Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• (Scheme 16) [33]. The reaction, which occurs with formation of C–C, C–N and C–O bonds, involves a nucleophilic addition of the activated alkyne XIV to the in situ-generated iminium ion XV, followed by cyclization to form a quinoxalin-2-one intermediate XVI. A subsequent 5-endo-dig cyclization involving

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

• catalyst C43 leads to allene intermediate Int-41. The enantiospecific intramolecular enamine–aldol cyclization and further dehydration provide the enantioenriched heterobiaryl product 189. The 5-endo-dig-cyclization reaction of N-pyrroloalkynylanilines 190 catalyzed by SPINOL-derived CPA C44 was utilized

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

• moiety of the organocatalyst, while the azadiene is activated by hydrogen bonding with the squaramide moiety. Then, the enolate attacks the Re face of the azadiene through a Michael addition which leads to intermediate A. Next, an intramolecular 5-endo-dig cyclization takes place by the attack of the

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• to obtain the 1,5-disubstituted tetrazole-alkyne 19 is well-documented and hence, it is not herein described in detail [1][26][31]. Thus, based on Pal and co-workers’ proposal [32][33], the second process involves two catalytic cycles: 1) a Sonogashira coupling, and 2) a 5-endo-dig cyclization. The

• , an intramolecular cyclization takes place, facilitated by CuI. This step involves a 5-endo-dig cyclization, where the negatively nitrogen atom of the sulfonamide 25 attacks intramolecularly to yield the intermediate 26. The final product is formed when iodide is regenerated as CuI, allowing it to re

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• intramolecular nucleophilic addition of the secondary amines to the internal alkyne was expected to occur, forming a new pyrrole ring in 93 through a 5-endo-dig cyclization. Unexpectedly, they observed the generation of 95 with a new pyridine ring. The authors proposed that the benzylamine unit of 92 was

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

• %). Under these conditions, the 5-endo-dig cyclization leading to the target spirobutenolide 2a proceeded rather slowly (about 25% conversion per day). However, an attempt to accelerate the reaction by using a stronger base (DBU) resulted in side processes with the formation of unwanted impurities, whereas

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• . This synthetic protocol offers increased functional group tolerance and moderate to good yields of the products by the coupling of various functional group-substituted acetylenes with o-iodophenol. The proposed mechanistic study involves a Sonogashira coupling followed by a 5-endo-dig cyclization

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• standard conditions. The proposed catalytic cycle included aza-Michael addition of arylamines, Lewis acid copper(II)-catalyzed intramolecular 5-endo-dig cyclization, protonation, and oxidation to provide the final products, tetrasubstituted pyrroles 39. The introduction of a trifluoromethyl group into

• products 52 were obtained efficiently through the cascade reactions of enynals 51, primary amines, aliphatic isocyanides, and trimethylsilyl azide. The following reaction involves Ag-catalyzed intramolecular 5-endo-dig cyclization and base (DMAP)-promoted oxidative isomerization. The presence of DMAP is

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• when using C,N-, N,S- and N,N-dinucleophiles. It is characterized by a selective 5-endo-dig cyclization to the corresponding five-membered rings. The obtained new compounds are of special interest due to the practical utility of the formed fused heterocycles, such as indoles [1], thiazolo[2,3-b][1,3,4

• ]thiadiazole [2], and benzo[4,5]imidazo[2,1-b]thiazole [3], as well as due to the simultaneous presence of a biologically active phosphorus function in the molecules. Recently, we have shown that the reaction of chloroethynylphosphonates with 2-aminopyridines proceeds through a 5-endo-dig cyclization to form

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• cyclization of readily available 4-alkynyl-3-hydroxy-1H-pyrazoles can be used as an efficient method to access many novel 2,5-disubstituted 2H-furo[2,3-c]pyrazoles. Keywords: 5-endo-dig cyclization; 2H-furo[2,3-c]pyrazole; pyrazole; silver(I) catalyst; Sonogashira coupling; Introduction Heterocyclic ring

• construction of the 2H-furo[2,3-c]pyrazole ring system by a Sonogashira-type alkynylation of 4-iodopyrazol-3-ol and subsequent intramolecular 5-endo-dig cyclization of the obtained hydroxyalkynyl substrate mediated by a Ag(I) catalyst. Results and Discussion The synthetic strategy designed to construct the 2H

•  1, entry 1). The formation through a 5-endo-dig cyclization of some amount of compound 4a was detected by LC–MS measurements only when the reaction mixture contained Cs2CO3 as a base and was heated at 120 °C for 4 days (Table 1, entry 2). Surprisingly, when K2CO3 was used instead of Cs2CO3, the

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• cyclization product 7a and not the 4-exo-dig-cyclization compound 7a' (Scheme 3). We rationalized, as per Baldwin’s rules, that the 5-endo-dig cyclization of a 1,4-Michael addition was more favorable than the 4-exo-dig-cyclization [50][51]. The structure of compound 7a was definitively confirmed by X-ray

• the exception of AgOTf/DCM (Table 1, entry 6), led to the formation of the desired 5-endo-dig cyclization product 7a and none of the 4-exo-dig cyclization product 7a' was observed. In Table 1, entries 2–5 and 7 show moderate product yields whereas entries 1 and 8 show superior yields of >80%. With the

• spirocyclic 2-oxindoles. Post-Ugi-4CR/transamidation/cyclization sequence. Base-promoted intramolecular 5-endo-dig cyclization. Reaction scope with varying combinations of substrates. Synthesis of 5-chloro-1'-phenylspiro[indoline-3,2'-pyrrolidine]-2,5'-dione (8a). Method applicability for the one-pot

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• %) and the optimal temperature was 60 °C. The aryl moieties on alkynes and glyoxals tolerated the presence of ED and EW groups. The proposed mechanism implied the coupling among reaction partners to give an α-amino-β,γ-ynone intermediate I capable to undergo a 5-endo-dig cyclization by an intramolecular

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

• as two carbon cycloaddition partners and IPrAuNTf2 as catalyst [Au2, IPr = bis(2,6-diisopropylphenyl)], is shown in Scheme 4. The reaction is initiated by a 5-endo-dig cyclization of the carbonyl oxygen onto the Au-activated C–C triple bond, giving rise to the oxocarbenium intermediate VIII. The

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

• involves mild conditions and short reaction times. 3.3 Amides, sulfamides and ureas as nucleophiles Using AuPPh3Cl/Ag2CO3-catalyzed 5-endo-dig cyclization in water under microwave irradiation, our group developed a fast and green route to prepare indole-1-carboxamides 137 from N'-substituted N-(2

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• . Cyclopropanes 85a are generated in situ by intermolecular cyclopropanation of enyne 84 and a carbene resulting from the rearrangement of propargyl ester 83. When tertiary propargyl esters are used, the 5-endo-dig cyclization generates the carbocation 89. Migration of the pivaloyloxy group affords the allylic

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• substituent at the alkyne terminus. An initial 5-endo-dig cyclization of the lactam nitrogen to the metal-activated alkyne was proposed, followed by the fragmentation of the lactam amide bond and the formation of an acyl cation. The above chemistry was extended to non-aromatic substrates, providing a new

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• cyclocondensation of alkyne diols to give substituted furans (Scheme 3, Reaction 3) [35]. Our objective, laid out in Scheme 4, was to initiate cycloisomerization with a 5-endo-dig cyclization of the homopropargyl alcohol 6, followed by 5-exo-trig cyclization onto the resulting dihydrofuran, whilst avoiding

• methanol. Path a, which corresponds roughly to our original experimental designs, involves initial gold-catalyzed 5-endo-dig cyclization to dihydrofuran 18. Once the regiochemistry is established, any number of condensation pathways would lead to spiroketal 17. For example, protonation of the enol ether

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• construction of the benzofuran moiety from intermediate 5. For the construction of 2-substituted benzofurans, the most widely used approach involves the palladium-catalyzed heteroannulation of 2-halophenols with a terminal alkyne via a tandem Sonogashira coupling-5-endo-dig-cyclization, largely based on the