Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• similar chemoselectivity has been previously observed, being explained as a consequence of the acidity of the C–H bond being cleaved [6][44]. Additional intramolecular cross-coupling reactions were carried out by utilizing dimethyl malonates 8k and 8l, which were prepared through the N-benzylation of 16c

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• pentafluoro-ʟ-phenylalanine derivatives 24a–c, respectively [41] (Scheme 5). The stereoselective benzylation of (S)-imidazolidinone ((S)-Boc-BMI) 25 with tetrafluorobenzyl bromides 26a,b afforded the benzylated imidazolidinones 27a,b. The acidic hydrolysis of 27a,b with simultaneous deprotection to release

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• reaction completely (not shown). Notably, PMP-protected THIQ was found to give a good yield of 61% (compound 24), which was specifically important since this group is relatively easily removed, contrarily to the unsubstituted phenyl group. The benzylation of THIQ 14 was accompanied by small amounts (3%) of

• benzylation of N-aryl-THIQs [47]: After excitation of the catalyst, the Katritzky salt is reduced via SET, giving a Ru(III) species and intermediate III, followed by C–N cleavage to give benzylic radical IV and triphenylpyridine [45]. The Ru(II) catalyst is regenerated by another SET from the THIQ derivative

• . Further investigations in this direction are ongoing in our labaratories. Kinetic profile for the benzylation of 1 to 3. Examples of photocatalytic C–C bond formation by nucleophilic trapping of a reactive THIQ intermediate. Benzylation of N-phenyl-THIQ. Benzylation of substituted N-arylTHIQs. Removal of

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• modifications to the pteridine core which disrupt the hydrogen-bond assembly, such as benzylation of the lactam oxygen or conversion of the exocyclic amine to the pivalic amide [12][13]. The installation and subsequent removal of these groups naturally affects the overall yield and time necessary to generate

Convenient synthesis of the pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia albertii O4

• Tapasi Manna,
• Arin Gucchait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 106–110, doi:10.3762/bjoc.16.12

• -1C), 5.50 (s, PhCH), 4.79 (d, J = 7.5 Hz, H-1B) in 1H NMR and at δ 103.3 (C-1B), 100.8 (PhCH), 99.0 (C-1A), 97.1 (C-1C) in 13C NMR spectra]. Compound 12 was subjected to a set of reactions consisting of a one-pot [32] de-O-acetylation and benzylation using benzyl bromide and sodium hydroxide in the

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• and mixed acetals [21][22]. Either by benzoylation or benzylation of 9α or 9β and subsequent deisopropylidenation, glycosyl acceptors 1α/β and 2α/β were efficiently obtained (Scheme 1). Compounds 1α and 1β were previously prepared, but in lower yield [23][24], and compound 2α was obtained as a

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• subjected to Zemplén de-O-benzoylation using NaOMe in MeOH to give compound 13 in 93% yield. Further, per-O-benzylation using BnBr in the presence of NaH [22] afforded the galactofuranosyl donor 14 in 89% yield. Glycosylation of the donor 14 with known rhamnose acceptor 15 [23] through activation of the

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• substituents into an aldehydes’ structure. Interestingly, to the best of our knowledge, there are no reports on ‘one-pot’ reactions leading to difunctionalization at both α and β-positions. To this end, in subsequent experiments, we attempted to merge two photochemical processes: β-benzylation (according to

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• stereospecific crotylation with a homochiral boronate to give the aziridine alcohol (2R,1'R,2'R,1''R)-140 (Scheme 36) [90]. After O-benzylation and N-methylation the ring opening in the intermediate aziridinium ion was tried. It appeared that the best regioselectivity (87:13) was achieved with cesium acetate and

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• . Accordingly, structure–activity relationship (SAR) studies have been performed, which indicate that benzylation of the hydroxy group and the complete demethylation of the core structure of AbC retain the antibiotic activity towards MRSA while simultaneously decrease cytotoxicity towards various human cell

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• reported earlier for their synthesis comprises the two-fold alkylation (methylation with Me2SO4 or benzylation using benzyl bromide) of some 1-hydroxyimidazole 3-oxides leading to symmetric 1,3-dialkoxyimidazolium salts [18]. In a recent publication, however, sequential alkylation of 1-hydroxyimidazole 3

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• offset the limitations of a resolution-based protocol, (R)-5 was hydrolyzed with alcoholic KOH to furnish (R)-4 (Scheme 1). Its inversion under the Mitsunobu conditions (Ph3P/DIAD/p-nitrobenzoic acid/THF; KOH/EtOH/25 °C/8 h, 91% over two steps) gave (S)-4 [46]. The benzylation of the hydroxy function in

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• removal of acetyl groups and benzylation using benzyl bromide and sodium hydroxide in one-pot [37] followed by removal of the p-methoxybenzyl group using DDQ [38] in 84% overall yield. Finally, stereoselective glycosylation of disaccharide trichloroacetimidate donor 18 with trisaccharide acceptor 23 in

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• )-5 which after O-benzylation provided an inseparable 1:3 mixture of compounds 8a and 8b. A six-carbon chain was shortened by a diol formation–diol cleavage sequence followed by aldehyde oxidation and esterification to give 9a and 9b after chromatographic separation. They were transformed into (2S,3R

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• problem during its preparation occurred, i.e., benzylation of the axial 4-OH only gave the desired 4-O-Bn product as a minor product, whereas the benzoyl migration from the 3-O to the 4-O, followed by benzylation of the 3-O, was the major, if not the exclusive, product. Despite several different

• benzylation procedures, i.e., NaH and BnBr, TriBOT [38] and TfOH or BnBr and Ag2O, the 4-O-benzylation remained inaccessible, with a 3-O-benzoyl group present. Using the 6-O-Bn-protected variant (2 in Scheme 1), a 1:2 mixture of the desired vs migrated product could be obtained. When using the more bulky 6

• -OTBDPS as protective group (1 in Scheme 1) and benzylation with freshly prepared Ag2O and BnBr in the solvent mixture CH2Cl2/cyclohexane 1:4 as described by Wang et al. [39], a 91% isolated yield of the migrated product, i.e., 3-O-Bn, 4-O-Bz, was obtained (Scheme 1). Following the apparent difference in

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• -Michael reaction, removal of a tert-butoxycarbonyl ester, base-promoted ring opening and tosylamide benzylation, without significant detrimental effect on the overall yield (see Supporting Information File 1). With the key precursor 4 in hand, the stage was set to study the Danheiser annulation step

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• directly to the selective N-benzylation with the corresponding 4-halobenzyl bromide under basic conditions to provide compounds 2b,c and 3b,c. By this way, the final compounds 2b,c and 3b,c were accessed in three steps in good yields (43–63%, Scheme 2). The next series of target pyrrolidines 4 and 5 could

• hydrogenolysis conditions furnished the free amine which was subsequently subjected to N-benzylation with the corresponding (4-halo)benzyl bromide to afford N-(4-halo)benzylpyrrolidines 19a–c. Acidic hydrolysis of the acetonide protecting group in 19a–c provided target compounds 4a–c in good yields (Scheme 3

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• different substitution pattern at positions 3, 4 and 5. PG: protective group, X: leaving group. Activation of 7 to oxocarbenium ion 9 in the Ritter reaction. Zemplén deacetylation of 10i. Benzylation of 10j to give 10b. Plausible mechanism of the Ritter reaction. For better clarity C-2 is not shown in

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• was prepared following literature procedures [26]. On the other hand the D-glucosyl thioglycoside 8 was converted to the known benzylidene derivative 9 [29][30] according to our previously reported procedure. Benzylation of 9 under phase-transfer conditions led to 10 [31] in 49% yield (Scheme 1

• 93% yield. Subsequent deprotection of isopropylidene ketal with pTSA/MeOH (aq) and then benzylation furnished 20 in 95% yield over two steps. Deprotection of the naphthylmethyl group in the presence of DDQ in aqueous dichloromethane (19:1) gave the glycosyl acceptor 7 [22] in 85% yield (Scheme 3). In

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• other approaches to the Manβ(1–4)GlcNAc (or equivalent) disaccharide. Elegant protecting group manipulations, involving the formation of a dibenzylidene derivative on the mannose ring, benzylation of the remaining free hydroxy groups on the glucosamine ring, and then regio- and chemoselective reductive

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• 62 (Scheme 8) [118]. To this end, GlcN hemiacetal 61 was reduced by treatment with NaBH4, the acetamido group was removed with barium hydroxide, and the resulting amine was transformed into azide 62. The primary alcohol in 62 was regioselectively protected as silyl ether, followed by benzylation and

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• -butynediol (13) by LiAlH4 to give trans-1 [27] was followed by benzylation [28] and epoxidation with m-CPBA to give (±)-trans-2 [28]. When the reaction was performed on a small scale, excess m-CPBA and the byproduct 3-chlorobenzoic acid were removed by extraction with a saturated Na2S2O3 solution. However

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• a nucleophilic trifluoromethylation reaction of Ruppert’s reagent on the (R)-Garner’s aldehyde 5 in THF and in the presence of a catalytic amount of TBAF. Benzylation of the alcohol of 6 was then performed to obtain the desired intermediate as two diastereoisomers 7a and 7b that were easily

• in good yield starting from the N-benzylation of L-proline in the presence of KOH, then activation of the carboxylic acid functionality of 10 using SOCl2 at low temperature, followed by condensation with 2-aminobenzophenone (Scheme 2). Complexation of 11 with nickel nitrate and glycine under basic

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• substitution between 1c and phenylacetate (2a) to phthalimide 6. Ester 6 was indeed obtained in 37% yield by gently heating a mixture of phthalimide 1c and phenylacetate (2a) in acetone/water. Subsequently, compound 5 was independently prepared by photodecarboxylative benzylation of 6 for 4 h in 91% yield

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• selective benzylation of its equatorial hydroxy group [14] followed by chlorochromate oxidation gave, after removal of the benzyl protecting group in 26, the diketone 27. Its reduction proceeded regio- and stereoselectively to afford the 2α,3β-diol 28. Finally, treatment of this compound with KOH in MeOH

• proceeded regioselectively at the diol group of the side chain and gave, after benzylation at position 2, the alcohol 36 (Scheme 8). The oxidation of the latter product afforded compound 37, which after deprotection, delivered the desired 3-dehydro-24-epicastasterone (38). Conclusion In conclusion, we have