Equivalent Loading of Directed Arenes in Pd(II)-Catalyzed Oxidative Cross-Coupling of Aryl C–H Bonds at Room Temperature

Abstract

The unsymmetrical biaryls (Ar1–Ar2) produced by the catalytic cross-couplings of aryl halides (Ar1–halo) with aryl metallics (Ar2–M) in the loading ratio of 1:1 are popular in chemical synthesis. In contrast, there has been less precedence on the same biaryls produced effectively from two normal aryl C–H bonds with equivalent loading. Here, we report that, in a palladium/oxidant/acid catalytic system at room temperature, one arene (Ar1–H, 1 equiv) can highly selectively couple with the other one (Ar2–H, 1 equiv) to afford the target Ar1–Ar2 just by controlling the directing groups and the substituted groups on their phenyl rings. The utility of this one–one cross-coupling is also demonstrated by synthesis of a few bioactive molecules.

Copper‐Catalyzed Regioselective Halogenation of Anilides with N‐Fluorobenzenesulfonimide

“…N ‐(4‐bromophenyl)pivalamide 3 c : [27] white solid (43.5 mg, 85 %); R f =0.3 (petroleum ether/ethyl acetate=5 : 1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.46–7.40 (m, 4H), 7.34 (br, 1H), 1.31 (s, 9H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 176.7, 137.1, 131.9, 121.7, 116.7, 39.7, 27.6; MS (C 11 H 14 BrNO): 256 [M+1] + .…”

“…N-(4-bromophenyl)pivalamide 3 c: [27] white solid (43.5 mg, 85 %); R f = 0.3 (petroleum ether/ethyl acetate = 5 : 1); 1 H NMR (400 MHz, CDCl 3 ) δ 7.46-7.40 (m, 4H), 7.34 (br, 1H), 1.31 (s, 9H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 176. 7, 137.1, 131.9, 121.7, 116.7, 39.7, 27.6 138.6, 134.7, 131.7, 131.4, 128.4, 127.7, 122.2, 115.3; IR (KBr, cm À 1 ): 3441 (br), 2357 (s), 1650 (m), 1387 (m), 822 (s); HRMS (ESI) calcd for C 13 H 10 BrNO + [M + H] + : 276.0019, found: 276.0015.…”

Palladium-catalyzed cross-dehydrogenative coupling of (hetero)arenes

“…The possibility that the second C-H bond activation step took place on a further molecule of pivalamide was excluded here by DFT calculations: the freeenergy barrier of the unsymmetrical diarylpalladium(IV) reductive elimination transition state to give CDC product Ar 1 -Ar 2 -TS (ΔΔG = 19.1 kcal mol −1 ) was lower than that of the symmetrical diarylpalladium(IV) reductive elimination transition state to give pivalamide homo-coupling Ar 1 -Ar 1 -TS (ΔΔG = 21.1 kcal mol −1 ); in other words, the rate of reductive elimination of the Scheme 8 ortho-Arylation of anilides bearing a strong amide coordinating group ( pivalamide, -NHPiv) with arenes bearing a weak coordinating group ( phthalimide, t-butyl benzamide, ethyl benzoate) by Pd-catalyzed CDC reactions, reported in 2021 by Lu and co-workers. 24 unsymmetrical Ar 1 -Pd(IV)-Ar 2 intermediate is faster than that of symmetrical Ar 1 -Pd(IV)-Ar 1 (Scheme 8b).…”

“…23 A very detailed study on the ortho-arylation of anilides via CDC reactions was reported in 2021 by Lu and co-workers, who described the preparation of unsymmetrical 2,2′-bisanilides by the Pd-catalyzed double C-H bond activation of two different anilides: one bearing a strong amide coordinating group ( pivalamide, -NHPiv), the other bearing a weak amide coordinating group ( phthalimide, -NPhth) (Scheme 8). 24 The protocol optimization was carried out using N-(3-methylphenyl)pivalamide and N-(3-methoxyphenyl)phthalimide as model substrates: interestingly, working with Pd(OAc) 2 as the catalyst and K 2 S 2 O 8 as the oxidant, in a TFA/MeSO 3 H mixture for 1 h at room temperature, the desired CDC product was obtained in good yield and excellent selectivity (i.e., a very low formation of homo-coupling by-products) even in the presence of an equimolar amount of both coupling partners. This methodology was then successfully extended to a broad range of substrates, with only a few variations in experimental conditions: Pd(OAc) 2 (5-10 mol%), K 2 S 2 O 8 (1.5-2.0 equiv.…”