Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling, and 2) immobilization on a solid support via reduction and reaction of the aniline with an electrophile such as polystyrene isocyanate. DOPO scaffold We previously reported the syntheses of both enantiomers of 8-phenyl DOPO 3 [38]. The syntheses proceed in only three steps (including the

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• derived from biomass pyrolysis, due to its reactive functionality, and the chirality which derives from glucose [4][5][6][7]. Reactions of 1 where the α,β-unsaturated ketone participates as an electrophile are usually completely diastereoselective, as the approach of the nucleophile is controlled by the

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• completed a selective anomeric deacetylation on a gram-scale using ammonium acetate in DMF, to afford hemi-acetal 15 in good yield (80%) [11]. This was followed by phosphorylation of the anomeric position using diphenylphosphoryl chloride as the phosphorous electrophile, following deprotonation of 15 using

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• isomers) is governed by the steric property of the substituent at the N6-position. Steric effects were evaluated by using Charton (empirical) and Sterimol (computational) parameters. The bulky substituents may shield the proximal N7 region of space, which prevents the approach of an electrophile towards

• approach of an electrophile (e.g., FcCOCl) towards the N7 atom. In the course of N9-isomer formation no similar steric hindrance is encountered. This is supported by our quantum-chemical calculations which compared the two transition state structures for the ferrocenoylation of the N6,N6-di-tert

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• from E, and thus affording the C3-lithiated furan derivative G upon 1,4-silyl migration as well as the electrophilic substitution product H in the presence of an appropriate electrophile (Scheme 3, bottom). However, treatment of aldehyde 1b with n-BuLi, followed by addition of benzaldehyde in THF/DMPU

• ] (402 mg, 0.72 mmol) was then added along with the corresponding electrophile (3 equiv). The mixture was stirred for 2–3 min at rt and then cannulated into the vial containing the copper complex. The mixture was stirred for 2 h at 30 °C and then quenched with aq KOH (6 M, 1 mL). The mixture was

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• diesters and ester amides as key intermediates (+)-Awajanomycin Diethyl mesoxalate (90a) is a valuable building block due to the high density of carbon atoms in high oxidation states. As a vic-tricarbonyl compound, its central keto group is an especially potent electrophile. The Koert group used this

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• medicinal importance is the reason that the synthesis of β-carboline-containing derivatives has been an exciting area for researchers [34][35][36][37][38][39][40]. The Morita–Baylis–Hillman (MBH) reaction is an astonishing C–C bond forming reaction between a carbonyl electrophile and an activated alkene

• leading to the formation of allylic alcohol; a highly functionalized product [41][42][43][44]. The chemistry of the MBH reaction is decorated with several unique features viz. atom economy, complexity generation and generation of a chiral center from a pro-chiral electrophile. The chemistry of the MBH

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• intramolecular nucleophilic dearomatization and protonation or electrophilic alkylation reactions, affording the corresponding dihydronaphthylene-fused γ-phosphinolactams 135–142. Methanol was used as the electrophile for protonation, while methyl iodide and allyl bromide were used as electrophiles for

• alkylation. A remarkable difference compared with the diphenylphosphinamides is the fact that the current reactions proceeded with excellent regio- and stereoselectivities and yields in THF without the use of the carcinogenic cosolvent HMPA (Scheme 24) [51]. With benzaldehyde as an electrophile, both

• alkylated and protonated benzocyclohexadiene-fused γ-phosphinolactams 143 and 136a were generated in 25% and 15% yield, respectively. However, two pairs of alkylated and protonated benzocyclohexadiene-fused γ-phosphinolactams 144 and 145, 136a and 146 were obtained with 4-chlorobenzaldehyde as electrophile

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• the most successful with an overall reaction yield as high as 82% and a ratio of O- to N-isomers 24a to 24b as high as 3.3:1 (Table 1, entry 7). As expected, the polar aprotic solvent dimethylformamide promoted the reaction of the electrophile with the more negatively charged oxygen atom by well

Comparative study of thermally activated delayed fluorescent properties of donor–acceptor and donor–acceptor–donor architectures based on phenoxazine and dibenzo[a,j]phenazine

• Saika Izumi,
• Prasannamani Govindharaj,
• Anna Drewniak,
• Paola Zimmermann Crocomo,
• Satoshi Minakata,
• Leonardo Evaristo de Sousa,
• Piotr de Silva,
• Przemyslaw Data and
• Youhei Takeda

Beilstein J. Org. Chem. 2022, 18, 459–468, doi:10.3762/bjoc.18.48

• the designed D–A molecule 1, an asymmetric dibenzophenazine electrophile was required. Recently, we have established a synthetic method for such a compound, i.e., 3-trifluoromethanesulfonyldibenzo[a,j]phenazine (DBPHZ-OTf in Scheme 1) to prepare linear-type A–D–A–D compounds [18]. Starting from the

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• amide functionality [13][14][15][16][17][18][24][25]. At the same time, norbornadiene derivatives are available from metalated substrates. Hence, norbornadiene is deprotonated with the Schlosser base and subsequently trapped by an appropriate electrophile [26][27]. In addition, halogenated norbornadiene

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• with an electrophile results in the formation of a cobalt(III) intermediate. Subsequent homolytic cleavage and generation of cobalt(II) complex C and radical D the radical undergoes addition to phenylacetylene to provide cobalt(III) intermediate E. The targeted compound 1-methyl-4-(2-phenylethynyl

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