One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• Substituted imidazoles are readily prepared by condensing the versatile isocyanide Asmic, anisylsulfanylmethylisocyanide, with nitrogenous π-electrophiles. Deprotonating Asmic with lithium hexamethyldisilazide effectively generates a potent nucleophile that efficiently intercepts nitrile and imine

• to substituted imidazoles. Raney nickel hydrogenolysis was effective in interchanging the C4 anisylsulfanyl group for hydrogen (Scheme 3); attempted lithium–anisylsulfanyl exchange [19] or palladium- [22] or nickel- [23] anisylsulfanyl cross coupling was not successful. Raney nickel reduction of 7f

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• Scheme 3 consisting of the following steps: (i) Wittig reaction of 2-bromobenzaldehyde with methyltriphenylphosphonium iodide ylide, (ii) lithiation of the resultant o-bromostyrene with n-BuLi and reaction of the aryl lithium species with ethylene oxide, and (iii) oxidation of the resultant primary

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• nucleoside 94 followed by treatment with lithium azide in DMF and saturated methanolic ammonia solution afforded nucleoside 95. Refluxing of nucleoside 95 with 13b, 45 and 53a–e in toluene produced the desired nucleosides 96a–g (Scheme 21) [51]. Shaikh et al. [14] reported the synthesis of double-headed

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• with these methods, the use of butyllithium for the generation of lithium alkylidene carbenoids limits the range of usable substrates in the Corey–Fuchs method, and the Ohira–Bestmann method cannot be applied to the synthesis of internal alkynes from ketones [3]. Magnesium alkylidene carbenoids 3 are

• )magnesium chlorides, CH2=CXMgCl (X = F, Cl, and Br) << (1-chlorovinyl)lithium, CH2=CClLi. If the 1-heteroatom-substituted vinylmetal displays vinylidene characteristics, the FBW rearrangement occurs to give the alkyne. If not, the vinylmetal is simply protonated to give a heteroatom-substituted alkene. A

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• demonstrates the ease with which highly reactive reagents such as lithium bis(trimethylsilyl)amide can be used to effect sensitive aldol reactions in flow. Another recent example of an aldol reaction on a complex system originates from the group of Gauthier, which details the production of the HIV non

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• important tool in the asymmetric synthesis of aziridines [25][26], α-amino acids [27][28], β-amino acids [23][29] and branched α-amines [30][31]. The Darzens-type asymmetric synthesis of N-(p-toluenesulfinyl)aziridine 2-carboxylate esters (7 and 8) was described through the addition of lithium α

• -bromoenolates to enantiopure p-toluenesulfinamide 5. cis-aziridine 7a was formed as the major diastereoisomer in 89% yield and the trans-isomer in 8% yield in a one-step procedure using lithium enolates of methyl bromoacetate 6a and sulfinyl imine 5. Lithium enolates of methyl α-bromopropionate gave trans

• [70]. The reactions were performed in THF at −78 °C, using lithium hexamethyldisilazide as base. Aziridines with relative trans-configuration were obtained in good yields and excellent stereoselectivities with methyl α-bromo-α-phenylacetate (26, R2 = Ph). Lower yields, and poorer

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• characterized by lithium cation basicity (LiCB) liquid SO2 (76.3) is similar to DCM (83) [67]. Thus, liquid SO2 could be classified as a non-coordinating solvent that unlikely coordinates to the oxocarbenium ion intermediate and affects the glycosylation stereoselectivity [1]. As a result, we can conclude that

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• trifluoromethylated product 126 (Scheme 44). As a rare example of EDA photochemistry in the catalytic system, only a catalytic equivalent of the electron donor was employed in this approach. Further experiments showed that the addition of inorganic salts, calcium chloride and lithium chloride, could increase the

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• formed. In fact, a series of spirocyclopentalydenemethanofullerenes 190–193 were obtained by the reaction of C60 with lithium salts of tosylhydrazone (Scheme 34) [154]. Spiromethanofullerene 194 was prepared on the basis of monoethylene glycol tosylhydrazone. Hydrolysis of the former resulted in 6,6

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• (II) chloride with an excess of lithium sand and a catalytic amount of 4,4’-di-tert-butylbiphenyl (DTBB, 10 mol %) as electron carrier, in THF as the solvent. Once the reaction mixture turned to black, indicating the formation of the CoNPs, the corresponding support was added and the resulting

• 284.8 eV. Catalysts preparation – general procedure Analogous as described in [57], a mixture of lithium sand (21 mg, 3.0 mmol) and 4,4'-di-tert-butylbiphenyl as electron carrier (DTBB, 26 mg, 0.1 mmol) was placed in a pre-dried Schlenk-type reaction vessel under nitrogen atmosphere. Then anhydrous THF

• (3 mL) was added and the reaction mixture was stirred at room temperature until it turned dark green (5–10 min), indicating the formation of the corresponding lithium arenide. Anhydrous cobalt(II) chloride was then added (130 mg, 1.0 mmol) and the resulting suspension was stirred until it turned

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• -protected phosphonodepsitetrapeptides 63 were obtained and further transformed to the N-protected phosphonodepsipeptide ester lithium salts 58 after aminolysis with tertiary butylamine and treatment with Dowex-Li+ (Scheme 10) [26]. Synthesis of β-phosphonodepsipeptides To develop iminocyclitol-based small

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• alcohols, ethers, esters, and amines (121, Scheme 53) [103]. They proposed that an initial tin–lithium exchange was followed by a β-elimination of LiF to form the intermediate cyclopropenes 119. The ring opening of the latter then generated the vinylcarbenes 120. The carbenes 120 could then insert into the

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• Ryouta Kawanishi Kosuke Nakada Kazutaka Shibatomi Department of Applied Chemistry and Life Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi 441-8580, Japan 10.3762/bjoc.17.23 Abstract Decarboxylative trifluoromethylthiolation of lithium pyridylacetates was

• achieved using N-(trifluoromethylthio)benzenesulfonimide as the electrophilic trifluoromethylthiolation reagent. The reaction afforded the corresponding trifluoromethyl thioethers in good yield. Furthermore, the preparation of lithium pyridylacetates by saponification of the corresponding methyl esters and

• lithium pyridylacetates undergo decarboxylative fluorination upon treatment with an electrophilic fluorination reagent to afford fluoromethylpyridines under catalyst-free conditions. Furthermore, we demonstrated the one-pot synthesis of fluoromethylpyridines from methyl pyridylacetates by saponification

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• was followed even when the temperature was decreased to 30 °C and the reaction time was 2 h, furnished 4aa in a 84% yield (Table 3, entries 6 and 7). The use of the corresponding lithium and sodium tert-butoxides was found to afford a lower yield, which clarified the importance of the ionic character

• seemed to be an important factor, and the corresponding lithium and sodium salts did not aid the reaction satisfactory. Moreover, EtONa was found to be inappropriate for this protocol (Table 3, entries 10 and 11). Determination of the appropriate conditions both for Michael addition as well as

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• followed by subsequent oxidation produced aldehyde (Z,Z)-61. After extensive unsuccessful efforts to produce enantiopure aldol fragment (Z,Z)-62 using the N-tosyl-ʟ-valine-derived oxazaborolidinone, the racemic synthesis of (Z,Z)-(rac)-62 was achieved by utilizing the lithium enolate of methyl isobutyrate

• derivative (rac)-63 was subjected to undergo acetylation, acid chloride formation, and quenching with ammonium hydroxide to produce amide derivative (rac)-64 in 70% yield. Finally, saponification of acetate (rac)-64 using lithium hydroxide gave racemic inthomycin A ((rac)-1) in 14% overall yield (Scheme 5

• Scheme 6, compound 70) [21]. Next, the key Stille coupling reaction of dienylstannane (E,E)-(–)-69 with oxazole vinyl iodide 48 using Pd(PPh3)4/CsF/CuI conditions [51][52] gave ester (+)-11 in 85% yield. The ester (+)-11 was then hydrolyzed with lithium hydroxide to give the corresponding acid (+)-73 in

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• , activated by lithium ion in a tricyclic N,O-acetal (−)-46, and an olefin metathesis (RCM) of a dialkenylpiperidine (−)-50 for the construction of an azabicyclononane system [48]. The synthetic sequence described by the authors is shown in Scheme 6. The lactam present in 43 was opened by treatment with

• . After the treatment of (−)-46 with the lithium acetylide ethylenediamine complex in THF, a nucleophilic alkynylation occurred, with a reversal of configuration in the reaction center. Then, removal of the 1-(2-hydroxyphenyl)ethyl group via cleavage of the C–N bond, leading to (6S)-ethynylpiperidine

• occurred by removing the TBDMS and formyl (CHO) groups via treatment with TBAF in dry THF and lithium–ethylenediamine complex, respectively. Finally, the resulting alcohol (+)-56 was oxidized in the presence of PCC to provide (−)-adaline (1). In this work, the quaternary center was successfully generated

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• evaluated reduction conditions on a simpler difluorinated hexopyranose analogue. Thus, difluoroglucose 21, easily accessible in 3 steps from levoglucosan (1) [21], was subjected to lithium aluminium hydride (LiAlH4) in THF (Scheme 1a) and difluoroglucitol 22 was isolated in 58% yield. The reaction was

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• 2 was dissolved in THF and lithium diisopropylamide (LDA) was added, followed by iodine in THF. The reaction temperature was kept strictly between −70 and −80 °C to make sure that iodination proceeds without further side reactions (Scheme 1) [28]. Despite the fact that the exocyclic amino group was

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• the generation of lithium(I) pulses that, using a chemical fuel, introduce the time domain in the operation of an AND gate and thus in the field of (supra)molecular logic [61]. Based on the experience in stoichiometric metal–ligand self-sorting, the Schmittel group designed a two-step cascaded metal

• -ion translocation scheme using five components: hexacyclen (49), nanoswitch 35, luminophore 36, zinc(II) ions, and lithium(I) ions in a 1:1:1:1:1 ratio (Figure 15). In this small collection, the initial networked state SelfSORT-I was defined by a clean self-sorting of the Zn2+ ions within the cavity

• of hexacyclen (49), and of the Li+ ions inside the triangular nanoswitch 35 while the lithium-sensitive luminophore 36 was left unloaded (Figure 15a). In the following, the addition of TFA initiated a second self-sorting. It was shown that the acid protonated the ligand 49, expelling zinc(II) from

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• -dibromothienothiophene 2 [39], which was obtained from thieno[3,2-b]thiophene (1) [38], was triisopropylsilyl (TIPS)-protected by lithium-halogen exchange with n-BuLi and triisopropylsilyl chloride to give thienothiophene 3 in 69% yield. A halogen dance reaction of 3, induced by lithium diisopropylamide (LDA) at −78 °C

• , the SN4’-intermediate was directly alkylated with 2-ethylhexyl bromide and the corresponding dialkylated SN4' system was subsequently obtained by removal of the bromines by lithium–halogen exchange and acidic work-up [28]. Synthesis of S,N-heterotetracenes SN4''. In contrast to SN4’, S,N

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• decarboxylation. The excited photocatalyst is reductively quenched by 242• to give the imine intermediate 243. Indoles 241 and 243 are then brought together by the chiral phosphate catalyst 244 and the lithium counterion in a hydrogen-bonded complex 245 to give the desired enantioenriched products 246 in

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• ]. Catechol ligands L-H2 with an ester functionality in the 3-position were prepared via conversion of the acid chloride of 2,3-dihydroxybenzoic acid to the corresponding esters. These ligands underwent a complexation with titanoyl(IV) bisacetylacetonate and lithium carbonate initially forming a mononuclear

• “Werner-type” triscatecholate titanium(IV) complex. Two of these monomers dimerized in a consecutive step to obtain a non-covalently linked helicate (Scheme 1). The dimerization took place via the coordination of three lithium cations acting as bridges between two monomeric complex units [13][14][15][16

• ). The yields of the reactions were rather moderate. On the other hand, the use of acetonitrile had no significant influence on the yield compared to acetone while the enantioselectivity dramatically dropped to 8% ee. In this case the lower selectivity correlated with the increasing lithium solvating

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• lithium acetylides [25]. By a photoredox-catalytic process, primary α-(trifluoromethyl)-α-(4-pyridyl)benzylamines were obtained from α-(trifluoromethyl)-benzaldoximes and 4-cyanopyridine [26]. We have recently introduced a new class of acetylenic iminium salts, namely 1-(trifluoromethyl)prop-2-yn-1

Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and ⁶Li/¹³C NMR spectroscopic data

• Jürgen Vollhardt,
• Hans Jörg Lindner and
• Hans-Joachim Gais

Beilstein J. Org. Chem. 2020, 16, 2057–2063, doi:10.3762/bjoc.16.172

• dianionic carbon atom, including its electronic structure and coordination geometry, together with the possibility of a coordination by two lithium atoms. The sulfonyl dilithio methandiides 2, carrying various substituents R1 and R2, have attracted particular attention [1][2][3][4][5][6]. Reactivity studies

• symmetric tetramer, (2a)4·(THF)6, containing six THF molecules (Figure 2) [44]. The lithium atom Li4 is not exactly located on the C2 axis. It is resolved by two Li4 in general positions near the C2 axis each with an occupancy of 0.5. Therefore, Figure 2 shows two positions for Li4 and the attached THF

• atom and only coordinated by oxygen atoms (2 Li1 and Li4). Lithium atoms Li3 and Li5, which are each coordinated by two dianionic carbon atoms, have planar trigonal coordination geometry. The coordination geometry of C1A and C1B is characterized by τ4 values [45] of 0.68 and 0.86, respectively