Rh(iii)-catalyzed direct C–H/C–H cross-coupling of quinones with arenes assisted by a directing group: identification of carbazole quinones as GSKβ inhibitors

Abstract

Rh-catalyzed direct C-H/C-H cross-coupling reaction of various (hetero)arenes with quinones is developed. This protocol is effective for a broad range of both quinone and arene substrates and a wide range of directing groups for this reaction, affording structurally diverse aryl-substituted quinones with high synthetic utility. Moreover, the present synthetic route allowed for the rapid construction of the carbazole quinone moiety that was identified as a new inhibitor scaffold for GSKβ.

Eco-Friendly, Catalyst and Solvent-Free, Synthesis of Acetanilides and N-Benzothiazole-2-yl-acetamides

“…26 However, a search in the literature revealed that when other substituted acetanilides are needed as starting material in the context of a research project, the preparation used is very similar to that of parent acentanilide, which is almost the same of one century ago, which uses large amounts of solvents and additives such as acetic acid and sodium acetate, for instance. [5][6][7][8][9][10][11][12][13][14][15][19][20][21][22][23][24] It should be pointed out that, although there are a few syntheses of acetanilides in the absence of solvent, it is always necessary the use of grinding or microwave heating in these previously described syntheses or, more recurrent, the use of catalyst such as morpholinium bisulfate, zirconyl triflate, tris(pentaflurophenyl)borate, anatase phase TiO 2 nanoparticles, or even the unconventional rice husk ash, Figure 2. 24 Despite that solvent-free catalyst's dependent approaches represent important contribution, more environmentally friendly procedures which reduce the use of chemicals and energy is still needed.…”

“…For instance, in medicinal chemistry they play a pivotal role affording chemically stable compounds as prodrugs with improved pharmacological profile, and many N-acylated derivatives are in clinical use. 3 On the other hand, acetanilides have natural aptitude to act as ortho directing group in C−H transformations to C−C bond formation, wherein functionalized benzophenone, 4 quinone, 5 bisphenyl, 6 or styrene 7,8 derivatives can be obtained by Pd or Rh catalysis, Figure 1. Besides, the reactivity of some ortho functional group of acetanilides is modulated by the presence of the N-acetyl moiety, which is thus selectively converted to more complex compound, constituting this kind of acetanilide into important synthetic intermediates.…”

“…Besides, the reactivity of some ortho functional group of acetanilides is modulated by the presence of the N-acetyl moiety, which is thus selectively converted to more complex compound, constituting this kind of acetanilide into important synthetic intermediates. 5,[9][10][11][12][13] Due to the abovementioned applications, new developments in the acetylation procedure are still desirables, and representative contributions are described, Figure 2. [14][15][16][17][18][19][20][21][22][23][24] Furthermore, in undergraduate courses, the parent acetanilide is extensively synthesized as classical preparation of aromatic amide.…”

“…Besides, the reactivity of some ortho functional group of acetanilides is modulated by the presence of the N-acetyl moiety, which is thus selectively converted to more complex compound, constituting this kind of acetanilide into important synthetic intermediates. 5,[9][10][11][12][13] Due to the abovementioned applications, new developments in the acetylation procedure are still desirables, and representative contributions are described, Figure 2.14-24 Furthermore, in undergraduate courses, the parent acetanilide is extensively synthesized as classical preparation of aromatic amide.25 Therefore, we recently developed a practical solvent-free green synthesis of such compound to experimental courses. 26 However, a search in the literature revealed that when other substituted acetanilides are needed as starting material in the context of a research project, the preparation used is very similar to that of parent acentanilide, which is almost the same of one century ago, which uses large amounts of solvents and additives such as acetic acid and sodium acetate, for instance.…”

“…313.1-314.3 °C (Lit. 27 312 °C); IR (KBr) n / cm -1 3278, 1654, 1649, 1583, 1516, 1490, 1431, 1365, 1317, 1284, 1128, 1039, 1018, 950, 867, 819, 709, 659, 613 5, 23.8, 124.3, 125.6, 128.7, 132.1, 136.2, 136.7, 3448, 1689,1566, 1427, 1369, 1296, 1230, 1168, 1068, 1041, 995, 972, 875, 821, 779, 709, 659, 628 3448, 1693, 1604, 1546, 1446, 1369, 1269, 1076, 1049, 999, 860, 759, 725, 675, 628 5, 120.4, 121.6, 124.1, 126.4, 131.9, 147.8, 159.7, 3196, 1691, 1606, 1541, 1460, 1365, 1288, 1267, 1247, 1224, 1041, 993, 873, 812, 723, 657 4, 23.5, 119.9, 121.5, 127.9, 132.0, 134.1, 145.6, 159.3, 3406, 1689, 1604, 1550, 1477, 1438, 1369, 1284, 1265, 1215, 1060, 1029, 898, 848, 813, 725, 702, 624 3288, 3088, 2931, 2852, 1714, 1643, 1633, 1556, 1446, 1373, 1315, 1255, 1153, 1129, 981, 891, 736, 607, …”