A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• which could not be fully purified or characterised but has a characteristic AQ quartet of two protons replacing the singlet for the N-methyl group in the 1H NMR spectra consistent with a cyclometallated complex from C–H insertion [31][32]. Three distinct sets of N-methyl and N-methylsulfonyl signals

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• , C–H insertion products 9 were also observed. Thus, when reacting with indole, the product of carbenoid attack at position 3 (9a) was isolated along with target compound 6a. Introduction of a carbomethoxy group into this position of indole leads to the exceptional formation of the N–H insertion

• product 6b in high yield. The reaction with methyl pyrrole-2-carboxylate resulted in the isolation of only the C–H insertion product 9c in low yield. Similar reaction progress was observed in the case with imidazole, the product N–H insertion was observed only in trace amounts (according to NMR data of

• the preparation of modified glutarimides with a wide range of aromatic and aliphatic NH-heterocycles under mild conditions in moderate to high yields. It is shown that electron-rich substrates tend to give C–H insertion products. The N-modification of tetrazoles and 1,2,4-triazoles using a

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• 44, from which reductive elimination of iodobenzene would generate 40. In 2021, Sen and Gremaud disclosed a blue LED-mediated formal C–H insertion reaction between iodonium ylides (e.g., 31) and pyrroles (e.g., 45), indoles and furans, producing malonate-substituted heterocycles 46 (Scheme 9) [126

• ]. The authors discounted a free carbene-based C–H insertion because conducting the reaction in the presence of the radical trap phenyl N-tert-butyl nitrone (PBN) and the radical scavenger TEMPO resulted in decreased yields and isolation of their iodonium ylide adducts. Additional kinetic isotope effect

• iodobenzene then generated a strained, cyclopropane-fused bicycle 49 that rearranged into the isolated C–H insertion product 46a. In addition to Neiland’s disclosure of the reactions between iodonium ylides and hydrochloric acid (Scheme 1) [1][102], others have also reported that both strong acids (e.g., TsOH

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• functionalisation of unsaturated bonds [1][2][3][4][5], and, more recently, frustrated Lewis pair (FLP) chemistries including small molecule activations and C–H insertion reactions [6][7][8][9][10]. Group 13 exchange is the transfer of one or more substituents from one group 13 element to another group 13 element

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• the 6-5-5 tricyclic skeleton includes the mediation of Nagata reagent for constructing the C1 all-carbon quaternary centers and gold-catalyzed cyclopentenone synthesis through C–H insertion. Keywords: aberrarone; C–H insertion; gold; Pauson–Khand; total synthesis; Introduction Marine natural

• one quaternary carbon stereocenter and 1,2-dikeone moiety, Nazarov cyclization [33] of 7 was proposed for synthesizing this challenging moiety. The corresponding precursor cyclopentenone 8 may be prepared from alkynone 9 through a gold-catalyzed C–H insertion [34]. Alkynone 9 could be achieved through

• strategy, the stereogenic center at C1 was synthesized, along with a smooth attachment of the cyanate group served for further functional group transformation to construct the C ring through C–H insertion. The stereochemistry finding of this conjugate addition from the convex face of the 6-5 ring system

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• [24]. Both monomesityl and dimesitylphosphinyl azides 14 generated 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 15 in 31% and 20%, respectively, via an intramolecular nitrene C–H insertion, for dimesitylphosphinyl azide (14b), with 51% yield of phosphonamidate 16 as byproduct. Bis(2,4,6

• ). Synthesis of 2-aryl-1-methyl-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 13 from N-aryl-2-chloromethylphenyl(methyl)phosphinamides 12. Synthesis of 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides from alkylarylphosphinyl or diarylphosphinyl azides via an intramolecular nitrene C–H insertion. Synthesis of 3

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• indole derivative 31 in 82% yield (Scheme 11) [22]. Being a kinetically very active catalyst, Rh2(OAc)4 favored the formation of the five-membered ring. On the other hand, employment of Pd(OAc)2-catalysis switched the regioselectivity of this C–H insertion reaction. More specifically, under Pd(OAc)2

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

• insertion and then oxidation (Scheme 54). This methodology was later successfully utilized for the total synthesis of raloxifene and benzo[b]thiophene derivatives [115]. Cyclization involving allenes (>C=C=C<) Hg(II) triflate salts had also been successfully employed for the arylallene 181 cyclization by

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

• substrates was reported by Yu and co-workers (Scheme 13) [50]. Enantioenriched benzyl fluorides were obtained by aid of a chiral α-amino amide transient directing group (TDG). Notably, the condensation of this bulky amino amide with the aldehyde led to control of the stereochemistry of the C–H insertion step

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

• carbene transfer reaction typically give N–H, C–H (at C3) and double N–H/C–H insertion products. The presence of electron-withdrawing groups on the indole nitrogen makes it possible to cyclopropanate the indole C2–C3 double bond and isolate indoline cyclopropanes. We recently discovered that Rh carbenes

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

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

• energy of the triplet excited state 3T1 of this sensitizer (64 kcal/mol) is somewhat lower than the corresponding energy of the diazodiketones 1 making it inadequate to initiate the C–H insertion reaction. On the other hand, the triplet excited state energy of benzophenone (69 kcal/mol) renders it a

• suitable sensitizer for this reaction. In the case of tricyclic diazodiketones 1d,f (with annulated furan and 2-methylfuran-motifs in their structures), a tandem photochemical process of C–H-insertion followed by cycloelimination of furan from the initially generated hydrazones 2d,f apparently occurs

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

• % enantiomeric excess) from bis(α-diazo-β-keto ester) 205 [86]. The key step of this synthesis was a double intramolecular C–H insertion process catalyzed by dirhodium(II) tetrakis[N-phthaloyl-(R or S)-tert-leucinate]. The resulting spiroindanone derivative 207 obtained from the intermediate 206, underwent

• was converted to the expected, estrogen receptor modulator 216 (Scheme 59). 3-Arylindan-1-ones 219, versatile intermediates for the synthesis of a number of biologically active compounds, have been synthesized from α-diazo-β-keto ester 218 via a intramolecular C–H insertion reaction catalyzed by the

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

• expansion [12], and C–H insertion and Si–H insertion reactions [13]. Under Rh(II)-catalysis conditions, 2b extrudes N2 much faster than 1 (15 s vs 8 min to 50% conversion) [14]. The higher reaction rate implies a lower turnover limiting barrier in the catalytic cycle with 2b compared to 1. This example made

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

• nearby methyl group to give 23 (Scheme 5) [29][30]. Competition with a transannular benzylic C–H insertion to give 24 was a minor outcome. This initial study provided a model system to confirm the proposed stereochemistry of atisine. A later study using the substrate 25 that lacked the benzylic C–H bond

• led to a formal total synthesis of garryine, which is closely related to atisine. The initial lactam 26 that was formed by methyl C–H insertion was quite unstable, and so it was quickly converted to the acetamide 27. Advancing that intermediate intercepted a route to garryine completed by Pelletier

• primary outcome. The major product with copper was insertion into the more electron-rich methine to give bicyclo[3.2.1]octane 29. The yields of both transannular C–H insertion products were increased relative to the Wolff rearrangement when a methyl group was present on the cyclohexyl carbon bearing the

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

• development of intermolecular C–H insertion in the application of C(sp3)–H bond functionalizations, especially for light alkanes, is reviewed. The challenging problem of regioselectivity in C–H bond insertions has been tackled by the use of sterically bulky metal catalysts, such as metal porphyrins and silver

• (1,5 C–H insertion). However, 1,3-, 1,4, and 1,6 C–H insertions are also possible, depending on the substrates and the catalysts. Although the site-selectivity of intramolecular metal–carbene C(sp3)–H bond insertion is affected by the combination of factors such as steric and electronic factors as well

• the late-stage C–H functionalization of complex alkaloids and drug molecules (Scheme 3) [25]. C–H bond insertions at the allylic and benzylic positions Metal–carbene C–H insertion is also favored for allylic and benzylic sites. In 2014, Davies and co-workers reported an enantioselective C–H insertion

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• -Boc-α-N-Cbz-L-ornithine (20) was transformed into sulfamate 21. Subsequently, the C–H insertion representing the key step of this synthesis was examined with two different catalysts and different reaction conditions. Despite different ratios in the outcome of the C–H insertion in favour of the

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• the tricyclic core were controlled via Rh-catalyzed stereoselective C–H insertion and the subsequent reduction from the convex face. Keywords: bifunctional catalysis; hydrogen bonding; organocatalyst; oxa-Michael; prostacyclin; Introduction Prostacyclin (PGI2, Figure 1) is a physiologically active

• ) at the ortho position was methyl, or via coupling reactions with C4 units when X was a bromo substituent. The cis-fused tricyclic core of 3 was assumed to be constructed by a stereoselective C–H insertion of diazoester 4, which can be readily prepared from the Weinreb amides 5 or 6 via Claisen

• -dimethylimidazolinium hexafluorophosphate (ADMP) [40][41][42] to give the diazoester 14. Rhodium catalysed C–H insertion [43][44] of 14 proceeded smoothly to furnish the tricyclic ketoester, which was found to be unstable to purification on column chromatography, presumably due to decomposition of the ketoester moiety

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

• many of the reactions between indoles and metal-bound carbenes are unclear [5][6][7][8]. We have for some time worked with halodiazoacetates and studied their reactivity in cyclopropanation reactions [17], C–H insertion and Si–H insertion reactions [18]. Halodiazoacetates can be made quantiatively and

• Scheme 5. We found no trace of a cyclopropanation-ring expansion product in the crude reaction mixture, but isolated ethyl 2,2-bis(1-methyl-1H-indol-3-yl)acetate in 69% yield. A possible explanation for the formation of the bisindol acetate can be rationalized by assuming a C–H insertion of the Rh

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• stereoselective preparation of such amines. Throughout the last decades, several strategies [3] such as stereospecific amination via C–H insertion [5][6][7][8] or asymmetric olefin hydroamination [9][10][11][12][13] have been investigated in order to obtain access to optically pure amines. However, the major

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• intermediate in the synthesis of 2 (see Scheme 1). We envisioned a rhodium-catalyzed C–H-insertion into the C17–H bond to occur with a high degree of selectivity (both regio- and stereoselectivity) to form the all-carbon E-ring (for its structure see 11, Scheme 2). Furthermore, a Wagner–Meerwein rearrangement

• this point, extensive experimentation suggested a change of protecting groups to enable the pending C–H insertion reaction at C17. Therefore, the i-steroid was reverted to the homoallylic alcohol (cat. para-toluenesulfonic acid, 1,4-dioxane/H2O, 10:1, 65 °C), the methyl ester was hydrolyzed under basic

• the corresponding acid chloride (oxalyl chloride, CH2Cl2, 25 °C; then diazomethane, THF, 25 °C, 85% yield for the two steps) [33]. The anticipated C–H insertion then proceeded uneventfully under oxygen-free conditions (cat. Rh2(OAc)4, CH2Cl2, 41 °C) [34][35] to give cyclopentanone 11 in 52% yield as a

Theoretical studies on the intramolecular cyclization of 2,4,6-t-Bu₃C₆H₂P=C: and effects of conjugation between the P=C and aromatic moieties

• Masaaki Yoshifuji and
• Shigekazu Ito

Beilstein J. Org. Chem. 2014, 10, 1032–1036, doi:10.3762/bjoc.10.103

• Abstract The intramolecular C–H insertion of the Mes*-substituted phosphanylidenecarbene [Mes*P=C:] (Mes* = 2,4,6-t-Bu3C6H2) and physicochemical properties of the cyclized product, 6,8-di-tert-butyl-3,4-dihydro-4,4-dimethyl-1-phosphanaphthalene were studied based on ab initio calculations. Whereas the

•  2) [15]. In contrast to the selective formation of Mes*C≡P from (E)-Mes*P=C(Cl)Li [11][12], facile removal of the bromide ion in Mes*P=C(Br)Li might be critical for the C–H insertion. The C–H insertion of carbene has been studied well [16], and thus intensive studies on the intramolecular

• conclusion, the chemistry of the intramolecular C–H insertion of phosphanylidenecarbene 1 affording 2 was studied by ab initio and DFT calculations. The intramolecular cyclization requires an activation energy, whereas the phosphorus version of the FBW rearrangement proceeded without an energetic barrier

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• , nitrogen C–H insertion [10][11][12], hydroamination [13][14][15][16], hydroaminoalkylation [17][18], reductive amination [19][20][21][22][23], and enamine reduction [23][24][25][26][27] are experiencing a renaissance; while imine reduction [23][28][29][30], N-acylenamide reduction [23][24], and carbanion

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• ozonolysis and acid-promoted cyclization afforded (+)-41 and (−)-41 in an overall yield of 60% and 46%, respectively. For the synthesis of staurosporinone (30) and its 3,4-dimethoxybenzyl (DMB)-protected derivative 45, a ruthenium-catalyzed C–H insertion/electrocyclization cascade using 2,2’-bisindole 44 and

Gold-catalyzed regioselective oxidation of propargylic carboxylates: a reliable access to α-carboxy-α,β-unsaturated ketones/aldehydes

• Kegong Ji,
• Jonathan Nelson and
• Liming Zhang

Beilstein J. Org. Chem. 2013, 9, 1925–1930, doi:10.3762/bjoc.9.227

• excellent regioselectivity, which is ascribed to inductive polarization of the C–C triple bond by the electron-withdrawing carboxy group. The gold carbene intermediates thus generated undergo selective 1,2-acyloxy migration over a 1,2-C–H insertion, and the selectivities could be dramatically improved by

• rationalized as the results of divergent transformations of the α-oxo gold carbene B: the former is formed via a two-step 2,3-acetoxy migration [22][23], and the latter most likely via a concerted carbene 1,2-C–H insertion[2]. The selective formation of the Z isomer of 5a-OAc can be attributed to that B adopts

• , better than ~7:1 in the latter case, albeit both lower than that by IPrAuNTf2 (>50:1, see Scheme 3). The enhanced preference of AcO migration en route to the formation of 5a-OAc over the 1,2-C-H insertion is attributed to attenuation of the electrophilicity of the gold carbene moiety via the formation of