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

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• yield and high enantioselectivity (Scheme 7) [15][16]. The Achmatowicz oxidation and ionic reduction generated the enone 58, which is regioisomeric with 53. The 1,4-addition of lithium dimethylcopper gave the desired cis-55 with high a diastereoselectivity (25:1). The cross-metathesis of 55 with 3

• fashion similar to that of the dihydropyranone 58 [16], the 1,4-addition of dimethyl copper lithium to 65 gave the desired cis-50 as a single diastereomer [31], allowing for a convergence with the route in Scheme 7. Alternatively, the Wittig methenylation of 63, followed by a silyl ether cleavage gave 66

• epoxidation [37] of 5-methyl-2-methylene-4-penten-1-ol gave the epoxyalcohol 92 in 94% ee, which was oxidized to the aldehyde 93. While the addition of the lithium salt of methyl propynoate proceeded in a nondiastereoselective fashion, the use of a zirconium/silver-mediated alkynylation gave the alcohol 94

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• phosphorylated using tetrabenzyl diphosphate in the presence of lithium bis(trimethyl)silylamide (LHMDS) in THF at −78 °C [23] to afford the anomeric phosphate 23 exclusively as the α-anomer. Finally, global deprotection of 23 (benzyl phosphate, Nap ethers, and naphthylidene acetal) were accomplished by

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• lactone product 15 (containing 10% of ester Z-13) and proved successful with phosphonolactone 21 being isolated in 77% yield after column chromatography (Scheme 7). To access tetrasubstituted alkenes, reduction of 21 to generate diol 22 was explored with lithium borohydride in Et2O. However, the reaction

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• this sense, while the addition of hard organometallic nucleophiles, such as lithium dialkylcuprates or Grignard reagents, failed, softer nucleophiles such as nitroalkanes cleanly added to the β-position, providing the Michael adduct 61. Unexpectedly, the conjugate addition reaction resulted in

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• to account for the deprotonation of the more acidic phosphonate product 7 versus the starting material 13, and potential lithium sequestration by chelation between an oxygen atom of the phosphonate and the nitrogen atom of the unsaturated ring. Monitoring of the deprotonation followed by quenching

• %, representing a significant loss of enantiopurity. It is believed that racemisation occurred during the olefination step, caused by a base mediated keto–enol tautomerisation. It was proposed that the use of lithium hydroxide would promote hydrate formation, mitigating racemisation of the aldehyde. However, this

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• with lithium sulfide followed by reaction with carbonyldiimazole (CDI), yielding the thietane derivative 153 and byproduct. The thietane derivative 153 was then converted into 7-deoxy-5(20)-thiapaclitaxel 154a in a three steps sequence [59] (Scheme 31). Another member of taxoids, 10-deacetylbaccatin

• nucleophiles undergo a further intramolecular addition to form iminothietanes 418. 2-Iminothiiranes 416 underwent a nucleophilic ring expansion with isocyanoalkanes 415 as nucleophiles to give rise to 2,4-diiminothietanes 418 in 33 to 52% yields [101] (Scheme 91). 3-Chloroallyl lithium (420) was also applied

• as a nucleophile to synthesize 2-vinylthietanes 421 in the electrophilic ring expansion of thiiranes 419. The corresponding thiiranes 419 reacted with 3-chloroallyl lithium (420), yielding vinylthietanes 421 in 10–73% yields. This was a general route towards the synthesis of 2-vinylthietanes 422

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• batch-to-batch variability. Tubular reactors of solid reagents combined with solution-phase reagents enable the continuous-flow preparation of organomagnesium reagents. The use of stratified packed-bed columns of magnesium metal and lithium chloride for the synthesis of highly concentrated turbo

• fresh organomagnesium reagents on a discovery scale and will do so independent from the operator’s experience in flow and/or organometallic chemistry. Keywords: Knochel–Hauser base; lithium chloride; magnesium; on-demand; packed-bed reactors; plug and flow reactor; synthesizer; turbo Grignard reagent

• chloride–lithium chloride complex (iPrMgCl⋅LiCl), known as turbo Grignard [45]. In addition to being widely cited, turbo Grignard is a popular discovery-scale tool in the pharmaceutical industry [32] and has shown an excellent selectivity on a large scale [46]. Halomagnesium amide LiCl adducts, e.g., the

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• the intended stereoselective reduction of cyclic ketones with the aim to obtain the 4-hydroxyisoxazolidines with a relative C-3/4-cis configuration. Whereas the initial attempts of the reduction of 9a with lithium borohydride resulted in a poor stereoselectivity (70:30 in favor of the desired cis

• Information File 1). The consecutive reaction of the O-benzoylated isoxazolidine 7b with TrocCl in the presence of lithium iodide [39][40] gave the protected N-Troc isoxazolidine 11 in 70% yield (Scheme 5). It is worth mentioning that considering suitable solvents, acetonitrile was superior to 1,2

• was successfully used for the inversion of the C-3/4-trans relative configuration of the isoxazolidine ring. The bulkier ʟ-selectride showed an excellent selectivity toward the C-3/4-cis isomer compared to lithium borohydride. The final N-debenzylation by a two-step procedure involving a basic

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• solutions Xu et al. used energy-rich carbon precursors for the spherical carbon preparation via ultrasonic spray pyrolysis. Lithium, sodium or potassium propiolates are one class of such energy rich materials and exhibit leaving groups such as CO, CO2 or C2H2 eliminated by decarbonylation or decarboxylation

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• with zincate 11 using a variety of catalysts and different reaction conditions, was unsuccessful. However, coupling of 4-[bis(dimethoxybenzyl)difluoromethyl]benzyl bromide (14) with the lithium enolate of William`s lactone 15 gave the protected amino acid 16 in 80% yield. The desired protected amino

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• affording a protected tetracyclic kempane derivative. The latter was further converted into (+)-kempene-2 (14a) in 91% yield by deprotection and acetylation (Scheme 17). A reduction of the intermediate ketone with lithium aluminum hydride followed by an acetylation finally led to (+)-kempene-1 (14b) and

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• 19 instead. This compound was obtained from both aldehyde 15 and its precursor ethyl thioester methyl ester 14, respectively (Scheme 3). Both substrates 14 and 15 were reduced to the corresponding diol 17 with lithium aluminum hydride with 73% or 83% yield, respectively. Next, the selective

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• ] were the phosphine boranes were prepared by reacting phosphines with sodium borohydride. Alternatively, the reduction of phosphine oxide byproducts with lithium tetrahydridoaluminate, calcium aluminum hydride, and hydrosilanes can also be used to regenerate the phosphine ligands. Hydrosilane reagents

• usually lead to stereoselective reduction products, hence, they are used for the synthesis of chiral phosphines from chiral oxides [53]. Lithium tetrahydridoaluminate is used for the reduction of achiral phosphines because its action on optically active phosphine oxides leads mainly to the optically

• lithium halogen elimination, halide migration, and ring-opening reactions [56][57]. Butylphosphines are also formed alongside the main product, and in most cases pure phosphine pyridines are obtained using column chromatography followed by extractions adding to the number of synthesis steps. This method

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• , lithium diisopropylamide (LDA)-mediated cyclisation of 2-(methylthio)benzamides, which were obtained by directed ortho-metalation of the respective benzamides followed by quenching with dimethyl disulfide [27] (Supporting Information File 1, Scheme S1). In general, we found the LDA-mediated cyclisation

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the

• lactone 4, which, however, was unstable towards chromatographic purification and used as crude material after lyophilization to remove the solvent. Coupling of 4 with the lithium salt of dimethyl methylphosphonate (5) in THF afforded the β-anomeric ketol phosphonate derivative 6 in 57% yield. The axial

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• stereospecificity make this transformation synthetically appealing [12][13]. Allyl esters of various carboxylic acids undergo rearrangement as their lithium enolates or silyl ketene acetals and the corresponding acids were isolated in 75–80% yields. Accordingly, the Ireland–Claisen rearrangement of lithium enolates

• the corresponding acid 3a in 63% yield at rt (Table 1, entry 1). At a higher temperature, the product yield decreased (Table 1, entry 2). The reaction of the related (E)-but-2-en-1-yl propionate (1b) gave acid 3b under similar conditions with slightly lower yields. The rearrangement of lithium enolate