Ruthenium-Catalyzed Meta-Selective C-H Difluoromethylation of Phenol Derivatives

Abstract

With pyrimidine as the directing group, we achieved the meta-selective difluoromethylation of phenol derivatives using ruthenium as a catalyst. This synthetic scheme provided an efficient method for the syntheses of fluorine-containing phenol derivatives. A wide variety of phenol derivatives were well-suited, affording the corresponding products in moderate-to-good yields.

Remote C–H Functionalizations by Ruthenium Catalysis

“…In contrast to typical secondary alkyl halides, the reaction with protected 2-bromoazetidine delivered the ortho-alkylated product. Very recently, further investigations of meta-C-H alkylations were carried out with arenes bearing different directing groups, such as aryl 2-pyridyl ketones 66 (Scheme 21a), 32 2-phenoxypyridines 42a (Scheme 21b), 33 and 2phenoxypyrimidines 70 (Scheme 21c) 34 at high reaction temperatures of 100-150 °C. In addition to strong N-directing groups, 2-biphenylphosphines 72 were employed as substrates in ruthenium-catalyzed meta-C-H transformation, as was reported by the group of Li (Scheme 21d).…”

Ruthenium-Catalyzed Radical Cyclization/meta-Selective C–H Alkylation of Arenes via σ-Activation Strategy

“…Transition-metal-catalyzed meta -C Ar –H functionalization has been intensively developed in recent years, and four main strategies have been investigated: (a) the steric regiocontrol mode typically realized by Hartwig; (b) the template directing group elegantly designed by Yu, Maiti, and others; (c) the palladium/norbornene cooperative catalysis pattern mainly developed by Yu, Dong, Lautens, and others; and (d) the ruthenium-catalyzed C–H functionalization via σ-activation strategy established by Ackermann, Frost, and others. σ-Activation benefits from the ortho -ruthenation strategy, such as a series of C–H sulfonation, alkylation, halogenation, benzylation, nitration, acetylation, and others, have been developed through the development of a free radical or electrophilic reagent (Scheme a). Most recently, Ackermann and Greaney developed a novel photoinduced ruthenium-catalyzed meta -selective C–H alkylation at room temperature.…”

Dienolate Annulation Approach for Assembly of Densely Substituted Aromatic Architectures

“…The 20 examples presented in Scheme highlight the synthesis of chiral salicylaldehyde imines with two meta -substituents ( R 2 and R 1 ) composed of aryl, alkyl, and trifluoromethyl substituents. Two meta -substitutions are particularly noteworthy given the natural bias of phenols toward substitutions at ortho - and para -positions making meta -substitutions very challenging, which has inspired innovative approaches in recent years. − Yields for the asymmetric amino-Cope step range from good to excellent (1st yield in parentheses) with yields for the DDQ driven aromatization step similarly successful (2nd yield in parentheses). Crystal structure analysis for bis-trifluoromethyl substituted product 10 afforded unambiguous confirmation of structure (CCDC 1451255).…”

“…Product was purified with a gradient of 5−15% EtOAc in hexanes on silica gel, giving 10 as a white solid from General Procedure A (54.4 mg, 0.1244 mmol, 85%): 1 H NMR (500 MHz, CDCl 3 ) δ 12.04 (s, 1H), 8.72 (s, 1H), 7.75 (d, J = 1.8 Hz, 2H), 7.46 (d, J = 1.8 Hz, 2H), 7.33 (d, J = 1.8 Hz, 1H), 7.13 (d, J = 1.8 Hz, 1H), 1.26 (s, 9H); 13 C NMR{ 1 H} (125 MHz, CDCl 3 ) δ 163. 2, 161.2, 145.4, 140.8, 135.4, 130.0, 125.8, 123.8, 126.2, 117.8, 117.6, 114.6, 58.3, 22.2; 19 (S,E)-N-((4″-Bromo-5′-hydroxy-[1,1′:3′,1″-terphenyl]-4′yl)methylene)-2-methylpropane-2-sulfinamide (11). Product was purified with a gradient of 5−15% EtOAc in hexanes on silica gel, giving 11 as a white solid and from General Procedure A (53.2 mg, 0.1165 mmol, 89%): 1 8, 161.5, 147.1, 145.4, 139.3, 137.4, 131.85, 131.3, 129.0, 128.7, 127.2, 122.8, 120.5, 115.0, 114.6, 57.9, 22.3;FT-IR (NaCl film) 3062, 3033, 2961, 2927, 2866, 1593, 1175 (12).…”