Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• compared to the more studied late TMs [39][40][41][42][43]. Besides the more recognized concept of TM cross-coupling reactions revolving around an organic electrophile bearing a leaving group and an organometallic nucleophile, there is another large area of cross-coupling reactions that have been under

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• -yl)methanols 87 as electrophile and 2-naphthols 88 or phenols 90 as nucleophile (Scheme 29) [45]. The (3-alkynylindol-2-yl)methanol 87 is expected to convert to the allene-iminium intermediate I-24 by accepting a proton from CPA 14. Then, the CPA anion activates the nucleophilic addition between 2

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• , underwent cyclization in the presence of silica gel to give ethyl 6-(hetero)aryl-2,3-dihydro-1H-pyrrolizine-5-carboxylates within minutes upon microwave heating in xylene at 150 °C. Instead of functioning as a nucleophile, the enaminone acted as an electrophile at its carbonyl group during the cyclization

• other words, the enaminone component did not act as a nucleophile towards the ester, as it did with the N-phenacylenaminones 11. Instead, it functioned as an electrophile at its carbonyl group by condensation with the methylene unit α to the ester, thereby forming the C5–C6 bond of the azabicyclic

• 5,6,7,8-tetrahydroindolizines 26, respectively, when subjected to microwave heating with silica gel in suitable solvents. The enaminone acted as an electrophile in these cyclization reactions rather than as a nucleophile, as had previously been found with N-phenacyl analogues [18]. The formation of

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• aliphatic amines [84] 46. The results of the mechanistic studies showed that a copper/tridentate carbazolide-bisphosphine ligand complex serves as a new photoredox catalyst engaged in the electron transfer to the electrophile. Under photoexcitation, the excited photoredox catalyst F reduces the alkyl halide

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• combining photoredox and diazonium chemistry. By starting from the commercially available 2,5-dichlorobenzoquinone (1), we eliminate the issue of regioselectivity and effectively create a green synthesis pathway towards a versatile bis-electrophile. Results and Discussion We initiated our investigation by

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• of HBr in these processes. The influence of steric and electronic factors from both the perspective of the nucleophile and electrophile were investigated and levels of enantiocontrol up to 90% ee obtained. The synthetic utility of the methodology was demonstrated via the concise enantioselective

• manipulations; C) This work: base-free enantioselective alkylation of 2-oxindoles 5. Enantioselective synthesis of a CRTH2 receptor antagonist. Catalyst evaluation. Electrophile scope. Supporting Information Supporting Information File 320: Experimental part. Funding This research emanated from investigations

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• demonstrated by Yu. A suitable halophosphine 75 was reacted with C2-deprotonated C3-tethered (77) or untethered (74) N-protected indoles for that purpose (Scheme 9a) [65]. Later, Wassenaar reported a similar strategy with trichlorophosphine as the electrophile for attaching three indole moieties to a single P

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• (ratio N-1:N-2 = 61:1 for indazole 22 and > 99:1 for indazoles 23 and 24), when employing Cs2CO3 in DMF (Table 2, entries 11–13). The latter exclusive formation of the corresponding N-1 regioisomer observed for indazoles 22 and 23 under conditions B may arise from the steric repulsion of the electrophile

• cation chelation via the N-2 atom electron lone pair and the C-3 substituent X=O functionality, respectively [24]. Tight ion pair formation with the sodium cation and both the N-2 atom and C-3 substituents of the indazole scaffold likely hinders the approach of the electrophile to N-2 and directs

• electrophile under conditions A (Table 6, entry 8) furnished the desired N-1 regioisomer 75 in very good isolated yield (81%). These latter results would suggest that secondary alkyl tosylates are more suitable than their corresponding halide counterparts, for N-1 regioselective alkylation, under these

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• to an activated electrophile, e.g., an electron-deficient olefin, generating a zwitterion (i, Scheme 1). In further course, the zwitterion acts as a nucleophile or as a base [1]. The efficiency of the formation of this β-phosphonium α-carbanionic species depends on the nucleophilicity of the

• formed by the conjugate addition of the phosphine to the Michael acceptor, is believed to be protonated by the alcohol forming the actual catalytically active species namely ion pair ii, consisting of a phosphonium cation and an alkoxide. The alkoxide in ii then reacts with another electrophile

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• ) [55]. A probable mechanism for this transformation was proposed as illustrated in Scheme 29. The cycloaddition reaction between copper(I) acetylide 99 and organic azide 95 occurs to obtain the triazole cuprate intermediate 100, which reacts as a nucleophile with the disulfide electrophile 97 to

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• alkyl-substituted olefins instead of the aromatic styrenes used in the majority of methodologies (Scheme 14) [47]. Two examples of quaternary carbon centers were described, and a reactivity difference was noted between acyclic 26 and cyclic nucleophile 8 toward the same electrophile. The authors

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• ][9][10][11] and other compounds that show different types of biological activities [12][13]. The way to achieve these transformations is by intramolecular cyclizations, involving the free primary amine, and appropriate reactive positions (those positions bearing a leaving group) in the electrophile

• carried out in the presence of the electrophile (chiral imine 79). Surprisingly, both diastereomeric aldimines 79 (RS and SS) gave similar results concerning the stereochemical outcome, suggesting that the chiral sulfonamide moiety was not involved in the stereocontrol during this tandem Barbier addition

• -phenylpiperidine (122d). The diastereoselective allylation of (SS)-N-tert-butanesulfinyl imines 119 mediated by indium metal under Barbier's reaction connections (formation of the allylindium intermediate in the presence of the imine electrophile) is the key step in these syntheses (Re-face attack). The natural

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• an electrophile, the crude product 2a was treated with butyllithium, followed by the reaction with carbon dioxide to afford pyrrole carboxylic acid 6 in a good overall yield (Scheme 5). The trifluoromethyl group on the nitrogen was not affected by these highly basic reaction conditions. The mechanism

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• simultaneous activation of both the nucleophile and the electrophile [12][13][14][15]. Quinine derived sulfonamides were first introduced to the literature by Song et al. [16]. Since then, many contributions were made regarding their applications in a variety of reaction types [17][18][19][20]. However, sulfa

• Houk’s mode of activation was of lower energy than Wynberg’s activation mode, in which the activation and orientation of the nucleophile is done by the quinuclidine core [43]. According to our proposed model, the protonated quinuclidinium ion stabilizes the newly forming alkoxide on the electrophile

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• nucleophilic esterification of potassium 1-(N-benzyloxycarbonylamino)alkylphosphonates 172 with alkyl halides in the presence of 18-crown-6. They also prepared a phosphonodepsidipeptide 174 with ethyl chloroacetate (173) as an electrophile (Scheme 33) [53]. The macrocyclic peptidyl phosphonodepsipeptide 180

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• nitrogen with a suitable electrophile, the use of a strong base (e.g., NaH) in combination with the chemical waste being generated (from the leaving group), and potentially unfavorable polar aprotic solvents (DMF, NMP) prompted consideration of a more atom-economical approach. The follow-on work focused on

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• pyridine as a scavenger for the liberated HCl, gave solutions of crude diacylated product 18 in acceptable purity after simple filtration as work-up. It was reasoned that the activation of the electron-rich pyrrole (with generic electrophile X2 as shown) would hasten cleavage of the ester and that

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• intermediate allylic cation which was the electrophile in a Friedel–Crafts reaction with 159. The subsequent desilylation of the Friedel–Crafts product gave an α-fluorinated ketone intermediate which then reacted with a second equivalent of 159 in a (Z)-stereoselective, chelation-controlled process. Fu et al

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• sulfides by the acetamidosulfenylation of alkenes [12], among others [13][14][15]. Sulfur-containing compounds are important intermediates in organic synthesis, being able to act as an electrophile or nucleophile in many organic transformations [16][17][18]. Still, many of them are pharmacologically active

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• of an alkyl electrophile has been reported to date [35]. This process used an umpolung strategy with activation of typically electrophilic perfluoroalkylsulfenamide reagents by iodide, releasing −SC2F5 or −SC3F7 anions in situ, which could then react with a selection of alkyl halides (Scheme 1b). In

• synthesis of BT-SCF3 from inexpensive 2-mercaptobenzothiazole (MBT) can be readily adapted to provide a wide range of different BT-SRF reagents. Moreover, in situ activation of the benzothiazolium salt by the alcohol provides a highly reactive alkyl electrophile, which can compensate for the inherently low

• substitution reactions of this type are synthetically appealing as they avoid pre-generation of an active electrophile such as an alkyl halide. A selection of benzylic alcohols 2 was reacted under the standard conditions with BT-SC2F5 (1.25 equiv) and NEt(iPr)2 (2 equiv) in MeCN at −40 °C, providing the

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• starting materials, rather expensive catalysts, harsh reaction conditions or low product yields. Transition-metal-catalyzed, electrophile-induced and oxidative radical cyclizations of ortho-alkynylated biaryls are widely used for the synthesis of polynuclear aromatics [57][58][59][60][61][62][63][64][65

• steps of the method are electrophile-induced 6-endo-dig cyclizations of ortho-alkynylated biaryls. The overall yields of helicenes in five stages of the synthesis exceed 30%. The single-crystal X-ray diffraction analysis revealed the non-planar crystal structures of the synthesized helicenes responsible

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• 1a and TBAI, leading to an excess of the CF3Se− species, no significant improvement was observed (Table 1, entry 8). On contrary, the use of 2 equivalents of the electrophile 2a, to ameliorate the CF3Se− anion trapping, had a significant effect and gave a very good yield of the product (Table 1

• ). Consequently, the nucleophilic substitution is in competition with this relatively fast oxidation. By adding an excess of the electrophile 2, the substitution is favored detrimentally to the oxidation. Nevertheless, with weaker or hindered electrophiles, the oxidation reaction is favored compared to the slower

• concerning the direct nucleophilic trifluoromethylselenolation. The nucleophilic fluoroalkylselenolation of alkyl bromides. Yields were determined by 19F NMR spectroscopy with PhOCF3 as an internal standard and yields of isolated products are shown in parentheses. aWith 1 equiv of electrophile 2. bStarting

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• , and 18b. The corresponding imidazo[1,5-a]pyridines 16g, 19ag, and 18bg were obtained in a highly efficient manner (Scheme 6). In addition, α-nitroacetic ester (1i) was probed as an electrophile in the reaction with substrate 12 in order to demonstrate that the phosphorylated nitronate function is a

• superior electrophile in comparison to the ester function. Indeed, this bielectrophilic reagent reacted only at the nitro group, providing the amide 20 as the sole product. The yield was quite marginal, primarily due to decomposition of the fragile ester functionality under the harsh reaction conditions