Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• Conia-ene-type cyclization, classically considered as a reliable method for the construction of bridged bicyclic structures [41], was envisaged. However, using a gold(I) catalyst the desired 5-exo-dig cyclization failed and only a 6-endo-dig cyclization was observed. Thus, Hong et al. explored a Mn(III

• )-mediated radical cyclization, an approach which had been previously reported by Jia and co-workers during the synthesis of glaucocalyxin A [42]. After treatment with Mn(OAc)3, the desired 5-exo-dig cyclization product 77 was obtained in 43% yield as an E/Z mixture. The TMS group was removed under acidic

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• scavenger [37]. After 4 h, NMR analysis of the crude reaction mixture revealed high conversion of the starting material with the formation of the 6-endo-dig rearranged diene 2a and the parental regioisomer 2b in a 1:1 ratio. Noteworthy, this latter is formed by an initial 5-exo-dig cyclization step (entry 1

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

• [59]. The authors proposed a plausible catalytic cycle based on a series of mechanistic studies (Scheme 3). First, FeCl2 will react with the aryl Grignard reagent to form an aryliron complex 8 which can undergo a SET with the iodoalkane to yield the radical substrate 9. A 5-exo-dig cyclization will

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

• ). However, an iodonium ion 6 was formed as a key intermediate in I2-mediated aza-annulations. Subsequently, the iodonium ion 6 proceeds through a 6-endo-dig cyclization to form the 5-iodopyridine 3. On the other side, the iodonium ion 6 may undergo 5-exo-dig cyclization to yield the 2-acylpyrrole 4

• -promoted 5-exo-dig cyclization of imine to form a zwitter ion intermediate 45. In 2017, the Reddy group also reported a method for the construction of 2-carbonylpyrroles 46 through Au/Ag-catalyzed intramolecular oxidative aza-annulation of 1,3-enynyl azides 1 (Scheme 18) [63]. The method is very applicable

• derivatives and the other is 5-exo-dig cyclization to afford the pyrrole derivatives. Considering the good biological activities and the wide applicability in synthetic organic chemistry, biopharmaceuticals, and materials, it is desirable to develop more efficient methods for the synthesis of diverse

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• group participation for 5-exo-dig cyclization from 3 to 4. It was further hypothesized that the reaction continues through an α-iodo intermediate 6, a tautomer of 5, from which deiodination followed by tautomerization of 7 produces the final product 2. In the studies described herein, NMR experiments

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• again released into the system. The propargylamine formed went through 5-exo-dig cyclization to form IPs (Scheme 16). An unprecedented CuI-catalyzed two-component synthesis of isoxazolylimidazo[1,2-a]pyridines 49 was reported by the group of Rajanarendar under aerial conditions. Differently substituted

• sodium ascorbate (NaOAs) helped in the reduction of Cu(II) to Cu(I) which then reacted with the alkyne moiety. The species thus formed participated in the reaction by reacting with imine of aldehyde and amidine. The intermediate thus formed undergo 5-exo-dig cyclization and 1,3-H shift to form the final

• reaction mechanism comprises of an in situ generation of the imine from the aldehyde and 2-AP. Further, the addition of alkyne and activation by CuO(II)/Cu2O(I) yielded the A3-coupled propargyl amine [40]. Tautomerization/5-exo-dig cyclization led to the formation of the final product. The reaction enjoyed

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

• nucleophilic substitution of chlorine in the chloroethynylphosphonate to form ynamine intermediate A, isomerization of which provides ketenimine B. Further formation of the imine tautomer C enables an intramolecular 5-exo-dig cyclization to furnish the title [1,2,4]triazolo[4,3-a]pyridines (Scheme 6

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• alkyne functionality to form the intermediate 21. In the next step, a nucleophilic attack on the methyl group by iodide forms the product 19c. All cyclization reactions of 7b–d with iodine underwent a 6-endo-dig cyclization. No 5-exo-dig cyclization was observed. To address this issue we performed some

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• biologically important compounds. Keywords: 6-endo-dig cyclization; 5-exo-dig cyclization; N-heterocycles; N-propargylamines; thiazoles; Introduction Thiazoles are an important class of azole compounds that have attracted considerable attention due to the fact that they exhibit a wide variety of

• proposed by Balova et al. In their approach, a sequential cyclocondensation/5-exo-dig cyclization process between 2-amino-N-propargylanilines 4 and CS2 afforded heterocyclic systems of type 5. Isomerization of the latter compounds upon heating in the presence of KOH in ethanol gave the corresponding 2

• bridged bromonium ion intermediate A; ii) regioselective 5-exo-dig cyclization of intermediate A to give dihydrothiazole B; and iii) addition of a second bromine to the alkene moiety in intermediate B to provide the corresponding thiazole 44 (Scheme 11) [94]. Recently, Alhalib and Moran reported two

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• an FeCl3-catalyzed Kabachnik–Fields reaction of 2-alkynylbenzaldehydes 72, anilines 73, and phosphonates followed by a PdCl2-catalyzed 5-exo-dig cyclization (Scheme 18) [45]. The desired (2H-isoindol-1-yl)phosphonates 74 were obtained under optimized conditions (5 mol % of FeCl3, 5 mol % of PdCl2

• acetylenic aldehydes 102. The Kabachnik–Fields adducts of various carbocyclic acetylenic aldehydes 104 and 105 in the presence of AuBr3, PdCl2, AgOTf, AgNO3 or I+ underwent a 5-exo-dig cyclization to give dialkyl 1H-pyrrol-2-ylphosphonates 106. However, iodine-mediated cyclizations lead to pyrrol-1

• corresponding 1,2-dihydropyridin-2-ylphosphonates 111 in the presence of CF3SO3Ag, while in the presence of AuBr3, PdCl2 or I+, they undergo a 5-exo-dig cyclization to give dialkyl 1H-pyrrol-2-ylphosphonates 110 or 112 (Scheme 24). Other cyclization reactions of Kabachnik–Fields adducts into isoquinolone-1

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

• p-TsNCO 18 to generate the acyclic urea IV, and the alkyne moiety of IV coordinates to gold to form a new alkyne π-complex V. A 5-exo-dig cyclization by nucleophilic attack of the urea oxygen forms the vinylgold carbamimidinium ion VI (the minor 6-endo-dig 19 product is not shown), which undergoes

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• schisanwilsonene A (126, see Scheme 15), isolated from Schisandra wilsoniana [111], a plant used in traditional chinese medicine. Submission of 1,6-enyne 116 to cationic gold-catalyst 117 led to 5-exo-dig cyclization and intermediate formation of bridged bicycle 119. Subsequent 1,5-acyl-shift afforded

• apply the transition metal catalyzed 1,2-acyl shift with subsequent vinyl carbenoid formation. Propargylic acetate 251 (see Scheme 33) has been shown to undergo 5-exo-dig cyclization via 252 to give zwitterionic intermediate 253. A concomitant fragmentation reaction yielded vinyl-carbenoid 254. Uemura

Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• bonds. Taking advantage of the specificity of [IPrAuNCMe][SbF6] complexes to favor the 5-exo-dig cyclization over the 6-endo-dig pathway, we report a high yielding and efficient method to generate substituted polyaromatic heterocycles under remarkably mild reaction conditions. Keywords: catalysis

• benzothiophene 7 was isolated in 89% yield. The formation of this unforeseen product can be explained by the proposed mechanism illustrated in Scheme 2. The gold(I) complexation of alkyne 4 triggers the 5-exo-dig cyclization to produce intermediate 9. At this point, a nucleophilic addition of the thiophene unit

Sequential Au(I)-catalyzed reaction of water with o-acetylenyl-substituted phenyldiazoacetates

• Lei Zhou,
• Yizhou Liu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2011, 7, 631–637, doi:10.3762/bjoc.7.74

• complexes (PMe3)AuCl and (IPr)AuCl were examined (Table 1, entries 7 and 8). It was found that (IPr)AuCl was an efficient catalyst for both carbene transfer and cyclization. Product 2a from 6-endo-dig cyclization and product 3a from 5-exo-dig cyclization were both obtained in nearly equal amounts in

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

• this reaction, a 5-exo-dig cyclization of the β-lactam nitrogen to the Au-activated C–C triple bond is followed by heterolytic fragmentation of the amide bond to form a reactive acyl cation. While substrates with substituents at the alkyne terminus did not undergo this catalytic reaction, various