On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• a mild and efficient protocol for the remote C4–H sulfonylation of 1-naphthylamine derivatives with sodium sulfinates in the presence of K2S2O8 as the oxidant (Figure 35) [99]. This strategy was based on the use of a bidentate picolinamide DG promoting the direct C–H functionalization of the

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• with aqueous H2SO4. However, the acid hydrolysis step was accompanied with extensive racemization [81][83] (Scheme 42). 4. Synthesis of α-fluorophenylalanine of type V via α-fluorination of Phe derivatives The successful α-fluorination of phenylalanine derivative 174 carrying a picolinamide auxiliary

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• . Herein, we explored a simple and facile protocol for cobalt-catalyzed picolinamide-directed alkoxylation of 1-naphthylamine derivatives with alcohols (Figure 1c). Results and Discussion Initially, N-(naphthalen-1-yl)picolinamide (1a) and hexafluoroisopropanol (HFIP, 2a) were chosen as the model

• amino group at C5 of the substrate 1g was also compatible with the transformation (33%). When a methoxy group was located at the C7 site of the naphthylamine, sterically hindered product 3ha was obtained in 81%. Besides, some benzylamine derivatives (N-(1-phenylethyl)picolinamide and N

• )picolinamide derivatives. Reaction conditions: 1 (0.2 mmol), 2a (1.0 mL), CoF2 (20 mol %), Ag2CO3 (1.0 equiv), Cs2CO3 (1.0 equiv), DCE (1.0 mL), 100 °C, air, 12 h. Reaction scope with respect to alcohols. Reaction conditions: 1a (0.2 mmol), 2 (1.0 mL), CoF2 (20 mol %), Ag2CO3 (1.0 equiv), Cs2CO3 (1.0 equiv

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• reported two-step oxidation/Reissert-type sequence [21][22]. The access to the key intermediate trithiazolylpyridine 9 was next investigated via two synthetic routes by exploiting BSC cross-coupling and Hantzsch condensation reactions from the picolinamide 5, which was produced by simple treatment of 6

• sequence to build and introduce both thiazole units to the picolinamide 5 (Scheme 1). Pleasingly, the application of the optimized BSC procedure based upon the use of Pd(OAc)2 as pre-catalyst allowed to achieve the cross-coupling of picolinamide 5 with methyl(4-bromothiazol-2-yl)ketone (8), providing the

• in fair 59% yield over 2 steps. Finally, the second synthetic pathway proved to be slightly more performant to produce the trithiazolylpyridine key-intermediate 9 from the picolinamide 5 in 58% yields over 3 steps (vs 55% for the first synthetic route). Then, the trithiazolylpyridine 9 was engaged in

Palladium-catalyzed picolinamide-directed iodination of remote ortho-C−H bonds of arenes: Synthesis of tetrahydroquinolines

• William A. Nack,
• Xinmou Wang,
• Bo Wang,
• Gang He and
• Gong Chen

Beilstein J. Org. Chem. 2016, 12, 1243–1249, doi:10.3762/bjoc.12.119

• Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China 10.3762/bjoc.12.119 Abstract A new palladium-catalyzed picolinamide (PA)-directed ortho-iodination reaction of ε-C(sp2)−H bonds of γ-arylpropylamine substrates is reported. This reaction proceeds selectively with a variety of γ

• many natural products and pharmaceutical agents [1][2]. Efficient and generally applicable methods for the synthesis of THQs with complex substitution patterns are still in great demand [3][4][5][6][7]. Recently, we reported a synthetic strategy for THQs based on picolinamide (PA)-directed sequential C

• LiBHEt3 to give 31 (Scheme 3) [10]. Conclusion In summary, we have developed a new palladium-catalyzed picolinamide (PA)-directed iodination reaction of ε-C(sp2)−H bonds of γ-arylpropylamine substrates. This method works well for arenes with a broad range of substituents and offers a complementary scope

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• formation of products 50–54 (Scheme 10). The ortho-acetoxylation of compounds containing picolinamide and quinoline-8-amine moieties (55 and 56, respectively) with the Pd(OAc)2/PhI(OAc)2 system in a AcOH/Ac2O mixture, resulting in the formation of products 57, 58, was performed at higher temperature (150 °C

• the ortho-position of the aromatic system, which is also adjacent to the directing group. The Pd(OAc)2/PhI(OAc)2 oxidative system was employed in the methoxylation of dimethylcarbamoyltetrahydrocarbazoles 76 [75] and the acetoxylation of compounds containing the picolinamide directing group 78 [76][77

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• ] (Scheme 11). This synthesis published by Pearson et al. was based on palladium-catalysed picolinamide-directed sequential C–H functionalization reactions, while readily available benzylamine and aryl iodide were used as precursors. In the first step the Pd-catalyzed reaction yielded a biaryl compound. The

• second step under the catalysis of Pd(OAc)2 comprised both cyclisation and oxidation in a single step: a dehydrogenative C–H amination with PhI(OAc)2 as oxidant and removal of the picolinamide group followed by oxidation with Cu(OAc)2. This strategy afforded phenanthridines in moderate to good yields (up

A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand

• Hideki Shimizu,
• Jeffrey C. Holder and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2013, 9, 1637–1642, doi:10.3762/bjoc.9.187

• and removing chromatographic purifications are currently underway. Experimental (S)-N-(1-hydroxy-3,3-dimethylbutan-2-yl)picolinamide (4): To a 200 mL round bottom flask was added picolinic acid (2.46 g, 20.0 mmol, 1.00 equiv), 50 mL CH2Cl2, and N-methylmorpholine (3.03 g, 30.0 mmol, 1.50 equiv). The

• , 1244, 1088, 1053, 998 cm−1; HRMS (MultiMode ESI/APCI) m/z: [M + H]+ calcd for C12H19N2O2, 223.1447; found, 223.1448; [α]25D −8.7 (c 1.17, CHCl3, >99% ee). (S)-N-(1-chloro-3,3-dimethylbutan-2-yl)picolinamide hydrochloride (11): A 500 mL 3-neck round bottom flask was charged with a stir bar, amide

Synthesis of phenanthridines via palladium-catalyzed picolinamide-directed sequential C–H functionalization

• Ryan Pearson,
• Shuyu Zhang,
• Gang He,
• Nicola Edwards and
• Gong Chen

Beilstein J. Org. Chem. 2013, 9, 891–899, doi:10.3762/bjoc.9.102

• States of America 10.3762/bjoc.9.102 Abstract We report a new synthesis of phenanthridines based on palladium-catalyzed picolinamide-directed sequential C–H functionalization reactions starting from readily available benzylamine and aryl iodide precursors. Under the catalysis of Pd(OAc)2, the ortho-C–H

• bond of benzylpicolinamides is first arylated with an aryl iodide. The resulting biaryl compound is then subjected to palladium-catalyzed picolinamide-directed intramolecular dehydrogenative C–H amination with PhI(OAc)2 oxidant to form the corresponding cyclized dihydrophenanthridines. The benzylic

• position of these dihydrophenanthridines could be further oxidized with Cu(OAc)2, removing the picolinamide group and providing phenathridine products. The cyclization and oxidation could be carried out in a single step and afford phenathridines in moderate to good yields. Keywords: C–H functionalization