N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• sulfenylation of yne-tethered ynamide 147 with N-thiosuccinimides 1 was possible in the presence of only methanesulfonic acid in dichloromethane at room temperature (Scheme 63) [93]. The electrophilic activation of propargylalkyne 147 generated in situ a sulfonium cation 1-I. Afterwards, 6-endo-dig cyclization

• conversion of 1-I to 2-II was confirmed by mechanistic studies due to the stability of the benzyl carbocation, followed by 6-endo-dig cyclization. In this method, toxic transition metal catalysts, oxidants, or bases are not used, which made it economically and environmentally reliable. In 2023, Gao et al

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

•  56B) [103]. These complex natural compounds exhibit strong pharmacological activities like anti-inflammatory, antituberculosis, analgesic properties, etc. The key reaction steps included a highly stereoselective gold-catalyzed or thermally activated Cope rearrangement and a gold-catalyzed 6-endo-dig

• cyclization. The chiral starting material was prepared by an asymmetric Cu-catalyzed tandem conjugate addition/acylation sequence using ethyl cyanoacetate (Mander’s reagent) as a trapping agent (Scheme 56A). Activation of the zinc enolate by MeLi was necessary, but with optimum reaction conditions the authors

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

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• the electron-donating phenyl ring enabled the coordination of the alkyne with the Au+ complex in the α-position, which promoted the silyl ether to attack the β-position of the alkyne to promote a 6-endo-dig cyclization. Next, compound 11 was subjected to a solution of tetrabutylammonium fluoride (TBAF

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

• -annulation of (E)-2-en-4-ynyl azides 1 was considered to involve 6-endo-dig cyclization to give a corresponding N-N2-substituted 1,2-dihydropyridine silver salt 5. This was protonated by TFA and the following species neutralized by base to provide a final 3,6-disubstituted pyridine product 2 (Scheme 2

• ). 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

• functionalizations of pyrrole derivatives, such as iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, and alkylation. The proposed mechanism generally involves two kinds of intramolecular cyclizations: one is 6-endo-dig cyclization to promote the formation of pyridine ring

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

• -endo-dig cyclization would result in diketone 18. Significantly, the iodine-mediated hydration of all substrates 11 that were studied gave rise to one type of product, 15 (Scheme 3). This indicated that the reaction with alkyl-capped, internal alkynes occurred exclusively through the 5-exo-dig route, a

• , internal alkynes results in a mixture of regioisomers [20][23][24]. Moreover, per Baldwin’s rules, with neighboring group participation, a 5-exo-dig (via 13 and 14) or 6-endo-dig pathway (via 16 and 17), or both, are possible outcomes for such alkynes [25]. The 5-exo-dig route would provide 15, while the 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

• by a copper-catalyzed cross-coupling reaction. Nucleophilic cyclization of N-alkyne-substituted methyl 1H-pyrrole-2-carboxylates with hydrazine afforded the 6-exo-dig/6-endo-dig cyclization products depending on the electronic nature of the substituents attached to the alkyne. On the other hand

• , cyclization of N-alkyne-substituted methyl 1H-pyrrole-2-carboxylates with iodine only resulted in the formation of the 6-endo-dig cyclization product regardless of the substitution of the alkyne functionality. Keywords: alkyne cyclization; pyrrole; pyrrolooxazinone; pyrrolopyrazinone; pyrrolotriazinone

• takes place with the terminal nitrogen atom forming a six-membered ring. Moreover, the n-butyl-substituted alkyne carbon atom undergoes a reaction to form 6-endo-dig cyclization product 12d. We assume that an allenic intermediate 17 (Figure 6) formed during the reaction is responsible for exclusive

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

• shown in Scheme 15 the target 2-phenoxy-substituted thiazolidine 51 was obtained in a yield of 54% along with the product originating from a 6-endo-dig cyclization [97]. Recently, Foroumadi and co-workers studied the possibility of synthesizing thiazole derivatives from N-propargylthioureas through a

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

• -ylphosphonates bearing a carbonyl (107) or 1-iodoalkenyl substituent (108) depending on the substituent R. In contrast, electron-deficient heterocycles 113 and 114 in the presence of CuI reacted through a tandem imine formation–6-endo-dig cyclization to give the corresponding 1,2-dihydropyridin-2-ylphosphonates

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

• undergoes a silver-catalyzed 6-endo-dig cyclization, thus giving rise to a key iminium intermediate suitable to react with a third nucleophilic component (Nu in Scheme 18). In these reactions the imine acts as a nucleophile and the silver serves as a π-philic catalyst enhancing the reactivity of the triple

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• reaction [15], a 6-endo-dig cyclization of heteroaryl esters to alkynes [16], or a Pd(II)-mediated cyclization of o-allylbenzaldehydes [17]. Salvinorin A, a natural product isolated from the hallucinogenic sage Salvia divinorum, which also contains a saturated isocoumarin ring, has been synthesized [18

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

• represented as two resonance structures highlighting both the carbocation or carbenoid nature of this intermediate (Scheme 2). Results and Discussion As established in Scheme 2, we were intrigued by the possibility that o-(alkynyl)-(3-methylbut-2-enyl)benzenes 1 could undergo a 6-endo-dig cyclization in the

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• °C, a series of 6-methyl-3-substituted 3,4-dihydro-2H-1,3-oxazin-2-ones 4a–j were exclusively formed (Scheme 2) [61][62][63][64][65][66][67][68]. The observed regioselectivity is worthy of note, because under our reaction conditions only 1,3-oxazinan-2-ones 3 (arising from 6-endo-dig cyclization) or

• vacant d atomic orbital of the gold atom in INT1-B [79]. Both complexes can undergo the corresponding oxyauration cyclization reaction. Thus, INT1-A is converted into INT2-A in a slightly exergonic process (ΔGR,298 = −0.4 kcal/mol) through the saddle point TS1-A, which is associated with the 6-endo-dig

• cyclization. Similarly, INT1-B is transformed into INT2-B in a slightly endergonic process (ΔGR,298 = +0.9 kcal/mol) via TS1-B, associated with the 6-exo-dig cyclization reaction. From the data in Figure 1, it becomes obvious that the 6-endo-dig transformation is kinetically favored over the 6-exo-dig

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• , pyrrolidine and salicylaldehydes led to a concomitant cycloisomerization followed by hydrolysis of the resultant vinyl ether to afford coumarins in a cascade process. The reaction proceeded through exclusive 6-endo-dig cyclization and is compatible with halo and keto groups giving coumarins in good to

• catalyst. That, after consecutive A3 coupling, cycloisomerization and hydrolysis of the resultant vinyl ether intermediate, should produce coumarins (Scheme 1, (d)). The reason for the selective 6-endo-dig cyclization of such a cooperative-catalysis reaction has been well documented through DFT

Dipyrazolo[1,5-a:4',3'-c]pyridines – a new heterocyclic system accessed via multicomponent reaction

• Wolfgang Holzer,
• Gytė Vilkauskaitė,
• Eglė Arbačiauskienė and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2012, 8, 2223–2229, doi:10.3762/bjoc.8.251

• once: condensation of 1a with p-toluenesulfonyl hydrazide and subsequent 6-endo-dig cyclization [28] of intermediate 2a in the presence of silver triflate produced p-toluenesulfonylazamide 3a in 91% yield (Scheme 1). The reaction of intermediate 3a with CH-acidic aldehydes or ketones in the presence of

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• corresponding pyridine 6a (81%) was obtained on a gram scale. With a chelation-stabilized vinyllithium being formed after the anionic 6-endo-dig cyclization, we next considered the possibility of trapping this vinyllithium with an electrophile, which might allow the introduction of an additional C-2 substituent

• pyridine ring. To our delight, treatment of 14 under our optimized conditions (treatment with s-butyllithium and tetramethylethylenediamine in THF at −78 °C for one hour followed by addition of acetic acid and o-chloranil) smoothly promoted the anionic 6-endo-dig cyclization to the 3,5-disubstituted

One-pot Diels–Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework

• Boubacar Sow,
• Gabriel Bellavance,
• Francis Barabé and
• Louis Barriault

Beilstein J. Org. Chem. 2011, 7, 1007–1013, doi:10.3762/bjoc.7.114

• ) are underway and will be reported in due course. Structures of naturally occurring PPAPs. Gold(I)-catalyzed 6-endo-dig cyclization. Synthesis of papuaforin A core 4. Proposed domino Diels–Alder reaction/gold(I)-catalyzed cyclization. One-pot Diels–Alder cycloaddition/gold(I) catalyzed carbocyclization

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

• phenylacetylene the ratio of vinyl ether 47 to ketal 48 can be controlled by the choice of catalyst (Scheme 8). The gold-catalyzed intramolecular 6-endo-dig cyclization of β-hydroxy-α,α-difluoroynones 50 under mild conditions has been developed (Scheme 9) [34]. The result indicated that gold catalysis is

• compatible with electrophilic fluorinating reagents. Furthermore, it is possible to couple the 6-endo-dig cyclization with iodination and bromination of the presumed vinyl–gold intermediate. However, attempted alkoxychlorination with N-chlorosuccinimide failed. Intermolecular hydroalkoxylation of non

• a 6-endo-dig cyclization to give 4H-pyrans 82. By contrast, alkylidene/benzylidene-substituted tetrahydrofuranyl ethers 80 are formed in a tandem nucleophilic addition/cycloisomerization in alcoholic solvents [44]. Similarly, Belot et al. reported a gold-catalyzed cyclization which led to nitro

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

• vinyl alkynyl cyclopropanes 85 to give arenes 86, 87 and cycloheptatriene 88 derivatives through 5-endo-dig and 6-endo-dig cyclization reactions, respectively, under careful control of the reaction conditions (Scheme 25) [58]. A mechanistic rationale for these transformations is shown in Scheme 26

• cations 90 and 91 by delocalization of the positive charge onto gold. The aromatic intermediate 92 is probably converted, via 93, into 86 and 87 by E1 and SN1 mechanisms, respectively. When secondary esters are employed, 6-endo-dig cyclization occurs to give 94, which forms the cycloheptatriene derivate

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

• the reaction of diazo compounds 1e and 1f with water, only 6-endo-dig cyclization products 2e and 2f were isolated as the sole product in yields of 69% and 75%, respectively. Functional groups such as bromo and hydroxy groups were tolerated under the present catalytic systems. When diazo compound 1g