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

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• between alkyne, sulfonyl azide and amine/alcohol was described as a synthetic route to generate sulfonyltriazole intermediates. However, the presence of additives and high catalyst loading (CuI 10 mol %) were required for the synthesis of N-sulfonylimidates (Scheme 1, left). Over the last two decades

• diphenylamine, only 20% of the desired product was observed (12c). Interestingly, with benzyl azide, a substrate not containing a sulfonyl moiety, the product obtained is the 1,2,3-triazole derivative [33], resulting from a [3 + 2] cycloaddition of azide and alkyne (Scheme 6). The catalytic system was also

• ). A proposed reaction mechanism occurring via formation of a copper-acetylide species is proposed and illustrated in Scheme 8. The bis-NHC copper(I) complex 6 reacts with the alkyne leading to the formation of an acetylide derivative A (left hand side, Scheme 8), with concomitant loss of a NHC ligand

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• )(xantphos)]PF6. Chlorosulfonylation of styrene and alkyne derivatives by ATRA reactions. Reduction of aryl and alkyl halides with the complex [Cu(I)(bcp)(DPEPhos)]PF6. aIrradiation was carried out at 420 nm. All redox potential are reported vs SCE. Meerwein arylation of electron-rich aromatic derivatives

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

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

• alkyne–azide cycloaddition reaction has been applied successfully to prepare click-phosphine ligands [72]. The presence of three nitrogen atoms within the five-membered ring results in a high activation of the α-position and the highly acidic nature of the proton makes it easy for abstraction. Sharpless

• stable up to 200 °C [109][110]. In these reactions the phosphine precursor can also be functionalized with appropriate groups for postfunctionalization. Detz et al. attached an alkyne to a phosphine which could easily be transformed to triazoles using click chemistry (Scheme 26) [111]. The click

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• -withdrawing and -donating groups were tolerated on the arylacetylene derivatives. Heteroaromatic as well as aliphatic alkyne derivatives could also be smoothly converted in these transformation. Noteworthy, the authors demonstrated that the reaction could easily be scaled up when almost two grams of a

• trifluoromethylselenolated alkyne product could be isolated. After that, the same group studied the α-trifluoromethylselenolation of ketones and esters starting from the corresponding halides or diazoacetates (Scheme 4) [19][20]. Both methods led to the desired products with moderate to very good yields, and the reactions

• starting alkyne derivatives contained an oxygen atom. This way, α-trifluoromethylselenylated vinylsulfones were obtained in moderate to excellent yields (Scheme 13). Mechanistic experiments revealed that copper(I) acetylides were the active species for the synthesis of the trifluoromethylselenylated

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• , Viale Morgagni 85, 50134 Florence, Italy 10.3762/bjoc.16.23 Abstract The Cu-catalyzed multicomponent ketone–amine–alkyne (KA2) reaction was combined with a Pauson–Khand cycloaddition to give access of unprecedented constrained spirocyclic pyrrolocyclopentenone derivatives following a DOS couple-pair

• [39][40], consisting of a [2 + 2 + 1] cycloaddition between an olefin, alkyne, and carbon monoxide. This reaction has been also applied in cascade approaches [41], and in combination with RCM [42], Diels–Alder [43] and Staudinger [44] reactions to produce novel structurally complex chemical entities

• . Following our interest to DOS as a synthetic strategy for the generation of molecular scaffolds according to a couple/pair approach [45][46][47], we reasoned to combine the copper-catalyzed ketone–amine–alkyne (KA2) multicomponent coupling reaction [48] with the Pauson–Khand cycloaddition as the pairing