Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• indication that the application of this highly-reactive intermediate has made the modified Mannich reaction to be a hot topic again in organic chemistry. This review presents a wide range of applications including cycloadditions and the synthesis of bifunctional amino- or amidonaphthols that can later be

• be explained by the generation of an o-QM intermediate followed by the nucleophilic addition of the amine component, the reverse reaction with the corresponding nucleophile is also feasible. Mechanistically, the Mannich adduct generates an o-QM via the loss of an amine, then this reactive

• intermediate reacts with the nucleophile (dienophile) species in different reactions to form a wide range of heterocyclic compounds. Reactions with C=C dienophiles Reactions of o-QMs with different C=C dienophiles are listed in Table 3. Osyanin et al. reported the efficient reaction of quaternary ammonium salt

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• form an aryl radical. This reactive intermediate reacts with the anion of the respective thiol to form the corresponding diaryl sulfide adducts. The reaction conditions tolerate functional groups like alcohols, esters, halides, the trifluoromethyl group and heterocyclic substrates like thiazoles or

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• . In comparison, the preactivation-based iterative glycosylation is unique, where a glycosyl donor is preactivated in the absence of an acceptor to produce a reactive intermediate (Scheme 1b) [18][19][20][21]. Upon complete donor activation, the acceptor is added to the reaction mixture, which

• drawbacks of the reactivity-based chemoselective glycosylation can be overcome through preactivation. Under the preactivation protocol, a thioglycosyl donor is activated in the absence of an acceptor to form a reactive intermediate (Scheme 13). Upon complete donor activation, a thioglycosyl acceptor is

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• anilines proceed through the formation of unisolable reactive intermediate, aryl N-thiocarbamoylbenzotriazole, which rapidly decomposes to the corresponding isothiocyanate in organic solvent [189]. The Štrukil and Friščić group successfully demonstrated the formation of aryl-N-thiocarbamoylbenzotriazole

• under the LAG (liquid-assisted grinding) synthesis (Scheme 58) [190]. Initially, in situ monitoring of mechanochemical thiocarbamoylation suggests the formation of reactive intermediate which gradually disappears with the formation of thiocarbamoylated product. Furthermore isolation and spectroscopic

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• almost quantitative yields. The in situ Raman monitoring of a 1:2 mixture of 26 and 4-bromoaniline, which results in the formation of symmetrical bis(4-bromophenyl)thiourea 28d revealed thiocarbamoyl benzotriazole 27d as the reactive intermediate (Figure 4). Starting from 27a or 29, bis-thiourea 22a can

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• group contains two heteroatoms, X and Y that can be activated at the remote atom (Y) by an electrophilic species (H of an alcohol) or a metal cation resulting in a reactive intermediate. This complex could then undergo an SN2-like attack of a hydroxy group to furnish the glycoside with inversion of

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• forming a stable reactive intermediate that lowers the overall energy barrier. This stabilization effect is unique to para-dialkylaminopyridine derivatives and much less significant for other pyridine type analogues like collidine. We suggested that the significant effect of DMAP compared to that of

• reactive intermediate. We proved that although it is completely unexpected for primary amines, the case here is very similar to alcohols and that the formation of the stable DMAP-SO2R intermediate is crucial for this transformation. Our calculations clearly indicate that collidine does not produce an

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• 292, which underwent thermal isomerization to give the reactive intermediate 293 [114]. As a result of the Diels–Alder reaction of the latter with cyclopentenone 239, the adduct 294 was formed, which was further subjected to the TEA-induced cleavage at 100 °C to give the desired 1-indanone 295 (Scheme

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland 10.3762/bjoc.13.44 Abstract An intriguing stepwise diradical mechanism of the dimerization of the reactive intermediate (thiocarbonyl S-methanide) appearing in the reaction of phenyl selenophen-2-yl thioketone with diazomethane was studied by means of

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• reaction; cf. Scheme 3). In this case the diol and the metal oxide form a glycol ester intermediate which then undergoes an intramolecular oxidative addition to a remote double bond. Thereby, type B oxidative cyclizations converge to the same (or very similar) reactive intermediate as is passed through in

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

• photochemical route developed for the synthesis of artemisinin the Hock rearrangement of hydroperoxide 223 selectively affords enol 224. This reactive intermediate 224 is then finally oxidized into artemisinin (Scheme 66) [334]. 1.4 Kornblum−DeLaMare rearrangement The Kornblum−DeLaMare rearrangement (KDLM) is a

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• ]. As for most pyranonaphtoquinones, seven rounds of chain extensions followed by controlled cyclisation yield the reactive intermediate 38 after release from the PKS [25][26]. The intermediate is prepared for the action of ActVI-1, which is annotated as a 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• +·, followed by an inductive cleavage with neutral loss of isobutyraldehyde to H2+·. This reactive intermediate can stabilise to the conjugated radical cations I2+· or J2+· by two alternative hydrogen rearrangements. PMA135 for the base peak ion m/z = 135 reveals that this fragment ion is produced from C1–C9

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• phosphorylated hemiorthoamide. This highly reactive intermediate ensures that the rapid elimination of phosphate to generate (ox/thi)azolines is thermodynamically favourable. [18O]-labeled precursor peptide was subsequently used to further substantiate this proposal [37]. A similar heterocyclisation mechanism

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• conditions with a desired primary alcohol. One such alcohol, 2-cyclopropylprop-2-en-1-ol, can be synthesized using a modified Suzuki coupling procedure developed by Soderquist [49] (Scheme 5b). A cyclopropyl boronate can be generated from propargyl bromide, 9-BBN, and aqueous sodium hydroxide. This reactive

• intermediate can be used in situ for the subsequent coupling reaction, which constructs the desired allyl alcohol after deprotection in a 52% yield over two steps. After alkylation, the newly-formed enynes can then be deprotonated with either n-BuLi or LiHMDS and trapped with an aldehyde to form a substituted

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• ; anal. cald for C22H22S6Si (506.89): C, 52.13; H, 4.37; S, 37.96; found: C, 52.44; H, 4.55; S,37.71. ‘Head-to-head dimerization’ of diarylthioketone S-methanides 3a,b leading to 2,2,3,3-tetrasubstituted 1,4-dithianes 4a,b. Diradical nature of the reactive intermediate 3c in the reaction of phenyl

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• an iodobromonium ion) results in a carbohydrate-derived oxocarbonium ion that functions as the reactive intermediate [35]. In the first step, acceptor 6b and glucopyranosyl bromide 13 as the donor were selected and tested in the presence of the above mentioned promoters (see Table 1, entries 1–4) in

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• reactive intermediate in several synthetic transformations [10][11][12][13][14][15]. The chemistry of 2H-azirines has been extensively explored because of its strained molecular structure, unique reactivity and synthetic applications [10][11][12][13][14][15][16][17][18][19][20][21][22]. α-Substituted 2H

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• inventory of the reactive intermediate reduced the safety concerns associated with the use of the azide. The choice of flow when handling hazardous materials like azides is a very frequently encountered driver and several publications detailing the associated benefits have emerged over the years [88][89][90

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• 17 on the oxirane ring in the 1,2-epoxybutane (Scheme 4). The reactive intermediate obtained by the ring opening of the 1,2-epoxybutane abstracts a methylene proton from the salt, generating the corresponding N-ylide (18) in situ. The N-ylide reacts further with the acetylenic dipolarophile to give a

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions

• Bichlien H. Nguyen,
• Robert J. Perkins,
• Jake A. Smith and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2015, 11, 280–287, doi:10.3762/bjoc.11.32

• reactions, the initial alcohol trapping reaction was found to be both exothermic and reversible. Hence, cooling the reaction to −78 °C helped to maintain the initial cyclization and to keep the cation character of the reactive intermediate low. This significantly increased the yield of the desired

Switching the reaction pathways of electrochemically generated β-haloalkoxysulfonium ions – synthesis of halohydrins and epoxides

• Akihiro Shimizu,
• Ryutaro Hayashi,
• Yosuke Ashikari,
• Toshiki Nokami and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2015, 11, 242–248, doi:10.3762/bjoc.11.27

• speed of organic syntheses and this is an example of integration of an electrochemical reaction and a chemical reaction using a reactive intermediate. Herein, we report that the reaction pathways of β-haloalkoxysulfonium ions can be switched to give different products by changing the base, thus

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• electrochemical anodic oxidation of an α-methylene group to an amide (or carbamate) to generate a new carbon–carbon bond via an anodic methoxylation step and Lewis acid mediated generation of an N-acyliminium ion reactive intermediate; Scheme 1 overviews such a process [11]. Although the anodic oxidation

• electrolysis of carbamates to accumulate the N-acyliminium ion reactive intermediate then under non-oxidative conditions the nucleophile is introduced. Importantly, the nucleophile cannot be present when the N-acyliminium ion is being formed under electrochemical conditions, as in most cases it is easier to

• in situ. The tagged and now stable “reactive intermediate” can then be removed from the electrolyte solution. Warming the tagged “reactive intermediate” converts the micelle (eicosane, a thermosensitive alkane) from solid to liquid and releases the thiomaleimide tagged N-acyliminium ion. Further

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• anodic oxidation of electron-rich olefins such as enol ethers 1 in methanolic solution generates radical cation 2 which can be used for a number of cyclization reactions (Scheme 2) [32][33]. Moeller et al. demonstrated that by intramolecular trapping of this highly reactive intermediate with a tethered

• vs. SCE. Furthermore, the use of PTFE-coated platinum as working electrode proved to be beneficial. Presumably, the reaction sequence proceeds within the hydrophobic electrode coating, where the highly reactive intermediate 53 is protected from side-reactions and the reaction with the hydrophobic

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• by the formation of 4-nitrobenzaldehyde. This can potentially occur by benzylic deprotonation, due to the enhanced acidity of these protons in 1o or a reactive intermediate. Such a problem was not encountered in the reactions of other benzylic alcohols. Use of K2CO3 in place of DBU did not ameliorate