Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• advancements in the synthetic transformations of dioxazolones, with particular examples of copper salts. Keywords: amidation; copper salts; dioxazolones; electrophilic nitrogen; N-acyl nitrene; Introduction Dioxazolones, first synthesized and reported by Beck and co-workers [1], have been employed as

• amidation Recently, Cao and co-workers reported the copper-catalyzed synthesis of 1,2,4-triazole derivatives via an N-acyl nitrene intermediate [76]. As illustrated in Scheme 3, dioxazolones 4 and N-iminoquinolinium ylides 5 served as reactive substrates, leading to the formation of various polycyclic 1,2,4

• ) nitrenoid intermediate INT-7. Subsequent nitrene insertion, protodemetalation, and intramolecular cyclization furnish the desired 1,2,4-triazole. 1.3 Three-component formation of N-acyl amidines In 2019, N-acyl amidines were prepared from dioxazolones using a copper catalyst with terminal alkynes and

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• -catalyzed aziridination of styrene (22) by chloramine-T (23, NaCl=NTs) as a source of nitrene in acetonitrile (Figure 5) [40]. No aziridine product was formed either without any source of copper or in the presence of a different copper salt, such as CuCl, CuCl2·2H2O, or CuOTf. Calix[4]pyrrole itself is

• activates the Cu–Cl bond via chloride···calixpyrrole (N–H···Cl) hydrogen-bonding interactions toward the formation of the nitrene intermediate from chloramine-T (NaCl=NTs). Additionally, calix[4]pyrrole served as a phase-transfer catalyst in this reaction. Since chloramine-T had low solubility in

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis. Keywords: aziridination; electrochemistry; H-bond activation; hypervalent iodine; nitrene transfer; Introduction Hypervalent iodine reagents find widespread application in selective oxidation chemistry due to

• ]. Iminoiodinanes (ArI=NR) are a subclass of hypervalent iodine reagents that function as nitrene equivalents in synthesis [5][6]. The direct reaction of iminoiodinanes with olefins, which could be envisioned to give rise to aziridines directly, is typically not observed and thus families of transition metal

• center [26][27]. Despite the prevalence of acid-activation in promoting carbon [28], oxygen [29][30], sulfur [31], chlorine [32], and fluorine [33] transfer reactions of hypervalent iodine compounds, these strategies have not been applied to activation of iminoiodinanes for nitrene transfer chemistry. We

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• eight possible regioisomers for bis-addition reactions. Hirsch and co-workers reported two-fold additions of C60 using the Bingel–Hirsch and the Bamford–Stevens reactions as well as nitrene addition reactions, indicating the formation of regioisomers as anticipated from the possible addition sites in

• Bamford–Stevens reactions, and nitrene addition, indicating that preferential formation of the e (e′ or e′′) isomers followed by trans-3 isomer when at least one of the two addends was sterically demanding [5]. The formation of 3 in the present bis-silylene addition is consistent with those earlier

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• morpholine as solvent (0.4 M) and 0.4 equiv LiHMDS as a base at 75 °C for 48 h. The only byproducts observed are anilines as a result of thermal decomposition of the organic azides via reactive nitrene species. No other byproducts were observed by TLC or crude 1H NMR. The volatility of the gem

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

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

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• of them (pathway a) includes the formation of the nitrene cation 11 [41][42][44][45][53] under action of PIFA as an oxidant. A subsequent electrophilic attack at the double bond provides aziridinium cation 12 that undergoes selective ring opening with the trifluoroacetate anion to give intermediate

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

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

• the azide group and the C=S moiety of the thioamide group (Scheme 7). The formation of nitrene-like products was excluded because of the high selectivity of the process, where only the thioamide group takes part, even with heterocyclic rings that contain other nucleophilic centers, and in one case, an

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• step, an azide group was introduced to 10 by lithiation with n-BuLi followed by the reaction with tosyl azide giving azide 11 in an excellent yield of 92%. Thermally induced ring-closure under release of nitrogen and formation of a nitrene intermediate was achieved by refluxing azide 11 in

• (19) in an increased yield of 58% (Scheme 4). Comparison of the reactions indicated that o-nitrophenyl substituents as in 18 give higher cyclization yields than the corresponding 3-nitrothienyls as in 16. We rationalize this finding by a higher reactivity of the intermediate thienyl nitrene, which is

• formed during the cyclization reaction of 16 compared to phenyl nitrene [42]. Besides H-SN4 13, which is formed by insertion of the nitrene N-atom into the C3–H σ-bond of the thienothiophene in 16 and simultaneous migration of the H-atom to the nitrogen, mostly undefined black oligomeric or polymeric

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• aziridination with redox-active complex Cu(SQ)2 17 [37], originally developed as a GAO mimic. The reaction worked very efficiently under ambient conditions with N-tosyliminobenzyliodinane (PhINTs) as a nitrene source. The reaction mechanism was proposed to involve a transient mono-nitrene CuII intermediate 18

• in equilibrium with a spectator bis-nitrene species 19 and proceeded through styrene 20 insertion, followed by ring closure and release of the aziridine. Interestingly, this otherwise classical mechanism is enabled by the accessibility of doublet and quadruplet states close in energy and this

• reminiscent of the entatic state model. The proposed mechanism (Scheme 12) involves the insertion of a nitrene or carbene group to the copper complex 22 to form intermediate 23. Subsequent alkene insertion yields species 25 and the group-transfer product (21a,h–j,n,o, 26a–g and 27a–o) is released upon ring

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• 63 with the groups R1 and R2 = H were not suitable for this transformation. The reason was because the formed intermediate was unstable under this conditions. A possible mechanism is outlined in Scheme 14. Initially, the Rh-nitrene intermediate 65 [83][84][85][86] is generated from the coordination

• of azide to Rh2(esp)2 complex (bis[rhodium-(α,α,α’,α’-tetramethyl-1,3-benzenedipropionic acid)]) and extrusion of N2. Then, the Rh-nitrene intermediate 65 goes through an intramolecular single electron transfer (SET) to give the nitrogen-centered radical intermediate 66 [87][88][89][90]. Next, the

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• introduction of nitrogen in the convenient position (C3) could be performed by a stereopecific nitrene insertion reaction catalyzed by rhodium(II) complexes [24][25]. Herein, we describe our outcomes related to the implementation of this strategy for the synthesis of L-vancosamine derivative 1, as well as its

• data [9]. As an example, the expected protected glycal of L-daunosamine 3 [9][47] was obtained by regioselective rhodium nitrene insertion thus demonstrating the usefulness of this strategy for the synthesis of such compounds. Conclusion We developed an alternative route to 3-aminoglycals through ring

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

• ]. Seminal catalytic nitrene transfers mediated by λ3-iodanes [86][87][88][89] were described from iminoiodinanes of general formula PhI=NR that can be prepared mainly from sulfonamides [90]. However, the scope of catalytic C(sp3)–H amination and alkene aziridination reactions has been greatly enhanced

• following the discovery of practical procedures for the in situ generation of iminoiodinanes, a synthesis which is known to be troublesome [91][92][93]. According to these protocols and following the design of dirhodium(II) complexes, highly efficient catalytic nitrene transfers have been reported from

• carbamates [92], sulfamates [94][95][96][97], ureas and guanidines [98], sulfamides [99], hydroxylamine-derived sulfamates [100], carbamimidates [101], and sulfonimidamides [102][103][104][105][106][107]. These reactions involve the formation of a metal-bound nitrene that can insert into a C(sp3)–H bond or a

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

• ][40][41]. They have been widely applied in C–H oxygenations, nitrene generations, oxidative dearomatisations and dehydrogenative couplings by transferring one of their two carboxyl ligands or external oxygen nucleophiles to a substrate. In all these “classical” reactions aryl iodides are produced as

• the sulfonimidamide 31 in the presence of the chiral rhodium(II) catalyst A. Hereby, one equivalent of iodoarene 2 is released. The insertion of the nitrene species into the C(sp3)–H bond affords the amination product C, which is the final product of the first reaction step. In the following step, C

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• ]. Several methods use prerequisite quinoline derivatives for the construction of the pyrrole ring of quindoline. 2-(2-Aminophenyl)-3-bromoquinoline cyclized to quindoline by reacting with pyridinium hydrochloride (d) [14]. Insertion of nitrene generated from 2-(2-nitrophenyl)quinoline by triethylphosphite

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• ). Formation of disulfides through reaction of thiols with E-1a. Formation of CT salts of E-1 with Mn2+ and Cr2+ metallocenes through one-electron transfer. Oxidation of diethyl dicyanofumarate (E-1a) with H2O2 to give oxirane 101. The aziridination of E-1b through nitrene addition. Acknowledgements The

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• maleimides in toluene provided a ready access to the fused ring-system 6a–c in excellent yields (81–91%; Scheme 3, middle). Finally, the [4 + 1]-cycloaddition with nitrenes was carried out (Scheme 3, right). To attain this transformation the required nitrene was formed in situ from an iminoiodinane precursor

• (25), 107 (26), 106 [C6H7]+ (100), 93 (81), 91 (86), 79 (37), 77 (59), 69 (60), 55 [C4H7]+ (42), 53 (37). Formal [4 + 1]-cycloaddition [47] Catalyst Cu(hfacac)2 (18 mg, 0.04 mmol, 5 mol %) and the nitrene precursor PhI=NTs (280 mg, 0.75 mmol, 1.0 equiv) were dissolved in chlorobenzene (5 mL, 0.15 M

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

• systems rapidly and efficiently, though additional catalyst development is needed. Keywords: bridged rings; carbene; cascade reaction; C–H bond insertion; nitrene; Introduction Bridged polycyclic natural products are an inviting challenge to the synthetic chemist for their rich display of functional

• access to multiple targets from a single intermediate produced on large scale that may be stored until needed [17]. The C–H bond insertion has great potential as a method to access different polycyclic isomers (e.g., 1 or 3) through C–C or C–N bond formation from a carbene or nitrene, respectively

• have organized this review by the catalyst used, with free carbenes first, followed by Cu, Rh, Au, Pt, and then W-catalyzed reactions. Review Metal-free reactions While transition metal catalysis has seen widespread adoption for carbene and nitrene reactions, it is not necessary for a controlled

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• the reaction mixture [30] and obtained a maximum yield of 20% and 50%, respectively, at a water content of 50%. Under these conditions, no formation of the primary amine 4 (a product of the typical triplet nitrene reaction (Scheme 1, intermediate D)) was detected. The replacement of the aprotic

• photolysis of 2-azidonitrobenzene through the intermediate singlet nitrene A (Scheme 1) without the formation of other intermediates. The formation of substituted 2,1-benzisoxazoles from aryl azides was reported for the first time by Smith et al. [24] in the synthesis of 3-phenyl-2,1-benzisoxazole (3

• -phenylanthranil) by thermolysis of 2-azidobenzophenone. In another work [55], the photochemical formation of 3-amino-6-nitro-2,1-benzisoxazole starting from 2-azido-4-nitrobenzamide was observed. The authors subsequently investigated the multiplicity of the involved nitrene by repeating the reaction in the

Copper catalysis in organic synthesis

• Sherry R. Chemler

Beilstein J. Org. Chem. 2015, 11, 2252–2253, doi:10.3762/bjoc.11.244

• been published in 2014. In point of fact, there has been a steady increase in publications on this topic since 1988. In the late 1980’s and early 1990’s, the topics centered on copper nitrene reactivity (e.g., aziridination), copper carbene chemistry, conjugate additions and cross-coupling reactions

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• provides a practical approach to complement the above catalytic version on the sulfonamidation of secondary and tertiary alkyl C–H bonds (Scheme 4) [46]. As an early known tactic with broad application, the nitrene insertion was frequently employed in the sulfonamidation of saturated C–H bonds. However

• , previously prepared nitrene precursors such as ArI=NTs [47] or chloramine-T [48] were required. To design a facile amidation method using this strategy, Yu and co-worker [49] developed a new method for the synthesis of tosyl-amidated esters 20 via C–H sulfonamidation of cyclic esters 19 under catalysis of

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• (Figure 2) [10][24]. In this article, we intend to demonstrate the reactivity of 2H-azirine A1 towards carboxylic acids [28]. α-Azidochalcones have been chosen to generate 2H-azirines via vinyl nitrene intermediates. α-Azidochalcones can be synthesized from the corresponding benzylidene acetophenones in