One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• (Scheme 8). After bromination of 40 with molecular bromine in carbon tetrachloride, direct dehydrobromination with lithium chloride in dimethylformamide gave 11 in 85% isolated yield. Müller’s group reported an alternative synthesis for 11 starting from the carbene adduct 41 over two or three steps [55

• as a fairly air-stable red-brown solid. b. Nucleophilic addition to 4,5-benzotropone (11): Ried’s group realized the reaction of 4,5-benzotropone (11) and its derivatives with lithium acetylide as a nucleophile between −50 and −32 °C [130]. While the possible 1,4-conjugate addition product 149 was

• bromination of Julia’s ketone 163 followed by spontaneous elimination of hydrogen bromide at the temperature of the reaction. 2,3-Benzotropone (12) was also prepared by bromination of 1-benzosuberone (162) using both NBS and molecular bromine followed by dehydrobromination (using lithium chloride in

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• )iodobenzene (DIB) and lithium bromide yield a dibromo adduct (Scheme 1, reaction 2), whereas a combination of (bis(trifluoroacetoxy)iodo)benzene (PIFA) and tetra-n-butylammonium bromide (TBAB) gives bromo(trifluoro)acetoxylated 3a (Scheme 1, reaction 3) [16]. We then decided to further explore the synthetic

• our previous study on the bromination of enamides [11]. Thus, using a slight excess of DIB along with a two-fold amount of lithium bromide at 0 °C in dry acetonitrile rapidly yielded dibromo adduct 2a in 91% yield (Table 1, entry 1). Switching the reaction conditions to bromo(trifluoro)acetoxylation

• to −10 °C and the amount of lithium bromide, which was added dropwise as an aqueous solution, was diminished to 1.3 equivalents. By doing so, both the selectivity and the yield of 4a were improved though full conversion was not attained (Table 1, entry 4). Keeping the same procedure, complete

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• bromide [52] afforded modest yields of the carboxylation product 2a (Table 1, entry 1). Interestingly, a dramatic influence was observed when altering the bromide source to other types; the use of lithium bromide or organic bromides, e.g., bromotrimethylsilane and tetraethylammonium bromide, instead of

• the potassium salt, were unsuccessful in forming the carboxylate 2a (Table 1, entries 2–4). The reason for this behavior was thought to be because lithium bromide or organic bromides in combination with PIDA generated the electrophilic ‘Br+’ species [71] and molecular bromine [72], or hypobromite and

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• lithium enolate followed by a second SET step to complete the transformation (Scheme 1a) [16][17]. A different approach, developed by Maulide, relies on the highly efficient umpolung of amides into enolonium species using triflic anhydride, a pyridine base and pyridine N-oxides (Scheme 1b). These

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• stereochemical inversion at C3' [75]. The desired stereoselectivity for 2'-deoxy analogues was obtained when BF3·OEt2 was used. Furthermore, another route to the synthesis of C-nucleosides was demonstrated by direct addition of aryl lithium reagents to the 2'-OMe ribonolactone (Figure 11B). While the expected

Stepwise radical cation Diels–Alder reaction via multiple pathways

• Ryo Shimizu,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 704–708, doi:10.3762/bjoc.14.59

• been developing oxidative SET-triggered cycloadditions of enol ethers by electrocatalysis [26][27][28][29][30][31][32] in lithium perchlorate/nitromethane electrolyte solution [33]. The reactions involve a radical cation chain process and are complete using a catalytic amount of electricity. During the

• “direct” or “indirect” pathways, affording the corresponding adduct 3 in excellent yield. Conclusion In conclusion, we have demonstrated that the radical cation Diels–Alder reaction initiated by electrocatalysis in lithium perchlorate/nitromethane electrolyte solution is not limited to styrenes but was

Investigating radical cation chain processes in the electrocatalytic Diels–Alder reaction

• Yasushi Imada,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 642–647, doi:10.3762/bjoc.14.51

• luminescence quenching experiments [19]. With such an understanding in hand, radical ion chain processes could be further optimized to realize greener transformations. We have been developing anodic cycloadditions [20][21][22][23][24][25] enabled by lithium perchlorate/nitromethane electrolyte solution [26

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• -1H-indole in the presence of lithium perchlorate as catalyst to afford the new 3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones and 3-substituted indoles. The process was then extended to isocyanides and new aminobenzofurans formed via [4 + 1] cycloaddition were isolated. Bharate et al. reported

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• enolates can be considered as valuable alternatives to lithium enolates. Consequently, a number of samarium-mediated Reformatsky reactions have been developed. For example, SmI2 was found by Rinner et al. to mediate the diastereoselective Reformatsky reaction between chiral aldehyde 11 derived from D

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• the 1,2-addition reaction of Int-I proceeds in preference to the conjugate addition reaction, the desired octa-1,7-diene 5a should be produced in higher yield. However, no significant improvement was observed after various attempts such as employing a more nucleophilic lithium reagent instead of the

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• TBS ether by treatment with HF in pyridine, followed by phosphorylation using tetrabenzyl pyrophosphate in the presence of lithium bis(trimethyl)silylamide [76] in THF at −78 °C. Final deprotection by catalytic hydrogenolysis over Pd-black provided target lipid A derivatives 8 and 9 corresponding

• hydroxyl group was regio- and stereoselectively phosphorylated using tetrabenzyl diphosphate in the presence of lithium bis(trimethylsilyl)amide [76] to provide glycosyl phosphotriester as exclusively α-anomer. Global deprotection was accomplished by catalytic hydrogenolysis over Pd-black to give

• isomerized in the presence of an Ir complex and the resulting prop-1-enyl group was then removed by aqueous iodine to yield hemiacetal 30 which was stereoselectively phosphorylated by reaction with lithium hexamethyldisilazide (LHMDS), and subsequent treatment with tetrabenzyl pyrophosphate. Final

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• ]. Vinylphosphonium salt can also be synthesized by dehydrohalogenation of α-bromoethylphosphonium bromide 13 in the presence of lithium bromide in anhydrous dimethylformamide (Scheme 10). α-Bromoethylphosphonium salt 13 was obtained according to the three-step procedure, starting from the alkylation of

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• + calcd for C16H16N2O5, 316.3086; found, 316.1051. (S)-N-(2,4-Bis((E)-3,3,3-trifluoroprop-1-en-1-yl)phenyl)-1-(2-(1,3-dioxo-2H-isoindolin-2-yl)acetyl)pyrrolidine-2-carboxamide (7): 5 (2 mmol) and lithium hydroxide (12 mmol) were placed in a flask. To the flask was added THF (4.8 mL), methanol (1.5 mL

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• choice of base, leading to the construction of a [7]annulene system (Scheme 5). The use of lithium bases, such as lithium diisopropylamide and lithium hexamethyldisilazide, induced HF eliminations as well as substantial HI elimination. However, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) exclusively

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