Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• ) carried out in refluxing toluene using a Dean–Stark apparatus followed by the reduction with NaBH4 (not shown). When the condensation of acetal 1 and aldehyde 2f and the subsequent reduction were carried out in EtOH at rt, according to our procedure applied for the synthesis of aminoacetals 3a–e, the

• proposed a plausible mechanism for the reaction of 6a with diluted HCl (Scheme 10). The mechanism consists of four major steps: the first step is an acid-catalyzed hydrolysis of the acetal function in 6a to afford aldehyde 15; the second step is the enolization of the aldehyde 15 to form the tautomeric

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

• and Gandhi reported an Ag-catalyzed cascade cyclization of 6-hydroxyhex-2-en-4-ynals 42 and primary amines to give the 2-(α-hydroxyacyl)pyrroles 43 in moderate to good yield (Scheme 17) [62]. The proposed mechanism involves the condensation of amine and aldehyde to give the imine 44 and the AgNO3

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

• the hydrogen source. Following protection of the alcohol moiety with PMBCl, ether 22 was realized in 93% yield. Afterwards, this species was transformed into the γ-keto α,β-unsaturated aldehyde 23 through an NBS-assisted furan oxidation procedure in moderate yield (65%). The keto functionality was

• liberated using TBAF to give compound 27 in 97% yield over two steps. The alcohol group in 27 was then oxidized to the corresponding aldehyde under Swern conditions and subsequently subjected to a Wittig reaction with a two-carbon phosphonium ylide reagent. The desired α,β-unsaturated ester 28 was then

• Jin’s one step dihydroxylation–oxidation protocol using a NaIO4/(cat.) OsO4 system. Allylation of the resulting aldehyde 74 was best performed under Brown’s protocol at low temperature utilizing a chiral allyl reagent prepared from allylmagnesium bromide and (+)-B-chloro-diisopinocampheylborane. By this

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

• was demonstrated to be useful for the synthesis of the natural product trisphaeridine (3) [17]. Exposure of 1-bromo-2,4,5-trimethoxybenzene (19) to Suzuki–Miyaura coupling reaction conditions with boronic acid 20 resulted in the formation of aldehyde 21 (Scheme 5). Treatment of 21 with hydroxylamine

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• potassium sodium tartrate solution (Rochelle salt) to furnish the aldehyde 5. Then, transformation of the 7-formyl into the 7-aminomethyl group proceeded via oxime formation, applying hydroxylamine hydrochloride in methanolic ammonia, followed by reduction with Raney nickel to yield the tritylated precursor

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• ] (Scheme 10c) described by Jacobsen and co-workers in 2010 and 2014, respectively [50]. In the one hand, while the thiourea unit in catalyst 43 abstracts the bromide in 45 and forms an electrophilic benzhydryl cation, the free amine group activates the aldehyde substrate 46. The resulting enamine can then

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• radical and toluene as well as aldehyde; iv) product formation in a nickel catalytic cycle; and v) regeneration of nickel(II) species. Recently, the group of Huo developed a nickel-catalyzed enantioselective acylation of α-amino C(sp3)–H bonds with carboxylic acids under visible light irradiation (Scheme

• catalysis under blue light irradiation (Scheme 45) [128]. Among the tested several commercially available photocatalysts, Ir[dF(CF3)ppy]2(dtbbpy)PF6 was found to provide the desired products in good yields. Aldehyde C–H functionalization Inspired by their earlier contributions on HAT-metallaphotoredox

• -mediated C(sp3)–H functionalizations [53][54], the MacMillan group reported a photoredox nickel-catalyzed aldehyde C–H arylation, vinylation, or alkylation [129]. The ketone-forming reaction was conveniently realized by the reaction of aldehydes 89 with aryl, alkenyl, or alkyl bromides in the presence of

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• dimerized 7,7’-bis(indolyl) products 185 with the 2-methyl group transformed to the aldehyde in the same step (Scheme 27) [118][119]. The less electronically activated N-acyl substrate gave a slightly better yield. Selenation occurs at C-3 instead of C-7 for the C-3 unsubstituted substrates. Conclusion This

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

• triarylmethane in 93% yield, indicating that this reaction strongly depended on the nature of the aromatic aldehyde [44]. Synthesis of substituted anthracenes from anthraquinones An easy and common method to obtain anthracenes is to reduce anthraquinones by using several reagents. An important advantage of this

• intramolecular Friedel–Crafts-type cyclization. This was the first report of the same molecule bearing an acid-sensitive acetal and dibenzyl alkoxy groups. The key steps described in the work were protection of the aldehyde group of 6-bromopiperonal (80) by using 1,2-ethanediol or 1,3-propanediol, followed by

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• synthesis of 3,4-dihydrocoumarins 80 bearing a cyclohexene ring, through [4 + 2] cycloaddition between 2,4-dienals 79 and 3-coumarincarboxylates 43. This stereoselective transformation was performed using a squaramide 81 derivative catalyst, which activates the aldehyde with the formation of an enamine

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

• inspired by the biocatalytic action of the cytochrome P-450 cycle, which is driven by a reductase or bioreductant, and presented high versatility in incorporating both aldehyde and ketone functionalities into unprotected arylboronic acids. The reaction consists of using a porphyrin-based iron catalyst, and

• same year, Wu, Li and co-workers described a successful cobalt-Cp*-catalyzed C–H amidation of benzaldehyde derivatives (Scheme 39B), in which the aldehyde portion works as the directing group [198]. After an acid workup using diluted hydrochloric acid, the desired ortho-amidated products were obtained

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• research. This has been explored utilizing the reactivity between primary amines and the aldehyde moiety of a 2’-O-(2-oxoethyl)uridine nucleotide, incorporated centrally in an 11-mer TFO, to form a Schiff base (monomers 41–45) [80]. All aminoalkylated moieties improved the triplex stability. Notably, a

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• with the prenylation of ʟ-tryptophan to dimethylallyltryptophan (DMAT). During several steps DMAT is converted to chanoclavine-I aldehyde, the last mutual intermediate. Branching into different pathways after this intermediate is mainly due to differences in the function of EasA, the enzyme catalysing

• the next biosynthetic step. In A. fumigatus EasA acts as a reductase and after additional steps chanoclavine-I aldehyde is converted into festuclavine (16) (Figure 6). Festuclavine is then oxidized to fumigaclavine B (17) which in turn is acetylated to fumigaclavine A (18). Finally a reverse

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• benzylic alcohol selectively to the aldehyde or ketone is still desirable. Recently, cerium photocatalysis was introduced as a robust alternative to generate oxygen or carbon-centered radicals under mild reaction conditions [57][58][59][60][61][62][63][64]. CeCl3 reacts via ligand-to-metal charge transfer

• 1ad and 1ae gave the ketones 2z, 2aa, 2ab, 2ac, 2ad, and 2ae in good yields. However, the primary aliphatic alcohol 3-phenylpropanol (1af) did not provide the desired aldehyde at all, and allylic alcohols such as geraniol (1ag) and cinnamyl alcohol (1ah) afforded the aldehydes 2ag and 2ah in very low

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

•  2). This second route commenced with a three-step protecting group manipulation of primary alcohol 6, delivering 7 in 63% yield over three steps (Scheme 2). Alcohol 7 was then subjected to Parikh–Doering oxidation to deliver a crude aldehyde in 98% yield, from which oxime 8 was subsequently formed

• latter synthetic steps towards 5, an alternative, one-pot three-component procedure (H2N-OH, NaN3 and catalytic [(NH4)4Ce(SO4)4]) was attempted from the crude C6-aldehyde [17]. TLC analysis indicated C6-nitrile formation was evident after 36 h, however, the desired C6-tetrazole 5 was not observed

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

• -promoted condensation of a homoallylic alcohol and an aldehyde to give an oxocarbenium ion, which is then reacted with an olefinic/alkynic bond generating a carbocation that undergoes a Friedel–Crafts reaction. Given the potential value of tetralin-2-ol scaffolds to drug research programs, we decided to

• develop a novel Prins/Friedel–Crafts cyclization strategy for the synthesis of 4-aryl-2-hydroxytetralins starting from 2-(2-vinylphenyl)acetaldehydes (Scheme 2). In this protocol, we envisioned that the aldehyde 5 would give rise to an oxocarbenium ion species 6 upon treatment with a Lewis acid. The

• hydrolysis using 18% aq HCl furnishing the corresponding aldehyde [21]. Without purification, the resultant aldehyde intermediate was then directly reduced using potassium borohydride to the corresponding primary alcohol 11a in 74% yield starting from 9a. Pd-catalyzed cross-coupling of 11a with pinacol

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

• 5, which undergoes nucleophilic addition with another molecule of aldehyde 1 to furnish the iminoalcohol intermediate 6. The iminoalcohol 6 undergoes dehydration under the reaction conditions to give E-imine/Z-enamine 7a or Z-imine/E-enamine 7c intermediates irreversibly, which plays a decisive role

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• subsequent functionalization giving rise to two C5 units with compatible groups required for linking: in this case an amine and an aldehyde. In order for the synthesis to yield ent-pavettamine instead of pavettamine, the key was to functionalize the “opposite end” of each of the C5 units required for linking

• , followed by hydrolysis with solid K2CO3 and water for 30 min (Scheme 5). The desired aldehyde 18 was recovered in an excellent yield of 99%, and product epimerization was not detected based on 13C NMR spectroscopic analysis. This was confirmed by analysis of the 13C chemical shifts of the acetonide group

• , whose values differ for the syn-1,3 diol when compared to the anti-1,3-diol as described after an extensive study by Rychnovsky et al. [21]. The reductive amination of the aldehyde with benzylamine allowed for the introduction of a protected terminal amine group to the C5 fragment, yielding 19 in a

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• hue dependent on the structure of the phenol. The mechanism of many color reactions popular in the 19th century is rather complex, and the one involved in the Schiff test of aldehyde is still not completely clear, despite the relevance in medical histology [22]. The report by Schiff on the Guareschi

• cyanoacetamide (and not a cyanoacetic ester) with a carbonyl derivative (aldehyde or ketone) was further investigated by the British chemist Jocelyn Fred Thorpe (1872–1940), a decade after the original studies by Guareschi [52]. In Thorpe’s modification, the reaction takes place in the presence of a secondary

• hydroperoxy radical that can next evolve into an aldehyde by β-elimination of water, or after reduction, into an alcohol. The stability of the radical 10 is surprising. Stable radicals (O2, NO, nitroxyl derivatives, DPPH) are characterized by a two-center three-electron bond [56]. Conversely, the stability of

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• benzaldehyde derivatives, such as p-anisaldehyde (23) and cuminic aldehyde (27), with propanaldehyde (24) are important transformations for the preparation of the corresponding anisylpropanal 26, and cyclamen aldehyde (29) (Scheme 2) [90][91]. The syntheses of jasmone derivatives also represent important

• flow reacting acetone with a wide range of aldehydes. In batch, acetone-based aldol reactions are typically performed under biphasic conditions by slow addition of the aldehyde to an acetone/NaOH mixture kept at low temperatures. Upon scale-up, this carries with it problems such as inefficient mixing

• , difficulty in maintaining the reaction temperature and the occurrence of greater amounts of acetone and aldehyde self-condensation/polymerisation. By adopting a flow protocol and using a Comet X-01 micromixer (with linear scalability), more efficient mixing was attained and less aldehyde self-condensation

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• the Duff formylation procedure, only traces of aldehyde 16 were detected. Rieche formylation with either SnCl4 or TiCl4 resulted in a low conversion of the starting material and only traces of 16 due to the limited solubility of 13 in DCM, DCE, or chloroform. Furthermore, 16 was isolated after a

• Reimer–Tiemann formylation; however, only in 13% yield. Finally, Casnati–Skattebøl formylation of 13 using MgCl2, iPr2EtN, and paraformaldehyde, i.e., (CH2O)n, has been successful in regioselectively affording aldehyde 16 in a reasonable yield of 39%. The regioselectivity of compound 16 was confirmed by

• 1H NMR spectroscopy, which indicated the presence of two doublets at δH 7.88 (d, J = 9 Hz, 1H) and δH 7.19 (d, J = 8.9 Hz, 1H), corresponding to the two adjacent hydrogen atoms of the phenolic ring. One singlet was observed at δH 10.58, evidencing the aldehyde proton. This access to previously

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• external nucleophile, the successive proton loss leads to the formation of the 2,6-disubstituted dihydropyran. The regioselectivity of the Prins reaction is explained through the intermediates formed during the course of the reaction (Scheme 4). The Z-homoallylic alcohol reacts with an activated aldehyde

• ][33]. The racemization occurs during allyl transfer as a result of 2-oxonia-Cope rearrangement through a 3,3-sigmatropic shift, which plays a crucial role during the reaction, as shown in Scheme 7. The Prins cyclization between alcohol (R)-35 and aldehyde 36 was investigated under different Lewis acid

• an oxocarbenium ion is generated from a masked aldehyde bearing a homoallylic alcohol moiety has been examined. In this context, the α-acetoxy ethers with different functionalities at C4 were examined in the presence of a variety of Lewis acids, and it was found that the α-acetoxy ether (R)-42

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

• moderate to good yields under catalyst-free conditions (Scheme 1). A rationale of mechanism proposed the transformation via a Knoevenagel condensation between aldehyde and a molecule of 6 affording A. The concurrent condensation of ammonium acetate with another molecule of 6 led to the formation of an

• the involvement of an elementary formation of Knoevenagel adduct A from the reaction between the aldehyde and 11. This adduct undergoes an intermolecular Michael addition to naphthylamine resulting in the formation of B. A subsequent intramolecular nucleophilic cyclization leads C followed by

• azepinone 22 and exemplified a modified Ugi reaction (four-component reaction). The aldehyde and acid component of the Ugi reaction was functionalized on the same biaryl ring employing a Suzuki–Miyaura coupling. The authors advocated the use of microwave as it consistently increased the yield from 49% to 82

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• to convert α,β-unsaturated aldehydes selectively into 4-ketoaldehydes (Scheme 38). The imine salt (electron acceptor) that forms EDA complex 112 with electron donor α-keto acid 109 is synthesized by secondary amine catalyst and α,β-unsaturated aldehyde 110. Compound 112 turns to excited state 112