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

• . Catalysis via covalent bonding Organocatalysts made from chiral secondary amines have been widely used in the last years. According to Jørgensen, in general, the carbonyl functionalization employing amine catalysts can be separated in four different types [29]. When aldehydes are employed, both

• electrophilic and nucleophilic α-functionalizations are possible, whereas with the use of α,β-unsaturated aldehydes the β-position is functionalized with nucleophiles and the γ-position with electrophiles. In this sense, Jørgensen and colleagues have developed the first organocatalytic asymmetric Michael

• acid (4) as catalyst [30]. Based on this pioneer work, our research group described an efficient, highly stereoselective, one-pot process comprising an organocatalytic conjugate addition of dimedone or 4-hydroxycoumarin 1 to α,β-unsaturated aldehydes 2 followed by an intramolecular isocyanide-based

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

• heterogeneous vanadium-based catalysts have been employed to obtain alcohols and carbonyl compounds through oxidation, including VOSO4, Na(VO3), VO(acac)2, VOX3, among others. Obtaining ketones and aldehydes from hydrocarbon compounds through vanadium-mediated activation of C(sp3)–H bonds in a benzylic position

• derivatives. Using H2O2 as an oxidant agent, ketones and aldehydes were obtained from hydrocarbons with high yields (85–99%, Scheme 9B and 9C). Although the authors did not explore the biological effects of the obtained products, this class of molecules resembles the basic structure of several important

• for the allylation of aldehydes promoted by a dual catalytic system comprising CrCl3 and an iridium-based photocatalyst that was recently developed by Schwarz and co-workers [119]. Similar conditions were further employed to synthesize monoprotected 1,2-homoallylic diols from aldehydes and silyl and

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

• , Universitätstraße 31, D-93053 Regensburg, Germany 10.3762/bjoc.17.121 Abstract We have developed a cerium-photocatalyzed aerobic oxidation of primary and secondary benzylic alcohols to aldehydes and ketones using inexpensive CeCl3·7H2O as photocatalyst and air oxygen as the terminal oxidant. Keywords: alcohol

• ; aldehydes; cerium; oxidation; ketones; visible light; Introduction The selective oxidation of alcohols to carbonyl compounds [1][2] is an important process for producing a wide range of value-added fine chemicals [3][4][5][6]. In the traditional oxidation process stoichiometric amounts of oxidants such as

• herein report a mild aerobic photocatalytic oxidation of benzylic alcohols to aldehydes and ketones using 10 mol % CeCl3·7H2O (Scheme 1). Results and Discussion A variety of reaction parameters was tested during the optimization of the reaction with 4-iodobenzyl alcohol (1a) as the model substrate and

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• ]. Endophytic fungi themselves can produce VOCs. Currently, around 300 fungal VOCs have been characterized, including aliphatic alcohols, ketones, aldehydes, acids and esters, terpenoids, benzenoids, naphthalene derivatives, and cycloalkanes [25][26][27]. Endophytic fungal VOCs are frequently described to

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• , and serine derivatives were proceeded to extend the scope of the reaction (Scheme 13) [44]. An efficient domino three-component route has been developed for the synthesis of fully decorated 1,2,3-triazoles 38 bearing a sulfonyl group in position 4. The synthesis required aldehydes 35, amines 36, α

• -diazo-ß-ketosulfones 37, I2, and K2CO3 in EtOH. The scope and limitations of the reaction were assessed using alkyl aldehydes, (hetero)aryl aldehydes, amines, and diazosulfones. Reactions of aryl aldehydes containing a range of different functional groups gave products 38 in very good yield. Because of

• the faster hydrolysis of the in situ generated imine intermediates, aromatic aldehydes containing electron-withdrawing substituents afforded no product in the reaction. It was proved that a variety of aliphatic primary amines can efficiently produce the triazole products (Scheme 14) [45]. This one-pot

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

• [10][11][12][13][14]. For example, Nagumo and coworkers have developed a Prins/Friedel–Crafts cyclization of homocinnamyl alcohols with aromatic aldehydes under the action of BF3·Et2O affording 2H-indeno[1,2-b]furan derivatives [15]. Likewise, Hinkle and coworkers reported in 2017 a three-step domino

• alkynyl-Prins cyclization, Friedel–Crafts alkenylation, and dehydration/aromatization reaction between 1-aryl-3-hexyne-2,6-diol derivatives and aldehydes, that led to the formation of 1,4-dihydro-2H-benzo[f]isochromenes [16]. The Prins reaction-induced cyclization, inter alia, became a versatile tool for

• . Results and Discussion Our research began with the preparation of 2-(2-vinylphenyl)acetaldehydes (13) required as substrates for the Prins/Friedel–Crafts cyclization reactions. Commonly, these aromatic alkenyl aldehydes were previously prepared via a three step process as exemplified by 13a shown in

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• derivatives have recently received increasing attention from synthetic organic chemists, biologists, and pharmacologists. In general, DIMs can be synthesized via electrophilic substitution of indoles by aldehydes or ketones in the presence of conventional Lewis or Brønsted acids as catalysts [19]. This

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

• alkaloid ingenine B [20]. The iodine-catalyzed [3 + 3] cycloaddition of indolyl alcohol to enaminones [21] and the thiourea-catalyzed iso-Pictet–Spengler reaction of isotryptamine with aldehydes [22], are some noteworthy contributions to the field. A cascade or domino reaction is an interesting approach

• salts has been discovered. Results and Discussion Optimization of reaction conditions and chemical synthesis The base-catalyzed imination of aromatic aldehydes is a valuable method in organic synthesis to synthesize a variety of heterocyclic building blocks [29]. Among all the reported iminoesters

• substituted pyrrole-2-aldehydes to 5-azaindole transformation during a base-catalyzed imination reaction [31]. However, we envisioned that our methodology might be strategically applied towards the synthesis of substituted γ-carbolines as a C-3 nucleophilic attack is more favored in indoles than in pyrroles

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

• critical for the identification of functional groups, being the equivalent of what next became IR spectroscopy. Schiff himself had contributed to this development with the discovery of the sulfite-decolorized fuchsine test for aldehydes and with the popularization of the biuret test for peptide bonds. It

• File 1, third paragraph). Despite the poverty of means, Guareschi established a laboratory in Livorno, carrying out independent research in the realm of organic chemistry. In 1874, Guareschi reported the reduction of amides to aldehydes and alcohols with sodium amalgam [23], nowadays an obsolete

• Guareschi imides, which, under the original protocol, is limited to ketones as the carbonyl component. When aldehydes are used, the adduct is aromatized to the corresponding 2-hydroxypyridone [50][51]. Finally, a modification of the type-IV Guareschi reaction that involves the condensation of two moles 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

• reaction [93]. A common synthesis of dihydrojasmone (35) uses an intramolecular aldol reaction to simultaneously form the cyclopentanone ring and the double bond in the correct positions [94][95]. Aldol reactions are most often exothermic, especially those involving highly reactive aldehydes (e.g

• 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

• method was applied on different aldehydes and ketones obtaining moderate-good yields (38–84%). The results obtained for aldehydes 39 and 56 are low as partial dehydration occurs. It was noticed that by reducing the quantity of catalyst less dehydrated product was observed. A similar approach in aqueous

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• of imidazo[4,5-e]thiazolo[3,2-b]triazines with carbonyl compounds, namely, aromatic aldehydes and isatins, are capable of skeletal rearrangement of the thiazolotriazine system proceeding in methanol upon treatment with KOH and resulting in the corresponding isomeric imidazo[4,5-e]thiazolo[2,3-c

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

• from the condensation reaction of aldehydes or ketones with tert-butanesulfinamides. In this work, the condensation with aldehydes was carried using Ti(OEt)4 in tetrahydrofuran (THF), or CuSO4 in dichloromethane at room temperature. The combination of MgSO4 in the presence of a catalytic amount of

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

• -1,3-diol [21][22]. For instance, deoxoprosophylline (5) as a cyclic 2-amino-1,3-diol target molecule was prepared by Kokatla et al. in an 8 step synthesis starting from Perlin aldehydes, via Pd(OH)2-catalyzed reductive azidoketon cyclisation [23]. Another synthetic pathway involves a stereoselective

• observed in the reaction of aminodiols 13 and 16 with aldehydes (see Scheme 4 and Scheme 5), but it is similar to that observed in our earlier study with pinane-based 3-amino-1,2-diols [41]. During the NMR spectroscopic study of 21A in CDCl3 for 30 days, an unknown slow ring–ring tautomerization was

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

• of aldehydes or ketones in the presence of acid (Scheme 2) [25]. Although the Kriewitz reaction was an ene reaction, the mechanism of the reaction was described to proceed via an oxocarbenium ion intermediate captured by a π-nucleophile, followed by the addition of an external nucleophile, leading to

• substituent. In contrast, the reaction with aromatic aldehydes equipped with the electron-deficient substituent produced the desired trisubstituted THP along with recovered starting material. The enantioenriched homoallylic alcohol bearing an electron-deficient substituent, 27 (94% ee), was investigated with

• reaction rate and yield of the reaction. In a related study, the synthesis of polysubstituted tetrahydropyrans was described by Amberlyst® 15-catalyzed cyclization of homoallyl alcohol 107 and aldehydes 108. This method was further employed for the synthesis of highly substituted tetrahydropyrans with

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

• ; 4, Figure 1) [36][37]. The relevance of acridine in drug discovery galvanized Singh and co-workers [38] to develop a water-promoted three-component reaction involving aldehydes 5, cyclic 1,3-diketone 6 and ammonium acetate powered by microwave irradiation resulting in 4-arylacridinediones 7 in

• -fused tetrahydrodibenzoacridinones 9 using phenanthren-9-amine 8, aldehydes 5, and cyclic 1,3-diketones 6 as structural units in ethanol under microwave irradiation to result in the targeted products in excellent yields. A conventional heating used for the same protocol delivered the desired products in

• exploring the MC-MWA reactions Jiang and co-workers [41] designed a microwave facilitated regioselective four-component domino reaction employing naphthyl- or anthracenylamine 10, aldehydes 5 and 2-hydroxy-1,4-naphthoquinone (11) in acetic acid for the construction of dibenzo[a,h]acridine-12,13(7H,14H

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• aldehydes were present, and that unreacted phenol comprised a further 26% of the mass balance. Thus, the reactivity of fluorobromocarbene in this case mirrored the tendency of difluorocarbene to react with phenoxides to form dihalomethyl phenyl ethers, rather than forming aldehydes as with dichlorocarbene

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

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• reviewed, including the phosphonylation of hydroxy esters with phosphonochloridates, the condensation of phosphonic monoesters and hydroxy esters, the alkylation of phosphonic monoesters with 1-(alkoxycarbonyl)alkyl halides or sulfonates, multicomponent condensation of amides, aldehydes, and

• -hydroxyglutarate (84) in a Mitsunobu reaction to generate the γ-phosphonodepsipeptide 79 in a high yield of 66% (Scheme 27) [28]. Synthesis of phosphonodepsipeptides via the multicomponent condensation of amides, aldehydes, and phosphites followed by alcoholysis with hydroxy esters Previously, the Mannich-type

• reaction of benzyl carbamate, aldehydes, and trialkyl phosphites in acetyl chloride gave rise to N-Cbz-1-aminoalkylphosphonates [40]. When the reactions were conducted in benzene followed by an aminolysis or alcoholysis, phosphonamidates [41], phosphonopeptide [42], and mixed esters [43][44] were obtained

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• compounds to trifluoromethyl carbinols because it does not require any expensive reagents nor very low-temperature conditions. Although the reaction has a broad substrate scope of embracing ketones, chalcones and aldehydes, the transformation of esters to trifluoromethyl ketones by this protocol was never

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• some of the investigated strains. A series of aldehydes ranging from hexanal (7) to tetradecanal (13) was found in strain specific patterns, with all identified compounds present in the bouquet from C. manganoxidans. A similar series of γ-lactones spanning from pentan-4-olide (14) to dodecan-4-olide

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

• bond alkynylations of heteroarenes [9]. The 1,1-dichloro-1-alkenyl moiety is found in a number of pyrethroid insecticides including permethrin and marine natural products such as caracolamide A [10] (Figure 1). 1,1-Dichloro-1-alkenes 2 are commonly prepared from the corresponding aldehydes 1 in one

• step with PPh3 and CHCl3 [11], CCl4 [12], or with the phosphonate reagent LiCCl2-P(O)(OEt)2 [13][14] (Figure 2a). Alternatively, the aldehydes are converted to trichloromethyl carbinols 3 using various methodologies [15][16][17], followed by acetylation and elimination to provide the desired

• researchers to utilise this functional group conversion in future syntheses of 1,1-dichloro-1-alkenes and to further investigate the unexpected reactivity of these compounds. Examples of biologically active 1,1-dichloro-1-alkenes. a) Common methods for the preparation of 1,1-dichloro-1-alkenes from aldehydes

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• Ph3P+CF2−, which was used for the Wittig olefination of aldehydes and ketones. However, heating PDFA in nonpolar solvents (e.g., xylene at 90 °C) favors the dissociation of the ylide to release difluorocarbene which is able to effect the cyclopropanation of alkenes [34]. Trimethylsilyl

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• between thiol-functionalized β-CD and oleic acid-protected CdS nanocrystals [29]. These spherical CdS–CD nanoparticles could be employed as a photocatalyst for the dehydrogenation of alcohols to aldehydes (at a low concentration of the reactant of 1 mM, ≥92% selectivity) or diols (at a high concentration

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• using a four-step sequence such as Negishi’s (Z) and (E)-stereoselective isomerization of the terminal alkyne followed by iodinolysis [19][70][71], oxidation to the corresponding aldehydes and enantioselective Kiyooka–Mukaiyama aldol reaction followed by TES protection of the resulting alcohols (Scheme

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• (1). Alternatively, the (±)-euphococcinine precursor 6 was prepared from 4, via deprotonation, silylation, and finally, silyl ether cleavage. Swern oxidation of alcohols 5 and 6 gave aldehydes 7 and 8, treated with allylmagnesium bromide, to generate secondary alcohols 9 and 10. These alcohols were

• provided aldehydes 59a and 59b (Scheme 7). The key step in this synthesis was the allylic transfer, conducted by the dropwise addition of 64 in PhCF3 at −20 °C to a mixture of 59a and 59b and the chiral catalyst S-BINOL-TiIV [OCH(CF3)2]2 providing alcohols 60a and 60b, after 12 h at −20 ºC. In addition to