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

• , 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

• led to decomposition of the diazo compounds 4a–c), and addition of an alcohol, a thiol, or an aromatic amine along with a RhII catalyst resulted in a rapid insertion reaction and the isolation of the desired α-substituted γ-lactams 7a–o in modest yields (Scheme 1). It should be noted that, after some

• substantially expanded, thereby making this approach more useful for potential medicinal chemistry exploration of these disubstituted γ-lactams. Previously reported uses of α-diazo-γ-butyrolactams 1 and 4. Generation and in situ RhII-catalyzed X–H insertion reactions of the diazo compounds 4a–c. Conditions

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

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

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

• ]. More recently, the formation of cyclic 3,3-disubstituted 3H-indazoles was reported to form mainly through the [2 + 3] cycloaddition of diazo compounds with arynes under mild reaction conditions [29][30][31]. However, none of these contained a 2-diphenylmethyl (benzhydryl) aniline system, as found in

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

• 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

• cyclopropanation using various diazo compounds with Ru(II)-Amm-Pheox Several diazoacetates and diazoacetamides were tested for asymmetric intramolecular cyclopropanation reactions using Ru(II)-Amm-Pheox catalyst (cat. 2) in H2O/ether biphasic medium as shown in Table 1. A diazo compound derived from allyl

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

• = 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

• spectroscopy. It is worth mentioning that when diethyl diazomalonate or ethyl 2-phenyldiazoacetate were employed as the carbene precursor, no cyclopropanes were detected, only olefins formed from carbene dimerization as well as unreacted diazo compounds were identified at the end of the reaction. Conclusion We

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 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

• 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

• without elimination of dinitrogen are essentially limited to their isomerization into α-ketodiazirines [19][20][21][22][23][24][25][26] which is usually observed upon irradiation of diazo compounds with longer wavelength UV light. Recently a new light-induced reaction of diazo compounds with retention 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

• 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

• bisoxazoline ligand, diazo compounds 42’ with various electron-withdrawing groups were efficiently oxyalkynylated affording highly enantioenriched propargyl esters 44 (Scheme 23). Subsequent reductive cleavage of the ester gave direct access to enantiopure propargyl alcohols. Besides EBX reagents

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

• 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

• Friedman showed that this also could be done by the reaction of diazo compounds with the terminal phosphates of an ON. Indeed, the reactivity of diazo reagents with terminal phosphates (phosphomonoesters) was much greater and more specific than that with the internucleoside phosphates (phosphodiesters) [74

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• was also shown that α-cyanothioacetamides easily interact with dirhodium carboxylates to give rather stable 2:1 complexes, resulting in an evident decrease in the efficiency of the catalytic process at moderate temperatures (20–30 °C). Keywords: [4 + 1]-annulation; catalysis; diazo compounds; domino

• domino reactions of diazo compounds with intermediate formation of ylides [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Thus, it was for example shown that ammonium or oxonium ylides generated in the course of intermolecular processes can be easily trapped by ketones, imines, α,β-unsaturated

• other diazo compounds [26][52][53]. The investigation of diazocyanoacetic ester 2d in reactions with thioamides 1, catalyzed by dirhodium pivalate, had shown that they produced the structural analogues of carboxylates 3, namely thiophenes 5. At the same time no concurrent formation of aminomalonates of

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• observed. Triphenylarsonium ylides were also studied in the reaction with nitrosoalkenes, yet lower yields of isoxazolines 93 were obtained as compared to sulfonium ylides [11]. Following the same reaction pattern, Cheng and co-workers [84] applied diazo compounds 96 instead of sulfonium ylides 92 in the

• . Unfortunately, the reaction is complicated by a concurrent [3 + 2]-cycloaddition of diazo compounds 96 to nitrosoalkenes leading to N-nitrosopyrazoles 98 via intermediates 99. A substantial improvement of this isoxazoline ring-forming strategy was recently introduced by Li et al. [85], who achieved the

• . [4 + 1]-Annulation of nitrosoalkenes NSA with sulfonium ylides 92. Reaction of diazo compounds 96 with nitrosoalkenes NSA. Tandem Michael addition/oxidative cyclization strategy to isoxazolines 100. Acknowledgements This work was supported by Russian Foundation for Basic Research (Grants 17-03

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• latter transformation was a rhodium octanoate-catalyzed intramolecular carbenoid insertion into an ortho CAr–H bond (Scheme 1) [21][22], which proceeded with good yields in most cases. However, with non-equivalent aryl ortho-positions in the starting diazo compounds, mixtures of regioisomers – virtually

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• on [3 + 2]-cycloadditions with thioketones and diazo compounds, we turned our attention to hetaryl thioketones [18]. It turned out that the presence of the hetaryl groups strongly influences the reactivity of these dipolarophiles in reactions with diazomethane (CH2N2, Schönberg reaction) [19][20][21

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• " for safety reasons, such as those involving diazo compounds, hydrazine, azides, phosgene, cyanides and other hazardous chemicals could be performed with relatively low risk using flow technology [72][73][74][75][76]. Several research groups investigated this aspect, as highlighted by several available

• reviews [77][78]. Here we describe very recent reports with the aim to highlight the potential of flow chemistry in the field of hazardous chemistry under a greener perspective. Diazo compounds are recognized as versatile reagents in organic synthesis. Nevertheless, diazo compounds are also considered

• highly energetic reagents [79][80]. For this reason, the in situ generation of such reagents has been investigated under flow conditions. Moody and co-workers reported a new method for the in situ generation of diazo compounds as precursors of highly reactive metal carbenes (Scheme 16) [81]. As reported

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• reactions leading to intermediates 197 and 198 [85]. The authors have also synthesized other fluorenone derivatives 200–204 by using this method (Scheme 56). 1.6 From diazo compounds Hashimoto et al. have proposed the synthesis of optically active 1,1’-spirobi[indan-3,3’-dione] derivative 208 (up to 80

• , potentially more selective than known compounds [87]. Transformation of diazo compounds 209 into 1-indanone derivatives 210, catalyzed by rhodium acetate, has been one of the steps in the total synthesis of atipamezole analogues 211 (Scheme 58). The most common symptom of the menopause is hot flash, which is

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• products. These oxidation processes are mediated by Rh(II) catalysts possessing perfluorinated ligands. The formation of pyrrolidine structures, characteristic for catalytic reactions of diazoesters, was not observed in these processes at all. Keywords: diazo compounds; N–H-insertion; oxidation cleavage

• intermediates generated from diazo compounds (ammonium, oxonium, C=X-ylides and others) to react with a variety of electrophiles/nucleophiles yielding complex and challenging organic molecules from relatively straightforward initial compounds [9][10]. The research group by Hu and co-workers elaborated recently

• system of the amino ester to afford N-arylpyrrolidines B (Scheme 1). It was suggested that this strategy for the synthesis of pyrrolidines could be extended to diazo compounds of other types and structures, and, as with diazoesters, multi-substituted pyrrolidines are the principal reaction products in

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• briefly studied the thermal, non-catalytic cyclopropanation of styrenes and compared the results to the analogous Rh(II)-catalyzed reactions. Keywords: carbenes; catalysis; cyclopropanation; halo diazoacetates; half-lives; thermal stability; Introduction The chemistry of diazo compounds has fascinated

• organic chemists ever since Theodor Curtius synthesized ethyl diazoacetate (EDA, 1) for the first time in 1883 [1]. Even today, after more than a century of research, diazo compounds still play an important role in state-of-the-art organic chemistry in areas such as for example C–H functionalization [2

• ]. The synthesis and properties of diazo compounds have been a topic of much interest, particularly relevant are their thermal stability and sensitivity towards Brønsted and Lewis acids. The monograph by Regitz and Maas gives an excellent overview on their preparation and properties [3]. The thermal

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• gold ketocarbenes 104 from alkynes (Scheme 22) [95]. Those carbenes are then capable of further transformations, including C–H bond insertion and the reaction with other alkynes. Notably, this approach avoids the use of unstable diazo compounds. The Zhang group also demonstrated that the gold carbenes

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• activation; chiral catalysis; diazo compounds; total synthesis; Introduction One of the major challenges met in organic synthesis is the formation of carbon–carbon bonds, in particular in a stereoselective way. Nucleophilic substitution reactions, radical reactions, cross-coupling reactions and the Heck

• the carbenoid intermediate can change its reactivity and hence the selectivity of the carbenoid reaction. The most commonly used diazo compounds rely on the formation of a donor/acceptor carbenoid intermediate type. The EWG increases the electrophilicity and reactivity of the donor/acceptor carbenoid

• insertion reactions into C(sp3)–H bonds and also the insertion into X–H bonds, where X = N, O, S, Si and others. Copper-based chiral catalysts In 2002, Müller and Boléa published a study evaluating the enantioselective insertion of copper carbenoids formed from phenyliodonium ylides and diazo compounds

Recent advances in C(sp³)–H bond functionalization via metal–carbene insertions

• Bo Wang,
• Di Qiu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2016, 12, 796–804, doi:10.3762/bjoc.12.78

• (I) complexes. In some cases, high regioselectivity and enantioselectivity have been achieved in the C–H bond insertion of small alkanes. This review highlights the most recent accomplishments in this field. Keywords: alkane; diazo compounds; C–H bond functionalization; C–H bond insertion; metal

• chiral porphyrins D4-por*, the enantioselective intermolecular carbene insertion into C(sp3)–H bonds was achieved with moderate to high selectivities (Scheme 7). Besides, the reaction of diazo compounds with benzylic, allylic and alkane C(sp3)–H bonds afforded the insertion products in up to 80% yield

Evidencing an inner-sphere mechanism for NHC-Au(I)-catalyzed carbene-transfer reactions from ethyl diazoacetate

• Manuel R. Fructos,
• Juan Urbano,
• M. Mar Díaz-Requejo and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2015, 11, 2254–2260, doi:10.3762/bjoc.11.245

• mechanism). Those intermediates are quite reactive, in contrast to similar but low reactive gold–carbene complexes recently and independently described by the groups of Fürstner [19] and Straub [20]. Scheme 4a shows a generally accepted mechanism for the metal-catalyzed carbene transfer from diazo compounds

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• transition metal-catalyzed C–H functionalization by diazo compounds [5][6][7][8]. The reactions of indoles with electrophilic metal-bound carbenes, or carbenoids, generated from diazo compounds, takes place under mild reaction conditions. The reaction has been studied for the three principle classes of