Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• ]. Following a procedure of Doyle et al. we reacted commercially available phthalan (8) with DDQ and methanol in dry dichloromethane under a nitrogen atmosphere at room temperature, and obtained DMIBF (7) with a yield of 85% (Scheme 2) [22]. DMIBF (7) was treated with freshly prepared lithium diisopropylamide

• (LDA) in benzene and IBF (1) was obtained as a solution in benzene which was washed with aqueous NH4Cl to remove lithium salts and amines (Scheme 2) [8][18]. To determine the yield of IBF (1), this solution was reacted with acetylenedicarboxylic acid dimethyl ester (DMAD, 9) and product 10 was obtained

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• HWE olefination (Scheme 5). The (E)-monofluoroalkene was thus obtained in an excellent selectivity using n-butyllithium in tert-butyl methyl ether. The resulting ester 21 was reduced using lithium aluminum hydride, and treatment with tartaric acid deprotected the OBO, thus providing the free triol 22

• . This was then converted into a protected amino group employing a Mitsunobu reaction. Finally, removal of the nosyl group, followed by hydrolysis using lithium hydroxide, afforded the targeted isostere 24. Sano and co-workers also worked on the Mg(II)-promoted stereoselective synthesis of (Z

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• % yield. Surprisingly, an attempt to reduce the carbonyl function in adenine derivative 3 failed. The reaction performed at the same conditions as for 2 afforded a complex mixture of products. In order to solve this problem, lithium aluminum hydride was used as reducing agent. In this case, the reaction

• mesh ASTM). Triethylamine, dimethylformamide, and tetrahydrofuran were distilled and deoxygenated prior to use. Other solvents were of reagent grade and were used without prior purification. Thymine, adenine, 3-chloropropionyl chloride, lithium aluminum hydride, sodium borohydride, and aluminium

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• article. Results and Discussion On the basis of our previous study [4], the chiral glutarimide 1a was employed as the starting material and optimization of reaction conditions with benzaldehyde-based imines 2 was performed (Table 1). Lithium enolate by the action of LDA to 1a was found to be ineffective

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

• -bromooxime 26 with lithium enolate 27 to give oxime 28 via the Michael addition to transient nitrosoalkene NSA6 [31]. Oxime adduct 28 existed predominantly in a cyclic 1,2-oxazine form (Scheme 11). Subsequent benzylation of oxime 28 and the thermal retro-[2 + 2]/[4 + 2]-cycloaddition cascade followed by

• reported the use of β-ketoxime sulfones 61 in the reaction with lithium acetylides that resulted in formal substitution of the sulfinate group through an elimination–addition mechanism (Scheme 21) [43]. Interestingly, unlike α-halooximes, 1,4-elimination in sulfones 61 to generate nitrosoalkenes NSA13

• proceeds only at elevated temperatures (50 °C), that may account for relatively low yields of products 62. Furthermore, the reaction of sulfone 63 with lithium (trimethylsilyl)acetylide furnished only enoxime 64. Apparently, the application of more convenient and selective nitrosoalkene sources (e.g., TBS

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• that when NaI, LiBr or KI was used alone in anhydrous solvents (acetone, MeCN or butanone) under heating (80–100 °C) a selective monodeprotection of the dialkyl phosphonates (alkyl = methyl or ethyl) was observed. The sodium or lithium salts being formed in high yields (87–97% yields) [170]. This

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• accessible from gem-difluoropropargylic alcohols C through a base-mediated isomerization process (Scheme 1) [26][27]. Results and Discussion The required propargylic alcohols 5a–e (type C, Scheme 1) were obtained in 27–73% yields by reaction of the lithium salt of the easily accessible gem-difluoro

Block copolymers from ionic liquids for the preparation of thin carbonaceous shells

• Sadaf Hanif,
• Bernd Oschmann,
• Dmitri Spetter,
• Muhammad Nawaz Tahir,
• Wolfgang Tremel and
• Rudolf Zentel

Beilstein J. Org. Chem. 2017, 13, 1693–1701, doi:10.3762/bjoc.13.163

• anchor group could bind to inorganic nanoparticle surfaces, where a second polymer block could be converted into a conductive carbon shell, improving the properties of nanoparticles like TiO2 or ZnO with respect to the reversible storage of lithium or sodium ions [22][23][24][25]. Using a block copolymer

• anode material in lithium or sodium ion batteries. Experimental All chemicals were acquired from commercial sources (Acros or Sigma-Aldrich) and used without further purification. Synthesis and structural characterization: NMR spectroscopy was applied with a Bruker ARX 400 spectrometer. Fourier

• of P (IL-b-DAAM): P (IL-b-NAS) (1 equiv) and lithium bromide (50 equiv) were dissolved in DMSO in a Schlenk flask. Dopamine hydrochloride (50 equiv) and triethylamine (50 equiv) were also dissolved in DMSO. The two solutions were combined and stirred overnight at 50 °C. For work-up, the polymer was

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

• K-10 and Pd/C as catalysts. The microwave-assisted synthesis of β-carboline 96 from tetrahydro-β-carboline 95 using catalytic Pd/C and lithium carbonate at high temperature is also reported [96]. This high yielding procedure gets completed within a few minutes (Scheme 36). Although the reaction

• lithium carbonate at high temperature. 4-Methoxy-TEMPO-catalyzed aerobic oxidative synthesis of 2-substituted benzazoles. Plausible mechanism of the 4-methoxy-TEMPO-catalyzed transformation. One-pot synthesis of 2-arylquinazolines, catalyzed by 4-hydroxy-TEMPO. Oxidative dehydrogenation – a key step in

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