Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• Ugi reaction we have attempted to stereodefine the chiral center at the peptidyl position through the post-Ugi functionalization. In order to achieve this, we chose to study 2-oxo-aldehyde-derived Ugi adducts many of which partially or fully exist in the enol form that lacks the aforementioned chiral

• associated with controlling their stereochemical outcome [33][34][35] severely restrict their applicability in medicinal chemistry [36]. The typical Passerini three-component reaction (P-3CR) of a carboxylic acid 1, an aldehyde 2, and an isocyanide 3 being conducted in a polar-aprotic solvent such as THF or

• -component reaction (U-4CR) a carboxylic acid 1, an aldehyde 2, and an isocyanide 3 are complemented by a primary amine 5 that altogether undergo a condensation into a peptide-like adduct 6. These reactions are typically conducted in polar protic solvents such as methanol or water. Several examples of

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

• ], anti-inflammatory [8][9], and antiviral [10][11]. The best known methods for the preparation of thiazolopyrimidines are based on condensation reactions. The most commonly used synthesis is the three-component condensation of 2-aminothiazoline, aromatic aldehyde, and ethyl cyanoacetate, which leads to

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• ) in different positions provided good to excellent isolated yields of the corresponding products 3b–g and 3j–o that ranged from 94 to 98% in a stipulated period of time, as specified in Table 5. Further, heteroaromatic aldehydes, such as furan-2-aldehyde (2p) and thiophene-2-aldehyde (2q) produced the

• 3-Br: 2s) underwent the reaction with ethyl acetoacetate (4) and urea (5) to form the corresponding products (7h–j) in good isolated yields that ranged from 93–96% (Table 6, entries 8–10). Heteroaromatic aldehydes, such as furan-2-aldehyde (2p) and thiophene-2-aldehyde (2q) showed a good reactivity

• use of pyridine-2-aldehyde (2u) resulted in a good isolated yield of 11i (93%, Table 7, entry 9). In a similar way, the reaction of benzaldehyde (2a) with malononitrile (8) and thiophenol (10) gave the product 11j in 98% yield (Table 7, entry 10). Benzaldehyde derivatives bearing various functional

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• aldehyde 4 (0.3 mmol, 1.5 equiv), N-benzylthiourea (0.2 mmol), and chiral phosphoric acid 3 (0.02 mmol) in CHCl3 (1.5 mL) was stirred at 25 °C for 2 h, cyclohexanone (1 mmol) was added. The resulting mixture was warmed to 50 °C, stirred for 6 days, and then silica gel was added. After removal of the

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• aldehyde and nitromethane, an easy modification of the aryl group at the 3-position of the 4-nitrophenol is possible. Thus, the proposed reaction would be a useful tool for the elaborate synthesis of aromatic compounds. Experimental General All reagents were purchased from commercial sources and used

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

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• 78% yield and an overall yield of 56% (starting from 4-bromobenzaldehyde). Azide-functionalized ortho-bromobenzaldehyde 4 was prepared by a similar route as aldehyde 3. Initially, oxazoline formation from 4-methylbenzaldehyde yielded 2-aryloxazoline 10 in almost quantitative yield. The introduction

• of benzyl bromide with sodium azide delivered the primary azide 13 in quantitative yield. Again, the final back-conversion of the oxazoline group to the corresponding aldehyde afforded azide-functionalized ortho-bromobenzaldehyde 4 in 85% yield and an overall yield of 41% (starting from 4

• -shifted compared to the emission bands in chloroform solution (see Figures S31 and S33, Supporting Information File 1). Aldehyde 23 exhibits a deep violet emission maximum at 360 nm in chloroform solution and no emission in the solid-state (see Figure S30, Supporting Information File 1). Lifetimes τ were

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

• corresponding aldehyde in a 41% global yield. Bicyclic product 49a underwent diastereoselective (dr > 20:1) hydrogenation using palladium over activated charcoal under an atmosphere of hydrogen to afford saturated derivative 50 (Scheme 26). On the other hand, the tert-butanesulfonyl group could be removed

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• , gave isomeric aldehyde 2a (48%) and the dimer-like racemic product 3a (11%). Both transformations were rationalized by the intermediacy of the isoindole 4a (Scheme 1). The formation of aldehyde 2a can be explained by a protonation of the ring tautomer 1a, followed by an acid-catalyzed water elimination

• to afford intermediate isoindole 4a [2][3][4][5][6]. Then, the addition of water to the sterically less-hindered site of the latter compound followed by ring opening resulted in the rearranged aldehyde 2a [1]. As regards the formation of dimer-like product 3a, the tendency of pyrrole [7][8], indole

• compounds 1a and 1b [2] in DCM in the presence of a catalytic amount (0.1 equiv) of TFA for 24 h at room temperature (Scheme 3) and the results are summarized in Table 1. In the case of aldehyde 1a, the yields obtained under these conditions were similar to those of the reaction mentioned above (Scheme 1

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• , GlaxoSmithKline disclosed a route to a fluoropyrrolidine 6 using a Wittig reaction between phosphonium salt 4 and aldehyde 5 [2]. The synthesis of phosphonium salt 4 (itself requiring 6 steps including partial saturation of a 1,8-naphthyridine moiety) and the formation of the triphenylphosphine oxide byproduct in

• 13 was obtained exclusively at both −42 and −78 °C. The addition of two equivalents of the chlorophosphate yielded diphosphorylated compound 7, albeit in poor yield (Scheme 4). The deprotonation of phosphonate 7 and subsequent reaction with aldehyde 5, formed in situ by oxidation of alcohol 14 using

• T3P® [17], yielded olefin 15 in 93% yield as a 94:5 mixture of stereoisomers – presumably E/Z, although this is not conclusive from the 1H NMR spectrum. Based on LC–MS and 1H NMR spectroscopy observations, it is believed that aldehyde 5 exists predominantly as the corresponding hydrate and an excess

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• enantioselectivity but requiring superstoichiometric quantities of quinone as an oxidant (Figure 2B) [47]. In our previous work, we have developed α-aroyloxyaldehydes as reactive, bench-stable precursors of azolium enolates [48][49][50][51][52][53], which can be synthesized in a single step from the desired aldehyde

• precatalyst 3 [58], reversible addition of the free NHC I to the aldehyde leads to adduct II [59]. A subsequent deprotonation allows access to Breslow intermediate III, which can eliminate para-nitrobenzoate to leave azolium enol IV. Deprotonation gives azolium enolate intermediate V, which undergoes a formal

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• from our own group include the synthesis of a polystyrene gel with a photocatalytic cross-linking monomer, 4,7-bis(4-vinylphenyl)benzo[c][1,2,5]thiadiazole (St-BTZ) [47]. Additionally, we showed the direct synthesis of a BODIPY photocatalyst as a postsynthetic modification to an aldehyde-functionalised

• the efficiency of synthesising and purifying immobilised photosensitisers [63]. A BODIPY photosensitiser was immobilised to an aldehyde-functionalised Merrifield resin (poly(styrene-co-divinylbenzene-co-4-formylstyrene)) in continuous flow and concurrently in an analogous batch procedure. The coupling

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

• , and this outcome was even better than that of treating the parent compound 1a analogously. The steric environment surrounding aldehyde group markedly affected the reaction, as 3-methylbenzaldehyde (1c) and 2-methylbenzaldehyde (1d) provided products 6ca and 6da in 72 and 48% yield, respectively. The

• reaction also worked well with other 4-alkylbenzaldehydes 1e and 1f, giving the expected products 6ea and 6fa in very good yields. We found benzaldehydes featuring other electron-donating groups such as methoxy (1g) and methylthio (1h) in the para-position of the aldehyde group were also applicable in the

• reaction, and provided products 6ga and 6ha in still moderate yields. When an electron-deficient aromatic aldehyde such as 4-phenylbenzaldehyde (1i) was used, the reaction effectively afforded product 6ia in 45% yield. Similarly, benzaldehydes having other electron-withdrawing groups such as cyano, nitro

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• decomposes into ketone or aldehyde products (Scheme 9). However, in the absence of light or oxygen, disulfide could not catalyze the oxidative cleavage of olefins. It was proposed that disulfide and the olefin might be able to form a charge-transfer complex, which may rationalize the unconventional homolysis

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• -hydroxyphthalimide (NHPI, OD22, similar to the benzophenone photocatalysts OD9 and OD10) can abstract an H atom from the aldehyde substrate 20.1. The resulting acyl radical adds to the (E)-β-nitrostyrene 20.2, and the following denitrosylation affords the chalcones 20.3. Alkenyl and aryl radical ions (radical

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes

• Dragana Vuk,
• Irena Škorić,
• Valentina Milašinović,
• Krešimir Molčanov and
• Željko Marinić

Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96

• ], previously done on similar furobicyclo[3.2.1]octadiene compounds. The previous study included the synthesis of aldehyde 03, which was via the corresponding styryl derivatives converted to the annulated products 04–07. These compounds were of particular importance due to their rigid methano-bridged junction

• only exception was the cyano derivative 6 which was proven to be non-reactive, since the reaction mixture showed solely the presence of the initial cis- and trans-isomers. Figure 9 presents the 1H NMR spectra of photoproducts 8 and 9, in comparison to the spectra of the starting aldehyde 1. The effect

• the bicyclo[3.2.1]octadiene aldehyde 1 and acetone was conducted (Scheme 4). After purification of the reaction mixture the product 12 was obtained. The aim of this experiment was to obtain a system with an extended conjugation of the heteroaromatic moiety under mild conditions, while leaving the

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• that the PhSO2CF2Cu species might be prepared from difluoromethylphenylsulfone (PhSO2CF2H) and used it to functionalize an array of (hetero)aromatic boronic acids [62] (Scheme 12). The transformation showed a good functional group tolerance (aldehyde, CN, halogens). Note that the synthetic utility of

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• 53a–h [48]. The free amino acid 53i was prepared by the same protocol [49] (Scheme 12). 2,5-Difluorophenylalanines with either R or S configuration were synthesized also via the Erlenmeyer azalactone method. The synthesis started with the multicomponent reaction of aldehyde 55, acetylglycine 51a and

• )-2,5-difluorophenylalanine derivative 115 was carried out by coupling the commercially available aldehyde 55 and N-Boc phosphonate glycinate 112 to generate the enamino ester intermediate 113. The asymmetric hydrogenation of this enamine afforded the N-Boc-protected (R)-2,5-difluorophenylalanine ester

• with LiBH4 resulted in alcohol 124 which was oxidized by Dess–Martin periodinane to give (S)-(−)-2-fluoro-2-phenylacetaldehyde (125). This aldehyde is prone to racemization and decomposition and therefore was directly converted to the arylidene derivative 127, by treatment with p-toluenesulfinamide

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• chemistry. The copper-catalysed ACA of organozinc reagents to 5,6-dihydro-2-pyranone is one of the best methods to obtain chiral lactones. During the past two decades, the research groups of Chan, Hoveyda (who applied an approach depending on the trapping by an aldehyde), Mauduit, and Wang reported a

• lead to versatile chiral building blocks, such as a β-alkyl-substituted aldehyde (66% yield, 94:6 er) or a β-bromo-γ-alkyl-substituted alcohol (71% yield, 93:7 er). The asymmetric allylic alkylation (AAA) is a very useful method that allows the enantioselective formation of C–C bonds, and copper

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• superoxide radical anion oxidizes the alcohol to aldehyde, which is then converted to an imine after coupling with the amine. The products are obtained after cyclization and oxidation of the cyclic intermediates (Scheme 21) [46]. Similarly, Jiang and co-workers reported the selective photooxidation of

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• scaffolds such as gem-disubstituted (21k) and trisubstituted (21i and 21n,o) aziridines (Scheme 11). Furthermore, the reaction conditions are compatible with aldehyde, ester or ketone functions. Metalloenzymes routinely rely on 3d metals and amino acid-derived coordination spheres to perform complex (multi

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• presented. Keywords: aldehyde; green chemistry; photochemistry; photoinitiation; sustainable chemistry; Introduction Photochemistry, and especially photoredox catalysis have altered the way that modern researchers treat radical species [1][2][3][4]. In most cases, a metal-based photocatalyst is employed

• that aldehydes can transfer their triplet state energy to an acceptor, inducing changes in the reactivity of the acceptor. Accordingly, the aldehyde can react with the higher-energy-state olefin via a Paterno–Büchi reaction, indicating that benzaldehyde (8) can have an EnT ability comparable to that of

• solvent [33]. Where the concentration of the aldehyde 8 is relatively high and the solvent is a poor hydrogen donor, such as acetonitrile, the HAT process from the solvent will not occur. In this case, a self-reduction of the excited benzaldehyde (9) will occur, leading to the formation of a radical pair

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• phosphite (1,0 equiv) and the appropriate aldehyde 4 (1,0 equiv). The reaction mixture was stirred at room temperature overnight, diluted with 20 mL of water and extracted with ethyl acetate (3 × 15 mL). The organic layers were washed with NaClsat., dried over MgSO4 or Na2SO4, filtrated and concentrated

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• , Ohmiya and co-workers envisioned inverting the polarity of an aldehyde 81 via conversion into the corresponding α-alkoxyalkyl Cu(I) anion 78. Utilizing 78, which undergoes transmetallation to an initially formed Pd(II) intermediate (from oxidative addition) led to cross couplings affording benzhydryl

• diborylated products 449–451; Scheme 71, top) [134]. The insertion of an in situ-formed Cu–B species into the aldehyde carbonyl was proposed, leading to the formation of a C–B bond. 1H NMR studies, however, did not confirm the formation of this Cu–O–C–B linkage 452. Instead, solely the Cu–C–O–B species 453

• was observed. Due to the possibility of facile rearrangement of the former to the latter, it could not be concluded that a direct insertion of the aldehyde into the Cu–B bond is taking place. The enantioselective borylation of aliphatic aldehydes 448 was first reported in 2015 using CuCl/KO-t-Bu/(R

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• (Scheme 2). Therefore, 4-hydroxybenzaldehyde (12) was chlorinated and phenol 13 was protected as TBS ether to afford aldehyde 14 which was then converted into dibromoolefine 15 in good yields using the Corey–Fuchs protocol. Uenishi et al. [21] published an effective way of defunctionalizing dihalogenated