Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• using a four-step sequence such as Negishi’s (Z) and (E)-stereoselective isomerization of the terminal alkyne followed by iodinolysis [19][70][71], oxidation to the corresponding aldehydes and enantioselective Kiyooka–Mukaiyama aldol reaction followed by TES protection of the resulting alcohols (Scheme

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

• (2) was synthesized from terminal alkyne 76 (Scheme 9). This alkyne was prepared from 5-bromopentene, according to the procedure described by Negishi [54]. Zr-catalyzed carboalumination furnished vinylalane, treated with p-menthane-3-carboxaldehyde providing the allylic alcohols (−)-77a and (−)-77b

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• (Scheme 9). With the aim to enable the further functionalization of the products of the oxaenediyne metathesis, we also synthesized substrates modified at the terminal alkyne positions with silyl or ester groups. Because these substrates were inaccessible by the above described methods, we obtained the

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• triazoles 33–44. General reaction conditions for CuAAC reactions: Azide (1.00 equiv), terminal alkyne (1.05 equiv), CuSO4·5H2O (0.1 equiv), sodium ascorbate (0.50 equiv), CHCl3, (0.1 M) and water (12.5 mM) at 25 °C for 48 h. b) Methylation reaction of adamantly-substituted triazole 42 with Meerwein′s salt

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

• cyclopentenone ring in all cases (Scheme 32). This was expected for terminal alkyne 58a, since this is the substitution pattern always found (see Scheme 4). On the other hand, for alkynes bearing substituents of similar steric bulk, the electron withdrawing group is expected to occupy the β-position. However

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• these species in inhibiting aconitase [22] must be reconciled with synthetic utility. To that end, catalysis-based strategies to unmask the venerable α-fluorocarbonyl motif [23] from a terminal alkyne were considered (Figure 1). This general strategy was appealing given the commercial availability of

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• proceeded efficiently for a wide range of substrates in moderate to excellent yield, including various alkyl halides 93, carbon tetrachloride, 2-norbornene, cyclic alkenes, a terminal disubstituted olefin, and a terminal alkyne. The reaction mechanism was thought to proceed via energy transfer from the

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• protecting groups [12]. Later, ruthenium complexes-catalyzed alkyne–azide cycloadditions (RuAACs) regioselectively produced the opposite form of the disubstituted triazoles. Thus, a wide range of azides was reacted with diverse nonactivated terminal alkyne substrates using ruthenium complexes to generate

• . Different ratios of Cu/Au (1:1, 3:1, and 5:1) were studied for the coupling reaction of a nonactivated terminal alkyne with an organic azide. Control measurements showed that 1:1 and 3:1 samples were more efficient than a 5:1 sample. The authors stated that increasing the Cu/Au ratio caused the formation of

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• Goki Hirata Yu Yamane Naoya Tsubaki Reina Hara Takashi Nishikata Graduate School of Science and Engineering, Yamaguchi University 2-16-1 Tokiwadai, Ube, Yamaguchi, 755-8611, Japan 10.3762/bjoc.16.45 Abstract A terminal alkyne is one of the most useful reactants for the synthesis of alkyne and

• reaction of 3 equivalents of terminal alkyne 1 (aryl substituted alkyne) and an α-bromocarbonyl compound 2 (tertiary alkyl radical precursor) undergoes tandem alkyl radical addition/Sonogashira coupling to produce 1,3-enyne compound 3 possessing a quaternary carbon in the presence of a copper catalyst

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• warranted, which at the same time may provide biologically active compounds. Results and Discussion Preparation of 5-alkynyluridines was carried out from acyl-protected 5-iodouridines (1a,b) [8][63] and the appropriate terminal alkyne in the presence of catalytic amounts of Pd(PPh3)4, copper(I) iodide

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• to α-pyrones through a consecutive alkynylation–Michael addition–cyclocondensation (AMAC) multicomponent synthesis [23]. The reaction can be rationalized by a Sonogashira coupling between an acid chloride and a terminal alkyne furnishing an alkynone, which is transformed without isolation by addition

Formation of alkyne-bridged ferrocenophanes using ring-closing alkyne metathesis on 1,1’-diacetylenic ferrocenes

• Celine Bittner,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2019, 15, 2534–2543, doi:10.3762/bjoc.15.246

• shown for complex I as well [13][16][46]. Beforehand, the promotion of terminal alkyne metathesis (TAM) proved to be difficult due to several deactivation pathways [47][48][49][50][51][52][53]. Regarding the metathesis of organometallic substrates, numerous examples of a conversion via olefin metathesis

• acetylenic sidechains show the characteristic triplet with a small coupling constant for the terminal alkyne proton at chemical shifts of 2.05 ppm and 2.01 ppm, respectively. The NMR data for the butynyl compound 1a fit the results of Suitor et al. that were published only recently [93]. From saturated DCM

• is in the same range as for the free ligand 2a. Conclusion The present paper reports a new application of terminal alkyne metathesis (TAM) using the highly active molybdenum pre-catalyst MoF6. For the first time, acetylenic ferrocenophanes were accessed using ring-closing alkyne metathesis

Click chemistry towards thermally reversible photochromic 4,5-bisthiazolyl-1,2,3-triazoles

• Chenxia Zhang,
• Kaori Morinaka,
• Mahmut Kose,
• Takashi Ubukata and
• Yasushi Yokoyama

Beilstein J. Org. Chem. 2019, 15, 2161–2169, doi:10.3762/bjoc.15.213

• century, Sharpless and co-workers proposed the concept of “click chemistry” [14], which stands for the secure, quick, selective, general and facile reaction between two organic functional groups. In click chemistry, the Huisgen cyclization, which occurs between an organic azide and a terminal alkyne

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• react with aldehydes 1 in the presence of NaHSO4·SiO2 and the product obtained was refluxed with phenylacetylene (as terminal alkyne, 2) in the presence of CuI to obtain the product, however, in the second pathway, 1 and 2 were taken together in the presence of CuI and the product obtained was treated

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• , leading to final lactams 20. This mechanism is partially corroborated by the following multicomponent synthesis where benzamide 21, ortho-functionalized with a terminal alkyne group (Scheme 5), a secondary amine 22 and carbon monoxide (23) react to produce 3-methyleneisoindolinones 24 [80]. A palladium

• conjugate addition of benzamide nitrogen onto the 2-ynamide generates the final cyclization product 24 through allene intermediate 28. Taking into account that the reaction does not take place with internal alkynes, the authors conclude that a terminal alkyne is necessary for the formation of the first

• through an addition of copper acetylide, generated from terminal alkyne and copper, to the imine formed by the reaction between the amine and the formyl group. Then, the secondary propargylamine intermediate would act as a nucleophile in a cyclization process to form the lactam ring. The same

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• applied a Diels–Alder reaction of 1,2,4,5-tetrazine with a terminal alkyne unit in a 21-crown-7-based [2]pseudorotaxane 14. The [2]rotaxane 15 was produced in 81% yield having pyridazine groups as stoppers (Figure 7). Very recently, Nierengarten and co-workers reported a solvent-free mechanochemical

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• approach to complex heterocycles. The aldehyde PM69 was further converted into the terminal alkyne PM73 by employing the Bestmann–Ohira protocol (Scheme 21). After its Sonogashira reaction with iodobenzene to the intermediate disubstituted alkyne PM74 this compound was converted into furopyrimidine

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• formation of alkylidenecyclopropanes 58a (86%), 58b (60%) and 58c (84%). It is worth mentioning that despite the use of a strong base (KHMDS) and the acidity of the “vinylic” protons of cyclopropenes which is comparable to that of a terminal alkyne [62], cyclopropenylcarbinyl glycolates devoid of

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

• Muhammad Israr,
• Changqing Ye,
• Munira Taj Muhammad,
• Yajun Li and
• Hongli Bao

Beilstein J. Org. Chem. 2018, 14, 2916–2922, doi:10.3762/bjoc.14.270

• , terminal alkyne 1 (0.5 mmol), diacyl peroxide 2 (0.75 mmol), TMSN3 (90.4 mg, 0.75 mmol), CuCl (4.9 mg, 0.05 mmol) and CH2Cl2 (2 mL) were added, respectively. The reaction mixture was stirred vigorously for 10 h at 50 °C. Then, the reaction mixture was cooled to room temperature, poured into saturated

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• , a novel competition assay employing ‘clickable’ active-site-labelling probes was developed. These compounds contain terminal alkyne moieties, which can be exploited for straightforward decoration via copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC), the prototypic click reaction. This

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• THF or DME was facilitated [49]. The molybdenum 2,4,6-trimethylbenzylidyne complex [MesC≡Mo{OC(CF3)2Me}3] (Figure 1, MoF6) represents the first alkyne metathesis catalyst capable of effective and highly selective terminal alkyne metathesis [49][51][52][53]. Later, a study was conducted to determine

• by a stoichiometric alkyne metathesis reaction of the ditungsten complex [(t-BuO)3W≡W(Ot-Bu)3] with MeC≡Ct-Bu (Scheme 1) [62]. Even though Schrock’s catalyst V was the most established alkyne metathesis catalyst for many years [63][64], it does not promote terminal alkyne metathesis efficiently and

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• lithium(trimethylsilyl)acetylide to get the coupled product 24. The latter compound on further treatment with K2CO3 in MeOH [26] furnished the desilylated propargylic alcohol 19 (Scheme 2). The copper(I)-catalyzed Cadiot–Chodkiewicz [27] cross-coupling reaction between bromoalkyne 18 [28] and terminal

• alkyne 19 provided the corresponding diynes 25 and 25a in a 1:1 ratio. Though we had an option to proceed further with the mixture of 25 and 25a affording both enantiomers that could be separated later, we focused our attention towards the synthesis of the required chiral compound. Thus, the mixture of

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• of Pd(OAc)2 in THF, and affords the dibenzoalkylidenefluorene 47 in an excellent 88% yield (Scheme 16). Ten years later, Huang, Wen and co-workers have demonstrated that, in the presence of both a terminal alkyne and a boronic acid, various cyclic diaryl-λ3-iodanes undergo a transition-metal

• non-symmetrical diaryl-λ3-iodanes raises the issue of regioselectivity. This strategy has been then extended to the preparation of alkyne-substituted alkylidenefluorenes 53 by replacing the arylboronic acid with a second equivalent of the terminal alkyne and performing the reaction at 35 °C (Scheme 18

• be resubmitted to the cyclization conditions in the presence of a different terminal alkyne, or an activated alkene. The same authors have then showed that the reaction of cyclic diaryl-λ3-iodanes in the presence of internal alkynes and the catalytic system Pd(OAc)2-PCy3 affords functionalized

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• mechanism). Copper-catalyzed reaction of sydnones with terminal alkynes A substantial breakthrough in the field of 3-arylsydnone-terminal alkyne cycloaddition was achieved by Taran’s group in 2013 [3]. They developed a regioselective Cu(I)-phenanthroline-catalyzed variant of this reaction (i.e., copper

• ) is observed in most cases when a terminal alkyne was used as a reactant. On the other hand, the recent discovery of Cu(I) catalysis in the sydnone–alkyne cycloaddition (CuSAC) enables regioselective formation of complementary 1,4-disubstituted or 5-halogeno-1,4-disubstituted pyrazoles under very mild