Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• substitution pattern, it requires a para-substituted ester as a directing group. The strategy furthermore cannot access 5H-dibenzo[b,f]azepines 1a as the ethylene bridge would cross react with the brominating agent [55][56]. N-Aryl and N-alkyldihydropyridobenzazepines 75 and 76 were synthesised by Tsoung et al

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• closely linked to the substitution pattern of the cyclopropane unit [2]. The prevalence of the biologically active cyclopropyl derivatives, either isolated from natural sources or rationally designed as pharmaceutical agents, has inspired chemists to find efficient methods for their preparation. Among

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• be shifted to the 1,4-addition producing a cyclopentene product leading to the conclusion that the substitution pattern on the boronate ester played a significant role in the selectivity between 1,6-addition and 1,4-addition. The mechanism proposed by the authors initially begins in the same manner

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• . The substitution pattern on the aromatic ring did not affect the reaction efficiency, the meta-substituted derivative 2e as well as the ortho-substituted derivative 2f were obtained in high yields (70% and 63% yields, respectively). It should be noted that the presence of ortho-substituents on the

• , from 52 to 91% yields). The substitution pattern of the aromatic ring had no impact on the outcome of the reaction as illustrated with substrates substituted by a methyl group (7b, 7d, and 7f) at the para-, meta- and ortho-positions, which were readily functionalized in 71%, 84% and 78% yields

• (CH3CN)3](SbF6)2 and N-trifluoromethylthiodibenzenesulfonimide VII as electrophilic SCF3 source (Scheme 12) [125]. Under these reaction conditions, 2-arylpyridines (9 examples, up to 94% yield) or 6-arylpurines (10 examples, up to 72% yield) were ortho-trifluoromethylthiolated. The substitution pattern

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• enzyme. Therefore, the next efforts should be focused on the identification of a novel N-substitution pattern of the DIM skeleton that would have more beneficial effects on the inhibition profile. Natural iminosugars (1,4-dideoxy-1,4-imino-ᴅ-mannitol (DIM) and swainsonine) and selected examples of

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• substituents in the one-pot reaction and showed that regardless of the substitution pattern, the reactions lead to the stereoselective formation (≥95% (2E,4E)) of the respective dienones under mild conditions. It was found that enynes with alkyl chains gave higher yields than the corresponding aryl-substituted

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• with the generated styrene in the reaction mixture (Scheme 18) [42]. One year later, the same group investigated the influence of the double bond geometry and the substitution pattern on the alkene. The results indicated that the double bond geometry plays a moderate role, while the bulkiness of the R

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• ) and in the substitution pattern of the macrocycle (R = H or iPr in the 3,5-positions of the phenylene linkers, for 56 or 57; see Figure 14). These heterobifunctional chiral catalysts were studied for the asymmetric Michael addition of malonic acid diethyl ester (59) to cinnamaldehydes 58. While the

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

• , lead us to believe that the substitution pattern is what determines the efficiency of the reaction rather than which of both rings the substituents are connected to. Surprisingly, fluorenone 10c was isolated in an excellent yield (92%). Based on these datapoints, no clear conclusion can be drawn as to

• ). Electronic effects propagated by substituents were observed to have an influence on the reaction. In general, electron-withdrawing groups on the radical accepting arene had adverse effects, while electron donating groups, depending on the substitution pattern, had either a positive or negative effect of

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• the substitution pattern of the azulene units on this behavior. The polymer containing entirely 1,3-substituted azulene, 117, exhibited a strong fluorescence at 420 nm in the protonated state and the attenuation of the fluorescence signals took place with the increasing population of 4,7-disubstitued

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• for the introduction of unnatural modifications. However, the control over the length and substitution pattern remains poor. To ensure good regio- and stereoselectivity, the starting material, often a polycyclic compound, has to be designed with suitable protecting groups (PGs). These structures can

• compounds with well-defined length and substitution pattern (Figure 1C), but requires a substantial synthetic effort. For this reason, only few examples of long polysaccharides prepared by chemical synthesis are available. Properly designed building blocks (BBs) are needed, often prepared following numerous

• towards the synthesis of well-defined polysaccharides, with particular focus on how to control the length and the substitution pattern. Each section describes a class of polysaccharides based on a particular monosaccharide backbone (Figure 2). For each class, we discuss the specific challenges associated

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• observed at the Dha-3 part and, according to the substitution pattern from the coupling partner, a higher preference for the substitution at the Dha-1 (product A) over the Dha-2 (product B) site was also observed (Scheme 38B), characterizing an excellent and valuable regio- and diastereoselectivity. In the

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• chemistry can produce any substitution pattern there are few unsymmetrical [2.2]metaparacyclophanes (3) and only one X-ray crystallographic structure found in the CCDC database, and this is a triple-layered cyclophane [44]. We have been interested in the formation of substituted [2.2]paracyclophanes for a

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

•  2). As expected, we observed that the initially formed cis-isomer of 14af turned gradually to trans-14af and finally reached 1:99 after 2 hours (for further details, see Supporting Information File 1). To further expand the substitution pattern, we then tried the reaction of 13a with allysilane as a

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• complexes rather than direct interactions and alkyl moieties form a plethora of halogen···hydrogen interactions. Additionally, the substitution pattern greatly affects the overall conformation. By comparing the DFT calculated geometries with crystal structures we have found that DFT is a good approximation

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

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• , MG, Brazil 10.3762/bjoc.17.66 Abstract Desulfonylative alkylation of N-tosyl-1,2,3-triazoles under metal-free conditions leading to β-triazolylenones is reported here. The present study encompasses the synthesis of triazoles with a new substitution pattern in a single step from cyclic 1,3-dicarbonyl

• efficient synthesis of triazoles with different substitution pattern. One important methodology developed by the Sakai group involved the reaction of α,α-dichloroketone, tosyl hydrazide and primary amine [20]. However, in this case, the unstable α,α-dichlorohydrazone intermediate had to be isolated which

• paved the way for further modification of the protocol (Scheme 1c). Direct functionalization of triazoles is an alternative strategy to access triazoles with the desired substitution pattern. However, such approaches are complicated by a low energy barrier between the N1 and N2 tautomers in solution

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• analysis. This is similar to the previously observed substitution pattern in SNAr reactions of 2,6-bistriazolylpurine derivatives with simple N- and S-nucleophiles. Experimental General information Commercially available reagents were used as received. The reactions and the purity of the synthesized

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• 42% yield along with the corresponding dehydrated alkenylpyridine compound 6d in 16% yield (Table 3, entry 3). Different from the 2,6-substitution pattern, 3,5-dimethylpyridine (1e) was also tested under standard reaction conditions upon increasing the reaction time to 48 h, which did not furnish the

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• , optical, and biological properties upon a careful selection of the substitution pattern [9], continually encouraged the scientific community to search for new powerful representatives and to elaborate advantageous synthetic protocols. Under chemical, biochemical, or electrochemical conditions the

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• the presence of AgNO3 the 3’-O-TBDMS derivative was always obtained in excess over the 2’-isomer. The differences in the reactivity of the 2’- and 3’-OH groups mirror the impact of the sugar conformation, which is dependent on the substitution pattern. Ribonucleosides favor the 3’-endo conformation

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• -phenyl migration have been found to be subtly dependent on the substitution pattern. For instance, the rate of 1,2-AS in 3b has been found to be much faster than the one of 3e. It is probably due to the extra hindrance of gem-dimethyl substituents at C-7 position in the latter. Moreover, only 1,2-AS

Synthesis of 6,13-difluoropentacene

• Matthias W. Tripp and
• Ulrich Koert

Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181

• -positions resulted in a larger HOMO–LUMO gap compared to PEN, while PFP showed a smaller gap than PEN. Another example for a partially fluorinated pentacene is the F6PEN 4 [9]. Its unilateral substitution pattern leads to a disctinct electronic structure and a criss-cross packing motif, unlike the

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• excellent yields. Remarkably, a high functional group tolerance was observed, including heterocyclic substrates. In contrast, the N-substitution pattern clearly impacted the efficiency of the reaction. Indeed, exchanging the N-sulfonyl or N-acetyl protecting group with other functionalities, such as

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• cyclopentenone ring in all cases (Scheme 32). This was expected for terminal alkyne 58a, since this is the substitution pattern always found (see Scheme 4). On the other hand, for alkynes bearing substituents of similar steric bulk, the electron withdrawing group is expected to occupy the β-position. However