Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• catalyst using 2-arylpyridines (Scheme 15). Earlier reports described the propenylation took place on the ortho-position of the phenyl ring [76][77], whereas this group achieved the propenylation of the pyridine moiety. The authors screened different allyl halides and Ru complexes as catalysts. With the

• and practical synthesis of 2-arylpyridines. The reaction starts with the formation of arylated pyridine N-oxide 116 by reaction of pyridine N-oxide 9 with the arylboronic ester 114 in the presence of Cu catalyst and base which is followed by deoxygenation to furnish the desired product 115 (Scheme 22b

• pyridine to form aryl–Pd(II) species 140 via intermediate C. Subsequently, oxidative addition takes place in the presence of the aryl halide to give the Pd(IV) complex 141 followed by reductive elimination furnishing 3-arylpyridines 138. Almost at the same time, Yu and co-workers reported the selective Pd

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• observed exclusively. By slightly altering the reaction conditions, 2-arylpyridines 85a were able to undergo the ring-opening/dehydration reaction with oxabicyclic alkenes to afford ortho-naphthylated products 86a. Concurrently, the Li group investigated the same ortho-naphthylation of N-pyrimidinylindole

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• several directing groups (Scheme 8) [121]. With this methodology, the functionalization of 2-phenylpyridine derivatives was possible (10 examples, up to 81% yield) using the Billard reagents III or IV [122]. The trifluoromethylthiolation of 2-arylpyridines substituted by electron-donating groups such as

• (CH3CN)3](SbF6)2 and N-trifluoromethylthiodibenzenesulfonimide VII as electrophilic SCF3 source (Scheme 12) [125]. Under these reaction conditions, 2-arylpyridines (9 examples, up to 94% yield) or 6-arylpurines (10 examples, up to 72% yield) were ortho-trifluoromethylthiolated. The substitution pattern

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• the natural abundance and versatile reactivity. Early examples of copper-promoted C−H activation of 2-arylpyridines were disclosed by Yu et al. [12] and Chatami et al. [13] independently. Inspired by these studies, various copper-induced C−H functionalizations, such as arylations, alkynylations

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• tricyclic indoles bearing 3,4-fused seven-membered rings, 2‑arylpyridines, aminonaphthalenes and 3-phenylisoquinolines. In addition, this catalyst showed to be recyclable and could be reused several times without significant loss in activity during the course of the reaction process. Keywords: biomass

• significant damage of the Cu species. The pyridine-containing moiety, such as arylpyridines, widely exist in natural products, pharmaceutical agents and functional materials [34][35][36][37]. Traditional methods for synthesizing pyridine-containing derivatives include condensation reactions, cross-coupling

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• the synthesis of (2-hydroxyaryl)pyridines from 2-arylpyridines via a direct C–H hydroxylation on the aryl ring using several expensive transition metal salts (e.g., Pd(II) [60][61][62][63], Rh(III) [64][65], Ru(II) [66]) as catalysts (Scheme 1a). However, the above methods have several drawbacks such

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• , Poland 10.3762/bjoc.14.214 Abstract Background: Atropisomers are very interesting stereoisomers having axial chirality resulting from restricted rotation around single bonds and are found in various classes of compounds. ortho-Substituted arylpyridines are an important group of them. A regio- and

• selectivity using a differently ortho-substituted phenylbornic acid was observed. Keywords: arylpyridines; atropisomerism; cross-coupling; palladium; Suzuki–Miyaura reaction; Introduction Axially chiral biaryls not only subsist in many classes of natural and bioactive compounds [1][2] but also are an

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• manner. Thus, Li et al. developed a cobalt-catalyzed hydroarylation of maleimides and maleate esters with arenes 48 (Scheme 30) [85]. A variety of arenes including indoles, 2-arylpyridines, 6-arylpurine, and vinyl pyridines were employed to give alkylated products 49 in good to moderate yields. As well

• -catalyzed hydroarylation of C=X bonds Transition-metal-catalyzed addition of C–H bond to polar π bonds such as imines, isocyanates and carbonyls is one of the efficient methods to incorporate heteroatoms in organic molecules [45]. Yoshikai et al. developed an addition reaction of arylpyridines 3 to imines

• using low-valent cobalt catalyst generated from CoCl2, IPr·HCl, and t-BuMgBr (Scheme 35) [95]. The reaction tolerated a wide range of arylpyridines and aldimines, giving diarylmethylamines 57 in good yields. The reaction possibly proceeds through the formation of neopentylcobalt ([Co]-R), which

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• phenols from arenes. 1.2.2.1 Pyridine and nitrogen containing functional groups as directing groups: In 2008, Kim and co-workers synthesized a series of 2-arylpyridines, in which another aryl group was located at 3-position and a benzyl group at 5-position of the pyridine ring. Then they developed a Pd

• °C (Scheme 31). In 2015, Itoh and co-workers employed PdCl2 as catalyst and the hydroxylation of arylpyridines was carried out in 4-methyl-2-pentanone at 100 °C in the presence of H2O2 (Scheme 32) [61]. In terms of reactivity, substituent at the para-position of the phenyl ring is more favored than

• at other positions. In 2015, Sun and co-workers developed a Pd(OAc)2 catalyzed ortho-hydroxylation of 2-arylpyridines using tert-butyl hydroperoxide (TBHP) as oxidant [62]. The reaction was carried out at 115 °C in 1,2-dichloroethane (DCE), affording the corresponding phenols in moderate to good

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• unsymmetrically substituted diarylpyridines, difficult to access by other methods. Keywords: arylpyridines; cross coupling reaction; heteroaromatics; one-pot reaction; palladium catalyst; Introduction Nitrogen heterocycles are an important class of compounds widely present in agrochemical products [1][2] and

• , the forensic community treats them as "route-specific impurities" or "route markers". The formation of these compounds results from the condensation of the drug precursors, like arylacetones with formamide or ammonia, in the presence of formic acid. This leads to di- and tetrahydrobenzyl/arylpyridines

• will be elaborated in a separate study. Types of aryl pyridines and pyrimidines already prepared in our group [23][24][25][26][27]. Synthesis of diarylpyridines 4–29. Synthetic routes leading to unsymmetrically substituted arylpyridines. Preparation of unsymmetrical 3,5-diaryl-2,4,6-trimethylpyridines

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• sulfonimidation [55]. In contrast to the direct transformation of the weakly acidic C–H bonds in these electron deficient arenens/heteroarenes, the amidation of normal aryl C–H bonds usually relied on the presence of a directing group (DG). In 2010, Li et al. [56] reported the o-amidation of 2-arylpyridines 34

• sulfonamidation of 2-arylpyridines via C–H activation. Besides the peroxide-free advantage, the C–H amination using aniline was found applicable to allow the synthesis of biarylamine. More recently, based on the DG strategy, the Yu group [59] designed the o-amidation of arylamides with copper catalysis under

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• rate-limiting step. In 2011, Cheng and co-workers discovered an alternative route of a C–H chlorination protocol of 2-arylpyridines by employing acyl chlorides 6 as chlorinating reagents [33]. A range of mono-chlorinated 2-arylpridines 2 were obtained in the presence of Cu(OAc)2 and Li2CO3 under O2

• atmosphere (Scheme 2). In the same year, Shen and co-workers reported the Cu-catalyzed sp2 C–H chlorination of 2-arylpyridines by using the salt LiCl as a new chlorine source in the presence of CrO3 and Ac2O [34]. Due to the oxidizing potency of the CrO3, the application scope of the method was not broad

• , the unavailability of a practical copper-catalyzed halogenation of alkyne C(sp)–H bonds is also an issue requiring urgent attention. Copper-catalyzed C–H bond halogenation of 2-arylpyridine. ortho-Chlorination of 2-arylpridines with acyl chlorides. Copper-catalyzed chlorination of 2-arylpyridines

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

• [25][26][27][28][29][30][31][32]. 1.1 Reactions involving C(sp2)–H bonds of aromatic C-reagents In one of the first publications on the preparative introduction of the –OR group into CH-reagents containing directing groups, 8-methylquinoline, 2-arylpyridines, N-phenylpyrazole, azobenzene, and

• regioselectivity of the ortho-acetoxylation of meta-substituted arylpyridines and N-arylamides 1 was studied [34]. The acetoxylation occurs mainly at the sterically more accessible para-position relative to the substituent R to form product 2. The lowest regioselectivity (2:3 = 6:1) was observed in the case of R

• , arylethylenes, and arylacetylenes were used as precursors of the acyloxy fragment. The cross-dehydrogenative C–O coupling with 2-arylpyridines 4 proceeds also in the presence of the Cu(OAc)2/O2 system [40] and under electrochemical oxidation in the presence of Pd(II) salts [41]. The pyrimidine (acetoxylation of

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• ) acetate as additives proved essential for achieving high yields of the desired trifluoromethylated arenes. 2-Arylpyridines, but also other aryl-substituted heteroarenes were successfully trifluoromethylated with complete regioselectivity in the position ortho to the aryl–heteroaryl bond, with moderate to

• additives have not been elucidated yet. The group of J.-Q. Yu further studied this reaction by adapting it to secondary N-arylbenzamides as more versatile substrates than arylpyridines [68]. In comparison with the previous reaction conditions, two equivalents of Cu(OAc)2 had to be used instead of one, and N

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• , efficiently leading to a variety of functionalized 2-arylpyridines [17]. More recently, this nickel-catalyzed reaction provided a convenient and mild method for a one-pot synthesis of substituted benzofurans, chromans and indoles by carbonickelation of alkynes [18]. We finally decided to extend the scope of

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• 3-arylpyridines also found application [43][44], and likewise falls into the category of indole ring closure onto an existing substituted pyridine, though in this case with the formation of the C–N bond. More recently, the group of Cuny has reported two strategies that exploit cross-couplings to