Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• intramolecular proton transfer and the methanol-mediated proton transfer, can occur. It has been described that intermediate B is more stable with enolizable electron-withdrawing groups such as esters [50] when compared to, e.g., a nitrile [49]. Accordingly, the intermolecular proton transfer pathway should be

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• active oxidative agent. Asymmetric quaternary ammonium phase-transfer catalysts proved to be effective in the asymmetric nucleophilic epoxidation of electron-poor alkenes by hydroperoxides [70] and the asymmetric hydroxylation of enolizable carbonyl compounds employing O2 or H2O2 as terminal oxidants [71

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• , including two all-carbon quaternary centers, together with the non-enolizable cyclic α-diketone moiety collectively render aberrarone as an attractive but challenging synthetic target. Its congener elisabanolide (2) with a lactone in the D ring shows their potential biosynthetic relationship [2]. These

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

• reactions with elemental sulfur [23][24][25], resulting in the generation of non-enolizable imidazole-2-thiones. At first, the alkylation of 2-unsubstituted imidazole N-oxides 40 took place in the presence of an equimolar quantity of benzyl bromide in CH2Cl2 at rt providing the (N-benzyloxy)imidazolium

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• as key intermediates for the total synthesis of natural products [1]. Thus, the high electrophilicity of the central carbonyl group in α,β-diketoesters 2 allows the formation of stable hydrates 5. In case of an enolizable position enolization (2→6) is facilitated. The chemistry of vicinal

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• metal-catalyzed reactions [31][32][33][34][35][36]. The most successful among them are the ʟ-proline-catalyzed reactions of enolizable aldehydes with nitrosoarenes [37][38][39][40][41][42][43]. Besides ʟ-proline and its derivatives, various secondary amines derived from BINOL and cinchona alkaloids were

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• are scarce and they have mostly been focused on the fluorinations of enolizable substrates. These considerations led us to explore the behavior of NFSI in fluorinations of activated arenes under ball-milling conditions towards an eventual implementation of mechanochemistry in late-stage C–H

• of 1-acetylindole (5) was found to proceed more efficiently under simultaneous thermal milling conditions. Altogether, the results of this work expand the applicability of NFSI by mechanochemistry beyond fluorination reactions of enolizable substrates and might facilitate the application of NFSI in

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• unit, which should engage in enamine activation of enolizable carbonyl compounds. The urea or thiourea moiety shall provide hydrogen-bond donating ability. Furthermore, these compounds possess a sulfinyl group with an additional stereogenic center on the sulfur. To verify the influence of a matched

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

• proton of the enolizable β-ketoester 49 and thus activating the nucleophilic species. This enolate then adds to the cationic substrate from in situ upon halide abstraction of α-chloro amino acid derivatives 48 by the thiourea moiety of the bifunctional catalyst (Scheme 10c, key intermediate), leading to

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• developed by Widenhoefer [25][29] relied heavily on the acidity of the carbonyl substrate, and this hampered the use of less enolizable substrates, like alkenyl β-ketoesters. The same group addressed this limitation by proposing the use of trimethylsilyl chloride (TMSCl) as an additive in the intramolecular

• because of the less enolizable character of these compounds. Deuterium incorporation at the olefin terminal carbon was obtained when the deuterated substrate α-13-d2 was subjected to the reaction conditions, indicating the participation of an internal proton source in the putative protodemetalation step

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

• amount of fluoroform was sufficient for this transformation. A wide variety of medicinally attractive aryl and alkyl trifluoromethyl ketones are obtained in good yields by a relatively simple procedure, although the protocol is not applicable to enolizable esters. Fluoroform is an economical feedstock

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• convenient source of trifluoromethylated iminium ions 187 (Scheme 45) [117][118][119]. Langlois, Billard, and Blond reported on the Mannich-type reaction between silylated trifluoromethylated hemiaminal derivatives 189 [120] and enolizable ketones 188 [121]. The intermediate formation of trifluoromethylated

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• reaction of trifluoroacetaldehyde hemiaminals with enolizable carbonyl compounds in the presence of a strong base [23], the reaction of aldiminium salts with (trifluoromethyl)trimethylsilane/Lewis base [24], and the preparation of secondary α-(trifluoromethyl)propargylamines from imines CF3CH=NR and

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

• DHPMs becomes an urgent and paramount task. In connection with this, multicomponent Biginelli and Biginelli-like reactions of aldehydes, urea/thiourea, and enolizable carbonyls revealed as very efficient tools to prepare DHPMs [3]. Although the Biginelli reaction was firstly discovered over a century

• ) H bondings with the enolizable ketone, respectively. This rigid chiral transition-state structure favored the stereoselective attack of the enol on the imine. Once the two hydroxy groups were etherified, the loss of the rigid structure would lead to low enantioselectivity. Additionally, this

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• for the construction of these heteropolycycles is of great significance to both organic and medicinal chemistry. The Castagnoli–Cushman reaction (CCR) between cyclic enolizable anhydrides (such as succinic (5) [9], glutaric (6) [10], and the corresponding oxygen (7) [11], sulfur (8) [11], and nitrogen

• recrystallization. Compounds comprising a benzo[a]quinolizidine ring system. Representative NOE interactions in cis and trans-21–24 (only one enantiomer is shown). X-ray crystal structure of products 25 and 26. Representative NOE interactions in 28 and 29. Reactions between enolizable anhydrides and imines

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• due to either reducing the electrophilicity of the ketone or the presence of enolizable protons in α-position to the keto group in basic medium. Supporting this hypothesis, the reaction of 1a with 1,1,1-trifluoro-3-phenyl-2-propanone (2l), which has a 3-methylene group also did not proceed at all. The

• interact with the base, thereby initiating the reaction. To find the importance of electrophilicity of ketones, different enolizable and nonenolizable ketones were screened with the reaction of 5-methoxyindole (1a). The enolizable ketones 2j–l failed to provide the products (see Table 2). Similarly

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• triflic acid via decomposition of ethyl triflate. As a limitation, substrates bearing a vinyl substituent or an enolizable ester group did not give any conversion. This methodology is also applicable to other dialkyl phosphonates as illustrated by the synthesis of enol phosphonates 3j, 3k and 3l

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• catalytic amount of isopropanol, or 18-crown-6, was necessary to facilitate the reaction and to reduce side-product formation under ambient conditions. Keywords: acylation; β-ketonitrile; enolizable; trifunctionalized; sustainable; Introduction β-Ketonitriles represent highly versatile intermediates for

• reported as feasible alternatives with varied success and usually a lack of general applicability (e.g., enolizable esters and ketone products may react undesirably under these highly basic reaction conditions). Furthermore, these methods constitute either expensive, less scalable procedures employing an

• , atom-economical ring opening of enolizable δ-valerolactone (3, Scheme 1). Although a two-step (or four-step, should hydroxy group O-protection prove to be necessary prior to acylation) protocol could, in theory, be envisaged to produce β-ketonitrile 2 from 3 by ring-opening esterification to afford

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• formaldehyde and 2,2-disubstituted acetaldehydes 28. Formaldehyde, as a non-enolizable compound is more likely to give Mannich base product 30. In contrast, enolizable 2,2-disubstituted aldehydes easily form enamines 31 that undergo cycloaddition with electron-deficient o-QMs giving 2,2-dialkyl-3-dialkylamino

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• : aldol reaction; ester enolate; fluorine; SF5 compounds; stereochemistry; Introduction The classical acid- or base-catalyzed directed cross aldol reaction of an aldehyde and an enolizable second carbonyl compound is one of the most powerful and reliable carbon–carbon bond-forming transformations in

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• aryl and heteroaryl ketones featuring a single enolizable position (Scheme 2) [22]. Notably, it was found that Cu(II) and Cu(I) salts gave similar yields. A radical trifluoromethylation was suggested for this transformation. The CF3•, which was generated by reaction of tert-butyl hydroperoxide with

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• obtained as well with less electron-deficient dienophiles such as dimethyl fumarate and maleic anhydride. Michael-type reactions Enolizable ketones 49 react with E-1 in ethanolic solution in the presence of HCl to yield, after heating for 5 h, the corresponding Michael adduct 50 in 68–76% yield [53

• succinate 91 (see chapter Michael type reactions) [54] (Scheme 28). In this case, the reaction pathway comprises the ring closure through the attack of the O-nucleophile onto the terminal cyano group. The analogous reaction was reported for the enolizable indane-1,3-dione. Redox reactions The replacement of

• (α-styryl)furan (47) with dimethyl dicyanofumarate (E-1b). Acid-catalyzed Michael addition of enolizable ketones of type 49 to E-1. Reaction of diethyl dicyanofumarate (E-1a) with ammonia NH3. Reaction of dialkyl dicyanofumarates E-1 with primary and secondary amines. Reaction of dialkyl

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• facilitates the cleavage of the highly polar Cα–P+ bond. Keywords: N-(1-arylalkyl)imides; α-imidoalkylating agents; imidoalkylation reactions; 1-imidoalkylphosphonium salts; Tscherniac–Einhorn-type reaction; Introduction The aminomethylation of C–H acidic compounds by the condensation of non-enolizable

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• Mannich-type reaction; rhodium–hydride; zinc enolate; Introduction The Mannich reaction is an important and classical C–C bond-forming reaction between an enolizable carbonyl compound and an imine to give the corresponding β-aminocarbonyl compound. For example, Shibasaki and his colleague reported the