Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• /arylation of cyclic oxalates 33 with terminal alkyne 34 and aryl bromides 3 (Scheme 20) [73]. As to the scope, aryl bromides 3 containing various electron-withdrawing substituents displayed better efficiency over the electron-rich aryl bromides. The authors proposed a plausible catalytic cycle to account

• ) photocatalyst 10-III. The active iridium(III) photocatalyst 10-I is regenerated by a SET process between 10-III and the nickel(I) species 10-X. The addition of the tertiary radical 10-IV to the terminal alkyne 34 followed by an intramolecular 1,5-HAT results in a nucleophilic secondary alkyl radical species 10

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• monofunctionalized naphthyl substrates. These authors demonstrated that the rhodium-catalyzed oxidative 1:2 coupling reactions of arylboronic acids 7 with alkyne 8 occurred in the presence of a copper–air oxidant, to give the corresponding 1,2,3,4-tetrasubtituted anthracene derivatives 9a and 9b (Scheme 1) [34

• aromatic ring were well tolerated during the cyclization, affording the corresponding anthracenes 14a–d. The authors expanded the scope of the reaction to internal alkyne substrates and obtained the corresponding substituted anthracenes. The most representative examples included compounds 14e–h [36]. In

• methodology was notable for being an alternative method to synthesize 2,3,6,7-halogenated anthracene derivatives, which are difficult to obtain. In 2010, Okamoto et al. published a three-step procedure to synthesize substituted anthracenes, pentaphenes, and trinaphthylenes via a [2 + 2 + 2] alkyne

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• containing a stretch of four DNA nucleotides in the middle, flanked by the modifications in a ´mixmer´ design, which is important for designing gapmer ASOs [31]. Another well-established method for C-5 pyrimidine modification involves the Sonogashira cross-coupling reaction between an alkyne group and a 5

• -iodo-modified nucleobase/nucleoside followed, if desired, by reduction [44] to give a more flexible group, or the alkyne group can be retained, depending on the modification needed [45][46][47]. This method has been extensively used to study various modifications, and some of them can be seen in Table

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• conjugative transformations, such as azide–alkyne [3 + 2]-cycloaddition [30][31][32][33][34][35][36][37]. Based on their previous late-stage fluorination studies [22][25], Groves et al. further showcased a manganese(III)–salen-catalyzed azidation process using an aqueous azide solution as a convenient azide

• ). Based on additional mechanistic investigations, it was proposed that substrate 23 forms five-membered manganacycle complex 23A under basic conditions, which undergoes alkyne insertion to provide seven-membered manganacycle complex 23B (Figure 7). Subsequently, intermediate 23B undergoes β-bromo

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• , in this case, the activity of the catalyst is not rate determining. This observation is rationalized by the occurrence of a non-productive acid–base equilibrium involving the de- and re-protonation of the considerably acidic alkyne proton in d (pKa = 15.61 [20]) [21]. The reaction conditions

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• -catalyzed azide–alkyne cycloaddition (CuAAC) for the synthesis of 1,4-disubstituted 1,2,3-triazole derivatives was initially discovered by the groups of Meldal and Sharpless. Then, Ru-catalyzed azide–alkyne cycloaddition (RuAAC), affording selectively 1,5-disubstituted 1,2,3-triazoles, was introduced [38

• decrease in the yield [47]. Some research groups have utilized strain-promoted azide–alkyne cycloaddition reactions (SPAAC) on side chains to afford polymer-based prodrugs. Generally, a range of key strained cyclooctyne derivatives 52 could be reacted with aliphatic azides 51 via this strategy to give

• bond of an alkyne into the Cu–triazole bond gives 64, which then undergoes syn-β-oxygen elimination to provide the target product. On the other hand, an oxidative addition and reductive elimination sequence can also generate the target product (Scheme 20) [50]. An immobilized copper complex has been

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• alkyne annulation was very recently achieved by Ackermann et al., which gave rapid access to synthetically meaningful isoindolones (Figure 1c) [34]. In spite of these indisputable advances, the successful removal of the directing groups to deliver the free-NH 3-methyleneisoindolin-1-one has thus far

• alkyne 2a and a stoichiometric amount of Cu(OAc)2 in DMSO (Table 1, entries 1–3). Reaction optimization revealed that the most appropriate temperature was 90 °C (Table 1, entries 3–6). An evaluation of bases showed that Na2CO3 was optimal (Table 1, entries 7–11). The best result was obtained when Cu(OAc

• complex mixture was observed when an aliphatic terminal alkyne was used, and no annulation product was detected for internal alkynes. Our copper-promoted C−H annulation protocol was not restricted to terminal alkynes. Under identical reaction conditions, commercially available alkynylcarboxylic acid 4

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• -ethynylpyrene (40) under copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction conditions to yield the double-headed nucleoside 41 (Scheme 10) [23]. The double-headed nucleoside 41 was phosphitylated and then incorporated into oligonucleotides and was found to form highly stable DNA duplexes and three

• nucleosides were further reacted with propargylated nucleobases through a copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction followed by treatment with methanolic ammonia to give the C-3′-substituted double-headed ribofuranonucleosides 46a–c and 50a–e (Scheme 11) [36]. The double-headed nucleosides

• ]. Hrdlicka and co-workers [24] also synthesized 5-C-triazolyl-functionalized double-headed nucleosides 154a,b starting from 5-C-ethynyl-functionalized LNA uridine 152. The LNA uridine 152 was reacted with 1-azidopyrene (153a) and 1-azidomethylpyrene (153b) separately under copper-catalyzed alkyne azide

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• magnesium alkylidene carbenoids was studied by using 13C-labeled sulfoxides and by using DFT calculations. Keywords: alkyne; 1-chlorovinyl p-tolyl sulfoxide; DFT calculation; Fritsch–Buttenberg–Wiechell rearrangement; magnesium alkylidene carbenoid; Introduction Alkynes are important compounds in organic

• )magnesium chlorides, CH2=CXMgCl (X = F, Cl, and Br) << (1-chlorovinyl)lithium, CH2=CClLi. If the 1-heteroatom-substituted vinylmetal displays vinylidene characteristics, the FBW rearrangement occurs to give the alkyne. If not, the vinylmetal is simply protonated to give a heteroatom-substituted alkene. A

• p-tolyl sulfoxide and alkyne 4a were obtained in 97% yield and 99% yield, respectively. This result shows that both the sulfoxide/magnesium exchange reaction and the FBW rearrangement occurred with high efficiency. A similar reaction of sulfoxide 2a with sec-butyllithium also gave alkyne 4a in 97

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• (Scheme 55). The methodology of alkynylsilane Prins cyclization was explored for the synthesis of 2,6-dihydropyran 238 by reacting secondary homopropargyl alcohol 236, having a trimethylsilyl group at the triple bond, with an aldehyde (Scheme 56) [98][99][100][101]. The reaction follows alkyne Prins

• -trimethylsilylalkenyl cation 242 formed by the Grob-type fragmentation (Scheme 57), which was trapped by the subsequent attack of the halide anion, leading to the formation of Prins product 244. On the basis of theoretical calculations, the authors could conclude factors controlling the alkyne Prins cyclization over

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• variety of terminal alkynes including both alkyl- and arylalkynes. Keywords: (E)-1,2-bis(diphenylphosphino)ethylene derivative; radical addition; stereoselective phosphinylphosphination; terminal alkyne; tetraphenyldiphosphine monoxide; Introduction Organophosphorus compounds are an essential class of

• absorption is located at a shorter wavelength (λmax = 318 nm) and the absorption intensity is lower than those of Ph2PPPh2 and Ph2P(S)PPh2 [46]. Indeed, the photoinduced addition of Ph2P(O)PPh2 to alkynes required prolonged reaction times (>40 h), and the scope of this alkyne addition was unexamined. Thus

• inhibited the desired phosphinylphosphination (see, alkyne 2f), probably because of the decomposition of Ph2P(O)PPh2. Furthermore, an electron-deficient alkyne such as methyl propiolate (2h) failed to provide the desired adduct (3h) [61]. 3-Phenyl-1-propyne (2i) and cyclohexylacetylene (2j) gave 3i and 3j

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• perfluoroalkyl iodide form a halogen-bond adduct, and then light-induced electron transfer happens in order to give a perfluoroalkyl radical. The protocol can realize alkene- and alkyne iodide perfluoroalkylation and C–H perfluoroalkylation of electron-rich heteroaromatic hydrocarbons, providing a novel protocol

• corresponding hydrotrifluoromethylation products with moderate to good yield. In 2017, Yu and colleagues [30] proposed an EDA-complex-induced alkyne trifluoromethylation reaction. The EDA complex formed by a catalytic quantity of Togni reagent 69 and NMM initiated the chain propagation, causing the final alkyne

• phenol anion is first added to the alkyne group of an EBX, forming electron acceptor 169, which causes the destabilization of the C–I bond. Then, electron acceptor 169 forms an EDA complex with phenol anion, along with light-promoted electron transfer occurring. Thereby, the C–I bond and the I–O bond

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• Meldal have independently developed a copper-catalysed azide–alkyne cycloaddition that accelerated the rate of the reaction and allowed the selective preparation of 1,5-disubstituted 1,2,3-triazoles [16][17][18][19]. As noted above, a wide range of methods are available in the literature for the

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• followed by microwave-assisted intramolecular azide–alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds

• to a large number of diverse heterocyclic compounds [10][11]. Over the past decade, several cases of using an Ugi four-component reaction (Ugi-4CR) in combination with intramolecular azide–alkyne cycloaddition (IAAC) for the synthesis of 1,2,3-triazolobenzodiazepines were reported [3][7][12][13][14

• availability of previously described methods for the synthesis of 1,2,3-triazolobenzodiazepines represented in Scheme 1, they have such drawbacks as long reaction time, use of toxic solvents, additional catalysts, etc. In this article, we present a novel tandem Ugi/catalyst-free intramolecular azide–alkyne

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• general trend in the efficiency of the reaction or product selectivity was observed. Hex-5-ynenitrile was used in the transannulation with 1a with the aim to assess the relative propensity of nitrile and alkyne groups in the reaction. The triple bond reacted in the transannulation about two times faster

• of the rhodium-catalyzed transannulation to pyrroles has recently been investigated computationally with N-sulfonyltriazoles [31]. It seems that the formed rhodium carbenoid B reacts with the alkyne in a concerted process and even in the presence of Ag+ salts, a nucleophilic addition of silver

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• of purine [73][74][75][76] or alkylation of inosine or guanosine derivatives (Ib→II, Scheme 1) [30][36]. In the next step, azide can be introduced either by a second SNAr reaction on the C2-halo derivative or by diazotization/azidation at C2. Then, the Cu(I)-catalyzed azide–alkyne cycloaddition

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• reactions (Scheme 1a). Diels–Alder (Scheme 1b) [15] and radical reactions (Scheme 1c) [16] directed toward helicene synthesis require high temperature conditions even for low to moderate yields. Olefin metathesis (Scheme 1d) [17] and alkyne trimerization (Scheme 1e) [18][19] require the use of expensive

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• chlorine at the purine C2 position by azide, and 3) copper-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) with different alkynes. Pathway B included: 1) the two-step synthesis of 2,6-bistriazolylpurine derivatives 6 from 2,6-dichloropurine derivative 1 [22] and 2) the SNAr–Arbuzov reaction with

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• , due to sample decomposition. Attempts to obtain crystals for X-ray analysis by slow diffusion of n-pentane into a DCM solution of the complexes were unsuccessful. Catalytic activity For evaluation of the catalytic ability of the new Au(III) complexes, alkyne carboalkoxylation [47][48] and

• activity was observed for cyclam–gold complex 6a-Au(III) versus the open cyclam analogues 5a-Au(III). Complex 5a-Au(III) afforded a full conversion in the alkyne carboalkoxylation in 5.5 hours, compared to in 24 hours for complex 6a-Au(III) (Table 1, entries 1 and 2). The same trend was observed for Au(III

• . A high catalytic ability was shown for novel N,N,N,N-Au(III) complexes 5a and 6a in alkyne carboalkoxylation and propargyl ester cyclopropanation (full conversion in 1–24 h, 62–97% product yields). No enantioselectivity was observed in the test reactions. The activity and stability of the Au(III

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• structures modified with sulfate groups, and their capability to interact with biological components has been demonstrated recently [31][32]. In this work, we therefore coupled dPGS to C2-symmetrical discotic peptide amphiphiles using copper-catalyzed azide alkyne cycloaddition chemistry. The evaluation of

• , post-functionalization using a subsequent copper-catalyzed azide–alkyne cycloaddition reaction became accessible [35][36]. At the same time the other two unmodified side arms of the dendritic amphiphile make sure that the fidelity of the β-sheet motifs and directed supramolecular polymerization remains

• copper-catalyzed azide–alkyne cycloaddition (Scheme 2). The reaction took place in degassed DMSO at 50 °C with CuSO4 pentahydrate, sodium ascorbate and tris(benzyltriazolylmethyl)amine (TBTA) as chelating species. HPLC-monitoring of the reaction showed a full conversion after three days and the crude

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• evidence [60]. The synthetic route was designed in such a way that intercept both Ryu’s intermediate (+)-69 [50] and Hatakeyama’s intermediate (+)-82b [22] (Scheme 12 and Scheme 13). In this approach, the asymmetric alkylation of 96 with alkyne 95 under Carreira’s conditions [61][62][63] afforded (−)-98 in

• 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

• -catalyzed nucleophilic alkyne addition of methyl propiolate, provided ynone 139 in 86% yield over two steps. When, compound 139 was treated with (+)-diisopinocampheylchloroborane (DIPCl) [75][76] at room temperature and the resulting mixture was processed as in the usual manner using diethanolamine, the

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

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• without THF solvent producing alkyne 9b in 82% yield (Table 4, entry 2). The structure of 9c was unambiguously proved by X-ray structural analysis (see Supporting Information File 1, Figure S34). Earlier, at the final step of a similar synthesis of the azine-fused [5]helicenes, we used trifluoroacetic