Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• -dichlorocamphorsultam) 17-2 [75] (Scheme 37). The maximum enantioselectivity of enolates of β-ketoesters with (−)-9-1 or (+)-9-2, first prepared by Lang in 1988 (see section 1-9), was 70% ee. The asymmetric fluorination with (+)- or (−)-17-2 afforded up to 75% ee as indicated in Scheme 38. The dichloro reagent 17-2

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

• esters 29, such as 1,3-diketones, β-ketoesters, cyclic 1,3-diketone (dimedone), and β-ketoamide, respectively, to afford desired 1,4,5-trisubstituted 1,2,3-triazoles containing glycosyl with high yield. It should be pointed out that no byproducts were recognized under optimized reaction conditions. In

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

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

• literature. To avoid the formation of two isomers, the reaction is generally carried out with β-ketoesters, α,γ-dicarbonyl esters, β-ketoaldehydes, or in later modifications acetylenic ketones [47][48]. The reaction was used for the 1939 commercial synthesis of pyridoxine (vitamin B6) [2], the first

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• equivalents of the β-ketoester ethyl acetoacetate (2) with benzaldehyde (1a) and ammonia (Scheme 1) [11]. This procedure was later optimized over the years using different substrates by varying the β-ketoesters and aldehydes in order to prepare a larger array of 1,4-dihydropyridines (1,4-DHPs) [12]. In

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

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

• bearing fluorine and nitrogen atoms involves the asymmetric addition of α-fluoro-β-ketoesters or α-fluoro-α-nitro esters to appropriate electrophiles [84][85][86][87][88][89]. Results and Discussion Initially, we prepared a series of Ugi adducts 8 by varying acid, 2-oxo-aldehyde, amine, and isocyanide

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

• the formation of 5- and 7-oxothiazolopyrimidine-6-carbonitriles (Scheme 1) [12][13]. The synthesis of thiazolopyrimidines through the reaction of 2-aminothiazoles with 1,3-ketoesters in the presence of acids, bases or condensing agents (Scheme 2) has been studied fairly well [6][8][14][15][16]. The

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• . 1,3-Diketones and 1,3-ketoesters 45 undergo cross-dehydrogenative C–O coupling with oximes under the action of oxidizing agents [46], such as KMnO4, Mn(OAc)3 or the KMnO4/Mn(OAc)3 system (Scheme 15). A radical mechanism is suggested for the formation of the C–O coupling products 46 in which the

• oxidizing agent serves to generate oxime radicals from oximes and perform one-electron oxidation of 1,3-dicarbonyl compounds 45. The formation of oxime radicals under the reaction conditions was confirmed by EPR spectroscopy [46]. 1,3-Diketones and 1,3-ketoesters with easily oxidizable groups, such as allyl

• the oxime group. The lowest yield was obtained with an aromatic oxime (product 46e, yield 27%). Later, the Cu(BF4)2 (cat.)/t-BuOOH oxidative system [87] was proposed as an alternative to stoichiometric metal-containing oxidants, such as KMnO4, Mn(OAc)3, and KMnO4/Mn(OAc)3 (Scheme 16). 1,3-Ketoesters

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• rearrangements of O-allyl β-ketoesters [35][36][37]. Hiersemann and Strassner studied the Claisen rearrangement with H-bond-donating organocatalysts by computational methods and concluded that thioureas are not efficient in transition-state stabilization [38]. Regarding the usefulness of the Ireland–Claisen

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• substrates were successfully fluorinated with high enantioselectivities. In 2013, the Kesavan group [73] reported the use of tartrate-derived bidentate bisoxazoline-Cu(II) complexes for the enantioselective fluorination of aliphatic cyclic and acyclic β-ketoesters with up to 98% yields (Scheme 30). In this

• method, (S,S)-Nap-(R,R)-Box as the most suitable diastereomeric ligand forms a 5-membered chelate with copper. In the same year, an efficient and highly enantioselective fluorination of β-ketoesters catalyzed by diphenylamine-linked bis(thiazoline)-Cu(OTf)2 complexes was reported by Du and co-worker

• (Scheme 31a) [74]. Che and co-workers [75] achieved a similar α-fluorination of β-ketoesters and N-Boc-oxindoles (Scheme 31b). Compared with Du’s method, Che employed both AgClO4 and chiral iron(III)-salan complexes as the catalyst. In 2016, the group of Nishikata [76] described a copper-catalyzed site

Enantioselective Diels–Alder reaction of anthracene by chiral tritylium catalysis

• Qichao Zhang,
• Jian Lv and
• Sanzhong Luo

Beilstein J. Org. Chem. 2019, 15, 1304–1312, doi:10.3762/bjoc.15.129

• the carbocation precursor [20][21]. In this latent strategy, the carbocation precursor can undergo facile ionic dissociation upon mild external stimulation such as polar substrates (such as α-ketoesters) to form a catalytically active chiral ion pair for substrate activation and chiral induction

• α-ketoesters 4 was subjected to the reaction with anthracene (3a) to give the desired cycloadducts 5a–n in moderate to good yields and with up to 93% ee. The bulkier isopropyl ketoester resulted in a lower yield and enantioselectivity (Table 2, entry 3 vs 1 and 2). Variations on the aromatic group

• of the ketoesters were well tolerated, giving the products in decent yields and high enantioselectivities. Unfortunately, no reaction was observed when an aliphatic substituted β,γ-unsaturated α-ketoester was used (data not shown). The Diels–Alder reaction of substituted anthracenes has been well

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• deprotect the TBDPS ether more slowly than FeCl3, and adjustment of the reaction conditions with AlCl3 (to 2 equiv in CH2Cl2, −78 °C, followed by slow warming to −50 °C) cleanly provided α-ketoester 20 (Scheme 6). α-Ketoesters can be prone to hydrate easily (2D TLC analysis of 20 indicated decomposition

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• construction of pyridines bearing a carboxylate or CN group at C3 position has been a lucrative target for chemists due to the pharmaceutically privileged status (Figure 1). In this context, Rodriguez’s group successfully established a one-pot three-component reaction between β,γ-unsaturated α-ketoesters, 1,3

• -dicarbonyl compounds, and ammonium acetate promoted by acid under aerobic conditions [37][38]. Furthermore, Brønsted- and Lewis-acid-catalyzed cyclization reactions between β-enamino esters (derived from β-ketoesters and ammonium acetate) and alkynones/α,β-unsaturated carbonyls/in situ generated α,β

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• of interest from a pharmacological point of view. The first and probably most frequently used method for the synthesis of pyrazolones is based on the Knorr condensation of β-ketoesters with substituted or unsubstituted hydrazines. However, these reactions often suffer from certain disadvantages, such

• -ketoesters 4 and 4' from pregnenolone acetate (1) and pregnadienolone acetate (1'). Cyclization of compound 4 with hydrazine hydrate (5a), phenylhydrazine (5b) and methylhydrazine (5c). Synthesis of steroidal N(1')-aryl-substituted pyrazol-5'-onesa. Antiproliferative effects of the synthesized compounds on

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• was proposed to proceed via the formation of the transition state 73 to avoid steric interaction between the R group of the aldehyde and the SMe of the toluene precursor, hence, led to anti selectivity. The biocatalytic reduction of α-sulfenyl-β-ketoesters 74 using Baker’s yeast was reported by

• aromatic thiols. Ring-opening reactions of cyclohexene oxide with thiols by using CPs 1-Eu and 2-Tb. CBS-oxazaborolidine-catalyzed borane reduction of β-keto sulfides. Preparation of β-hydroxy sulfides via connectivity. Baker’s yeast-catalyzed reduction of sulfenylated β-ketoesters. Sodium-mediated ring

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• more effective chiral iodonium salts 16 which were used for the α-arylation of β-ketoester 86 to deliver α-arylated β-ketoesters 87 with moderate enantioselectivity (Scheme 17) [63]. This was the first example of an asymmetric α-arylation of β-ketoesters using hypervalent iodine reagents. A more

• could be achieved even by using a 50 mol % catalyst loading. A nucleophilic attack of the fluoride ion to the intermediate 104 or a possible ligand coupling pathway via 105 could justify the product formation (Scheme 23). Waser et al. developed an asymmetric alkynylation of β-ketoesters and amides 107

• for the alkynylation of β-ketoesters [76]. Pouységu and Quideau et al. prepared new axially chiral biaryl I(III) reagents 18 assembled with alkynyl ligands. They were able to achieve alkynylation of β-ketoesters 114 as well as dearomative alkynylation of phenolic derivatives 118 to obtain derivatives

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• -membered heterocycles such as thiophenes, furans, and pyrroles. Consequently, numerous multistep approaches to unsymmetrical 1,4-dicarbonyl compounds involving, e.g., SN2-type displacements [1] or highly functionalized substrates such as β-ketoesters [2][3] or β-ketosulfones [4] have been developed

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -ketoesters and phenols (the Pechmann condensation) [17]. Recent studies for the metal-catalyzed reactions for the synthesis of the coumarin skeleton are as follows: the Yb(OTf)3-catalyzed microwave irradiation of phenols and propynoic acids [18], the Pd(OAc)2-catalyzed oxidative cyclocarbonylation of 2

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• environments. All the synthesized compounds were reported as good antimicrobial agents. Recently the reaction of β-ketoesters 81 as in the three-component reaction with 5-aminopyrazoles 16 and substituted salicylic aldehydes 83 was also studied by Fan et al. [69]. An extensive survey of catalysts and solvents

• -aminopyrazole derivatives 115 with acetylacetone (104) and various β-ketoesters 81, respectively, in refluxing acetic acid with catalytic amount of suphuric acid (Scheme 32). The reaction of 3(5)-amino-5(3)-hydrazinopyrazole dihydrochloride (118) with symmetrical and unsymmetrical diketones 119 was studied by

•  41. 7-Chloropyrazolo[1,5-a]pyrimidines 140 obtained by 4-H/cyano/carboxylate-5-aminopyrazoles 126 (X = H, Y = R) and β-ketoesters 81 followed by chlorination with POCl3, were converted to 7-aminopyrazolo[1,5-a]pyrimidines 142 and 7-methoxy/thiomethoxypyrazolo[1,5-a]pyrimidines 143 on treatment of NIS

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• starting material and resinification. Apparently, it was caused by interaction of Et3N with ANBF because the blank experiment (1 + Et3N with no ketone added) also resulted in decomposition of ANBF. Therefore we studied reactions of 1 with more acidic 1,3-diketones, ketoesters and related compounds. The

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• , Shibata, Toru and co-workers used CF3SO2Cl for the enantioselective chlorination of β-ketoesters and oxindoles in the presence of a dbfox-Ph/Ni(II) system (dbfox-Ph = [(R,R)-4,6-dibenzofurandiyl-2,2'-bis(4-phenyloxazoline)]) (Scheme 42) [58]. The reaction proceeded in good to excellent yields and

• phenols. Mono- and dichlorination of carbon acids. Monochlorination of (N-aryl-N-hydroxy)acylacetamides. Examples of the synthesis of heterocycles fused with β-lactams through a chlorination/cyclisation process. Enantioselective chlorination of β-ketoesters and oxindoles. Enantioselective chlorination of

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• Irwan Iskandar Roslan Kian-Hong Ng Gaik-Khuan Chuah Stephan Jaenicke Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 10.3762/bjoc.13.270 Abstract Two regiodivergent approaches to intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters

• , In(OTf)3, results in the regioselective nucleophilic attack at both carbonyl groups forming benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones instead. Keywords: cyclization; fused-ring systems; indium; radical; regiodivergent; Introduction β-Ketoesters are versatile substrates frequently used in

• ][12][13] with leaving groups, thus switching to an electrophile [14][15][16], or convert to an α-radical carbon with an oxidant [17][18][19]. β-Ketoesters are also inexpensive, abundant and commercially available, making them attractive substrates. In our continuing effort to develop green and atom

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• enantiomerically pure β-ketoamides (Scheme 34) [49]. 2.2.4. Reactions with carbon nucleophiles: The first reaction of vinylphosphonium salts with carbon nucleophiles was reported by Schweizer and O'Neill in 1965. The authors used vinyltriphenylphosphonium bromide (8) and ketoesters in the presence of sodium

• of cyclic alkenes in the intramolecular Wittig reaction from vinylphosphonium bromide and ketoesters as precursors of carbon nucleophiles. Synthesis of 1,3-cyclohexadienes by reaction of 1,3-butadienyltriphenylphosphonium bromide with enolate anions. Synthesis of bicyclo[3.3.0]octenes by reaction of

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• [1,5-b]pyridazines along route B, 1-aminoimidazoles with no substituents at the C-5 atom of the original heterocycle and 1,3-dielectrophilic reagents are used, e.g., 1,3-diketones [24][25][26], β-ketoesters [24], α,β-unsaturated ketones [27][28], including those obtained in situ [29][30] or containing