All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• triquinane (±)-hirsutene (14) [24] (Scheme 1D). In 2011, the same research group used allenyl diazo compound 38, which was generated from the reaction between aldehyde 37 and p-toluenesulfonehydrazide in the presence of sodium hydride upon heating, to produce diyl 40 [29] (Scheme 2A). The intramolecular

• trimethylenemethane diyl [3 + 2] cycloaddition of 40 led to the formation of angular fused triquinane 41 in 98% yield. The authors suggested that an intramolecular cycloaddition of the diazo group and allene 38 produces tetrahydrocyclopentapyrazole 39. Extrusion of nitrogen from the newly formed 39 produces diyl 40

• 2014 and 2017, respectively (Scheme 2B and Scheme 2C). The synthesis of (−)-crinipellin A (15) began with the treatment of hydrazone 42 with sodium hydride under reflux to produce the tetraquinane 46 in 87% yield [30] (Scheme 2B). The authors suggested that the diazo compound 43 formed undergoes an

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• reactions of 2-diazomalonates with aliphatic amines [40][52]. The first approach leads to a mixture of two regioisomers and the second method involves the use of explosive diazo compounds. Therefore, such compounds are better prepared by a recently found method in our laboratory which includes the reaction

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• recently reported [8][9][11], for example the trifluoromethylation of hydroxyaryls [12][13][14], and the direct introduction of the -OCF3 moiety into an organometallic species [15], a diazo compound [16][17], or an unfunctionalized C–H bond (Scheme 1B). The latter method is particularly interesting

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• formation started in 2016 with the report from Gryko’s group on the photoredox α-alkylation of aldehydes with diazo compounds using 1 mol % of TPP or ZnTPP as photocatalyst [10] (Scheme 1), thus obtaining functionalized aldehydes in 47–90% yields. These results are similar to those previously reported by

• this transformation involves the formation of an aryl radical by SET between the diazo compound and the porphyrin in its excited state (Scheme 3). The authors demonstrated that meso-arylated porphyrins can efficiently act by an oxidative quenching. However, issues about why an electron-poor porphyrin

• excited state potentials, including porphyrin derivatives. Adapted from [10][12][22]. Electronic configurations of the species of oxygen. Adapted from [66]. Photoredox alkylation of aldehydes with diazo acetates using porphyrins and a Ru complex. aUsing a loading of 0.1 mol % for ZnTPP. Proposed mechanism

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• ; difluoromethyl compounds; fluorinated diazo reagents; strong Brønsted acids; Introduction Chiral aziridines are prevalently found in natural products and artificially made bioactive molecules, thus receiving significant attention in the past decades [1][2][3][4][5][6]. Among them, the introduction of fluorine

• ), and PhSO2CF2CHN2 (3, Ps-DFA). Initial screenings were focused on the evaluation of various chiral phosphoric acids that have proven effective in similar aza-Darzens reactions of diazo esters and trifluorodiazoethane [36][37][38][39]. Unfortunately, these endeavors resulted in either no conversion or

• -methoxyaniline (2a, 40.6 mg, 0.33 mmol), 2-boronobenzoic acid (COOH-BA, 3.98 mg, 0.024 mmol), anhydrous Na2SO4 (200 mg) and toluene (1 mL) at room temperature under an argon atmosphere. After reacting for 30 minutes at room temperature, ((2-diazo-1,1-difluoroethyl)sulfonyl)benzene (Ps-DFA 3, 104.5 mg, 77.4 uL

Preparation and in situ use of unstable N-alkyl α-diazo-γ-butyrolactams in Rh^II-catalyzed X–H insertion reactions

• Maria Eremeyeva,
• Daniil Zhukovsky,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2020, 16, 607–610, doi:10.3762/bjoc.16.55

• Maria Eremeyeva Daniil Zhukovsky Dmitry Dar'in Mikhail Krasavin Laboratory of Chemical Pharmacology, Institute of Chemistry, Saint Petersburg State University, 26 Universitetskii prospect, Peterhof 198504, Russian Federation 10.3762/bjoc.16.55 Abstract N-Alkyl α-diazo-γ-butyrolactams, previously

• , the reactions tended to yield enamine adducts. Keywords: in situ reactions; N-alkyl 2-pyrrolidones; RhII-catalyzed insertion reactions; stability of diazo compounds; Introduction Recently, we described the first synthesis and subsequent transformations of a rare type of cyclic α-diazocarbonyl

• compounds, namely, α-diazo-γ-butyrolactams [1]. In particular, N-aryl-α-diazo-γ-butyrolactams 1 were efficiently transformed into pyrrolinones 2 upon the treatment with AgOTf (1 mol %) and into α-alkoxy derivatives 3 via Rh2(OAc)4-catalyzed O–H insertion reactions with various alcohols. In contrast, N-alkyl

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

• moieties. One year later, the group of Goossen demonstrated the direct conversion of diazo compounds into trifluoromethylselenolated products using a catalytic amount of copper(I) thiocyanate (Scheme 11) [28][29]. The reaction proceeded under mild conditions, and the desired products were usually obtained

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• attacking of nucleophilic partners, followed by a protodemetalation step to form the alkene motif (Scheme 1, path a) [9][10][11]. However, the formation of a silver carbene intermediate, which could be generated usually from relevant diazo precursors [12][13][14], appears to be an unusual event in silver

• species could be also involved mechanistically in the Ag-mediated reaction of enynals with conjugated dienes [18] and the homodimerization of enynals [19][20]. So, the studies on the reactions of alkynes involving the generation of silver carbene species from non-diazo precursors are of great value for

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• decomposition of diazo compounds, are particularly versatile intermediates in organic synthesis, as they partake in cyclopropanation and C–H insertion reactions with high levels of selectivity [2]. This transition-metal-catalyzed carbene transfer has emerged as a mild and attractive route to indole

• functionalization [3][4][5][6]. The metal carbene reactions with indoles have been studied for the three types of carbenoids: acceptor–acceptor [7][8][9], mono-acceptor [10] and donor–acceptor carbenoids [11][12][13][14]. Depending on the metal and the diazo compound, the chemo- and regioselectivity in the metal

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• ? Answers to these questions were sought. Results and Discussion Phenyl-substituted systems The first compounds to be examined were the mesylates 19 and 20. These substrates were prepared as shown in Scheme 4. Irradiation of ethyl 2-diazo-2-phenylacetate (15) in vinyltrimethylsilane as solvent gave an

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• a = 9.2107 (4), b = 10.0413 (5), c = 14.4363 (6) Å, α = 78.183 (2), β = 87.625 (2), γ = 71.975 (2)°. The formation of 8 proceeded through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate 9. The molecules of 8 are organised by edge–face Ar–H···π, face–face π···π, and bifurcated

• OCH2–H···N interactions. In addition to these, there are Ar–H···H–Ar close contacts, (edge–edge and surrounding inversion centres) arranged as infinite tapes along the a direction. Keywords: Ar-H...H-Ar contact; [2 + 3] cycloaddition; diazo; 3H-indazole; X-ray structure; Introduction The use of

• -related counterpart: C6C···C5C = 3.50 Å (Figure 4b). The C4 methoxy and the heterocyclic diazo functionality of 8 are linked through an interesting arrangement along the b axis that can be described either as a OCH2–H···π (N=N) or as a bifurcated N···H(CH2O)···N interaction. This motif is close to

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• acetonide removal, this would give an α-ketoester 10. The latter should in principle be a progenitor to the desired α-diazo ester 3, following condensation with tosylhydrazide, then Bamford–Stevens-type base-induced sulfinate elimination [20] and oxidation of the secondary silyl ether. Results and

• % yield [21], gave α-diazo ester 13 in 76% yield following reaction with NaOMe. Furthermore, our earlier racemic model study had established that deprotection and oxidation of a secondary silyl ether in the presence of α-diazo ester functionality was feasible, which constitutes precedent for the

• ); therefore, 20 and the derived tertiary TBS ether 21 were carried on directly to form hydrazone 22 (51% yield over 3 steps from hydroxy acetonide 19a). Unlike with hydrazone 12 (Scheme 3), application of NaOMe was not conducive to effective diazo formation from hydrazone 22, giving a mixture of unidentified

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• 3 were easily prepared through the well-known RhII-catalyzed decomposition of diazo esters in the presence of alkynes to give cyclopropenyl esters 1. Reduction of 1 using DIBAL-H afforded cyclopropenyl alcohols 2 and subsequent protection of the primary alcohols gave 3 in good yields (Scheme 3

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• [39] proved to be superior to the more commonly employed n-BuLi/MeI reagent combination that led to the formation of a series of side products. We also attempted a Bestmann–Ohira reaction with in situ formation of the diazo phosphonate [40] that gave a slightly inferior yield after methylation of the

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• Hibarigaoka, Tempaku-Cho, Toyohashi 441-8580, Japan 10.3762/bjoc.15.31 Abstract A reusable and highly enantioselective catalyst for the intramolecular cyclopropanation of various diazo ester and Weinreb amide derivatives was developed. The reactions catalyzed by a water-soluble Ru(II)-Amm-Pheox catalyst

• intramolecular cyclopropanation of a variety of diazo compounds such as diazoacetates and diazoacetamides in a biphasic medium. Diazoacetates were tested in our catalytic system because they are widely used for intramolecular cyclopropanation reactions and also the resulted lactones are widely distributed in

• ][36]. Diazoacetamides, in particular, diazo Weireb amides were tested in our catalytic system because the resulting cyclopropane products can be easily converted into the corresponding aldehydes, ketones, and alcohols [37][38][39][40][41][42][43][44][45][46][47][48]. Results and Discussion Asymmetric

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• –vinyl carbenes generated from vinyldiazoacetates (Scheme 1b) [14][15][16]. This reaction has been fruitfully exploited, although it is inherently limited by the restricted availability of potentially explosive diazo compounds. Consequently, the use of alternative vinyl carbene precursors is highly

Gold-catalyzed ethylene cyclopropanation

• Silvia G. Rull,
• Andrea Olmos and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2019, 15, 67–71, doi:10.3762/bjoc.15.7

• transfer; cyclopropane; cyclopropylcarboxylate; ethylene cyclopropanation; ethyl diazoacetate; gold catalysis; Introduction Nowadays the olefin cyclopropanation through metal-catalyzed carbene transfer starting from diazo compounds to give olefins constitutes a well-developed tool (Scheme 1a), with an

• exquisite control of chemo-, enantio- and/or diastereoselectivity being achieved [1][2]. Previous developments have involved a large number of C=C-containing substrates but, to date, the methodology has not been yet employed with the simplest olefin, ethylene, for synthetic purposes [3]. Since diazo

• = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) catalyzes the ethylene cyclopropanation with ethyl diazoacetate as the carbene precursor, under mild conditions, with moderate yields (ca. 70%, EDA-based). Results and Discussion Diazo compounds N2=CRR’ usually react with metal complexes of groups 8–11 with

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• -(phenylselanyl)-1H-pyrazol-5-amine was submitted to an oxidative dehydrogenative coupling to produce a diazo compound confirmed by X-ray analysis. Keywords: diaryl diselenide; diazo compound; 1H-pyrazole; molecular iodine; multicomponent reaction; Introduction Selenium-containing compounds are of great

• hydroperoxide in dichloromethane at room temperature for 2 h, the respective diazo aromatic compound 6 could be obtained in 50% yield (Scheme 5). As can be seen, the reaction proceeded smoothly allowing formation of the new N=N bond without cleavage of the C–Se bond under the oxidant media and the presence of

• -(phenylselanyl)-1H-pyrazol-5-amine proved to be a promising starting material for synthesizing new diazo compounds with higher added value. The protocol described here can be considered a valuable tool for the advance of the synthesis and pharmacological studies of selenium-containing pyrazoles and derivatives

Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• , 3 Nobel st., Russia 10.3762/bjoc.14.200 Abstract The sensitized photoexcitation of 2-diazocyclopentane-1,3-diones in the presence of THF leads to the insertion of the terminal N-atom of the diazo group into the α-С–Н bond of THF, producing the associated N-alkylhydrazones in yields of up to 63–71

• with up to 90–97% yield. Keywords: C–H insertion; diazo compounds; excited state; photochemistry; Wolff rearrangement; Introduction Photochemical reactions of diazocarbonyl compounds are well-known transformations in the synthesis of the diversified acyclic, carbo- and heterocyclic structures [1][2

• ][3][4][5]. A direct irradiation of diazo compounds by UV light usually gives rise to nitrogen elimination and generation of carbenes [6][7][8][9][10] or ketenes [11][12][13][14][15][16][17][18] and their ensuing transformations. On the other hand, photochemical reactions of diazocarbonyl compounds

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

• including the cleavage of the triple bond and the fragmentation of the carboxylate unit, would finally lead to the furans 24 and the formamide 25. The group of Waser has discovered an atom-economical multi-component process between alkynylbenziodoxolones 22 and diazo compounds, which is catalyzed by the

• benzoate motif and the alkynyl group are obtained from various acceptor or donor–acceptor diazo compounds 30, while the use of vinyldiazo derivatives 32 leads to enynes 33 arising from the vinylogous addition of the carboxylate. Significantly, the benzoyloxy-alkynylation reaction can be applied to the late

• , the same group has demonstrated the ability to perform the reaction with TIPS-EBX 37 in an enantioselective manner using the cyclopropylbisoxazoline ligand 38 (Scheme 12) [47]. Starting from various acceptor diazo compounds, the gem-addition of the carboxylate and the alkyne proceeds with ees of up to

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• -catalysed reaction with diazo compounds 42 (Scheme 22) [56]. This strategy is not only atom economic regarding the applied hypervalent iodine reagent but also with regard to the chosen substrate. The metal carbene species generated from the diazo compounds displays nucleophilic as well as electrophilic

• reactivity at the same carbon atom and only gaseous dinitrogen is produced as stoichiometric waste. The reaction provides oxyalkynylated products 43 in high yields and addresses a broad scope of diazo derivatives 42 and EBX compounds 36a. For diazo compounds bearing hydrogen, alkyl or aryl groups (R1

• of elemental nitrogen is lost over the course of the reaction. The overall AE is only diminished by the necessity to use two equivalents of the diazo compound (AE = 74% for 43b). Furthermore, an enantioselective version of this oxyalkynylation (for R1 = H) was developed [57]. Employing a chiral

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• benzotropones 11 and 12 (Scheme 14 and Scheme 33) [78]. Diazo compound 76 was prepared from 4,5-benzotropone hydrazone under oxidative conditions. Irradiation of matrix-isolated 7-diazo-7H-benzo[7]annulene (76) afforded a mixture of triplet 7H-benzo[7]annulenylidene (77), 2,3-benzobicyclo[4.1.0]hepta-2,4,6

• ], while the allenic rearrangement product 183 for the carbene 75 was not detected in the photolysis of a diazo compound (Scheme 33) [78]. 2,3-Benzotropone (12) was converted to gem-dichloride 187 to achieve diazirine as carbene precursor (Scheme 33) [77][144]. 3.2.2. Ring-expansion reactions via a tropone

• of azo, nitro, and amino derivatives of 6-hydroxy-2,3-benzotropone (239) (Scheme 42) [164]. While 7-amino derivative 264 was prepared via diazo coupling of 239 with diazotized p-toluidine in a pyridine solution followed by hydrogenation, the nitration of 239 in acetic acid solution afforded nitro

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• Discussion Addition to α,β-unsaturated ketones Since we could show the benefits of a use of dithi(ol)anylium TFBs instead of ketene 1,3-dithioacetals for the addition of diazo components [31], we were interested in a more general use of dithi(ol)anylium TFBs for the addition to electrophiles in α-position to

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• suitable reagent, which generally is a diazo derivative bearing a photoresponsive moiety, or b) incorporation of an appropriate photocaged phosphoramidite during the solid-supported ON synthesis [73][78]. The advantage of the first approach is that the functionalization results from a reaction with

• available unmodified ONs, while the second approach first requires the synthesis of a modified unit followed by its incorporation into ON during solid-phase synthesis. However, the first approach is far less efficient than the second one because the labeling of phosphodiester linkages with diazo compounds

• is not specific to a given phosphodiester in siRNA and cannot be controlled in location and the amount of caging units, yielding a random mixture of ONs. Moreover, diazo compounds exhibit certain reactivity toward nucleobases that can lead to undesired side reactions [74]. Considering their RNAi