Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• processes with low catalyst loading. It involves the kinetic resolution of alcohols, amines, and esters using chiral phosphoric acids [6][7][8][9][10][11][12][13] and sulfoximines with enals using chiral N-heterocyclic carbene (NHC) catalysts [14]. Additionally, these processes have been conducted using

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• acetone, allowing the pre-activation of the ruthenium complex with the successive release of an N-heterocyclic carbene ligand and a chlorine atom, which are replaced by two acetone molecules to form compound 2. Simultaneously, excitation of the osmium(II) complex in the red region (660 nm) decreases its

• catalysis for carbene transfer reactions and radical-based functionalizations [41]. In another study by Derksen et al., thiaporphyrins were introduced as highly effective catalysts for red-light-mediated photoreductive dehalogenation [42]. These thiophene-modified porphyrins exhibit excellent absorption

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• organocatalytic reactions are discussed according to the dominant catalyst activation mode. For covalent organocatalysis, the typical enamine and iminium modes are presented, followed by N-heterocyclic carbene-catalyzed reactions. The bulk of the review is devoted to non-covalent activation, where chiral Brønsted

• axially chiral N-aryl succinimides 54. The tentative mechanism comprises the formation of the Breslow intermediate Int-31 from the catalyst carbene and aldehyde 52, which then adds to the electron-deficient double bond of maleimide giving rise to Int-32 (Scheme 17). Chi and co-workers developed an

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• -workers reported a dihydroquinine-derived squaramide-catalyzed (3 + 2) cycloaddition reaction of isocyanoacetates 26 and saccharin-derived 1-azadienes 14 [32]. In this work, the azadiene works as a C2 synthon, while the isocyanoacetate, bearing a protected carboxylic acid and a carbene-like divalent

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• situation. Dibenzyl ester 11c was prepared using traditional activation of carboxylic acid 6a, although the yield was only 23%. A higher yield of the branched ester 11d (86%, as a mixture of diastereomers) was obtained by carbene insertion, generated by blue LED irradiation of methyl 2-diazo-2-phenylacetate

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

• and a photosensitizer, facilitating photoinduced electron transfer (PET) to form the active cation radical B, and intersystem crossing (ISC) for energy transfer to generate the triplet carbene C. Radical B then reacted with biradical C, producing the new radical D, which accepted an electron from the

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• )triphenylphosphonium salt 6 and (iodomethyl)triphenyl-phosphonium salt 7. Homolytic or heterolytic scission of the I–C(ylid) bond with loss of ArI (path a) would result in a carbene, though it is unclear how this would transform to compound 6. Alternatively, scission of the I–C(Ar) bond with loss of benzyne (path b

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• -depleting sulfur dioxide as side products [46][47]. Later, Ichikawa and co-workers established the release of difluorocarbene from TFDA with catalytic amounts of an N-heterocyclic carbene and a base (Scheme 1C) [29][48][49]. In these reactions, difluoromethyl enol ethers were obtained, which were

• reaction time of 60 min, both reducing and increasing the amount of 2 (from initially used 2.0 equiv to 1.5 equiv and 3.0 equiv, respectively) reduced the yield of 3a by about 10% (Table 1, entries 3–5). Probably, with less carbene precursor the amount of generated difluorocarbene was insufficient, and

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• carbene (NHC) framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts, which demonstrated strong catalytic activity in gold-catalyzed alkyne hydration and arylative cyclization reactions [14]. The synthesis of this new carbene involved the use of a novel nitrenoid reagent that was

• successfully synthesized on a gram scale through a three-step reaction sequence. The process began with 2,6-diisopropylphenylamine, which underwent alkylation, formylation, and substitution reactions. The carbene synthesis was then achieved via a two-step process involving ynamide annulation, followed by

• imidazolium ring formation. The resulting carbene was metalated at the C2 position with Au(I), Cu(I), and Ir(I), obtaining an L-shaped NHC ligand scaffold. Līpiņš et al. introduced a new method for synthesizing 4-azido-6,7-dimethoxy-2-alkyl/arylsulfonylquinazolines, which are key intermediates in the

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• phenanthridines via silver-catalyzed radical sulfonylation–cyclization of 2-isocyanobiphenyls (Scheme 25) [98]. Wang et al. reported a radical borylative cyclization of 2-isocyanobiaryls with N-heterocyclic carbene borane (Scheme 26) [99]. The boryl radical generated via hydrogen abstraction in the presence of di

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• -Methylene spirolactones at C-3 11a and 11b derived from dihydrocholesterol and stanolone were also obtained in 41% and 52% yields, respectively (dr > 20:1) (Scheme 3). More recently, a functionalized spiro-β-lactone was obtained via a metal-free procedure involving photoinduced carbene C–H insertion in a

• diazo precursor. To achieve this, cholesterol was first esterificated using 2-(4-methoxyphenyl)acetic acid and DCC. The resulting arylacetic ester 12 was then reacted with 4-acetamidobenzenesulfonyl azide (p-ABSA) and DBU in anhydrous acetonitrile to yield the diazo compound 13 in 22% yield. The carbene

• C–H insertion to produce the spiro-β-lactone was accomplished by simply exposing the diazo derivative to 440 nm blue LEDs (Kessil lamp) at 50 °C, that favored the formation of a singlet carbene that reacted selectively by insertion into the C(3)–H bond. Spiro-lactones 14 were obtained in 80% yield

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• fractionated cell cultures of M. alba with 49 was followed by irradiation with 365 nm light to generate reactive carbene from diazirine. This sequence allowed the formation of covalent bonds between the synthetic probe and binding proteins. The resulting mixture was subjected to a copper-catalyzed click

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• reaction. AlCl3-mediated Cannizzaro disproportionation of aldehydes. Ru–N-heterocyclic carbene catalyzed dehydrogenative synthesis of carboxylic acids. Intramolecular desymmetrization of tetraethylene glycol. Desymmetrization of oligoethylene glycol dialdehydes. Intramolecular Cannizzaro reaction of calix

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

• 305-8577, Japan 10.3762/bjoc.20.100 Abstract The addition reaction of C60 with silylene 1, a silicon analog of carbene, yielded the corresponding bis-adduct 3. The structure of 3 was determined by single-crystal X-ray structure analysis, representing the first example of a crystal structure of a

• silicon analog of carbene, were described as providing silirane (silacyclopropane)-type 6,6-mono-adducts Dip2SiC60 (2, Scheme 1) and Dip2SiC70 [15][16]. Furthermore, bis-adducts (Dip2Si)2C60 and (Dip2Si)2C70 were obtained as byproducts, but no details of these bis-adducts have been clarified [15][16]. The

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• mechanism suggested that dearomatization–aromatization pathways operated for the dehydrogenation of the alcohol and C–C bond formations. After the successful attempt of bidentate N-heterocyclic carbene-manganese complex-catalyzed N-alkylation of amines with alcohols at room temperature [41], Liu and Ke's

• ]. Under optimized conditions (2 mol % Mn(CO)5Br, 10 mol % t-BuOK, t-AmOH, argon atmosphere), various quinoline derivatives were successfully synthesized with this protocol (Scheme 71). In 2019, Liu et al. used a bis-N-heterocyclic carbene-supported manganese complex for quinoline synthesis by coupling

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• vinyl propargylic esters could be employed as five-carbon atom building blocks in [5 + 2] cycloadditions with alkynes or alkenes by carbene intermediates. Starting from those results they envisaged the benzannulation of heteroaryl propargylic esters favored by CO [44]. The process led to the desired

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• carbene insertion into bicyclobutane was reported in 2022 by Bychek and Mykhailiuk [74]. Previously the same group had also reported the synthesis of BCPs containing a difluorinated bridge by CF2 carbene insertion into bicyclobutanes [75]. More recently Davies and co-worker reported the one-pot synthesis

• of bridge difluorinated BCPs from α-allyldiazoacetates. In their reaction sequence, intramolecular cyclopropanation first forms the bicyclobutane which is then subjected to CF2 carbene insertion to yield the BCP [76]. Another useful pathway to 1,2,3-BCPs is strain release functionalisation as was

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• a highly emerging area of research and exhibit complementary reactivity to those well-developed carbene-mediated MCRs [30][31][32][33][34][35][36][37][38][39][40][41][42]. In the radical-mediated difunctionalization of alkenes, the carbon-centered radical species from a diazo compound can add to

• -catalyzed carboamination of 1,3-dienes (Scheme 5, lower left) or allenes (Scheme 5, lower right) with diazo esters. There are two possible paths to generate the hybrid α-ester alkylpalladium radical I. Path a undergoes an oxidative addition of HX with Pd(0)Ln, followed by the formation of Pd–carbene species

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

• -step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions. Keywords: annulation; carbene; gold

• contrast to the most widely used ‘umbrella-like’ NHCs (Figure 1) [2][3]. An extended π-system influences the donor and acceptor properties of the carbene whilst substitution on the polycycle can position groups adjacent to the active centre. The imidazo[1,5-a]pyridin-3-ylidene motif (ImPy), independently

• fused imidazolium core (Scheme 2). No reaction was observed between 6a and [Ir(cod)Cl]2 in the presence of NEt3. A solution of the free carbene was prepared from 6 and reacted with [Ir(cod)Cl]2 and then CO to afford the AImOxIr(CO)Cl complex 15. A minor side-product with a strong red colour was formed

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• alcohols, followed by base-promoted cyclization to afford the target spirocyclic compounds in good to high yields. Keywords: diazoarylidene succinimides; intramolecular cyclization; rhodium(II) carbene O–H insertion; spirocycles; Introduction Spirocyclic motifs have emerged as auspicious frameworks for

• this protocol for spirocyclization and spiroheterocycle formation. The first step of the synthesis, the insertion of rhodium carbene into the O–H bond of 3-bromopropanol, was carried out under standard conditions in the presence of 0.05 mol % Rh2(esp)2 in dry DCM. 1H NMR spectroscopy was used to

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• carbene (NHC)-catalyzed radical relay, and (iv) mechanisms under electrochemical activation. By discussing selected literature examples, we illustrate how the activation mode of NHPI esters, and the reactivity of the resulting radical species, can vary depending upon the choice of catalytic or

• , accompanied by the formation of cyano-B(pin) 142. Importantly, in the absence of ZnCl2, intermediate 140 could be detected by HRMS and 11B NMR, highlighting the pivotal role of ZnCl2 in promoting rearomatization. N-Heterocyclic carbene (NHC) catalysis In 2019, Nagao and Ohmiya reported the decarboxylative

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• organic synthesis, as they can be used as diazo intermediates or carbene precursors for the rapid construction of complex molecules along with the introduction of fluoroalkyl groups [14][15][16]. Although the reaction of trifluorodiazoethane [17][18][19][20][21][22][23][24][25][26][27] as well as α-diazo

• reacts with the copper catalyst generating the Cu-carbene intermediate B, which undergoes nucleophilic attack by acetonitrile to form the intermediate C. Subsequently, nucleophilic addition of benzoic acid to intermediate C affords the acetimidic anhydride D with the release of CuI catalyst for the next

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• ][19]. These mesoionic carbenes (MICs), together with their pyrazolin-4-ylidene [20] and 1,2-isoxazol-4-ylidene cousins [21], are the strongest donors among the various types of carbene ligands known thus far [22]. A distinct class of mesoionic or abnormal carbenes based on the 1,2,3-triazole ring

• report described the preparation of a CAAC·CS2 zwitterion. Thus, in 2009 Bertrand et al. obtained the betaine 2 by reacting the free carbene 1 with a slight excess of CS2 in THF at room temperature (Scheme 1) [62]. The starting material that featured a bulky and rigid spirocyclic alkyl group derived from

• free carbene [39][41][42][58]. Hence, we decided to probe the feasibility of this approach for the synthesis of CAAC·CS2 and MIC·CS2 betaines from readily available aldiminium or 1,2,3-triazolium salts. Synthesis of CAAC·CS2 zwitterions To begin our study, we investigated the synthesis of CAAC·CS2

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

• acknowledged to be effective in introducing substituents to the nitrogen atoms of NH-heterocycles by means of carbene insertion into the N–H bond upon catalytic or photolytic decomposition of diazo compounds [25]. Furthermore, the reaction of N-heterocycles containing multiple non-equivalent nitrogen atoms

• will be reported in the following works. Conclusion In summary, a new diazo reagent for the convenient incorporation of heterocyclic substituents at the alpha-position of glutarimide by Rh(II)-catalyzed insertion of carbene into the N–H bond of nitrogen heterocycles has been proposed. The method allows