Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• their biological activity and potential applications, continuous efforts have been dedicated to the synthesis of DHPI derivatives. Various synthetic strategies have been explored (Scheme 1), including transition-metal-catalyzed cross-coupling reactions [8][9][10], annulation reaction of carbenoids [11

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• organic synthesis as versatile building blocks [1][2][3][4][5]. In general, some synthetic procedures for cyclopropane derivatives have been discovered, e.g., the Simmons–Smith reaction and the use of metal carbenoids being two of the more prominent and reliable methods [6][7][8][9]. Aggarwal and

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• alkoxide. Keywords: alkenes; aziridines; epoxides; lithiation; synthetic methods; Introduction Methods for the convergent generation of alkenes can be of significant utility in organic synthesis [1]. A relatively under-examined approach is through the interaction of two carbenoids [2]. Dimerisation of

• carbenoids may compete with a desired carbenoid transformation although its value has been demonstrated in, for example, our studies on lithium 2,2,6,6-tetramethylpiperidide (1, LTMP)-induced syntheses of 2-ene-1,4-diols and 2-ene-1,4-diamines from terminal epoxides [3] and aziridines [4][5], respectively

• (Scheme 1). The eliminative cross-coupling of carbenoids can provide a way to unsymmetrical alkenes, provided the differential reactivity of the two carbenoids is suitably matched [2]. In the current letter, we report preliminary results on the latter strategy to form alkenes which possess an allylic

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• al. reported a Hg(II) chloride-mediated cyclization reaction of 2-alkynylphenyl alkyl sulfoxide 179 to synthesize benzothiophene derivatives 180 with good yields [114]. In this case, the reaction was believed to proceed via the initial formation of metal carbenoids followed by a sequential C–H

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

• prepared from carbonyl compounds and chloromethyl p-tolyl sulfoxide and were converted into alkynes via the sulfoxide/magnesium exchange reaction and subsequent Fritsch–Buttenberg–Wiechell (FBW) rearrangement of the resulting magnesium alkylidene carbenoids. The mechanism of the FBW rearrangement of

• 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

• with these methods, the use of butyllithium for the generation of lithium alkylidene carbenoids limits the range of usable substrates in the Corey–Fuchs method, and the Ohira–Bestmann method cannot be applied to the synthesis of internal alkynes from ketones [3]. Magnesium alkylidene carbenoids 3 are

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• difluorocyclopropane and its derivatives can be distinguished: carbene and non-carbene methods of cyclopropanation along with functional group transformations of existing cyclopropanes. The most popular route to prepare fluorocyclopropanes is to generate fluorine-containing carbenes (or carbenoids), which then react

• with multiple bonds, resulting in cyclopropanation. One of the important properties of fluorine-containing carbenes and carbenoids is their electrophilicity, which is a result of the high electronegativity of fluorine. Also, fluorine has an +M effect which tends to reduce the reactivity of the carbenes

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

• 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

• derived from ethyl α-halodiazoacetates (X-EDA) react readily with unprotected indoles to form ethyl 3-carboxyquinoline structures (Scheme 1) [15]. The Rh carbenes derived from X-EDAs stand out from the three other types of classified carbenoids with respect to chemoselectivity in reactions with indoles

• . These halo-acceptor carbenoids undergo cyclopropanation of N–H indoles with high selectivity, and only traces of C–H or N–H insertion products were observed. The yield of ethyl quinoline-3-carboxylate is dependent on the halogen in X-EDA (Cl: 90%, Br: 84%, I: 70%). The reaction works well for

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

• ylide with the rhodium catalyst. Within the adopted general scheme, the occurrence of thiophenes 4 could be rationalized by partial hydrolysis of carbamates 3 under the reaction conditions with the initial formation of the primary heteroaromatic amines 7. The latter then interact with carbenoids A, to

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

• the possibility to generate highly reactive intermediates, such as halomethyllithium carbenoids, that need to be used under internal-quenching technique in batch mode. In 2014, the first example of effective external trapping of a reactive chloromethyllithium (CML) has been reported [28]. α

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

• compounds 3а–с can be apparently explained by some sterical reasons and, first of all, by the problems associated with the approach of the N–H-group of the bulky secondary amine 1 to the electrophilic carbon atom of H-Rh-carbenoid C (Scheme 2). Carbenoids from perfluorinated carboxylates F-Rh(II) are

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

• pre-functionalization of the chemical structure of interest with halogen atoms or pseudohalogen functional groups. One approach that has been gaining increasing attention, by not requiring the presence of a strongly polarized chemical bond, is the C(sp3)–H bonds activation by carbenoids [1]. The

• chemical properties of the ligands around the metal center also determine significantly the type of insertion performed by the carbenoid intermediate. The complexes used for the formation of carbenoids in enantioselective insertion reactions must present a balance between steric and electronic factors, to

• rhodium have been the most frequently used ones in carbenoid insertion reactions. Copper carbenoids having a higher electrophilic character display a great reactivity, but little selectivity in insertion reactions. Despite these features, only recently the insertion of chiral copper carbenoids into a C

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

• carbenoids: acceptor-acceptor [9][10][11], mono-acceptor [12] and donor-acceptor [13][14][15][16], and all the carbenoids react preferentially at the electron rich C2–C3 double bond. The catalysts used for the generation of the carbenoids are typically salts of Cu [9][11][13], Rh [10][12][16], Fe [14] and Ru

• proposed reaction pathway by using N-Boc-indole as a substrate (Scheme 4). Reactions between N-Boc-indole and carbenoids typically give N-Boc-indoline cyclopropanation products that can be purified and isolated [5][6][7][8]. We exposed Br-EDA to Rh2(esp)2 in the presence of N-Boc-indole in order to obtain

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• , rhodium carbenoids derived from α-diazocarbonyl compounds transform 2H-azirines 1 to azirinium ylides 5 (Scheme 1) which undergo facile N–C2 bond cleavage to give 2-azabuta-1,3-dienes 3. Recently we showed that the use of α-diazo-β-ketoesters 2 in these reactions, which are finished by 1,6-cyclization of

• the mechanism of trapping of dihydroazireno[2,1-b]oxazole intermediates by acetyl(methyl)ketene were investigated by the DFT method. Results and Discussion Rhodium(II) carbenoids generated from α-diazoketones or 2-diazo-1,3-diketones react with various nitrogen-containing compounds, such as amines [16

• ], amides [17][18][19], and nitriles [20][21], to give N–H insertion products or N- or N,O-heterocyclic systems. The reactivity of acyl- or diacyl-substituted Rh(II) carbenoids toward an sp2-hybridized nitrogen [22][23][24] is much less studied, while examples of their reactions with 2H-azirines are unknown

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• latter to give oxazine E (Scheme 2) [10][11]. Azirinium ylides G, formed by the reaction of azirines F with carbenoids, can transform into (3Z)- and (3E)-1-oxa-5-azahexa-1,3,5-triene D, but only the former can cyclize into 1,3-oxazines E. In contrast, the reaction of isoxazoles with carbenoids results in

• isoxazoles capable of providing stable 1-oxa-5-azahexa-1,3,5-trienes D under reaction with diazo esters and by comparing the experimental results of the reactions of carbenoids with a complementary pair of isoxazole and azirine. An analysis of recent literature shows that 2H-1,3-oxazine derivatives exhibit

• structures of compounds 4a–f were verified by 1H, 13C NMR, IR spectroscopy, and HRMS. Furthermore, the structures of compounds 4a,b were confirmed by X-ray analysis (Figure 4). According to 1H NMR no corresponding 1,3-oxazines were formed. Thus, only reactions of carbenoids with 5-alkoxy-substituted

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• ) inclination toward cycloalkyne formation through the Fritsch–Buttenberg–Wiechell (FBW) rearrangement [13], whereas SNV reactions of acyclic Mt,Hal-carbenoids often have to compete with FBW processes forming acyclic alkynes. The α,α-dibromo analogue of 6 (available [14] from 6 in two steps) was found to

• possible SNV reaction of 12 with DMSO and/or dimsyl-K (11), as proposed in Scheme 3 and later on as follows. In a rapid oxygen-transfer reaction that is known [31][32] for saturated carbenes or carbenoids, 12 will attack the solvent DMSO to generate the K,O-carbenoid 15 which decays in an E1cb-like

• -carbenoid 12 (indicated by the observation of its reversible protonation) is compatible and appropriate as the first intermediate in the route from 6 to acid 10. This formal “hydrolysis” of 6 makes use of the impressively enhanced electrophilicity of “unsaturated” carbenoids [13] such as 12, which property

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• cyclic amide side chains. Keywords: α-halo-β-lactam; diazo; halocarbonylcarbene; halogenation; thermolysis; Introduction Diazocarbonyl compounds are popular precursors for carbonylcarbenes and -carbenoids, the synthetic utility of which is thoroughly established through their successful employment in

• the halogenation of diazoacetamides. We report herein the bromination of the diazoacetamides derived from a selection of cyclic secondary amines, using DBU and N-bromophthalimide (NBP), as well as an investigation of the ability of the carbenes/carbenoids derived from the resulting α

• ][77]. The observed selectivity of the more stabilised carbenoids is attributed to the donation of electron density from the 4d orbitals of the dirhodium(II) complex to the vacant carbenoid 2p orbital [76][78][79][80][81], which attenuates its electrophilicity. This effect is analogous to the increased

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• Fabrice Chemla Florian Dulong Franck Ferreira Alejandro Perez-Luna Institut Parisien de Chimie Moléculaire (UMR 7201), FR 2769, UPMC Univ Paris 06, CNRS, Bâtiment F 2ème et., Case 183, 4 place Jussieu, F-75005 Paris, France 10.3762/bjoc.9.28 Abstract The formation of alkylidenezinc carbenoids by

• a formal anti-selective carbozincation reaction. Upon warming, the zinc carbenoid is stereochemically labile and isomerizes to its more stable form. Keywords: carbenoids; carbometallation; carbozincation; radicals; tandem reaction; Introduction The last few years have witnessed a gaining interest

• transition-metal-mediated carbozincations, which are generally syn-selective [41][42][43][44][45][46]. To explore further the possibilities offered by zinc atom transfer processes we considered the possibility to prepare alkylidenezinc carbenoids by radical-based carbozincation of haloalkynes. Such

Alkenes from β-lithiooxyphosphonium ylides generated by trapping α-lithiated terminal epoxides with triphenylphosphine

• David. M. Hodgson and
• Rosanne S. D. Persaud

Beilstein J. Org. Chem. 2012, 8, 1896–1900, doi:10.3762/bjoc.8.219

• way than the above approaches to β-lithiooxyphosphonium ylides 4 (R2 = H), we were attracted to the possibility of phosphines intercepting α-lithiated terminal epoxides 10 (Scheme 2) and report here the results of that study. Such carbenoids 10 are unstable, but they can be easily formed from terminal

• epoxides 8 by using hindered lithium amides, such as lithium tetramethylpiperidide (9, LTMP) [20], and have shown synthetically useful carbene reactivity (e.g., cyclopropanation [21][22], dimerization [23][24][25]). The reaction of carbenes and carbenoids with heteroatom lone pairs is a popular strategy to

• access ylides [26], although phosphonium ylides for carbonyl-olefination chemistry are usually prepared by deprotonation of phosphonium salts [1][2][3][4]. In fact, phosphine trapping of lithium carbenoids followed by carbonyl olefination has been little studied since Seyferth and Wittig independently

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• intermediate gold carbenoids of type XXIII’, resulting from 1,2-acyloxy migration on propargyl esters such as 31 (pivalates, acetates or benzoates), with external alkenes. Usually, the reactions are highly stereoselective, predominantly affording the cis-cyclopropanic adduct 32. Moreover, the reaction

• transformation is somewhat related to those previously described by Doyle and by Barluenga that involved α,β-unsaturated imines and rhodium–vinyl carbenoids (Doyle) or Fischer carbenes (Barluenga). However, the stereochemical outcome of these three processes is different [78][79]. Therefore, the reactivity of

• gold species of type XXIII may be sometimes similar to that of other transition metal carbenoids or even to that of alkenyl Fischer carbenes. However, in many other cases, it is markedly different. For instance, while alkenyl Fischer carbenes act as two-carbon atom components in (3 + 2) cycloadditions

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• ]. From the discovery and development of metal–carbenoids in cycloadditions with alkenes, as well as the internal redox reactions on alkynes, a further extensive investigation was focused on the new redox/cycloaddition cascades on alkynes to obtain azacyclic compounds 363 [171]. The central cores of the

• products were constructed through a formal [2 + 2 + 1] cycloaddition that involved α-carbonyl–carbenoids, nitroso species and external alkenes (Scheme 58). A gold(I)-catalyzed cascade cyclization/oxidative cross-coupling process has been devised to prepare β-alkynyl-γ-butenolides 366 directly from

High chemoselectivity in the phenol synthesis

• Matthias Rudolph,
• Melissa Q. McCreery,
• Wolfgang Frey and
• A. Stephen K. Hashmi

Beilstein J. Org. Chem. 2011, 7, 794–801, doi:10.3762/bjoc.7.90

• intermediates A or B. Apart from intermolecular trapping [26][27][28][29][30][31][32][33], intramolecular trapping of such carbenoids has also been reported [34]. One option would be to offer a competing carbonyl group, to produce a carbonyl ylide, which could then undergo a 1,3-dipolar cycloaddition [35]. The

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• gold-carbon order in the so-called organogold carbenoids. In the broad repertoire of gold-catalyzed organic transformations, gold-stabilized carbocations or, more often gold carbenes, can be found as intermediates in proposed mechanistic pathways, but the true nature of the organogold species had been

• . Conclusion Though relatively recent, the entry of cyclopropenes into the area of gold catalysis has already led to interesting contributions exploiting different aspects of the reactivity of alkenyl organogold carbenoids. It is obvious that the possibility to generate gold carbenes from cyclopropenes opens

Synthesis of highly substituted allenylsilanes by alkylidenation of silylketenes

• Stephen P. Marsden and
• Pascal C. Ducept

Beilstein J. Org. Chem. 2005, 1, No. 5, doi:10.1186/1860-5397-1-5

• of novel 1,3-disubstituted and 1,3,3-trisubstituted allenylsilanes. Additionally, we have demonstrated for the first time that titanium carbenoids can be used to methylenate silylketenes, providing the first access to 1-substituted allenylsilanes from these substrates. Given the broad range of useful