Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• side-product/byproduct can significantly affect the yield of the subsequent reaction step. Reactions involved in a multistep synthesis can be classified in many ways. The general approach for classification of reactions is based on the activation methods like radical reaction, electrophilic reaction

Highly reactive, liquid diacrylamides via synergistic combination of spatially arranged curing moieties

• Maximilian Maier,
• Magnus S. Schmidt,
• Markus Ringwald and
• Christoph P. Fik

Beilstein J. Org. Chem. 2017, 13, 372–383, doi:10.3762/bjoc.13.40

• −1. After one intramolecular ring is formed, there are three general options for a further radical reaction: a) Intermolecular radical propagation, b) intermolecular cyclization, and/or c) intramolecular cyclization. Assuming an incomplete conversion and judging from the remaining IR signals in the

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• temperature (Table 1). The bromination reaction activated by heating in the dark produced a 62.9% yield of the monobrominated product 1-(bromomethyl)-2,5-dichloro-4-methylbenzene (2a) accompanied by a small amount of 1,4-bis(bromomethyl)-2,5-dichlorobenzene (2b) (Table 1, entry 2). Next, a radical reaction

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• -dithiolanes, supports the proposed stepwise radical reaction mechanism via a stabilized 1,5-diradical as an intermediate. Finally, in the case of ferrocenyl methyl thioketone used as a dipolarophile, the concerted [3 + 2]-cycloaddition dominated due to the reduced stabilizing effect of the methyl group

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• cycloalkanes 2 and N-methyl-N-(2-methylallyl)benzamide (4a). As indicated in Scheme 3, several cycloalkanes were well-tolerated in this radical reaction resulting in the corresponding product. In the case of cyclopentane (2b), a slightly lower chemical yield was obtained (46%, 5ab), while the reactions of

Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated compounds

• Gerold Heuger and
• Richard Göttlich

Beilstein J. Org. Chem. 2015, 11, 1226–1234, doi:10.3762/bjoc.11.136

• catalysis and amidyl radicals, a concerted mechanism has been ruled out and a polar mechanism via chloronium ions would lead to the opposite regiochemistry. Keywords: addition reactions; catalysis; N-chlorosulfonamides; haloamination; radical reaction; Introduction In earlier publications we described the

• wanted to verify the radical-type mechanism which we initially anticipated. Ionic or radical reaction mechanism For these studies we first chose vinylcyclopropane as the substrate to rule out a concerted mechanism, as this alkene upon addition of a radical or a cation should react fast under ring-opening

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

• -BuOOH in the presence of Bu4NI [143]. It is proposed that tert-butyl peresters 144 are produced as a result of the recombination of acyl radicals 145 and tert-butyl peroxide radicals. The radical reaction mechanism was confirmed by the experiment, in which acyl radicals generated from aldehyde 146 were

• ketones 203 [196]. Coupling products 203 were synthesized mainly from benzyl alcohols and propiophenone (Scheme 42). The authors proposed two radical reaction pathways, including the formation of C-radicals from ketones. One of these pathways involves the formation of tert-butyl peresters from alcohols

Direct C–H trifluoromethylation of di- and trisubstituted alkenes by photoredox catalysis

• Ren Tomita,
• Yusuke Yasu,
• Takashi Koike and
• Munetaka Akita

Beilstein J. Org. Chem. 2014, 10, 1099–1106, doi:10.3762/bjoc.10.108

• catalysis; radical reaction; trifluoromethylation; Introduction The trifluoromethyl (CF3) group is a useful structural motif in many bioactive molecules as well as functional organic materials [1][2][3][4][5][6]. Thus, the development of new methodologies for highly efficient and selective incorporation of

One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions

• Shuhei Sumino,
• Akira Fusano,
• Hiroyuki Okai,
• Takahide Fukuyama and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2014, 10, 150–154, doi:10.3762/bjoc.10.12

• bromides and nucleophilic addition of a cyanide ion was investigated, which gave moderate to good yields of cyanohydrin derivatives in one-pot. Keywords: alkyl bromide; carbon monoxide; cyanohydrin; ethyl cyanoformate; multicomponent; radical reaction; Introduction Radical carbonylation reactions have

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

3-Pyridinols and 5-pyrimidinols: Tailor-made for use in synergistic radical-trapping co-antioxidant systems

• Luca Valgimigli,
• Daniele Bartolomei,
• Riccardo Amorati,
• Evan Haidasz,
• Jason J. Hanthorn,
• Susheel J. Nara,
• Johan Brinkhorst and
• Derek A. Pratt

Beilstein J. Org. Chem. 2013, 9, 2781–2792, doi:10.3762/bjoc.9.313

• resultant phenoxyl radical (ArO•) is sufficiently unreactive toward the substrate (RH) that it reacts with a second peroxyl radical (reaction 2 in Scheme 2), thereby breaking two oxidative chains per molecule of antioxidant – a ratio commonly referred to as the stoichiometric factor (n). However, under some

Iron-catalyzed decarboxylative alkenylation of cycloalkanes with arylvinyl carboxylic acids via a radical process

• Jincan Zhao,
• Hong Fang,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2013, 9, 1718–1723, doi:10.3762/bjoc.9.197

• alkenylation of cycloalkanes with high selectivity and stereospecificity remains a great challenge and attracted a lot of attention in the past years. In 1996, the Fuchs group described the alkenylation of cyclohexane by a radical reaction with vinyl triflone [58]. In 2003, the Yao group reported that styryl

Bromination of hydrocarbons with CBr₄, initiated by light-emitting diode irradiation

• Yuta Nishina,
• Bunsho Ohtani and
• Kotaro Kikushima

Beilstein J. Org. Chem. 2013, 9, 1663–1667, doi:10.3762/bjoc.9.190

•  1, entry 9), showing that the present reaction was a radical reaction. Based on the assumption that the initial formation of bromine radicals would be important, addition of catalytic amounts of CBr4 along with various bromination sources was examined (Table 1, entries 10–12). The combination of

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• indanes or dihydrobenzofurans are too slow to be useful synthetically. Keywords: aromatic substitution; computational chemistry; DFT-D3; free radical; polar effects; radical reaction; Introduction The development of efficient catalytic reactions is one of the central issues of chemistry [1][2]. Radical

• our system and that are experimentally well investigated. An ideal radical reaction in this respect is the 5-exo cyclization (Scheme 2) of the 5-hexenyl radical. The reaction is preparatively highly important and has been used in many syntheses of complex molecules [3][4][5]. Moreover, the kinetics of

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• the reaction were also revealed. This stereoselective radical reaction was used for synthesis of chiral pyroglutamic acid derivatives starting from a commercially available chiral amino acid. Keywords: chelation controlled reaction; diastereoselective reaction; free radical; lactams; pyroglutamic

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• 2002 that hydroxamic acid derivatives are useful achiral templates in enantioselective Diels–Alder reactions [69][70]. To study the effect of hydroxamate ester as an achiral template in the intermolecular radical reaction, our experiments began with the investigation of cascade radical addition

Photoinduced synthesis of unsymmetrical diaryl selenides from triarylbismuthines and diaryl diselenides

• Yohsuke Kobiki,
• Shin-ichi Kawaguchi,
• Takashi Ohe and
• Akiya Ogawa

Beilstein J. Org. Chem. 2013, 9, 1141–1147, doi:10.3762/bjoc.9.127

• ). In 1999, Barton and co-workers reported that diaryl selenide was obtained by the reaction of triarylbismuthine with diphenyl diselenide under heating at high temperature (140 °C) [65], but the photoinduced reaction was not investigated. In this letter, we will report the radical reaction of diaryl

• a bed of celite (Celite 535). The crude product was purified by preparative TLC on silica gel (eluent: hexane/EtOAc). Details about compounds 3ab [30], 3ac [14], 3ad [17], 3ba [17], 3bb [31], 3ca [17], 3da [32], 3ea [28] and 3dc [30] were reported in the corresponding articles. Photoinduced radical

• reaction of diaryl diselenide with triphenylbismuthine. Photoinduced reaction of diphenyl disulfide with triphenylbismuthine. A plausible reaction pathway for the photoinduced reaction of diaryl diselenide with triarylbismuthine. Reaction of diphenyl diselenide with triphenylbismuthine under different

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• through a second radical reaction with dichlorovinyl ethylsulfone (132) [54]. The ethylsulfonyl radical created in the addition–elimination process of intermediate radical 133 fragments to liberate sulfur dioxide and an ethyl radical that is capable of propagating the chain. The resulting product 134