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

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• corresponding diethyl amide 12. For this purpose, ester 10c was reacted in a Weinreb amidation [32] with a mixture of trimethylaluminium and diethylamine to give the amide 12 in 31% yield (Scheme 5). The diethyl amide moiety was designated to promote a directed remote metalation by lithium diisopropylamide (LDA

• metalation at C-6 of the benzamide moiety was not followed by an equilibration giving the desired 8’-metalated intermediate (which in turn should be trapped by the amide group to give the tetracyclic ketone 6). Probably, the DreM at C-8’ is prevented, since the amide moiety forms a chelate with a lithium ion

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• reported. Apart from traditional hydride reducing agents like lithium aluminum hydride and sodium borohydride [1][2], different modifications were applied, using transition metal salts as catalysts or additives to change or enhance the properties of these reagents [3][4][5][6][7][8]. Hydrogenation is

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

• resulted in poor yields (Table 2, entries 2 and 3). Notably, we found that 3 equiv of LiCl was an effective additive for shortening the reaction time (3 h) and improving the yield (73%, Table 2, entry 4) [34]. Other lithium halides, except for LiF, were also effective (Table 2, entries 5–7). However

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• of the GHPD side chain building block. Thus, Cudic’s SPPS approach should be combined with the advantages of the late stage coupling employed by Jolliffe. Synthesis The C13-fragment was prepared starting from erucamide (6) in three simple operations. Reduction of the amide with lithium aluminium

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• ], or oxidised to oxaziridines used as efficient chiral oxidising reagents [13][17][18][19]. The reaction of the oxoimide 3 with two equivalents of the lithium salt of a terminal alkyne leads to compounds 4 where two alkynyl substituents, a sulfonamide and a hydroxy group are found in vicinal positions

• ) reaction of such mixed substituted compounds. Results and Discussion For the preparation of the diynes 4, a 2:1 ratio (or slightly larger for complete reaction) of the lithium salt of a terminal alkyne and of the oxoimide 3 is applied. The ratio should, however, not be increased too much. For instance

• , with benzylacetylene, the expected diyne 4e (Scheme 3d) is obtained, with only traces of monosubstituted compounds. However, with a 3:1 ratio, the main product is formed by reaction of only one equivalent of lithium salt with the C=N double bond, leaving the carbonyl group intact. In addition, the

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• lithium dimethylcuprate. In comparison with the likewise attempted Stork–Zhao olefination this protocol by Tanino and Miyashita was superior in yield and stereoselectivity [80]. To complete the fragment synthesis the [Ru]-catalyzed Trost–Alder-ene reaction [81] generated the desired primary alcohol which

• switched to the stannane 56 by lithium–halogen exchange and further treatment with Bu3SnCl [92] in 90% yield. The synthesis of the coupling partner 55 started with known Weinreb amide 64 which underwent a syn-selective palladium-catalyzed hydrostannylation and was then transformed to phosphonate 65 in good

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• 10.3762/bjoc.13.105 Abstract A concise and practical stereoselective synthesis of ipragliflozin L-proline was presented starting from 2-[(5-iodo-2-fluorophenyl)methyl]-1-benzothiophene and 2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyl bromide without catalyst via iodine–lithium–zinc exchange. The overall

• was developed. The route initiated from compound 4a and pivaloyl-protected glycosyl bromide 2b, the β-C-arylglucoside 5 was obtained with high stereoselectivity in one step after a halogen–lithium exchange/transmetalation/coupling sequence. Cryogenic temperatures and catalysts were not required. The

• equiv 2b gave a good result, the amount of 5” was greatly reduced (Table 1, entry 4), while the content of 5 in the crude product was increased to 68% and the isolated yield was 77.7%. It was presumable that a iodine–lithium–zinc exchange and the transmetalation proceeded better than a bromide–lithium

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• terminal alkyne with n-BuLi and subsequent quenching with ethyl chloroformate provided the desired ester 3 in 43% yield. The subsequent stereoselective addition of lithium iodide [17] provided the Z-vinyl iodide 4 in 76% yield with no trace of the undesired E-isomer. After extensive screening (see

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• Scheme 2. A Weinreb amide (1 equiv) and PhMgBr (2 equiv, Grignard’s reagent) are reacted in a 10 mL PFA coil at 60 °C for 5 min residence time. The reaction is quenched using aq HCl and the ketone is isolated with 97% yield. The aryl lithium compound is produced simultaneously by reacting aryl bromide (1

• equiv) with n-BuLi (1.1 equiv) at −50 °C in 10 mL PFA reactor with 7 min residence time. This lithium compound reacts with the ketone intermediate at 30 °C for 2 min in 5 mL PFA reactor coil. The intermediate lithium alkoxide is further reacted with trifluoroacetic anhydride (2 equiv) in a 10 mL PFA

• reactor will be similar to the previous reactor. This lithiated intermediate and the ketone intermediate obtained by the simultaneous process can be mixed using a ratio controller at the optimum stoichiometric amount. The obtained lithium alkoxide can be monitored inline using a suitable analytical

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

• for their synthesis have been developed. Among them are reactions between lithium or sodium acetylides and electrophilic selenium reactants [23]. The use of hypervalent iodine(III) species [24] or alkynyl bromides with RSeLi [25] as nucleophilic selenium species or the reaction of alkynyl bromides

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• -diketones with arylhydrazines, halogenation of the resulting 1,3,5-triarylpyrazoles in the 4-position and further functionalization via Negishi cross-coupling [23][24] or halogen–lithium exchange reaction (Scheme 1). The resulting compounds amongst others seem to be interesting as potential complexing

• out to be superior to the reaction of compounds 2 with N-iodosuccinimide. Species 3a–d served as educts for the investigations concerning further functionalization at pyrazole C-4. Carboxylation of 4-iodopyrazoles 3a–d The lithium–iodine exchange proceeded quickly and quantitatively in case of 3,5-di

• -pyridinyl congeners 3c,d gave markedly lower conversion rates in all reactions investigated. 1H NMR (in italics), 13C NMR and 15N NMR (in bold) chemical shifts of compound 9a (in CDCl3). Envisaged general approach for the synthesis of the title compounds. Synthesis of 4-iodopyrazoles of type 3. Lithium

Molecular-level architectural design using benzothiadiazole-based polymers for photovoltaic applications

• Vinila N. Viswanathan,
• Arun D. Rao,
• Upendra K. Pandey,
• Arul Varman Kesavan and
• Praveen C. Ramamurthy

Beilstein J. Org. Chem. 2017, 13, 863–873, doi:10.3762/bjoc.13.87

• , 1,2-difluorobenzene was reacted with trimethylsilyl chloride in the presence of lithium diisopropylamide to afford the 1,4-disilylated intermediate 4 and bromination of the latter compound in neat bromine afforded the desired 1,4-dibromo-2,3-difluorobenzene (5). Nitration of 5 by treatment with fuming

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• Bu, the nucleophilic substitution of the fluorine atom at the para position to boron is the predominant route. When R = Ph, the ratio M[4-RC6F4BF3]/M[2-RC6F4BF3] is ca. 1:1. Substitution of the fluorine atom at the ortho position to boron is solely caused by the coordination of RLi via the lithium

• and PhLi were prepared from lithium and MeI or PhBr, they contain the corresponding lithium halides. It follows that the precipitate consists of KI and KBr, respectively, and the actual boron-containing reactant is lithium pentafluorophenyltrifluoroborate (1-Li). Independently, Li[C6F5BF3] was

• prepared by metathesis of 1-K with LiHal (Hal = Cl, Br, I) in an approapriate solvent (Scheme 8). After determination of the salt concentration by 19F NMR, 1-Li was used in DME without isolation. When the metathesis was performed in MeCN, the lithium salt was isolated from MeCN as solid solvate Li[C6F5BF3

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• 2010, the Zhou group developed a CuI catalyzed protocol for hydroxylation of aryl iodides and bromides using lithium pipecolinate (L11) as ligand, yielding phenols in moderate to good yields (Scheme 20) [44]. The reaction proceeded in the presence of (n-Bu)4NF and NaOH. Notably, the reaction was

• carried out in water, avoiding the use of an organic solvent. In addition, a broad substrate scope was observed; some sensitive functional groups, such as carboxylic acid, aldehyde and cyano were well tolerated. In 2013, the Zhou group used lithium L-prolinate (L12) as ligand and developed a CuCl2

• (L15) catalyzed coupling of aryl bromides and TIPS-SH, where the reaction was carried out in the presence of lithium bis(trimethylsilyl)amide (LiHMDS) in toluene at 110 °C (Scheme 56) [100]. The coupled product of 1-bromonaphthalene and TIPS-SH could be readily converted to 1-thionaphthol when treated

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• microreactor system [19]. In particular, they reported that starting from different substituted carbamoyl chloride 1 and lithium naphthalenide (LiNp) it was possible to generate the corresponding carbamoyllithium 2, that upon trapping with different electrophiles provided several amides and ketoamide 3 (Scheme

• been optimized in a green solvent such as 2-MeTHF by a precise control of the residence time, and without using cryogenic conditions (Scheme 6). In addition, many organolithiums were generated from the corresponding halo compounds by a halogen/lithium exchange reaction using hexyllithium as a more

• -substituted pyridines. The regioselective lithiation of halopyridines with lithium diisopropylamide (LDA) was conducted under mild conditions on substrate 6 (Scheme 10). The addition of a little amount of THF was necessary in order to avoid clogging and the tendency of the lithiated intermediate to eliminate

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• using lithium, nickel and palladium catalysts (Scheme 15). A general mechanism illustrating the role of transition metal complexes and CO in this reaction is shown in Scheme 15. Cyclic esters were also used in the syntheses of 1-indanones. Thus, by adding β-propiolactone to aluminum chloride in benzene

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

• overcome using K/HMPA/t-BuOH [17][18] or K/dicyclohexano-18-crown-6/toluene [19][20]. In the latter case, the toluene radical anion is believed to be the reactive species. LiDBB (lithium di-tert-butylbiphenylide) and Li naphthalenide are also common electron donors [15][21][22]. Because of the mechanism

• efficient synthesis of (±)-xanthorrhizol (8) [39]. The authors prepared the intermediate 7 by dialkylation of 6 and attempted to carry out a one-pot decyanation and demethylation [40] with a suspension of lithium in THF. The target compound 8 was obtained in 74% yield together with 24% of the byproduct 9

Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

• Vinicius R. Campos,
• Ana T. P. C. Gomes,
• Anna C. Cunha,
• Maria da Graça P. M. S. Neves,
• Vitor F. Ferreira and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2017, 13, 195–202, doi:10.3762/bjoc.13.22

• . Attempts to improve the efficiency of the process just by changing the catalyst to tris(dibenzylideneacetone)dipalladium(0), [Pd2(dba)3], and the base to lithium tert-butoxide, led to the same low efficiency. This fact prompted us to select the catalytic system described by Wang et al. [38]. In their work

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

• employing a more nucleophilic and less basic reagent such as a lithium hydroxide/hydrogen peroxide mixture did not provide relief from the problem, but instead also produced a mixture of undesired products. Adjustments in the sequence of deprotection steps by first carrying out hydrogenolysis using Pd/C in

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• the benzyl ester 19 with lithium diisopropylamide and quenching the enolate with carbon dioxide (Scheme 2a). Benzyl 2-tert-butylmalonate (6) was prepared in good yield using a method of Krapcho et al. [18], by double deprotonation of 3,3-dimethylbutyric acid (20) with LDA and quenching the dianion

• lithium aluminium hydride in THF to 3 and 31a in 90% (Scheme 5) and with 30b (Scheme 5) and DIBAL in toluene 92% of 31b were obtained [50]. 30c could be cleaved with lithium aluminium hydride in THF to 83% 3 and 90% 31c [51]. However, to our great disappointment the successful cleavage with 30c could not

• be transferred to the structurally similar compounds 23a/b and 25a/b. Using the same reaction conditions as with 30a both with lithium aluminium hydride in THF and DIBAL in toluene with 23a/b and 25a/b the starting material was completely reisolated. Apparently the carbonyl group is so much shielded

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• lithium chloride [35] leading to the expected coupling products syn-13 and syn-14 in 39% and 82% yield, respectively (Scheme 5). In both cases, only the E-configured 2-substituted alkyl acrylates were isolated. The moderate yield in the Heck reaction with methyl acrylate 12a is very likely caused by the

From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• quantitative yield at rt with lithium bis(trimethylsilyl)amide in THF/pyridine due to its superior solubility. As evidenced by 1H NMR and 13C NMR spectroscopy, the carbene 7 proved to be stable in pyridine-d5 solution up to 50 °C. The resonance frequency of the carbene carbon atom can be detected at δ = 203

• ) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif. Preparation of lithium 2-(3-butyl-1H-imidazol-2-ylidene-1-yl)phenolate (7): A solution of 0.02 g (0.09

• mmol) of 2-(3-butyl-1H-imidazolium-1-yl)phenolate [35] and 0.10 mL of lithium bis(trimethylsilyl)amide (1.0 M solution in THF) in 0.7 mL of pyridine was stirred for 30 minutes at rt. The product was characterized in solution, as traces of moisture reconstituted the starting material. Concentration of

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• trace amounts of triphenylphosphine residues; our best yield for the product was only 25% [19]. Reduction of the diastereomeric mixture of esters 12b to the corresponding alcohols was achieved with a slurry of lithium aluminium hydride in diethyl ether. The reduction afforded a mixture of

Effects of solvent additive on “s-shaped” curves in solution-processed small molecule solar cells

• John A. Love,
• Shu-Hua Chou,
• Ye Huang,
• Guilllermo C. Bazan and
• Thuc-Quyen Nguyen

Beilstein J. Org. Chem. 2016, 12, 2543–2555, doi:10.3762/bjoc.12.249

• 3 was obtained through lithium–halogen exchange with n-BuLi followed by addition of trimethyltin chloride. Segments 2 and 3 were cross-coupled using a microwave-assisted Stille reaction to afford the target p-SIDT(FBTThCA8)2. The thermal transitions of p-SIDT(FBTThCA8)2 were evaluated by