Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• of oxidizing agents, oxidizing systems, and radical initiators on a set of model molecules 2 (see Table 1) in a preliminary screening for suitable oxidants for the intramolecular ring-closure reaction. The set of model molecules 2 bears different benzylic N-containing functional groups, including

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• Michael-initiated ring closure cyclopropanation at the more electrophilic olefin. The α-keto cyclopropyl intermediate 53 was formed in 79% yield with a dr value of >20:1. Reducing the proportion of DMF to 5% with respect to THF in the reaction mixture was hypothesized as the key factor for maximizing the

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

• -) Hg(II)-salt-mediated cyclizations were also observed in the case of alkynes. Arylalkynes 72 were cyclized via Hg(II)-salt-induced reactions to form benzopyran derivatives 73 [73][74][75]. Interestingly in the case of 1-aryloxy-4-arylthio-2-butyne derivatives 74, selective ring closure on the oxygen

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• )-isomers by reaction initally with hydroxylamine followed by acetyl chloride (Scheme 3). The next step was the key photochemical ring closure to determine the scope and limitations of the novel phenanthridine-forming reaction from biaryl oximes (i.e., 14 → 15). Exposure of the substrates 14a–f to UV

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• as AlCl3, H2SO4, or H3PO4, which have generally corrosive properties, were used, in this study, an intramolecular ring closure reaction was carried out under easy operating conditions with an organic Brønsted acid catalyst with high yields. So, the xanthene synthesis with alkene activation was

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• Wittig reaction affording naphthalenes 144. Isomerization of compounds 144 produced substituted styrenes 145. With the styrenes 145 in hands, the authors employed the Grubbs II catalyst-promoted ring closure to obtain the benzo[a]anthracenes 146a (85% yield) and 146b (43% yield) [67]. Other procedures In

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• , indazole ring-closure [10][11]. For example, several reports have highlighted the use of N-alkyl or N-arylhydrazines in the regioselective synthesis of 1H-indazoles, from the corresponding ortho-haloaryl carbonyl or nitrile, in good to excellent yield (Scheme 1) [12][13][14]. Alternative strategies to

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• . In contrast to previous approaches, the azo cyclization (ring closure) was achieved via the oxidation of the bis-anilines 7 with mCPBA (≈60% yield). Among the nitrogen-bridged diazocines compounds 10a and 11c are water soluble and retained their high switching efficiency (≈70%) also in water. The

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• in determining ring closure either via path a or path b. In path a, the protonation of the imine nitrogen in 7a by the conjugate acid (+ BH) leads to an electrophilic aromatic substitution at the 3-position of the indole unit to form a carbon–carbon bond in the intermediate 8. A further proton

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• -hydroxybiguanide intermediate, and subsequent dimethylamine evolution. The synthesis of this oxadiazole was then optimized by using triethylamine and room temperature, which resulted in a 78% yield of the desired product (Scheme 19, bottom). Another interesting example of a ring closure by the intramolecular

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• -amino-1,3-diols, which underwent a regioselective ring closure with formaldehyde or benzaldehyde delivering pinane-condensed oxazolidines. During the preparation of 2-phenyliminooxazolidine, an interesting ring–ring tautomerism was observed in CDCl3. Keywords: 2-amino-1,2-diol; monoterpene; oxazolidin

• regioselectivity of the ring closure of the resulting 2-amino-1,3-diols to obtain promising 1,3-heterocycles. To reach our goal, (1S)-(−)-α-pinene (6) and (1R)-(−)-myrtenol (10), two naturally occurring monoterpenoids were selected as precursors, as both are commercially available, cheap starting materials

• regioselective ring closure resulting in 21A. The structure of 21A was determined by 1H (whereas the CH-OH gave a dublet in DMSO-d6 while the CH2-OH of 21B could be detected as triplet) and 2D NMR spectroscopic techniques (HMBC). It is important to mention that this regioselectivity is the opposite to that

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• synthesis of LNA involves the tosylation of a 4'-C-hydroxymethyl derivative, followed by a base-induced ring closure to afford the 2'-O,4'-C-linked bicyclic nucleoside derivative (Scheme 6) [127][128]. Incorporation of LNA into a variety of oligonucleotides with varying lengths and sequences has shown

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• consecutive ring closure yields the desired product 75 aided by the attack of nitrogen lone pair in Michael’s adduct C via a sequential ethanol elimination (E) from D followed by aerial oxidation of intermediate F. Another proposed mechanism follows the formation of imine derivative G produced by the reaction

• potential rearrangement explained the regioselectivity during ring closure as depicted in Scheme 44. Theoretically, two regioisomeric pairs of adenine (115, A) and isoadenine are possible (C, D) (Scheme 44). However, using the multicomponent approach one product, 4-amino-7-arylimidazo[1,2-a][1,3,5]triazines

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• ] with n-butyllithium in dry THF at −78 °C and subsequently with dichlorophenylphosphine resulted in ring closure, affording the desired product containing 6-phenyl-6H-benzo[f]naphtho[2,3-b]phosphoindole (2) in 52% yield via the 3,3′-dilithio-2,2′-binaphthyl intermediate. The chemical modification of the

• above. Conclusion In summary, a novel pentacyclic phosphole, 6-phenyl-6H-benzo[f]naphtho[2,3-b]phosphoindole, was prepared by performing the ring-closure reaction of 3,3′-dilithio-2,2′-binaphthyl with dichlorophenylphosphine. The obtained product was used as a key compound for the chemical modification

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• ), a single product was isolated from the reaction that, after careful elucidation (see Supporting Information File 1), was identified as the bicycle 17. This compound could potentially arise via an initial conversion to the dichloroalkyl cation 18, followed by a ring closure and elimination of HCl to

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• chiral mono-Boc-1,2-diamines and (dialkyl)malonyl dichloride via open diamide-bis(N-Boc-amino) intermediates (65–91%). Deprotection and ring closure with a second malonyl unit afforded the cyclam tetraamide precursors (80–95%). The new protocol allowed the preparation of the target cyclam derivatives (53

• reaction of the mono-Boc-protected diamine (A-Boc) followed by Boc deprotection with HCl, and final ring closure of diamide–diamine intermediate 1a with a second malonyl unit to give tetraamide product 2a (Scheme 1a). The equivalent ethyl-substituted cyclam 4a was prepared in comparable yield (63% over the

• -Boc-1,2-diamines and (dialkyl)malonyl dichloride. The four-step approach included ring closure of the initial open diamide–diamine intermediates 1 with a second malonyl unit, affording the cyclam tetraamides 2. The target cyclam derivatives 5 and 6 were obtained by optimized LiAlH4 reduction by AlCl3

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• of the base (Table 3, entries 8 and 9). For the present transformation, Hu and Guan already reported a similar type of ring closure of the substrate 3fa [30], which allowed the conversion to the phenolic product 5f as a result of the cyclization and was accompanied by deacetylation under the

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• piperidine derivatives 1 because of the accelerating effect of the nitrogen atom that stabilizes the oxyallyl cation intermediate 4 formed upon the ring closure. This was in analogy to that found for the classical Brønsted or Lewis acid-catalyzed Nazarov reaction involving N-heterocycles [27][28][29][30][31

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• step, an azide group was introduced to 10 by lithiation with n-BuLi followed by the reaction with tosyl azide giving azide 11 in an excellent yield of 92%. Thermally induced ring-closure under release of nitrogen and formation of a nitrene intermediate was achieved by refluxing azide 11 in

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• , we performed reactions of unsubstituted and substituted 2-thiouracils 1a–e with chloroethynylphosphonates 2a–c. We found that the reaction with 6-substituted 2-thiouracils bearing either methyl or phenyl groups occurred regioselectively with a N3 atom ring-closure to afford the 3-phosphonylated

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• in Figure 1). For these reasons, apart from the well-known dehydrative ring-closure of acyl-o-xenylamines in the presence of phosphorus oxychloride proposed by Morgan and Walls [16], several synthetic protocols for constructing the phenanthridine structure have been reported [17][18]. These include

• , among the others, the anionic ring-closure of 2-cyanobiaryls by using organometallic reagents [19][20], and an impressive number of transition-metal-catalyzed C(sp2)–C(sp2) cross-coupling processes [21][22][23]. In the last decade, however, photochemical reactions, especially those promoted by a

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• ][14][20][21]. The mechanism of the reaction is still under debate with two prevailing versions in the literature (Scheme 2) [16][17][22][23][24]. The first reaction pathway includes the formation of an N-acyliminium ion 15, followed by a ring closure through an enolate ion 16. The other mechanistic

• ring opening. In the case of anhydrides 6 and 7, a 6-exo-trig ring-closure reaction of the tautomer form 30a leads to the observed products 25 and 26, according to the plausible mechanistic suggestion presented in Scheme 7. In the case of compound 27 (X = direct bond), the reaction could be

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• -dihydro-1,3,5-triazine-2(1H)-thione (6za). However, no product was detected starting from paraformaldehyde and paraldehyde. Presumably, this result could be either due to the aliphatic aldehydes' lower reactivity with thiourea to generate the intermediate imines undergoing ring-closure and subsequent

• its ring closure product 7 (Scheme 5a). It is worth mentioning that reacting compound 7 with trimethyl orthoformate (1.0 equiv) under the optimized conditions for 5 h furnished product 6aa in only 35% yield (Scheme 5b). On the other hand, repeating the same reaction in the presence of thiourea (1.0

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• cyclopropylcarbinyl radical 5. Then, the radical 5 opens to form the homoallylic radical 6, followed by the addition of olefins to this radical form the 5-hexenyl radical 7. The ring closure of the radical 7 and the elimination of a thiyl radical furnishes the final product 9. When it came to annulations of complex

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• strongly favored over the ring closure between the thiolate and the 2-position, since the SN2 displacement of a mesylate leaving group adjacent to the anomeric center is known to be restricted [50] (Scheme 20). The same group synthesized a thietane-fused gulopyranoside starting from methyl 4,6-O