Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• to the PBTA scaffold is an annulation of benzothiazoles with a pyrrole moiety (Scheme 1). It includes intramolecular cyclizations of benzothiazoles bearing a 3'-chloro substituent at C2 position (Scheme 1, entries 1 and 2) [5][6][7], intramolecular catalytic carbene cascade reactions of propargyl 1,3

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• ring, while flavylium triflate and 2,4,6-triphenylpyrylium tetrafluoroborate were not compatible with our reaction conditions. Heterodonor ferrocenyl phosphane–carbene ligands efficiently promote the conjugate addition of Grignard reagents to α,β-unsaturated lactones [58]. Building on this knowledge

• the trapping of metal enolates by Michael reactions with nitroalkenes 122 and disulfonyl ethylenes 124 (Scheme 31) [67]. The conjugate additions of dialkylzinc, Grignard, and trialkylaluminum reagents to cyclic enones 121 were realized using previously established chiral phosphoramidite, carbene or

• , which begins with a Cu-catalyzed enantioselective conjugate addition/enolate alkylation tandem reaction sequence utilizing the N-heterocyclic carbene ligand L40 [112]. Ketone 232 was isolated in 61% yield and 81% ee. Hereafter, the authors were able to synthesize the complex tetracyclic structure within

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• -Innovation Center of Efficient Processing and Utilization of Forest Resources College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China 10.3762/bjoc.19.39 Abstract A synthetic route to the bench-stable fluorinated masked carbene reagent diethyl 2-diazo-1,1,3,3,3

• fluorinated diazo compounds might be rationalized by their low accessibility and high volatility [44]. As a part of our continuing investigations in fluorinated carbene chemistry [45][46][47][48][49], we hypothesized that the synthesis of cyclopropanes with geminal trifluoromethyl and

• difluoromethylphosphonate groups at the ring might be possible by using our newly developed bench-stable diazo reagent CF3C(N2)CF2P(O)(OEt)2. Therefore, we report herein our preliminary results toward this goal via copper iodide-catalyzed cyclopropanation reaction of an acceptor carbene precursor with selected terminal

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

• would afford the [2 + 2] adduct. Hydroruthenation of the allene produces 103 which can either undergo reductive elimination to afford the cyclopropanated bicyclic alkene or undergo a [2 + 2] cycloreversion to generate the Ru–carbene 104. The Ru–carbene 104 can rearrange to 100 through a 1,3-migration of

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• , Germany 10.3762/bjoc.19.34 Abstract A protocol for the mechanochemical synthesis of copper(I)/N-heterocyclic carbene complexes using cheap and readily available K3PO4 as base has been developed. This method employing a ball mill is amenable to typical simple copper(I)/NHC complexes but also to a

• sophisticated copper(I)/N-heterocyclic carbene complex bearing a guanidine moiety. In this way, the present approach circumvents commonly employed silver(I) complexes which are associated with significant and undesired waste formation and the excessive use of solvents. The resulting bifunctional catalyst has

• focus has seldomly been on the preparative methods to access the required catalysts themselves. As case in point, we decided to re-investigate the synthesis of copper(I)/N-heterocyclic carbene (NHC) complexes, which are broadly applicable catalysts for a wide variety of transformations [4][5][6]. While

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• triazoloporphyrins 32a–c and triazole-bridged bisporphyrins 34 in good yields. The “click reaction” of azidoporphyrin 30 with the terminal alkynes 31a–c and 33 in a THF/water (3:1) mixture was investigated by using different catalytic systems. Among these, copper carbene (SIMes)CuBr proved to be a better catalyst

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

• /B‒H exchange [114]. Hevia reported a combination of a tris(alkyl)gallium species and bulky N-heterocyclic carbene acted as an FLP for B‒H insertion, and was used subsequently as a catalyst in the hydroboration of ketones, aldehydes, esters, and imines with HBpin [115]. Using an ONO-pincer-supported

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• Langemann reported an efficient and short total synthesis of the natural product dactylol (72) (Scheme 12) [37]. The main originality of this work was the use of the Schrock molybdenum carbene catalyst 73 for the ring-closing metathesis reaction. The metathesis precursor 70 was obtained in 4 steps from

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• expected allyl cation (3 + 2) cycloaddition reactivity is not operating under gold(I) catalysis, but instead it behaved as a reliable and quite stereoselective vinylgold carbenoid species, affording exclusively cyclopropanation products with a wide range of olefin substrates (Scheme 18c). The carbene-type

• formation of the cis-vinylcyclopropanes (Scheme 18c and 18d). Desulfurization of the adducts again yields the product of a formal cyclopropanation with a ‘naked’ vinyl carbene species, as demonstrated by the stereoselective synthesis of the protected cis-2-vinylcyclopropan-1-amine 123 (Scheme 18d). 7

• of dithiin-fused allyl alcohols and similar non-cyclic sulfur-substituted allyl alcohols. Applications of dihydrodithiins in the rapid assembly of polycyclic terpenoid scaffolds [108][109]. Dihydrodithiin-mediated allyl cation and vinyl carbene cycloadditions via a gold(I)-catalyzed 1,2-sulfur

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• ]. Compared with highly sensitive diazo compounds, iodonium ylides are known to show ready availability and good stability [29][30]. Our group has recently demonstrated that iodonium ylides can be used as carbene precursors in the Rh-catalyzed [4 + 2] cyclization of pyrazolidinones [31]. During the

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• pyrrole-fused heterocyclic tricycles [33]. The involvement of Nazarov and in particular aza-Nazarov reactions in the cyclization of alkynes that go through metal carbene intermediates has recently been reviewed by Gao and co-workers [34]. In 2019, we reported a highly effective aza-Nazarov cyclization for

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• calculation methods, as were the remarkably downfield shifts for the novel di- and trications 21 and 22, for which even drawing suitable resonance structures is a challenge. Two phosphinidenes (23, 24), i.e., carbene analogues with potentially anionic phosphorus atoms, have remarkably upfield chemical shifts

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• addition to the electron-rich C=C bond [58] or proton loss followed by β-functionalization [59][60][61]. The iminium cation catalysis is used in the activation of electrophilic properties of enones for the nucleophilic epoxidation by hydroperoxides (Scheme 2B). N-Heterocyclic carbene (NHC) organocatalysis

• -organocatalysts. Organocatalysis classification used in the present perspective. Oxidative processes catalyzed by amines. N-Heterocyclic carbene (NHC) catalysis in oxidative functionalization of aldehydes. Examples of asymmetric oxidative processes catalyzed by chiral Brønsted acids. Asymmetric aerobic α

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• arylidene succinimides; intramolecular oxa-Michael addition; rhodium(II) carbene O–H insertion; spirocycles; Introduction Spirocycles undoubtedly occupy a special place in drug design [1] and, in general, spirocyclic compounds intended for the interrogation of biological targets have been associated with

• cyclohexanone (as well as other cyclic ketones) which delivered spiro-annulated 2-benzoxepines (such as 2a) along with a minor byproduct 3a identified by 1H NMR as the product of formal insertion of the rhodium(II) carbene species into the O–H bond of cyclohexanone enol form. This minor byproduct, on heating at

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• generate an intermediate followed by immediate reaction with another 1.0 equiv CH-acids to form another reactive species which reacted with substituted imidazole N-oxide to produce desired products. Synthesis and trapping of optically active carbene In 2019, Grzegorz Mlostoń and co-workers disclosed an

• excellent synthetic route for the preparation of chiral 3-alkoxyimidazol-2-ylidene intermediates [22]. Optically active 2-unsubstituted imidazole N-oxides were converted to carbene intermediates with retaining their stereochemistry. The appearance of the carbene intermediate was verified by trapping

• salts 41. The latter underwent deprotonation in the presence of triethylamine in pyridine to generate the carbene intermediates 42 (Scheme 9). After that, the optically active imidazole-2-thiones 43 were obtained through the reaction with elemental sulfur. In CHCl3 solutions, the study of the optical

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• corresponding 1,2,3-cyclopropenium bromides was realized by a classical approach: combination of C1 and C2 building blocks, i.e., the addition of a carbene species to a triple bond of diarylacetylene, followed by treatment of the produced cyclopropene with HBr to convert it to the corresponding cyclopropenylium

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• from the anodic electroactivity of the electrogenerated carbene. In order to have NHC accumulation in the catholyte, the Nafion membrane (cell separator) was pretreated with an alkaline solution. The formation of NHC was quantified as its reaction product with elemental sulfur. The NHC was successfully

• used as organocatalyst in two classical umpolung reactions of cinnamaldehyde: its cyclodimerization and its oxidative esterification. Keywords: Breslow intermediate; cathodic reduction; flow electrochemistry; N-heterocyclic carbene; oxidative esterification; Introduction Ionic liquids (ILs) are well

• can be modified by the presence of a base or by a single electron cathodic reduction of the C–H between nitrogen atoms of the imidazolium ring (Scheme 1), inducing the formation of a N-heterocyclic carbene (NHC) [7][8]. In recent years, NHCs have achieved great success: they have been frequently used

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

• ) from the reaction of dimethyl 2-(methylamino)benzoylphosphonate (70) and trimethyl phosphite at 105 °C through an ylide intermediate D. The ylide D was generated via deoxygenation of benzoylphosphonate 70 with trimethyl phosphite to form a carbene intermediate B, and trimethyl phosphite nucleophilic

• attacking to the carbene B followed by an intramolecular displacement. The yield was not reported (Scheme 13) [33]. Synthesis via P–C bond formation In 1979, Coppola at Sandoz, Inc. reported an alternative strategy for the synthesis of tricyclic γ-phosphonolactams 74, 78, and 81 from N-(3-chloropropyl)-2

• 105 via the copper-catalyzed intramolecular carbene aromatic C–H bond insertion (Scheme 20) [44]. This is an efficient synthetic strategy for 3-benzoyl-2-ethoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 106 through the formation of the C–C bond neighboring at the ring phosphorus atom. Synthesis

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• , yielding a reduced arylation product 77 [86][87]. Mechanistically, either diazo or carbene intermediates can be proposed, as Barluenga has outlined, and migration of the aryl group leads to an alkylboronic acid, which is hydrolyzed by protodeboronation, yielding the arylation product 77. A two-step flow

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• at the double bond underwent cyclization as the result of intramolecular interception of the rhodium carbene, which led to the formation of indolizine [6] or 2H-chromene [7] derivatives, respectively (Figure 1). At the same time, Rh2(esp)2-catalyzed reactions of DAS with nitriles and carbonyl

• analysis (see Supporting Information File 1). A plausible mechanism of the observed transformations of DAS (shown for 1a) is presented in Scheme 2. The initially formed rhodium carbene A undergoes 1,5-electrocyclization to form intermediate B which turns into indene C as the result of a 1,5-suprafacial

• hydrogen shift. Indene C can either convert into the final indene 3a via a slow 1,3-migration of the hydrogen atom, or is intercepted by carbene A with the formation of cyclopropane D. The relative rates of these competing processes likely determine the composition of the final product mixture. The

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• metal. Ruthenium complexes have astonishing characteristics such as high electron transfer ability, low redox potentials, high Lewis acidity, and greater stabilities of the reactive metallic species like oxometals, metallacycles, and metal carbene complexes [27]. The wide availability of highly reactive

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• causes the tautomerization of complex 5 [30] to zwitterionic carbene 6 which can now isomerize through the C–C bond rotation to the thermodynamically more stable palladium complex 7, followed by reductive elimination to enamide 3. A possible isomerization of enamides 2 or 3 in the presence of a catalyst

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• ][35][36]. In this context, Huang, Fu and co-workers reported carbene-catalyzed enantioselective formal [4 + 2] annulation reactions of β-silyl enones with enals and with active acetic esters (Scheme 1g) for the preparation of chiral organosilanes [34][35][36]. Very recently, during the final stage of

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• chiral N-triflylphosphoramide. Aza-Michael addition of primary amines to β-trifluromethyl-β-phenylnitroolefin catalyzed nitrogen heterocyclic carbene. Asymmetric aza-Michael additions of pyrroles to protected (E)-4-hydroxybut-2-enals. Asymmetric aza-Michael addition of purine bases to aliphatic α,β

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

• with high selectivity using this strategy. In these transformations, two Hg-carbene intermediates were proposed to be involved (Scheme 52). Mercury-catalyzed reactions were also well known for the formation of various complex scaffolds like tricyclic pyrazinones from the corresponding starting