Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• the target compounds required the prior preparation of a panel of variously substituted 1,4-diketones 5. The 1,4-diketones 5 have been prepared either by a Nef reaction [56] from the corresponding nitroenone 3 or a Wittig reaction [57] from 1,2-cyclohexanedione and the corresponding ylide 4 (Scheme 2

• route remains limited in terms of chemical diversity as it depends on the availability of the corresponding nitro derivative. It was thus decided to move on to the Wittig reaction [57], offering a much more straightforward and efficient route to a panel of new diketones, 5e–k, from 1,2-cyclohexanedione

• and the corresponding Wittig ylides 4a–g (readily accessible from the corresponding halogenated derivatives, Scheme 2). Indeed, the Wittig reaction leads exclusively to the isomerized products 5. With the 1,4-diketones 5 in hand, we first investigated the synthesis of indole and indolone derivatives

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

• integrin inhibitors. Commonly used synthetic routes to tetrahydro-1,8-naphthyridine moieties by hydrogenation of saturated naphthyridines 3. Previous synthetic route to fluoropyrrolidine 6 utilising a Wittig reaction and the novel, higher yielding route using a Horner–Wadsworth–Emmons reaction. Synthesis

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

• [3.2.1]octadiene compound with an extended conjugation. Keywords: bicyclo[3.2.1]octadiene; photocyclization; thiophene; Vilsmeier–Haack reaction; Wittig reaction; Introduction The bicyclo[3.2.1]octane skeleton has become the subject of intensive research in recent years [1][2][3]. Its presence in

• purification, the aldehydes 1 and 2 were obtained in very good yields (1: 79%; 2: 68%), and subsequently used as novel starting substrates for further addition/condensation reactions. The Wittig reaction of the prepared aldehydes with the corresponding triphenylphosphonium salts provided five new styryl

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• obstacle was overcome by using a modified Fieser work-up procedure to yield the aldehyde 6 in high yield, 78%. Then, aldehyde 6 was converted to the α,β-unsaturated trans-ester 7 through a Wittig reaction with the phosphorane synthon 8, which was derived from ethyl bromoacetate at 60 °C for 8 h in THF in

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• synthesis of compound 15 from ʟ-dimethyl tartrate and butanone was 32%. We initially attempted to carry out the Wittig reaction of compound 15 with n-pentyltriphenylphosphonium bromide and the conditions of the individual reactions are collected in Table 1. Product 16 was obtained with various yields

• then used in the synthesis of (+)-disparlure (1), (−)-disparlure (3), (+)-monachalure (2), and (−)-monachalure (4). First, the (+)-enantiomers 1 and 2 were synthesized (Scheme 4). In a Wittig reaction with n-nonyltriphenylphosphonium bromide followed by reduction of the double bond, the longer chain of

• of the Wittig reaction. Supporting Information Supporting Information File 239: Experimental procedures of the synthesized compounds. Supporting Information File 240: Copies of 1H NMR and 13C NMR spectra. Acknowledgements We thank Dr Marietta Białoń for performing the GC–MS analysis. Funding A.D

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• cross-coupling reaction [17], Negishi cross-coupling reaction [18] and Wittig reaction [17]. The concept of the incorporation of fluorine into organic molecules has gained much interest since Fried and Sabo reported the improvement of the therapeutic index of cortisol by the incorporation of a fluorine

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• antimicrobial drugs. C-glycosidically-linked phospholipid derivatives of 4-amino-4-deoxy-ʟ-arabinose have been prepared as hydrolytically stable and chain-shortened analogues of the native undecaprenyl donor. The C-phosphonate unit was installed via a Wittig reaction of benzyl-protected 1,5-arabinonic acid

• ). Conversion of benzylated reducing sugars, such as glucose [15], N-acetyl-ᴅ-glucosamine [16], and galactose [17], into the corresponding C-glycosyl phosponates using a Wittig reaction with methylenetriphenylphosphorane furnished the respective glycoenitols, which were then subjected to mercuriocyclization

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• the corresponding α-bromo esters 16 and 17, in 68% and 72% yield, respectively. Finally, intramolecular Wittig reaction of 16 or 17 in the presence of N,N-diisopropylethylamine and triphenylphosphine provided building blocks 4 and 5 in 75% and 77% yield (43% and 51% overall yields from

Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• and Discussion The synthetic route to the β-isoxazoline-substituted porphyrin is depicted in Scheme 1, in which the double bond was furnished by Wittig reaction, followed by 1,3-dipolar cycloaddition reaction with stable dipoles. In detail, tetraphenylporphyrin (TPP) was used as starting material. A

• the β-position, a Wittig reaction was performed, in which the porphyrin phosphonium salt 1 reacted with 4-MeCO2-benzaldehyde in the presence of DBU to furnish the double bond, followed by insertion of Zn ions into the porphyrin cavity to give compound 2. Nitrile oxides [45] as one of the most reactive

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• -enynes through lithiation, borylation and rearrangement of cis or trans-alkynyloxiranes. This cascade reaction is stereospecific, probably due to the stereocontrolled group transfer from boron to the adjacent oxiranyl carbon in an oxiranylborate complex intermediate, followed by an internal bora-Wittig

• reaction. This method is particularly appealing, providing with good to high yields a wide diversity of functionalized E or Z tri- or tetrasubstituted α-enynes. Stereospecific formation of α-enynes from alkynyloxiranes. Trapping experiments of the oxiranyllithium derived from cis or trans-alkynyloxiranes

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• of the aldehyde function as the dimethyl acetal [16][17][18], hydroboration and oxidative work-up of 10 provided a mixture of epimeric alcohols 11 that was unified by Ley–Griffith oxidation [19] to give ketone 12 [20]. Subsequent Wittig reaction with ylide 13 and acetal cleavage of the resultant

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• . In most cases, the C2–C3 bond was formed by Ireland-, Johnson-, or Eschenmoser–Claisen rearrangement [10][11][12][13][14][15][16][17]. Alternatively, Evans methodology has been used [18][19][20]. The central C4–C5 double bond has also been constructed by Wittig reaction, cross metathesis, and ring

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• aldehyde (S)-18 prepared from O-benzyl-L-serine in three standard steps [53] was elongated by a two-carbon fragment employing a Wittig reaction to give Z-alkene 19. To introduce the next center of chirality of the required configuration a iodocyclocarbamation reaction was applied to give trans-oxazolidin-2

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• obtained for the desired products due to the formation of substantial amounts of ring-opened byproducts 10 resulting from the hydride addition to the carbonyl group of the oxazolidinone ring [33][34]. The alcohols 9 were then subjected to a Swern oxidation followed by a Wittig reaction to generate the

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• ring-opened product 18 using an alternative path. The double bond in the norbornene nucleus in compound 17 was cleaved in the traditional way by treatment with OsO4/NaIO4 and the resulting dialdehyde on Wittig reaction provided the diene 18 in 66% yield in two steps. Amazingly when compound 18 was

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• reaction steps. A common aldehyde intermediate has been used for the synthesis of both strongylodiols. Keywords: alkylation; Cadiot–Chodkiewicz coupling; Corey–Bakshi–Shibata reduction; Mosher’s analysis; Wittig reaction; Introduction Diacetylenic polyol compounds [1][2] originated from marine sources

• strongylodiol I The retrosynthetic analysis for strongylodiols H and I is delineated in Scheme 1. We envisaged that the target molecules strongylodiol H (9) and strongylodiol I (10) can be synthesized by a Wittig reaction of a common intermediate aldehyde 14 with triphenylphosphonium Wittig salts 15 and 16

• deprotection to give the primary alcohol which was subjected to oxidation to yield aldehyde 14a (Scheme 6). The latter was then subjected to a Wittig reaction with 15 followed by silyl deprotection as performed for 14 to furnish 9a (see Supporting Information File 1 for experimental details). The sign of the

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

• presence of the hydroxy functional group acting as a transition-state analog. The synthesis of the inhibitors commenced with the conversion of aldehyde 127 into alkene 128 via a Wittig reaction followed by epoxidation to furnish epoxide 129. Regioselective opening of the epoxide ring with a thiolate gave

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• by manipulations of 5. After acetal hydrolysis and the subsequent hydride reduction, 4-thioarabinose derivative 9 was obtained in good yield. Introduction of a TBDPS group at the primary hydroxy group of 9, oxidation and Wittig reaction, followed by deprotection of the benzyl group, gave allyl

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

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

• (compound 23) is shown in Figure 9, which involves installing an allyl group at C1' (20) and converting the C2'–CN to an aldehyde (21) followed by a Wittig reaction to install a second allyl group at C2' (22). Second generation Grubb’s catalyst was used for the ring formation, followed by hydrogenation to

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• used in liquid-assisted grinding (LAG) and properly chosen counter-ion pairing increases the percentage conversion of stilbenes in a mechanochemical Wittig reaction. Utilizing stepwise addition/evaporation of ethanol in liquid-assisted grinding also allows for the tuning of the diastereoselectivity in

• the Wittig reaction. Keywords: green chemistry; high-speed ball milling; HSBM; LAG; liquid-assisted grinding; Wittig; Introduction Mechanochemistry is maturing as a discipline and continuing to develop and grow [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Thus it is important to continue

• of the Wittig reaction under mechanochemical conditions [17][18]. The Wittig reaction is one of the most useful reactions for the synthesis of olefins [19][20][21][22][23]. Aside from its synthetic utility, its unique reaction mechanism (shown in Figure 1) and inherent diastereoselectivity has led to

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

• attention is paid to the use of these compounds as building blocks for the synthesis of carbo- and heterocyclic systems after their prior transformation into the corresponding phosphorus ylides, followed by the intramolecular Wittig reaction with various types of nucleophiles containing a carbonyl function

• in their structures. Keywords: 2-aminovinylphosphonium salts; nucleophilic addition; phosphorus ylides; vinylphosphonium salts; Wittig reaction; Introduction Vinylphosphonium salts have been known for a long time, although significant interest in these compounds dates back to 1964, when Schweizer

• to vinylphosphonium salt. A phosphorus ylide thus generated undergoes a subsequent intramolecular Wittig reaction, leading to a carbo- or heterocyclic ring closure (Scheme 2) [1][2][3]. This reaction can be considered as a general method for the synthesis of carbo- and heterocyclic systems

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -free Wittig reaction of organic halides with aldehydes or ketones (Scheme 6) [55]. Suzuki Coupling In 2000, Peters and co-workers first reported the palladium-catalyzed Suzuki coupling reaction under ball-milling conditions [56]. In a planetary mill for 30–60 min, the mixture of aryl halide (1.0 equiv

• ) compared to the conventional method that generally takes days to a week for completion. The reaction of methyl acrylate with different para-substituted aryl aldehydes in the presence of 20 mol % 1,4-diazabicyclo[2.2.2]octane (DABCO) catalyst at 0.5–45 h yielded the MBH products in 28–98% yield [53]. Wittig

• Reaction Pecharsky and co-workers reported the solvent-free mechanochemical synthesis of phosphonium salts [54] and phosphorus ylides [55] in the presence of the weak base K2CO3. Mechanochemically prepared phosphorous ylide from triphenylphosphine in presence of K2CO3 was utilized for a one-pot solvent

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• Wittig reaction followed by different metal-catalyzed reactions and harsh conditions are usually required [60][61][62]. In our case, the desired product was obtained under environmentally friendly reaction conditions and in a short reaction time. Thus, the PVP-Pd NPs proved to be an effective catalyst to