Borylation of azines via a Minisci-type reaction

C–H borylation of N-heteroarenes is an efficient yet highly challenging route to borylated aromatics. In a recent issue Nature, Leonori and co-workers demonstrated novel strategy toward this end by utilizing boryl-radical-based Minisci-type reaction that shows orthogonal site selectivity transition-metal-catalyzed approaches. Direct aromatic bonds straightforward means accessing diverse arene structures. Although considerable progress has been made via transition-metal catalysis,1Mkhalid I.A. Barnard J.H. Marder T.B. Murphy J.M. Hartwig J.F. C-H activation for the construction C-B bonds.Chem. Rev. 2010; 110: 890-931Crossref PubMed Scopus (2025) Google Scholar,2Larsen M.A. Iridium-catalyzed heteroarenes: scope, regioselectivity, application late-stage functionalization, mechanism.J. Am. Chem. Soc. 2014; 136: 4287-4299Crossref (245) Scholar site-selective remains challenging, primarily because catalyst deactivation through binding with basic nitrogen atoms. As such, basicity atoms on heteroarenes profound influence reactivity such reactions. Clearly, mechanistically distinct necessary circumvent problem. context, photoinduced proceeds single-electron manifold emerged as promising alternative well-established two-electron polar reactivity, providing series radical-based protocols organoboron compounds.3Tian Y.M. Guo X.N. Braunschweig H. Radius U. Photoinduced synthesis compounds.Chem. 2021; 121: 3561-3597Crossref (61) describe elegant approach valuable azines trimethylamine borane (Me3N–BH3) borylating reagent.4Kim Constantin T. Simonetti M. Llaveria J. Sheikh N.S. D. A radical selective azines.Nature. https://doi.org/10.1038/s41586-021-03637-6Crossref (18) The Minisci reaction,5Minisci F. Vismara E. Fontana Recent developments free-radical substitutions heteroaromatic bases.Heterocycles. 1989; 28: 489-519Crossref (377) originally developed in late 1960s, evolved into powerful method alkylation, acylation, arylation electron-deficient (Figure 1A).6Proctor R.S.J. Phipps R.J. advances reactions.Angew. Int. Ed. Engl. 2019; 58: 13666-13699Crossref (273) Mechanistically, involves addition nucleophilic carbon-centered protonated followed oxidation, leading overall homolytic substitution compounds. On basis mechanistic understanding photocatalysis, envisioned replacing commonly used carbon boryl might provide Moreover, regioselectivity should resemble classical alkylation (for example, C-2 C-4 pyridines quinolines, respectively) thus be catalysis. strategically appealing, successful realization design requires identification reagent (1) compatible acidic conditions are typically reactions, (2) can generate under (3) product not reactive conditions. authors proposed desired achieved blueprint shown Figure 1B. Photoexcitation photocatalyst (PC) visible light would produce excited-state PC∗. This species potent reductant reduce persulfate (I), which oxidant widely conventional chemistry, form sulfate dianion anion II.7Minisci Citterio A. Giordano C. Electron-transfer processes: peroxydisulfate, useful versatile organic chemistry.Acc. Res. 2002; 16: 27-32Crossref (366) Given hydrogen-atom abstraction Lewis-base-borane complexes (L–BH3, L = amines, phosphines, or N-heterocycle carbenes) tert-butoxyl (tBuO⋅) documented,8Roberts B.P. Polarity-reversal catalysis reactions: concepts applications chemistry.Chem. 1999; 25-35Crossref (582) Scholar,9Taniguchi Boryl multiple synthesis.Eur. Org. 2019: 6308-6319Crossref (41) postulated II promote analogous transfer (HAT) event, especially where electrophilicity could enhanced protonation. Once III formed, it expected undergo heteroarenes, key step proposal. unprecedented literature, density functional theory (DFT) calculations reveal trimethylamine-boryl radical, typical derived from amine-borane complex, even more than its isoelectronic carbon-based counterpart, i.e., neopentyl radical. N–B dative bond (1.603 Å) much longer corresponding C–C (1.503 making significantly less hindered alkyl these two computational findings, facile. final rearomatization then deprotonation intermediate IV oxidation oxidized PC (PC⋅+) (path a). An chain pathway involving direct (SET) also deliver b). practice, stable readily available was identified suitable transformation. presence (4CzIPN), oxidant, trifluoroacetic acid, lepidine 88% yield blue-light irradiation at room temperature. carbene boranes (NHC–BH3) competent NHC-boryl radicals HAT SET process,3Tian Scholar,10Jin Xia Zhang Wang Y. Lewis-base enabled borylation, reduction reactions.Youji Huaxue. 2020; 40: 2185-2194Google no observed chemistry. Similarly, triphenylphosphine (Ph3P–BH3) failed react optimized Collectively, results indicate high nucleophilicity amine-boryl critical importance reactivity. impressive scope functional-group tolerance 1C). broad range industrially relevant N-heteroarenes, including phenanthridines, isoquinolines, phtalazines, quinazolinols, pyridines, pyridazines, pyrimidines, were manner (2–9). Of particular note C4-substituted (5) C2-substituted pyrimidines (7), whose C2 C4 selective, respectively, whereas approaches target C3 C5 sites.1Mkhalid Synthetically functionalities chlorine, hydroxyl, free amino, ester, nitrile all well tolerated practicality methodology gram-scale functionalization pharmaceuticals agrochemicals (8 9). azine products exhibit remarkable bench stability, they retain certain further transformations synthetic building blocks. For C–B oxone phenols, coupled aryl iodides palladium catalysis, converted C–N C–O Chan-Lam amination etherfication, respectively. summary, have disclosed strategy, represents major breakthrough field borylation. complements well, thereby easy access wide variety otherwise inaccessible difficult prepare. More importantly, study spur ligated photocatalysis. Financial support National Natural Science Foundation China (grant no. 22001163 ), “ Thousand Youth Talents Plan ,” Shanghai Jiao Tong University our own research area acknowledged.