Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• motif in bioactive compounds and the synthetic utility of its olefinic C=C bond. The most extensively explored approach to this transformation is the transition metal-catalyzed C–N coupling between azoles and vinylating agents, including vinyl halides [4], boronates [5], sulfonium salts [6][7][8], and

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• in moderate to good yields, employing 2,7-dimethoxythioxanthone (2,2’-OMeTX) as a triplet sensitizer for BCB excitation (Scheme 3A) [38]. Starting from BCB 24, alkenes including styrene derivatives, enol ethers, and vinyl boronates could be incorporated to give 1,2-BCHs (±)-25a–d. Brown and co

• and co-workers employed an intramolecular coupling of sulfonylhydrazones and boronates to access 1,2,3-trisubstituted BCPs (1,2,3-BCPs). They also showed that their method can be extended to the synthesis of different bicyclic systems [41]. The synthesis of bridge mono-fluorinated 1,2,3,-BCPs by

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• -workers [61] extended the application of NHC–copper catalysts to the conjugate addition of boronates to acyclic α,β-unsaturated carboxylic esters, ketones, and thioesters leading to the enantioselective formation of boron-substituted quaternary carbon stereogenic centers (Scheme 43). All transformations

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• , transformation to potassium trifluoroborate salt, hydrolysis, C–C cross-coupling, base-mediated elimination, radical C–B cleavage) [72]. Therefore, enantioenriched boronates are commonly applied intermediates in organometallic, medicinal, and other fields of chemistry. At the same time, some organoboronic acid

• -workers explored the copper-catalyzed asymmetric conjugate borylation of β-substituted cyclic enones using chiral bisphosphine ligand L21 [77]. Other than the oxidation and hydrolysis of the produced enantiomerically enriched tertiary boronates, in one example, they have demonstrated the utilization of

• borylation/aldol cyclization methodology provides rapid access to various indane derivatives 160 (Scheme 41A) with good yields and excellent chemo-, and stereoselectivities. Next, they successfully extended this process to 6-, and 7-membered benzocyclic compounds and the corresponding boronates 162 were

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• of allenes, using various boronates as the terminal reductant (Scheme 5) [68]. Experimental and computational studies suggested the reaction proceeded by hydroboration of the allene 14 by bis(pentafluorophenyl)borane to give an allylborane 15, which underwent allylation of a second equivalent of the

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• alcohols 20 (Scheme 5) [35]. In the first step, a solution of terpenyl pinacol boronates 17 and bromochloromethane in tetrahydrofuran is mixed with n-butyllithium in n-hexane at −40 °C. By using a specifically designed, 3D-printed micromixer made from stainless steel, ultrafast mixing of both solutions is

• achieved within milliseconds initializing bromine–lithium exchange of bromochloromethane to generate (chloromethyl)lithium. This carbenoid species readily reacts with terpenyl pinacol boronates 17, resulting in the formation of intermediate 18, which undergoes 1,2-anionotropic rearrangement to the

• homologation reactor module (and then, if desired, even to a third) to reiterate homologation. The resulting reaction mixture is either collected directly to provide the homologated pinacol boronates 19, e.g., menthol-derived compound 21, which was found to have a “rather sweet, slightly apple-like, fruity

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

• as Mn(0) and MnO2, that had been employed in the previous work by the same authors to ensure catalytic turnover [110]. Substrates containing functional groups, like esters, phthalimides, silyl enol ethers, boronates, ketones, tertiary alcohols, epoxides, and cyclobutanes, were compatible with the

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

• . Fujioka and Amii [27] prepared the versatile building blocks 16 by the reaction of 12 with alkenyl boronates 15 (Scheme 8). Although this method is one of the most popular and reliable ones, it does have some drawbacks, particularly the high temperatures that are required (180–190 °C). Another

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• -3,5-dimethoxybenzene, where the longest linear sequence consists of five steps. The key reaction was a palladium-catalyzed Suzuki coupling of an aromatic boronate with a brominated resorcin derivative. Keywords: biaryls; boronates; mycotoxins; polyketides; Suzuki coupling; Introduction 5’-Methoxy-6

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• (Scheme 23). The aldehyde (Z)-(+)-143a was the common intermediate for the synthesis of (E)- or (Z)-selective vinyl boronates or vinyl halides (+)-145 to accomplish total syntheses of all inthomycins A–C ((+)-1, (+)-2 and (–)-3, see Scheme 25 and Scheme 26). With the key intermediate (Z)-(+)-143a in hand

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

• acids as catalysts for C-allylation of unprotected oximes with allyl boronates [58]. After screening to find the best reaction conditions, oxime 103 was converted to α-tertiary acetal-protected hydroxylamine (±)-104 in the presence of 3,5-difluorophenylboronic acid and diisopropyl allyl boronate (108

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• show excellent nucleophilicity arising from the oxindole–hydroxyindole tautomerization [18][19], this synthetic approach is undoubtedly attractive because it could complement our previous one using nucleophilic amido-functionalized allyl boronates in terms of the structural diversity as well as

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• corresponding boronic acids 2g,q,s. Pinacol alkenyl boronates 7a–h smoothly furnished the corresponding N1-alkenyl-substituted pyrimidones 5a–h. Product 5f obtained from the simplest vinylboronic acid pinacol ester (7f) appears to be of special value [55][56]. However, we did not succeed in reacting substrate

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• . The removal of the silyl protecting group and hydrolysis of the methyl ester afforded the carboxylic acid 108. A subsequently attempted Suzuki–Miyaura coupling of 108 with vinyl boronates was described as “capricious”, and thus the acid was esterified with the tert-butyl donor reagent 109 to afford

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

• formations of enantioenriched α-substituted allylic boronates take place in high yields and site-selectivity (>98% SN2′) starting with either trans- or cis-disubstituted alkenes 313, as well as linear or branched alkyl and aryl trisubstituted allylic carbonates 314. The further oxidation of the boronated

• )boronates 320–322. High functional group tolerance and enantioselectivities are characteristics of this reaction. The stereoselective formation of a 3,3-disubstituted cyclopentene scaffold (e.g., 331), containing three contiguous asymmetric centers, was also developed starting from an achiral cyclic acetal

• (335; Scheme 53) [96]. The first Cu(I)-catalyzed allylic displacement on alkenes containing a CF3 group was reported in 2018. Enantioenriched γ,γ-gem-difluoroallylic boronates 339–341 can be obtained via this process. Once the obtained difluoromethylene scaffolds are formed, they are readily converted

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

• AgNO3-catalyzed synthesis of alkyl fluorides through radical deboronofluorination of alkyl boronates and boronic acids in acidic aqueous solution was also developed by Li and co-workers in 2014 [89]. This method features good yields and a wide functional group compatibility (Scheme 42). Recently, the

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• coupling reaction is a powerful method for the synthesis of ubiquitous biaryls and has been extensively employed in the synthesis of natural products, pharmaceuticals, agrochemicals, and polymers. The reaction usually involves a palladium-catalysed coupling of aryl boronates with aryl halides in organic

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• phosphinoferrocenyl-substituted calixarene ligands 27–29. Asymmetric coupling reaction of aryl boronates and aryl halides in the presence of calixarene mono and di(ferrocenylphosphine) ligands 27 and 28. Asymmetric allylic alkylation in the presence of calix[4]arene ligand (S,S)-29. Asymmetric Tsuji–Trost reaction in

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• modular synthesis of carbocyclic C-nucleosides [53]. The boronic acids/boronates (inset, Figure 13) of several (hetero)aryls were conducive to Suzuki coupling with the best result obtained when the C2', C3' and C5'–OHs were protected with TIPS and pivaloyl groups, respectively [53]. The cross-coupling

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

• iminyl anion 19. After protonation and hydrolysis of the imine function, the α-trifluoromethylated ketones 16 were obtained in moderate to good yields (Scheme 8) [27]. Alkenyl MIDA (N-methylimidodiacetic) boronates 20, as functionalised alkenes, were transformed into α-trifluoromethyl-α-boryl ketones 21

Mechanochemical borylation of aryldiazonium salts; merging light and ball milling

• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1463–1469, doi:10.3762/bjoc.13.144

• . Simultaneous neat grinding/irradiation of the reactants and the photocatalyst led to the formation of boronates in a molten state. On the other hand, the catalyst-free liquid-assisted grinding/irradiation reaction also led to product formation, featuring a direct photolysis pathway facilitated by substrate

• ). With the optimized reaction conditions in hand, we explored the photomechanochemical borylation of the halogenated aryldiazonium salts 1a–d (Table 2). Analogously to the case of 1a, the fluoro and chloro substituted aryldiazonium salts 1b and 1c did react affording the boronates 3b and 3c (Table 2

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• sequence starts with the reaction of diazo compound 20, generated under flow conditions, and boronic acid 19 (Scheme 19). Further sequential coupling with diazo compounds 21 and 22 led to boronates 23 or protodeboronated products 24 at the end of the sequence (Scheme 19). With the aim to exploit the

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• to generate vinyl stannanes [3], silanes [4] and boronates [5]. One of the most significant features of the Takai olefination is that it is generally highly selective for the formation of (E)-alkenes ((E):(Z)-product ratios are typically around 4:1 or greater). This selectivity has found wide use

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• 5c. The resulting triazines 3b and 3c can then be coupled to boronic acids or boronates to give substituted and elongated triazine-based linkers. Furthermore, the reduction of the nitro group or cleavage of the methoxy group will give additional substituted linkers, amino and hydroxy-substituted ones

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• ester 11 as boron source (Scheme 2) [22][23][24]. 2-Pyridineboronic acid 11 was chosen due to its increased nucleophilicity compared to other boron sources like pinacol boronic esters or MIDA boronates [25][26]. The cross coupling proceeded smoothly in THF and gave ligands 9 and 10 in good yields