Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• ). For this reason, another strategy of obtaining high % ee of d was employed. Chiral resolution of racemic-d with (R)-menthyl chloroformate gave a high % ee of this key intermediate d. After column chromatographic purification of the crude reaction mixture, the corresponding diastereomers (R)-e or (S)-e

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• the addition of a protecting step of the unstable key intermediate 4,5-dihydroisobenzofuran-5-ol. Oxidation and deprotection steps were also studied in order to provide an effective availability of these two dialdehyde compounds that may increase their future applications. Keywords: demethylation

• ). To our delight, the remarkable stability of the methoxy group under the same synthesis conditions introduces the key intermediate 4-methoxyphthalaldehyde (5b) with an excellent conversion rate and minimal OPA formation (Table 2, entry 6). Compound 5b was then isolated by column chromatography in 63

• key intermediate 4,5-dihydroisobenzofuran-5-ol (3) before reaching the oxidation step. The methoxy protecting group and the DDQ oxidation reagent were found to be the most efficient. Moreover, deprotection of 4-methoxy-ortho-phthalaldehyde (5b) was successfully achieved using [Bmim]Br and p-TsOH on

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• -identical functional groups on the primary side. Three different types of reactions were investigated to obtain 6A-monoazido-6X-monotosyl-β-CD (a key intermediate for the preparation of various hetero-difunctionalized β-CDs), having three possible regioisomers and consequently three pairs of

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• as key intermediate. A [2 + 2] cycloaddition with a second olefin leads to the formation of intermediate IV, followed by a retro [2 + 2] cycloaddition that regenerates catalyst I and releases the metathesis product. This visionary mechanistic proposal was later confirmed by experimental studies [17

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• key intermediate of the domino sequence (Scheme 1, reaction 1). Taking into account the capability of 2-iminochromenes to perform as Michael acceptors [39][40][41], we envisioned the diversification of the substitution pattern at the chromene ring to be a realizable and an appealing target

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• yield for two steps. The silyl group of compound 22 was cleaved using tetrabutylammonium fluoride (TBAF) in THF to form alcohol 23 which was used directly in the next step [48]. At this stage, we envisioned that 23 could be also a key intermediate to access the ristosamine derivative by reversing the

• for access to 3-amino glycals. Synthesis of key intermediate 23 for the C-3 unbranched amino glycals preparation. Access to diastereoisomeric compounds 3 and 4 from 23. Supporting Information Supporting Information contains detailed experimental procedures with full characterization of all compounds

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• pyrrolidine-based hamamelitannin analogues is depicted in Scheme 1. The synthesis of 4 as a key intermediate allows to gain access to a diverse set of analogues by chemoselective late-stage derivatization of the pyrrolidine nitrogen. Previously, we used the iminosugar 5 to prepare a series of 2

Oxidative and reductive cyclization in stiff dithienylethenes

• Michael Kleinwächter,
• Ellen Teichmann,
• Lutz Grubert,
• Martin Herder and
• Stefan Hecht

Beilstein J. Org. Chem. 2018, 14, 2812–2821, doi:10.3762/bjoc.14.259

• ][47] as the key intermediate undergoing thermal cyclization or cycloreversion, typically in the context of so-called “ECE” and “EEC” mechanisms, respectively [48]. To contribute to this discussion, nonsymmetrical DAEs bearing two electronically distinct aryl moieties (CF3- and Me-thiazole) [5] or

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• key intermediate 15, of which the sulfanyl group would intramolecularly migrate to produce 16 stereoselectively (path c, not d). The hydrolysis of 16 using TBAH yields diol 17. We further confirmed the mechanism of the 1,7-S shift reaction by performing density functional theory (DFT)-based

• calculations (Table 2) [36]. Whether the reactions lead to the formation of pyrroloazepines or diols clearly depends on the substituents in the alkenyl group. We performed DFT calculations for the reaction pathways starting from the key intermediate 14 bearing methyl and phenyl groups. The DFT-calculated ΔG

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• key intermediate 13 removing the p-methoxybenzyl group [24][26][27][28] from 11 failed. Finally, compound 13 was successfully obtained by modifying the sequence of reactions. Deprotection of compound 10 with TFA [24], followed by selective alkylation with benzyl tosylate as previously described

A novel and practical asymmetric synthesis of eptazocine hydrobromide

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

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• ][12][13]. In our prior publication [14], this method was selected as the technology for the development of a process to prepare (R)-(+)-1-(5’-bromopentyl)-1-methyl-7-methoxy-2-tetralone, a key intermediate of dezocine, and N-(p-trifluoromethylbenzyl)cinchonidinium bromide (3) among 17 cinchona

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• cyclopentane 5, a functionalized key intermediate, is presented. Compound 5 is involved in hydrolysis, α-allylation at C-8 and α-methylation at C-10 stereoselectively from the convex face. Then it is subjected to cross metathesis to give α,β-unsaturated ketone 11 as precursor in the total synthesis of

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• [36] were synthesized according to the previous literature. The key intermediate compound 5, containing a prior DBA recognition station and possessing alkynyl and ethylenic groups at two terminals respectively, was prepared from aldehyde 1 and amine 2. A “Schiff base” reaction was introduced at first

• alcohol with saturated NH4PF6 solution to obtain compound 5. For another key intermediate 8, containing an amide site for stabilizing the DB24C8 macrocycle, a 1,2,3-tris(dodecyloxy) benzene group as a stopper and an azide group which is used for the reaction with other moieties, was prepared through the

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the sulfonamidation of other heterocycles and was not successful. The authors attribute this lack of reactivity to the limited oxidising power of the excited acridinium salts and to the relative instability of the heterocyclic radical cation, which is a key intermediate in the proposed mechanism

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• using PIDA (15) at 4 °C (Scheme 41). This oxidative cyclization of enamide substrate 113 afforded synthetically useful spiroenamide 114, which was used as key intermediate for total synthesis of annosqualine (1). The synthesis of natural product 1 was achieved in two steps starting from synthesized

• compound 136 was achieved in 87% yield by the reaction of PIDA (15) with the naphthol derivative 135 in trifluoroethanol at room temperature. Additionally, synthesized compound 136 was used as key intermediate in the total synthesis of natural products 137 and 138 (Scheme 50). Additionally, more analogues

• -mediated radical cyclization wherein the oxazaspiroketal moiety is formed which is further used as key intermediate for the synthesis of the natural product cephalostatin. Additionally, spiroketals 159 were also synthesised by enatioselective spirocyclization of ortho-substituted phenols 158 using similar

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