactive phosphonamide resins.J. Appl. Polym. 47411Crossref (12) gain nickela-electrocatalytic conducted 5 S2–S23). Intermolecular competition between diisopropyl (2a) morpholine (2n) clearly showed achieving S7–S10). kinetic isotope effect kH/kD ≈ 3.2 independent experiments, indicating rate-limiting step 5A S17). H/D exchange reisolated isotopically labeled tBuOD cosolvent S13–S15). typical radical scavenger, 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO), 4 equiv, did prevent activation, rendering radicals unlikely operative 5B). Headspace gas chromatography confirmed formed byproduct S18 S19). monitored consumption along phosphonated no sign induction period S24 S25). HR-ESI-MS, two 6 S26–S31). peak 581 (m/z) related species NiII-M1 NiII-M2, NiIV-M3 NiII-M4 745 6). Ni-amide dimer NiII-M5 6D) eventually after approximately 7 h. order get further mechanism carried out DFT key steps PBE0-D3(BJ)/def2-TZVP+SMD(DMA)//PBE0-D3(BJ)/def2-SVP level theory.52For details, please see supplemental information.Google Our indicated activations TMG-coordinated NiII-H1 S55, barrier 27.6 kcal/mol) Ni(III) NiIII-H3 27.3 favorable, NiII-H5 shows unfavorable energy 33.7 kcal/mol S56). NiIV-H7 NiII-H9 energetically viable S57, 2.8 kcal/mol). Additionally, orbital process intermediate NiIII-H10 Ni(IV) NiIV-H11, occurs non-cyclometallated S59). Before following state TS(H7-H8) S57), spin-crossover event triplet singlet Ni-H7 will complex. double-occupied highest occupied unoccupied lowest S58). NiII-M6 bulky carboxylate NaO2CAd used, NiIII-M7 assistance 7A S32). Notably, TMG proper coordinating stabilize initially nickelation complex forming stable NiII-H2, crystallography 7B, 7C, S33, S34). NiII-H2 easily oxidized generate cyclonickelated substrate 7B S39). Treating led homo- cross-cyclonickel dimers, suggesting protodemetallation followed irreversible S13, S14, S40–S44). waves potential −0.20 V versus Fc0/+ +0.50 Fc0/+, providing Ni(II/III) Ni(III/IV) events 7D S64–S67). Accordingly, 7E S45–S51). highlight outstanding approach, set AgOAc, Cu(OAc)2, Mn(OAc)3, K2S2O8, PhI(OAc)2, oxygen, all fell short 8A). These emphasize served low-cost oxidant unique transformation. studied comparing AgOAc applying 8B 8C). therefore NIII-M7, Ni(II), conversion final 8B, 8C, S39, S47, S52–S54). Based studies, plausible cycle depicted Figure 9. Initial upon NiIII-B. Subsequent sets stage NiIV-E. proposed NiII-G coordination.53Puleo T.R. Sujansky S.J. Wright S.E. Bandar J.S. 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