Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• and aldehyde–amine–alkyne (A3) coupling reactions [16]. Off this discovery, in this letter, we further expand the scope of using both ChNCs and ChsNCs as a catalyst support for Pd NPs to allow access towards other highly relevant C–C bond-forming reactions. A one-pot fabrication method is used to

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• alkyne–azide click cycloaddition as the linking step, and ester saponification as the cutting step [13][21] (Supporting Information File 1). The target trefoil knot using host 1 and guest 2 is shown in Figure 2c. The binding event during the double-threading step was modeled after previous literature

• more than twice as high and this route is more amenable to multigram scale reactions. Azido-bromide 6 can undergo both alkyne–azide click cycloaddition and etherification and the effect of the reaction order on the overall yield was explored next. The click cycloaddition was pursued first and reaction

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• corresponding trimer of the fluoroalkylated alkyne, as reported by our group [27]. Finally, only 2-iodoaryl ketones (R3 = Me, Cy, Ph) were applicable in this catalytic reaction, whereas the cycloaddition using 2-iodobenzaldehyde (R3 = H) did not work at all. Therefore, the development of practical protocols for

• cobalt(II) species as a catalyst to suppress the trimerization products (Scheme 1d). Results and Discussion Initially, we carried out the screening of the reaction conditions for the cobalt-catalyzed [2 + 3] cycloaddition using fluoroalkylated alkyne 1a and 2-formylphenylboronic acid (2A) [28]. The

• results are summarized in Table 1. The cycloaddition of the fluoroalkylated alkyne 1a with 2.0 equiv of 2-formylphenylboronic acid (2A) in the presence of 10 mol % each of Co(acac)2·2H2O and 1,2- bis(diphenylphosphino)ethane (dppe) in CH3CN at 80 °C for 18 h proceeded to afford the corresponding cyclic

Efficient [(NHC)Au(NTf₂)]-catalyzed hydrohydrazidation of terminal and internal alkynes

• Maximillian Heidrich and
• Herbert Plenio

Beilstein J. Org. Chem. 2020, 16, 2080–2086, doi:10.3762/bjoc.16.175

• alkynes (7a–j, 10 examples, 0.2–0.5 mol % [(NHC)Au(NTf2)], T = 60–80 °C) utilizing a complex with a sterically demanding bispentiptycenyl-substituted NHC ligand and the benign reaction solvent anisole, is reported. Keywords: alkyne; gold; homogeneous catalysis; hydrohydrazidation; NHC ligand

• oxygen and nitrogen-containing molecules, which tend to be more difficult for catalytic transformations utilizing other transition metals [32][33][34][35][36]. The [LAu(NTf2)]-catalyzed reaction can be described by a general mechanism (Scheme 1), in which the coordination of LAu+ by the alkyne [37][38

• activating the alkyne. Consequently, even at 0.05 mol % catalyst loading virtually quantitative substrate conversion was observed after extending the reaction time to 96 h (Table 2, entry 3). In the absence of the Au catalyst, no product was formed. Hydrohydrazidation reactions of terminal alkynes: Following

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

• effect of the iminium activation. The Diels–Alder reaction of alkyne 1a with 2,3-dimethylbutadiene also occurred under very mild conditions and yielded the iminium-substituted 1,4-cyclohexadiene 4-Ch (Scheme 2), which, due to its high sensitivity toward moisture, was not purified but was further

• , 22 h; 3. o-chloranil, CH2Cl2, rt, 12 h. Diels–Alder reaction of 1a and anthracene followed by an intramolecular SE(Ar) reaction. Reactions of propyn-1-iminium salt 1a with styrenes. A mechanistic proposal for the reaction of alkyne 1a with styrenes. Reaction of alkyne 1a with 1,2-dihydronaphthalene

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• in a high yield and enantioselectivity (Scheme 5) [17][18]. The Rubottom oxidation [28] of 43 gave a separable mixture of the desired 44 and its C-14 epimer (≈7:1 ratio). The reductive deoxygenation of 44 proceeded via the tosylhydrazone to afford 45, which upon desilylation and alkyne isomerization

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• synthesize a series of phosphine oxide and phosphonate-functionalized chroman-4-ones. Unfortunately, the preparation of the substrates involved a Rh-catalyzed hydrophosphinylation of a protected functional alkyne, and the subsequent deprotection with Hg(O2CCF3)2, which is not environmentally benign (Scheme

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

• undergoes cyclometalation via a concerted metalation–deprotonation (CMD) process furnishing a cyclometalated intermediate. Thereafter, coordination and subsequent insertion of the alkyne into the Co–C bond delivers a seven-membered cobaltacycle. The desired coupling product is then liberated by reductive

• et al., allowing the synthesis of N-heterocycles such as indoles and pyrroles. The targeted heterocyclic products were obtained by cyclization of acetanilides with alkyne derivatives via a direct ortho-metalation pathway (Figure 17) [79]. Acetyl substituents acted as DG in this transformation

• , followed by the insertion of an alkyne into the C–M bond. The key step of the dual catalysis is the reductive quenching of the photoexcited catalyst by Rh(I), a low-valent metal obtained after C–N reductive elimination. Hence, the Rh(III) active catalyst is regenerated and the resulting reduced

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

• cycloadditions with model alkynes. Besides two ortho- and para-bromo-substituted benzaldehydes, the azide functionalization of a fluorene-based structure will be presented. The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of the so-synthesized azide-functionalized bromocarbaldehydes with terminal

• oxazoline 24, oxazolidine 27 cyclized already during the reaction, caused by the increased basicity of the ring nitrogen. CuAAC reactions of bromocarbaldehydes We further investigated the reactivity of azide-functionalized bromocarbaldehydes 3, 4, and 5 in copper(I)-catalyzed azide–alkyne cycloaddition

• 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

• the PKR of enynes containing a fluoride moiety. Keywords: alkene; alkyne; enyne; fluorine; Pauson–Khand; Introduction The prevalence of fluorine-containing molecules in drug-discovery programs is nowadays unquestionable [1][2][3]. The presence of fluorine atoms or fluorine-containing units at

• between an alkyne, an olefin and carbon monoxide, resulting in the regioselective formation of a cyclopentenone derivative (Scheme 1) [18][19][20][21][22]. This cobalt-mediated reaction was initially discovered by Pauson and Khand in the early 70s [23][24][25] and has since become a powerful

• transformation widely used in the synthesis of polycyclic complex molecules. The intermolecular variant shows a wide alkyne scope, but in terms of the olefin counterpart is limited to the use of ethylene or strained alkenes, such as norbornene and norbornadiene. The high prevalence of five-membered ring systems

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

• suppressed catalysis. The prerequisite for this substructure was established by molecular editing and was complemented with a physical organic investigation of possible determinants. Keywords: α-fluoroketone; alkyne; fluorination; hypervalent iodine; organocatalysis; Introduction The venerable role of

• 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

• exposure of a model internal alkyne to the standard conditions proved also successful affording 6 in 46% yield. Finally, replacement of the benzoate unit by a phthalimide moiety was possible and led to the protected amine derivative 7 (64% yield). The structure of α-fluoroketone 2 was unequivocally

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• approach was based on the one-electron reduction of diazonium salts (see the case of 13.3+ in Scheme 13), formed in situ by the reaction of the chosen 2-heteroaryl aniline (e.g., 13.1) with tert-butyl nitrite (1.5 equiv). Formation of the aryl radical 13.4· and following addition onto an alkyne moiety (e.g

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• , which should have remained intact under the conditions applied (Table 1, entry 1). The disappearance of the alkyne proton signals in the 1H NMR spectrum (δ 2.32 ppm (t, 4JHH = 2.6 Hz) and δ 4.28 ppm (dd, 3JHH = 5.2 Hz; 4JHH = 2.5 Hz)) and, instead, the appearance of signals at δ 2.44 ppm (d, 4JHH = 3.5

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• oxidized to the corresponding sulfonyl radical by the excited state of eosin Y (OD13). The resulting reduced eosin Y•− could then perform a reduction of the alkyne to generate a radical anionic species. The latter would be subsequently protonated before recombining with the sulfonyl radical to afford the

• oxidation of 29.1 was achieved using Mes-Acr-Me+ (OD2) and a cobalt cocatalyst, ensuring an efficient dehydrogenation. Various N-heterocycles 29.3 were accessed via a radical cyclization cascade with the alkyne derivatives 29.2. Amidyl radical generation The oxidation of amides is more difficult compared to

• -butyl peroxide (40.1), generating a hydroxy radical and a tert-butoxy radical. The latter promotes an H abstraction from the substrate tetrahydrofuran (8.1), giving access to an α-oxy C(sp3) radical, which is trapped by an alkyne 40.2, providing the desired vinylation product 40.3. Sulfur-centered

Development of fluorinated benzils and bisbenzils as room-temperature phosphorescent molecules

• Shigeyuki Yamada,
• Takuya Higashida,
• Yizhou Wang,
• Masato Morita,
• Takuya Hosokai,
• Kaveendra Maduwantha,
• Kaveenga Rasika Koswattage and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 1154–1162, doi:10.3762/bjoc.16.102

• materials. Keywords: alkyne oxidation; benzils; bistolanes; fluorinated compounds; phosphorescence; Introduction The development of organic light-emitting molecules is recognized as one of the most important studies because of the broad application of these compounds as fluorescence probes, bio-imaging

• corresponding bis-oxidized bisbenzil derivatives. Based on theoretical calculations, the selective formation of the fluorinated analogues stemmed from the slight modulation of the charge distribution at the alkyne moiety of the reactant induced by the electron-withdrawing fluorine atoms. Evaluation of the

• pathway for fluorinated benzil (2) and bisbenzil (3) derivatives. Proposed mechanism of Pd(II)-catalyzed alkyne oxidation by dimethyl sulfoxide (DMSO). Photophysical data from ultraviolet (UV)-visible absorption and steady-state photoluminescence (PL) measurementsa. Supporting Information Experimental

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• intramolecular alkyne insertion in the initially formed arylpalladium iodide A (leading to B) occured faster than the direct reaction of A with arylboronic acids or with 2-alkynyltrifluoroacetanilides. Experimental General methods Melting points are uncorrected. IR spectra were recorded with a Perkin Elmer

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

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• Road, Hong Kong, China 10.3762/bjoc.16.72 Abstract A novel dicyclopenta-fused peropyrene derivative 1 was synthesized via a palladium-catalyzed four-fold alkyne annulation of 1,3,6,8-tetrabromo-2,7-diphenylpyrene (5) with diphenylacetylene. The annulative π-extension reaction toward 1 involved a

• an efficient method to develop π-extended aromatic hydrocarbons with cyclopenta moieties. Keywords: alkyne annulation; cyclopenta-fused polycyclic aromatic hydrocarbons; nonplanarity; peropyrene; regioselectivity; Introduction Significant efforts have been recently devoted to the synthesis of

• [4 + 2] benzannulation, instead of the desired tetracyclopenta[cd,fg,jk,mn]pyrene (2). The selective formation of 1 could be rationalized by the steric hindrance of the phenyl rings after the twofold [3 + 2] alkyne pentannulated intermediate (Scheme S2, Supporting Information File 1), and the sequent

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

• of known, in vivo effective substances but also for designing chemically modified analogs as valid alternatives for further therapeutic agents. Keywords: bioactive compounds; enyne metathesis; ring-closing metathesis; ruthenium catalysts; tandem reactions; Introduction Alkene and alkyne metathesis

• potential of enyne metathesis in providing sustainable access to bioactive organic compounds, when used in conjunction with a number of name reactions. Enyne metathesis is a fundamental chemical transformation involving an alkene and an alkyne to produce a dienic structure through unsaturated bond

• coordinated to the metallacarbene and cleaved (Scheme 3 (a)) and the formed alkylidene species is inserted into the alkyne unit through a metallacyclobutene intermediate. This metallacyclobutene, through the rearrangement to a vinyl metal-alkylidene (Scheme 3 (b)) and subsequent metathesis with the alkene

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• the Oestreich group in 2016 [27]. The reaction could be performed using CuCN as catalyst in the absence of a ligand. A wide variety of triflates 9, including some containing a remote tosylate, bromide, alkene, or alkyne functionality, afforded the desired alkylsilanes 10–16 in fair to good yields

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• was proposed in Scheme 4. First, oxidation of AgSCF3 by (NH4)2S2O8 generates AgIISCF3, which could be further transformed to the CF3S radical or CF3SSCF3 [23][36]. Then, the addition of a CF3S radical to the alkyne function of substrates 1 or 3 afforded intermediate A. Subsequently, cyclization of

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• -tethered BODIPY derivatives serve as a substrate in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, which is known as “click” reaction, allowing for a biological tissue labelling [35][36]. In addition, ethynyl-substituted BODIPYs yield unique π-conjugated BODIPY-based macrocycles by

• ) catalyst at room temperature gave only traces of 5a with a large amount of unreacted starting material remaining. The addition of acid in expectation of the activation of TIPS-EBX was effective in promoting the gold–alkyne interactions [40][41]. After the investigation of various reaction conditions, such

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

• employed procedures for the creation of triazole products is the Huisgen azide–alkyne cycloaddition, and the reaction selectively forms one type of triazole products. Many of the alkyne and azide substrates are commercially available, many others can easily be prepared with a good range of functional

• groups. The intramolecular reaction of an alkyne as a dipolarophile with an azide as a 1,3-dipole to produce the desired 1,2,3-triazole motif is a model of “click” chemistry. The concept of “click” chemistry is an idiom that was developed by Sharpless and Meldal and later by others to describe organic

• definition and fails as a real “click” reaction. Although this cyclization reaction requires elevated temperatures and often yields both the 1,4- and 1,5-regioisomers, the Cu or Ru alkyne–azide cycloaddition falls exactly into the above definition [11]. In this respect, the copper-catalyzed cycloaddition

Synthesis of triphenylene-fused phosphole oxides via C–H functionalizations

• Md. Shafiqur Rahman and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2020, 16, 524–529, doi:10.3762/bjoc.16.48

• through two distinct C–H functionalization reactions as key steps. The phosphole ring was constructed by a three-component coupling of 3-(methoxymethoxy)phenylzinc chloride, an alkyne, and dichlorophenylphosphine, involving the regioselective C–H activation of the C2 position of the arylzinc intermediate

• and the carbohelicene moieties (Scheme 1) [16]. The approach focused on the regioselective one-pot synthesis of a 7-hydroxybenzo[b]phosphole derivative from an 3-alkoxyphenylzinc reagent, an alkyne, and dichlorophenylphosphine [17]. The hydroxy group of this key intermediate served as a handle for the

• π-extension through a Suzuki–Miyaura coupling, Sonogashira coupling, and electrophilic alkyne carbocyclization [18]. Given the successful synthesis of the angularly fused phosphahelicenes, we became interested in the further exploitation of 7-hydroxybenzo[b]phosphole as an intermediate for the

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

• alkene derivatives. Because an alkyne undergoes addition reaction at a C–C triple bond or cross-coupling at a terminal C–H bond. Combining those reaction patterns could realize a new reaction methodology to synthesize complex molecules including C–C multiple bonds. In this report, we found that the

• 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