Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• from di-tert-butyldiazocarboxylate (23), aryl-substituted di-Boc-hydrazines 26 were prepared by the addition of aryllithium species generated in situ by lithium-halogen exchange of aryl halides [55]. Gerstenberger et al. used this entry for the one-pot synthesis of N-arylpyrazoles 25, as depicted in

• pyrazole 88 (Scheme 31) [114]. In addition to pyrazoles, functionalized pyrimidines can also be prepared in a one-pot process using this method. In 2001, Bouillon et al. reported a one-pot process for synthesizing fluorinated pyrazoles. Initially, a lithium–halogen exchange was carried out on fluorinated

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• synthesis of some 1,5-BCHeps, including 134b, was also possible on mmol scale. Through derivatization of iodine-substituted 1,5-BCHeps 134f and 134g, an even larger number of 1,5-BCHeps were accessed (Scheme 14B) [27][47]. For example, lithium–halogen exchange was used to prepare acids 135f–g and boronic

• ]. A wide variety of 1,2,3-BCPs bearing substituents in the bridge position were reported by Measom and co-workers in their study on the lithium–halogen exchange of 2-bromo-1,2,3-BCPs [78]. Larger bridged bicyclic structures such as bicyclo[2.1.1]hexane offer multiple different exit vectors for

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• , resulting in the formation of compound 75. Further transformation through lithium–halogen exchange, followed by reaction with Me3SiCl, yielded bis(trimethylsilylated) intermediate 76 in a 90% yield. By utilizing the conditions outlined in the prior investigation [49], compound 76 was subjected to a reaction

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• authors brominated 2a in acetic acid, resulting in a tetrabrominated intermediate 154 in excellent yield (90%). Selective lithium–halogen exchange and reaction with a chlorophosphine, followed by debromination with BuLi/MeOH, gave the desired bisphosphine 155 in good yield (Scheme 36). Conclusion The

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• with Davis’ oxaziridine and subsequent oxidation using Dess–Martin periodinane. Initial attempts for the key step (15 → 16) like a Nozaki–Hiyama–Kishi reaction failed, but lithium–halogen exchange using t-BuLi at low temperatures gave the desired vinyllithium intermediate I which successfully added to

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

• from the carbocupration of 85, a Grignard derivative of 1-heptyne [56]. After a lithium–halogen exchange, the corresponding vinyllithium was treated with p-menthane-3-carboxaldehyde to give the isomeric allylalcohols (−)-87a and (−)-87b in a 5:1 ratio. After chromatographic separation, (−)-adaline (1

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

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• . The strategy to “oxidize” the 3-position of AQs via iodination, lithium–halogen exchange and electrophilic trapping can offer a flexible approach to new 3-substituted AQs starting from an easily available synthetic intermediate. While we decided to oxidize the newly formed boronic acid ester in situ

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

• 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

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

• –halogen exchange and subsequent carboxylation with iodopyrazoles 3a–d. Attempted cross-coupling reactions with 4-halopyrazoles 5 and 3a. Negishi couplings with 4-iodopyrazoles 3a,b. Formation of pyrazoloquinolizin-6-ium iodide 12 upon reaction of 3a with (phenylethynyl)zinc bromide. Prototropic

• -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

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

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• via a carbanion generated through a lithium–halogen exchange [169][170][171]. The first method has limited utility because toxic byproducts are produced in the reaction that can be difficult to remove. The application of the second method is limited because the high reactivity of the lithium reagents

Aryl substitution of pentacenes

• Andreas R. Waterloo,
• Anna-Chiara Sale,
• Dan Lehnherr,
• Frank Hampel and
• Rik R. Tykwinski

Beilstein J. Org. Chem. 2014, 10, 1692–1705, doi:10.3762/bjoc.10.178

• acetylide to pentacenequinone (Scheme 1) [21][35][36][37][38]. With these two ketones in hand, a second nucleophilic addition was initiated. Thus, commercially available aryl halides dissolved in dry THF were subjected to lithium halogen exchange at −78 °C using n-butyllithium. A substoichiometric amount of

Continuous flow photocyclization of stilbenes – scalable synthesis of functionalized phenanthrenes and helicenes

• Quentin Lefebvre,
• Marc Jentsch and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 1883–1890, doi:10.3762/bjoc.9.221

• derivatives. We choose stilbenes with bromide and methyl substituents, as the latter can be used in subsequent oxidation, deprotonation, and radical addition reactions, whereas the former opens access to various functional groups via lithium-halogen exchange or cross-coupling chemistry. Methoxy groups were

Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer

• William F. Bailey and
• Justin D. Fair

Beilstein J. Org. Chem. 2013, 9, 537–543, doi:10.3762/bjoc.9.59

• temperature. Keywords: carbolithiation cascade; carbometallation; intramolecular carbolithiation; intermolecular proton transfer; lithium–halogen exchange; strained hydrocarbons; Introduction The first publication describing an intramolecular carbolithiation appeared in 1968: Drozd and co-workers reported

• -heptadiene (2), required for the lithium–halogen exchange step that initiates the cascade, was prepared as illustrated in Scheme 2 (for details, see Supporting Information File 1). Vinyllithium 3 was cleanly generated in virtually quantitative yield at –78 °C by addition of 2.2 molar equiv of tert

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• carbenoids are multipurpose reagents [47] that are typically prepared from 1,1'-dihaloalkenes, either by lithium/halogen exchange followed by transmetallation with zinc salts or by direct zinc/halogen exchange [48][49][50]. Alternatively, they can also be prepared efficiently by selective monohalogenation of

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• derivative 27 could be accessed in excellent overall yield [3][23]. Alternatively, lithium–halogen exchange carried out on diiodohydrobenzoins 25 or 26, followed by reaction with various electrophiles affords access to a wider array of hydrobenzoin derivatives than those highlighted above in Scheme 3 [17

The use of silicon- based tethers for the Pauson- Khand reaction

• Adrian P. Dobbs,
• Ian J. Miller and
• Saša Martinović

Beilstein J. Org. Chem. 2007, 3, No. 21, doi:10.1186/1860-5397-3-21

• : lithium-halogen exchange, Grignard-based methodologies and catalytic hydrosilylation. The approach decided upon used the Grignard and hydrosilylation reactions. Work by Swisher and Chen showed that by using a solution of chloroplatinic acid (H2PtCl6 in isopropyl alcohol) compounds containing terminal

Total syntheses of oxygenated brazanquinones via regioselective homologous anionic Fries rearrangement of benzylic O-carbamates

• Glaucia Barbosa Candido Alves Slana,
• Mariângela Soares de Azevedo,
• Rosângela Sabattini Capella Lopes,
• Cláudio Cerqueira Lopes and
• Jari Nobrega Cardoso

Beilstein J. Org. Chem. 2006, 2, No. 1, doi:10.1186/1860-5397-2-1

• , involves first the preparation of aryllithium intermediates 3 from the carbamates 2a-2b by the reversible metathesis reaction known [21][22][23] as the lithium-halogen exchange which has been widely employed for replacement of a bromine or iodine atom in a substrate by lithium. The intermediate 3 then