Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• coupling with gold(I)-mediated 6-endo cyclization streamlines the rapid and modular assembly of the substructure of bis-tetrahydroisoquinoline (THIQ) alkaloids. The design of the key synthetic intermediate bearing a 2,3-diaminobenzofuran moiety allows both gold(I)-mediated regiocontrolled 6-endo

• , followed by gold(I)-promoted 6-endo cyclization between the internal alkyne and 2,3-diaminobenzofuran moieties with spontaneous transformations into the left THIQ segment in 14. Results and Discussion As outlined in our modular synthetic approach (Scheme 1c), the copper(I)-catalyzed three-component

• form 2,3-diaminobenzofuran 11. The subsequent gold(I)-mediated intramolecular 6-endo hydroamination of 11 would construct the left THIQ ring to furnish the substructure 14 of saframycin A (1) [47][48][49][50][51]. To selectively promote the desired 6-endo cyclization (11 → 12) over the competing 5-exo

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

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• unit cyclized exclusively in the 5-exo-trig mode and provided the pyrrolidone 12f with a quaternary center at C4 in moderate yield and similar diastereoselectivity as for 12a–d (Table 3, entry 7); a product of potentially competing 6-endo cyclization was not detected. Amides 9g,k with trisubstituted

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• (sp3)–H bond α to a tertiary amine nitrogen through [1,5]-hydride shift (rac-6→A) (Scheme 1) to afford the zwitterionic intermediate A and (2) subsequent 6-endo cyclization (A→rac-7a,b). The stereoselective version of “tert-amino effect” induced cyclization using chiral metal-catalyzed [12][13][14][15

• ]-hydride shift with participation of the benzylic hydrogen to result in the zwitterionic iminium ion intermediates A. The 6-endo cyclization of this intermediate gave rac-trans-7a,b with high diastereoselectivity, which was governed by the C-2 chirality center of intermediate A. In contrast to the domino

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• intermediate. The competing 6-endo cyclization mode and formation of distonic cation radical 9 ultimately provides access to the more stabilized cation radical 10, which undergoes oxidative cleavage to afford the corresponding α-allyl ketones (Scheme 4). In the absence of the geminal dimethyl group (2r, 2s

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 a third nucleophilic reagent (Nu) in the presence of a silver triflate catalyst (Scheme 19). All reported reactions share the same key iminium intermediate 28 generated in situ from imine 27 via a silver triflate catalyzed 6-endo cyclization, but differ in the third reaction partner (Scheme 20 and

• carbene. (Scheme 24) [67]. As mentioned above, N’-(2-alkynylbenzylidene)hydrazide 42 could easily be transformed to isoquinolinium-2-ylamide 43 by a 6-endo-cyclization in the presence of silver triflate catalyst. Meanwhile, the in situ formed homoenolate 45 (derived from α,β-unsaturated aldehydes 44 in

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• external nucleophiles undergo skeletal rearrangements to afford products such as III (single cleavage) [14]. However, reactions of II with alcohols or water give the corresponding products of alkoxy(hydroxy)cyclization IV [15][16][17] (Scheme 1). The less common 6-endo cyclization via metal carbenes V was

• to cyclopenta[b]naphthalenes VIII or, alternatively, a 6-endo cyclization to bicyclo[4.1.0]hept-4-enes like IX [18][19] (Scheme 1). In the case that MeOH is present a 5-exo methoxycyclization is observed, e.g., in the formation of X resembling the behaviour of I [16][20]. In addition, the gold

• with some other unidentified minor products. The two major products resulted to be inseparable by column chromatography and were isolated in 68% overall yield. It is remarkable that compound 2a, derived from a 6-endo cyclization and further proton elimination from intermediate resonance structures 4a

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• the addition is about as fast as the 6-endo cyclization of the hexenyl radical. Such reactions and other even slower cyclizations are well documented in titanocene mediated and catalyzed radical processes [61][62][63][64][65][66][67][68][69]. Therefore, the relatively high computational rate constant

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• the desired 4,4-spirocyclic oxindole γ-lactam 2f in 62% yield (Table 1, entry 6). On the other hand, the reaction of 1g gave the cyclized product in only a trace amount, and instead THF-incorporating 6-endo cyclization product 3 was obtained in 60% yield (Table 1, entry 7) [28]. Based on the known

• indoline γ-lactam 2f and a (TMS)3Si radical, thus creating a radical chain. On the other hand, the unusual formation of THF-incorporating lactam 3 from 1g may be rationalized by the consecutive 6-endo cyclization of E and β-elimination of an azidyl radical from the resulting F, to give 2-methylene lactam G

• in the contrasting results of acrylic amides 1f and 1g, to cause the requisite 5-exo cyclization of aryl radicals onto allylic azide in preference to the 6-endo cyclization, the angle compression caused by the substitution on the nitrogen has to be considered carefully. Nevertheless, our method can

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• Pictet–Spengler reaction catalyzed by cyanuric chloride (trichloro-1,3,5-triazine, TCT) is described. The 6-endo cyclization of tryptophan/tryptamine and modified Pictet–Spengler substrates with both electron-withdrawing and electron-donating aldehydes was carried out by using a catalytic amount of TCT

• (10 mol %) in DMSO under a nitrogen atmosphere. TCT catalyzed the Pictet–Spengler reaction involving electron-donating aldehydes in excellent yield. Thus, it has a distinct advantage over the existing methodologies where electron-donating aldehydes failed to undergo 6-endo cyclization. Our methodology

• provided broad substrate scope and diversity. This is indeed the first report of the use of TCT as a catalyst for the Pictet–Spengler reaction. Keywords: β-carboline; cyanuric chloride; 6-endo cyclization; Pictet–Spengler; TCT; Introduction The Pictet–Spengler reaction is an important class of name

Engineering of indole-based tethered biheterocyclic alkaloid meridianin into β-carboline-derived tetracyclic polyheterocycles via amino functionalization/6-endo cationic π-cyclization

• Piyush K. Agarwal,
• Meena D. Dathi,
• Mohammad Saifuddin and
• Bijoy Kundu

Beilstein J. Org. Chem. 2012, 8, 1901–1908, doi:10.3762/bjoc.8.220

• ). After successfully accomplishing the synthesis of amino-functionalized meridianins 2, we next examined their abilities to undergo 6-endo cyclization in the presence of aldehydes (Scheme 4). Initially we treated the substrate 2a with 4-chlorobenzaldehyde using a variety of traditional Pictet–Spengler

• considered to be an important factor [67] in promoting cationic π-cyclization by enhancing the electrophilicity of the imines, we envisaged that employing stronger acids may facilitate 6-endo cyclization. Accordingly, the amine 2a was treated with 4-chlorobenzaldehyde by using strong Brønsted acids, such as

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

• AuNTf2 led to 6-endo cyclization [133]. The methodology was applied in a direct synthesis of the relevant 6,9-dihydropyrido[1,2-a]-1H-indole core 250. A similar strategy was adopted by Ferrer and co-workers [134], who prepared the 1H-azocino[5,4-b]indole skeleton 252 of the lundurines by the 8-endo-dig

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• stabilizing substituent at C2 were found to undergo a cascade consisting of 6-endo cyclization and a subsequent pinacol-type shift [37][98]. Since the 5-endo cyclizations discussed above most likely proceed through cationic intermediates, external nucleophiles were shown to trap these intermediates at C1 in

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

• ring expansion which involves the cleavage of the bridging C–C bond and a formal [1,2]-alkynyl shift. A mixture of regioisomers resulted due to an unexpected equilibration of the starting material 53 to 53' via 6-endo cyclization of the olefin with the gold-activated alkyne. 3 Ring expansions of

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

• blocking one of the alcohols as an acetal (the alcohol that otherwise could undergo either 5-exo or 6-endo cyclization [9][13][36]), thus favoring the initial 5-endo cyclization of the other. In this way we aimed to ensure that the desired regioisomer could form, with the expectation of acetal hydrolysis

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals

• Mohan Mahesh,
• John A. Murphy,
• Franck LeStrat and
• Hans Peter Wessel

Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1

• TDAE to the arenediazonium salt 62 afforded the aryl radical 67, with release of molecular nitrogen. The aryl radical 67 would be expected [3][11][70] to cyclise onto the aryl ring A either through 5-exo or 6-endo cyclization. The radicals 68 and 69 could interconvert. Alternatively, aryl radical 67