Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• synthesis of arylpyrrolo- and pyrazolopyrrolizinones, in which the Clauson–Kaas reaction was used as key step for the preparation of pyrrole derivatives 13. The condensation of amines 12 with 2,5-DMTHF (2) was carried out in the presence of p-chloropyridine hydrochloride as catalyst and dioxane as reaction

• 28 with squaric acid afforded anilinium squarate salt A. Further, a catalytic amount of squaric acid hydrolyzes 2,5-dimethoxytetrahydrofuran (2) to give a 1,4-dicarbonyl compound B in water. Finally, N-phenylpyrrole 29 was obtained by condensation of activated 1,4-dicarbonyl compound with aniline. In

• conditions in 90–96% yields (method 2). The optimization of the reaction conditions was performed in search of suitable conditions for this condensation reaction. Various acid catalysts (SiO2, HPA, HPA/SiO2, catalyst loadings (1 mol %, 2 mol %, 2.5 mol %, 0.3 g), solvent-systems (petroleum ether 40/60

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

•  4), the biosynthesis starts from hexanoic acid which, upon its thioesterification, is elongated by three decarboxylative Claisen condensations with malonyl-CoA to a 6-pentylsalicyl thioester. A condensation with cysteine and a subsequent cyclization generate a 6-pentylsalicyl-thiazolinyl thioester

• protein RS02200: FAAL: fatty acyl-AMP ligase; ACP: acyl carrier protein; KS: β-ketoacyl synthase; AT: acyltransferase; KR: ketoreductase; C: condensation; A: adenylation; MT: methyltransferase; PCP: peptidyl carrier protein. A discrete enzyme, the thiazolinyl imide reductase RS02195 (Red), catalyzes the

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• pyridine syntheses have relied on the condensation of carbonyl compounds and amines for a very long time [11]. The classical methods for the synthesis of functionalized pyridine include the Hantzsch pyridine synthesis and the Bohlmann–Rahtz synthesis (Scheme 1a and b). Furthermore, alternative

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• have developed a new convenient protocol for the synthesis of 3-sulfonyl-substituted quinolines (sulfonamides and sulfones). The approach is based on a Knoevenagel condensation/aza-Wittig reaction cascade involving o-azidobenzaldehydes and ketosulfonamides or ketosulfones as key building blocks. The

• , the method for the synthesis of 3-acyl-substituted quinolines from o-azidobenzaldehydes and 1,3-dicarbonyl compounds was reported [70][71] (Figure 2a). A combination of Knoevenagel condensation and aza-Wittig reaction allowed to build up target products in high yields. In case of [70], the procedure

• quinolines (sulfonamides and sulfones) (Figure 2b). Herein, we report the successful implementation of this approach. Results and Discussion The Knoevenagel condensation/aza-Wittig reaction cascade was used for the preparation of 3-sulfonyl-substituted quinolines. The process proceeds in a domino fashion

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• and involves the condensation of 3-(dimethylamino)-1-phenylprop-2-en-1-one with cyanamide (14) in NMP in the presence of N-methylmorpholine [29]. However, this reaction led to a mixture of products and the yield of the target pyrimidine did not exceed 10%. It was assumed that the reported conditions

• various solvents in the absence of a base (Table 1, entries 3–7) and the best results were obtained using alcoholic media (Table 1, entries 5 and 7). Probably, this is due to the protic nature of these solvents facilitating the studied condensation. Also, we have found that a decrease in the reaction time

• -bottomed glass flask. Synthesis of photoproducts 12. Reaction conditions: method A) 10 (0.5 mmol), DMF (15 mL) irradiation for 48 h; method B) 1) 9 (0.5 mmol), DMF (15 mL), irradiation for 96 h; 2) CDI (1.75 mmol, 0.28 g), MeCN (5 mL), reflux, 2 h. Optimization of the condensation conditions.a Ratio of

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• condensation of aromatic aldehydes and sulfonamides (Scheme 1a) [3][5][6][7][8]. Because of the poor nucleophilicity of sulfonamides, the condensation reactions generally require harsh reaction conditions involving the use of strong acids, elevated temperature, and metal catalysts. Other methods include a non

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

• of o-nitrotoluene (22) Reduction to 2,2'-diaminobibenzyl (20) Ring-closing via amine condensation Catalytic dehydrogenation 1.1 Oxidative coupling of o-nitrotoluene (22) and reduction to 2,2'-diaminobibenzyl (20) The preparation of dinitrobibenzyl (21) can be achieved by the oxidative coupling of

• transition metal (Ni, Fe, V) porphyrin catalysts and oxygen. Catalytic reduction (H2, Pd/C) affords 2,2'-diaminobibenzyl (20) in the subsequent step [28]. 1.2 Ring-closing via amine condensation The initial synthesis of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a) was reported in 1899 by Thiele and Holzinger

• '-diaminobibenzyl (20). Synthesis of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a) via amine condensation. Catalytic reduction of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a). The Wagner–Meerwein rearrangement of acridin-9-ylmethanol (23) into 5H-dibenzo[b,f]azepine (1a). Oxidative ring expansion of 2-(9-xanthenyl

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• bioconjugates with different degrees of fluorescence labelling were synthesized as guests by controlling the feed ratios (Rf) of 4-(1,2,2-triphenylvinyl)benzaldehyde (TPE-CHO) [23] to 2 mol %, 10 mol %, and 20 mol %, respectively. They were obtained with chitosan and TPE-CHO through an aldimine condensation

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

• (Scheme 47B). The authors concluded that the new structure 186 is formed by intramolecular ring opening of the oxazolidine unit initiated by the hydroxy group either following the aldol condensation or during the reaction workup. In 2021, Zhang and Oestreich presented a Cu-catalyzed tandem conjugate

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• ), differing only in the linker length between the aromatic units, have been prepared by condensation of two different pyrenecarboxylic acids with phenanthridine-labelled amino acid (Scheme 2). The influence of the linker length on the molecule flexibility, intramolecular conformation, spectroscopic properties

• -Py-1: endothermic reaction with an increase of entropy. The analogous guanidiniocarbonylpyrrole–pyrene conjugate showed a negative enthalpy change and an increase of entropy [17]. Conclusion Two novel phenanthridine–pyrene conjugates Phen-Py-1 and Phen-Py-2 were prepared by the condensation of

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• , the authors employed an Ullmann-type condensation [28] between ester 14 and 4-iodobenzaldehyde (15) to give the corresponding diaryl ether 16 in 78% yield. The subsequent demethylation reaction using boron triiodide also promoted the hydrolysis of the ester, and thus a re-esterification step was

• reaction [33]. Thus, Knoevenagel condensation using the diaryl ether 29 and malonic acid gave the corresponding α,β-unsaturated compound 30, which was submitted to a concomitant hydrogenation of the double bond and the nitro group to give compound 31. Sequential diazotization/halogenation and

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• nucleophilic attack of morpholine (C) on elemental sulfur may react with the intermediate 13 to afford another intermediate 15, which undergoes oxidation to release the thioamide-tethered pyrazole 1C. On the other hand, the pyrazole carbaldehyde 1 forms imine intermediate 16 by condensation with 2

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

• from a haliclona marine sponge [4], and vertinolide (5) from Verticillium intertextum [5] (Scheme 1). As outlined in Scheme 2, a variety of methods has been reported for the synthesis of conjugated dienones, mostly via addition/elimination reactions such as Knoevenagel condensation or Claisen–Schmidt

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• -haloalkylsulfide via a cyclic sulfonium intermediate, which then ring opens and eliminates the halide to give the unsaturated 1,4-dithiane ring. We have found this Parham ring expansion to be the most practical preparatory procedure for 2 on large scale [30]. Thus, a simple condensation of ethane-1,2-dithiol (10

• access to building block 2. The benzannelated series of 1,4-dithiane heterocycles 5–7 can in principle be obtained using Parham’s α-halocarbonyl condensation and rearrangement approach, starting from benzene-1,2-dithiol. More conveniently, however, ethanedithiol and cyclohexanone can be condensed, and

• ) may superficially look like a sulfur-substituted acrolein derivative, with a reactive vinylogous thioester moiety, but in fact their reactivity is more akin to that of an arylaldehyde, as shown by the example of the synthesis of Hantzsch ester 20 from a condensation of ammonia with 18 and

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• aza-Nazarov reactions of such imines were found to proceed successfully, albeit with slightly lower diastereoselectivities (ca. 4:1 to 16:1 dr) compared to their cyclic counterparts (Scheme 3). The reaction of the aldimine formed via the condensation of benzaldehyde and n-propylamine with acyl

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• (–)-eburnaminol (132), (+)-larutenine (133), (–)-terengganensine B (134), and (–)-strempeliopine (136), as well as the asymmetric formal total synthesis of (–)-terengganensine A (not shown, Scheme 11). The requisite common synthetic intermediate 129 for the cascade was accessed by an acid-promoted condensation of

• total synthesis of (−)-FR901483 (160) through an aldol reaction, and an intramolecular condensation resulted in the synthesis of (+)-TAN1251C (162, Scheme 13). Divergent synthesis of bipolamine alkaloids (Maimone 2022) [88]: Bipolamines were isolated from the fungi Curvularia sp. IFB Z10 and Bipolaris

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• minimally harbors three core domains, responsible for the activation and loading, tethering, and condensation of building blocks and intermediates. The biosynthesis is directional and starts at the N-terminal module with the activation and loading of the first building block onto the assembly line (Figure

• additionally taking gaps and incomplete sequences into consideration. In addition to whole genes or proteins, sequences of conserved key domains of assembly line-like pathways like PKSs (e.g., acyl-carrier-proteins, AT or KS domains) [25] or NRPSs (e.g., peptidyl-carrier-proteins, A domains, condensation (C

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• aldol reaction is one of the most powerful tools to achieve this transformation [1][2][3][4][5][6][7][8]. In particular, the intramolecular aldol condensation is an important approach to the formation of ring systems such as cyclic β-hydroxy carbonyl products or cyclic α,β-unsaturated carbonyl products

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• -acetalation and decarboxylative [3 + 2] cycloaddition is shown in Scheme 4. With the promotion of the protonic solvent EtOH, compound 3 (N,S-acetal) from the condensation of cysteine and an aldehyde reacts with a second equivalent of aldehyde followed by cyclization to generate thiazolooxazol-1-one I

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• position of the imidazole moiety was captured by triethylamine as base to provide the expected product 23. Multicomponent reactions In 2016, Vitaly S. Mityanov and co-workers unfolded a multicomponent condensation reaction methodology for the C-2 functionalization of 2-unsubstituted imidazole N-oxides

• mixture of 2.0 mmol of imidazole N-oxides 32, 2.0 mmol of aldehyde 33, and 2.0 mmol of barbituric acid 34 was refluxed in the solvent mixture of 5.0 mL of MeCN and 2.0 mL of water for 6 h. Under the optimized conditions, the study of the substrate scope showed that the corresponding condensation products

• reaction between the aldehyde and C–H acids followed by the attack of the imidazole N-oxides led to the generation of the final product. In 2020, Valery P. Perevalov et al. introduced one more interesting simple and metal-free three-component condensation methodology for the C-2 functionalization reaction

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• temperature control during the acetolysis step. The silylation method requires careful drying of 1 before the silylation but is otherwise experimentally simple. Hexol 6 was then DCB-protected using 2,4-dichlorobenzyl chloride and sodium hydride in DMSO. As self-condensation of the alkylating agent is possible

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• could be obtained by the condensation reaction of 2-aminobenzaldehyde (5) with acetophenone (6) in the absence of cyclometalated iridium (Figure 4c). According to experimental results and literature findings [19][28][29][43][44], a possible mechanism of cyclometalated iridium-catalyzed ADC reaction was

• released from the dehydrogenation of 2-aminobenzyl alcohol/1-phenylethanol according to the previous literature [28]. Lastly, the desired product 3aa was obtained by the condensation and cyclization of the aldehyde 5 with acetophenone (6) under base conditions. The potential antimicrobial activity of the

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• benzazoles containing oxazole and imidazole skeletons are the most commonly used scaffolds [1][2][3][4][5]. Therefore, it is crucial for the drug industry to develop methods for their syntheses [1][2][4][6]. For example, conventional benzoxazole synthesis methods involve the condensation of 2-aminophenol

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• -substrate catalyzed the macrocyclization with pyrrole. Interestingly, only 5 mol % of catalyst loadings were necessary in order to promote the condensation processes, and calix[4]pyrrole derivatives were obtained in moderate to high yields. Mild reaction conditions were employed, thus highlighting the

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• ]. The reaction is interesting as both furfural and 1 are present along with water in crude biomass pyrolysates, and so the reaction could affect yields of 1 [3][17][18]. Samet and co-workers have reported a similar condensation of 1 with salicylaldehyde resulting in chiral chromene derivative 4 [19][20

• yields (Table 1, entries 5 and 7). Electron-poor aromatic aldehydes including 3-nitrobenzaldehyde and 3-pyridine carboxaldehyde also afforded good yields of the expected products 5g and 5j (Table 1, entries 10 and 13). The reaction of 5-methylfurfural afforded a low yield of 7, and the aldol condensation