β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• notable synthesis of leukotriene C-1 (119), Corey and co-workers synthesized (−)-methyl trans-5(S),6(S)-oxido-7,9-trans-11,14-cis-eicosatetraenoate leukotriene A methyl ester (120), the key intermediate in its synthesis and biosynthesis, starting from the 2,3,5-tribenzoyl derivative of D-(−)-ribose [82

• mixture of potassium carbonate and potassium bicarbonate in 95:5 water–methanol at 23 °C for 12 h proceeded quantitatively to afford the product leukotriene C-1 (Scheme 42). The epoxide 120 has been the key intermediate in all syntheses of LTC4, -D4, and -E4; upon exposure to the desired amino acid, it

• the N-Boc protected β-hydroxy sulfide 130 as a key intermediate. Deprotection of the Boc followed by the imidation of the free amine with protected dipeptides that mimic Leu-Val produced the inhibitors of human renin 131 as depicted in Scheme 44. Yoshioka and co-workers reported two synthetic routes

Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119

• 10.3762/bjoc.14.119 Abstract In order to prepare asymmetrically (R)-(+)-1-(5-bromopentyl)-1-methyl-7-methoxy-2-tetralone (3a), a key intermediate of dezocine, 17 cinchona alkaloid-derived catalysts were prepared and screened for the enantioselective alkylation of 1-methyl-7-methoxy-2-tetralone with 1,5

• key intermediate of dezocine, in the catalysis of the quaternary ammonium benzyl bromides from cinchonidine was investigated and the best catalyst (C7) was identified. In addition, the preparation of 3a with the optimized conditions was performed and the product was isolated in 77.8% yield with an

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• reaction pathway to proceed via the corresponding N-phenylnitrilimine. The yields (Table 3) are generally lower than those of reactions performed under thermal conditions – most probably due to the lower stability of the key intermediate – N-phenylnitrilimine – which can undergo dimerization or reverse

• -oxohexanoic acid with 4-fluoro-3-(4-methylphenyl)sydnone (Scheme 12). Unfortunately the regioselectivity of the reaction was not specified. An aryne generation (Scheme 13) was also used for the synthesis of a key intermediate of the potent antitumor PARP inhibitor – niraparib – containing an indazole core

• -disubstituted pyrazoles. Unsuccessful reaction with phenylpropiolic acid. Synthetic strategy leading to 1,4,5-trisubstituted pyrazoles. Reaction of sydnones carrying in position 4- six-membered 2-N-heterocyclic ring. Strain-promoted sydnone alkyne cycloaddition (SPSAC). Synthesis of a key intermediate of

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• mechanism for this FPID-mediated amide bond formation reaction was proposed with the acyloxyphosphonium intermediate B being the key intermediate (Scheme 1). Herein, as part of our continuing exploration of the application of FPID in peptide synthesis, we disclose its successful application in solid-phase

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• -amino-13α-estrone (13) itself may possess promising pharmacological properties or may serve as a key intermediate in the synthesis of biologically active 2-(subst.)amino-13α-estrones. The structures of the newly synthesized phenylamino derivatives 5–13 were established through 1H, 13C, HSQC and/or HMBC

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• . The commercial HCQ synthesis employs a key intermediate, 5-(ethyl(2-hydroxyethyl)amino)pentan-2-one (6), which is a major cost driver in the process. The protection–deprotection strategy of chloro-ketone starting material 3 used in the commercial route (Scheme 1a) [21] has been targeted as a

• of 68% for compound 12. With an optimized continuous process for producing the key intermediate 12 in-hand the reaction conditions for the conversion of 12 to HCQ (1) were examined. In the commercial process this step is carried out in batch under neat reactant conditions and requires a relatively

• were obtained in accordance with those previously reported [38][39]. Commercially available antimalarial drugs. Current batch syntheses of the key intermediate 5-(ethyl(2-hydroxyethyl)amino)pentan-2-one (6). Retrosynthetic strategy to hydroxychloroquine (1). Schematic representation for continuous in

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• mechanistic studies (Scheme 35). First, the key intermediate CF3CuILn is generated in situ by the reaction of TMSCF3 with Cu(II) reagent, followed by transmetalation with activated Ar−H generating the (aryl)CuI(CF3) species C, which might be oxidized to the corresponding (aryl)CuIII(CF3) intermediate D

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

• ]. The thiyl radical was generated as reactive key intermediate from a variety of thiols by photooxidation using [Ru(bpz)3](PF6)2. Aliphatic and aromatic thiols react with aliphatic and aromatic alkenes and alkynes in high to excellent yields to the anti-Markovnikov addition adducts. However, an excess

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• -hexadecanoyloxy-15-methylhexadecanoic acids an efficient cross-metathesis has been employed [98]. Reduction of the 2-azido group with Zn in acetic acid, followed by acylation with the respective 3-O-benzyl protected fatty acid provided the key intermediate 45. Sequential protecting group manipulation (3’-O-Lev, 3

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

• straightforward methodology and we have adapted Zeng’s synthesis starting from the (R)-Garner’s aldehyde. (2S,3R)-Boc-CF3-Thr(Bzl) was obtained with satisfactory yields (Scheme 1). In this synthetic pathway, the key intermediate 6 was obtained, as a mixture of two diastereoisomers (9:1, evaluated by 19F NMR) via

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• ’, as illustrated in Scheme 4. Initially generated from diazoester 2 carbenoid A attacks the sulfur atom of thioamide 1 to give the key intermediate S-ylide B [36][37][38][59][60], which is stabilized by ‘thioamide resonance’ [36][37][38]. The anion center of S-ylide B then attacks the carbon atom of

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• syntheses of alstilobanines A, E and angustilodine, functionalized indole 33 was initially chosen as a key intermediate [33]. However, attempts of its preparation by Michael addition of substituted indole enolate 34 to nitrosoalkene NSA8, generated in situ either from the corresponding chlorooxime 35 or its

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• would form as the key intermediate. Upon dissociation of the anomeric C–S bond of the sulfonium intermediate 102, an oxygen nucleophile on the boronate ester would attack the C-1 center on the opposite side resulting in 103 with good stereoselection (Scheme 23). Initial trials with 3-methylbenzyl

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• chemistry and related sciences. The key intermediate in the reaction is the 1,3-dithiolane carbanion, which, in contrast to the 4,5-unsubstituted analogues, undergoes a spontaneous cycloreversion reaction to give tetraarylethene and dithioformate anion. This method supplements the list of preparatively

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• differences are also elements of complexity. The mechanical processing of CDs in the absence of solvent therefore promises to simplify the work-up and allows the almost complete utilization of the CD key-intermediate [13], in comparison with the classic method [6]. Moreover, the absence of a solvent, high

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• of molecular oxygen and with catalytic copper acetate (Cu(OAc)2) generated the desired pyrimidine 102 which was converted to the final products in a few more steps. This is one of the noteworthy examples where oxidative dehydrogenation has been utilized for the synthesis of a key intermediate of an

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• trisubstituted oxazoles. Herein, we described an efficient method for the synthesis of trisubstituted oxazoles through a one-pot oxazole synthesis and subsequent Suzuki–Miyaura coupling. Results and Discussion The study was initiated with the preparation of the key intermediate, 5-(triazinyloxy)oxazole 3, from

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• reported two-step oxidation/Reissert-type sequence [21][22]. The access to the key intermediate trithiazolylpyridine 9 was next investigated via two synthetic routes by exploiting BSC cross-coupling and Hantzsch condensation reactions from the picolinamide 5, which was produced by simple treatment of 6

• in fair 59% yield over 2 steps. Finally, the second synthetic pathway proved to be slightly more performant to produce the trithiazolylpyridine key-intermediate 9 from the picolinamide 5 in 58% yields over 3 steps (vs 55% for the first synthetic route). Then, the trithiazolylpyridine 9 was engaged in

• the key-intermediate 6-chloro-5-thiazolylpicolinate ester 4, which was obtained in multi-gram amounts in 57% yield over 3 synthetic steps (13% global yield) from the readily available ester ethyl 5-bromopicolinate (1) as starting material. Main synthetic strategies towards heterocyclic cores of D

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• afforded 64% yield of phenylacetylene (6a), while the elimination reaction was quantitative with 2 equiv of the base. These results suggested that 6a is a key intermediate in the reaction. Furthermore, the fact that in the presence of 1 equiv of base the elimination product was obtained in approximately 50

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• observed. React-IR studies under hydrothermal conditions, but at a lower temperature of 70 °C, helped the team to identify a reactive iminium species, which is formed from the reaction between the sugar aldehyde and an amine present in the reaction mixture, and is a key intermediate in the initial stages

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• . First, a SET from the electron donor to the nitrile forms a radical anion. This radical anion can fragment into a cyanide ion and a radical which is rapidly reduced into a stabilized carbanion before protonation. This carbanion appears as a key intermediate leading to complex mixtures when method A is

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• reducing to the non-reducing end (Scheme 8). Union of 4 and 5 (Scheme 7) produced disaccharide 41 as the key intermediate, the naphthyl protecting group of which was cleaved in 70% yield using DDQ [37] to afford 42. Thioglycoside 43 failed to react with disaccharide 42 to furnish the desired trisaccharide

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• ring toward the neighboring alkyne in the iodine-mediated cyclization reactions were explored. Starting from the symmetrical 3,5-dimethoxybenzyl alcohol, this route allowed rapid access to 2,3-diarylbenzofuran, a key intermediate to several oligostilbenoid natural products, in good overall yields

• element [19] of the target molecules. We expected that the key intermediate (inset box of Scheme 1) could be constructed from the monoiodo compounds 1, 2, or 3 through a sequence involving Sonogashira coupling, iodocyclization [20][21][22][23][24][25][26], and Suzuki coupling. As the starting materials (1