Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• liberated using TBAF to give compound 27 in 97% yield over two steps. The alcohol group in 27 was then oxidized to the corresponding aldehyde under Swern conditions and subsequently subjected to a Wittig reaction with a two-carbon phosphonium ylide reagent. The desired α,β-unsaturated ester 28 was then

• primary alcohol 99 (90%). Oxidation of this moiety with IBX to its corresponding aldehyde served as a substrate for the two-carbon homologation via Wittig reaction giving ester 96 in 80% yield over the two steps. After reduction of the ester group to its primary alcohol counterpart, the Sharpless

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• as only γ-amino ether 25 was observed in its absence. It was also important to carry out the reaction at −78 °C to avoid a 1,2-Wittig rearrangement of the lithiated benzyl ether [22]; this restricts the reaction to N-Bus-aziridines, as epoxides are not deprotonated by LTMP at such low temperatures

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• under mild reaction conditions and have widened the substrate scope of alkenes to those containing varied electronic and steric properties. Results and Discussion Our starting alkenes 4a–l are original and were synthesized in four steps involving coupling, Grignard, oxidation, and Wittig reactions. We

• fourth and final step, phenoxydiphenylalkene derivative 4a was prepared by a Wittig reaction, which was carried out using methyltriphenylphosphonium bromide with ketone 3a, in basic medium, at room temperature, and dry THF. After the structures of the starting compounds were elucidated, the method

• synthesized by Grignard reaction of 1a–l and aryl(or alkyl)magnesium bromides. Then 3a–l were prepared by oxidation of 2a–l using PCC. The final alkene compounds 4a–l were obtained by Wittig reaction using Me(Ph)3PBr, t-BuOK, and NaH. All substrates were purified by crystallization or column chromatography

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• methodology, they synthesized 2,3,6,7-anthracenetetracarbonitrile (90) in a good yield (84%) by double intermolecular Wittig reaction of the protected benzenetetracarbaldehyde 87 with reagent 88, followed by deprotection and double ring-closing reaction of intermediate 89; they used a mixture of triflic acid

• /water in the first step and trimethylamine in the next reaction step [56]. Other procedures In 2008, Lin et al. reported a homo-elongation protocol to obtain acene diesters and dinitriles starting from dialdehydes (Scheme 23) [57]. This methodology was based on a Wittig reaction between substituted [n

• ]acene-2,3-dicarbaldehydes 91 and the Wittig reagents 92; DBU was employed to produce the corresponding substituted [n+1]acene-2,3-diethyl diesters 93. Then, in two steps (reduction and Swern oxidation), the authors converted the diesters 93 to the dialdehydes 94, which could be transformed into the

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• Scheme 3 consisting of the following steps: (i) Wittig reaction of 2-bromobenzaldehyde with methyltriphenylphosphonium iodide ylide, (ii) lithiation of the resultant o-bromostyrene with n-BuLi and reaction of the aryl lithium species with ethylene oxide, and (iii) oxidation of the resultant primary

• -vinylphenyl)acetaldehyde (13a) using the route as outlined in Scheme 4. The synthesis started with the Wittig reaction of 2-bromobenzaldehyde (9a) with (methoxymethyl)triphenylphosphonium chloride (MTPPC) upon action with n-butyllithium in THF at 0 °C to give the vinyl ether 10a that was subjected to acidic

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• Wittig reaction with methylenetriphenylphosphorane (Ph3P=CH2) produced the 5′-methylene derivative [62]. Finally, oxidation with meta-chloroperbenzoic acid (mCPBA) afforded the nucleoside 97. Treatment of the nucleoside 97 with Grignard reagent PhMgBr in THF produced nucleoside 98, whose secondary

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• homologation [3]. Much effort has been devoted to developing a procedure for the synthesis of alkynes from carbonyl compounds, and the Corey–Fuchs method, the Seyferth–Gilbert method, and the Ohira–Bestmann modification have been developed (Scheme 1) [4][5][6][7]. These methods consist of the Wittig or Horner

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• . Consequently, we decided to develop a new synthetic strategy for the preparation of trigonoine B (1). Carbodiimides are valuable synthetic intermediates that can be obtained by an aza-Wittig reaction of isocyanates with iminophosphoranes or by dehydration of urea [26]. Molina et al. previously reported the

• synthesis of 2-aminopyridine derivatives through an electrocyclization of conjugated carbodiimides derived from an aza-Wittig reaction of iminophosphoranes and isocyanates [27]. Hibino and co-workers also achieved the preparation of mutagenic amino-α-carbolines (2-amino-9H-pyrido[2,3-b]indole, AαC) and

• MeAαC by the electrocyclization of 3-alkenyl-2-carbodiimidoindole derivatives obtained by an aza-Wittig reaction of indol-2-yl-iminophosphoranes and isocyanates [28]. In this work, we report the first total synthesis of trigonoine B (1) involving the construction of a pyrrolo[2,3-c]quinoline framework

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

• Ph3P+CF2−, which was used for the Wittig olefination of aldehydes and ketones. However, heating PDFA in nonpolar solvents (e.g., xylene at 90 °C) favors the dissociation of the ylide to release difluorocarbene which is able to effect the cyclopropanation of alkenes [34]. Trimethylsilyl

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• required vinylstannane and iii) Stille coupling between them (Scheme 3) [39]. The required divinyl halides 36 were prepared, starting from phenylacetaldehyde (33), by using the Takai [38] or Wittig procedures [40] as shown in Scheme 3 (68% of a 3.3:1 mixture of (E,E)/(Z,E)-36b and 69% yield of a 8:1

• followed by immediate TBS ether formation produced (+)-110a in 82% yield over 2 steps. Wittig olefination of (+)-110a with phosphonate 111 furnished the desired (E)-(+)-112a, which was then converted into Hatakeyama’s enynol (−)-82b using a four-step sequence to complete the formal synthesis of inthomycin

• , it was transformed into (E)-vinylboronate (+)-145b in perfect stereoselectivity by using the recently developed boron-Wittig reaction with bis[(pinacolato)boryl]methane (144) [79]. By applying the Corey–Fuchs dibromoolefination and followed by Pd-catalyzed hydrogenolysis under Uenishi's conditions

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• sp. and displaying inhibitory activities towards telomerases. The classical synthetic approach for carbohelicenes is the oxidative photocyclization of stilbene derivatives [1][2][3][4][5][6][7][8][9][10][11]. The latter are generally available via the Wittig, Heck-type or McMurry couplings. It is

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• ). A Wittig reaction with pentylphosphonium bromide resulted in bromoalkene 21 in a 9:1 Z/E-mixture. In the following step, the Grignard reagent of 21 was converted into the respective Gilman cuprate with Cu(I)I for the selective reaction with the epoxide function of (S)-22 [34]. The hydroxyester 23

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• relatively short list: the reduction of the OH group of the C(CF3)2OH moiety (this protocol was employed in the synthesis of enantiomerically pure (S)-5,5,5,5',5',5'-hexafluoroleucine [1]); the Wittig reaction of Ph3P=C(O)C(O)OR with hexafluoroacetone, followed by the hydrogenation of the CH=C(CF3)2 unit

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• context, their journey started from syn-tris(oxonorborneno)benzene 23, obtained via palladium-catalyzed cyclotrimerization of iodonorbornene. The C3-symmetric compound 23 was then converted into the methylene groups containing compound 103 using Wittig reaction which on further treatment with

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• Kitahara’s synthesis [8][9], the Wittig olefination of 24, followed by a catalytic hydrogenation, removal of the dimethylaminal protecting group, and lactonization gave 25 as a mixture of diastereomers (Scheme 2). The further transformation of 25 afforded the dihydropyran 26, which upon catalytic

• hydrogenation over Pt2O and then low-temperature DIBAL reduction afforded the all-cis tetrasubstituted tetrahydropyran 27. In Koide et al.’s synthesis, the unsaturated lactone 29 was prepared via the Wittig methenylation of 24, followed by aminal hydrolysis, methallylation of the 2° alcohol 28, and ring-closing

• ] was followed by a 3-O-vinylation. A thermal 3,3-sigmatropic Claisen rearrangement of 62 gave the cis-2,6-disubstituted dihydropyran 63, which upon sequential Wittig olefination with 2-(triphenylphosporanylidene)propanal and then methylenetriphenylphosphorane yielded the diene 64. The removal of the di

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

• the Wittig step presented complications on both gram and kilogram scales. Herein, we report a novel synthetic sequence to tetrahydro-1,8-naphthyridines using a Horner–Wadsworth–Emmons reaction using diphosphorylated compound 7, proceeding in high yields and high purities without the need for

• defluorination, presumably via a Tsuji–Trost-like elimination of the allylic fluoride [18][19]. This sequence represents a marked improvement from the Wittig-including route, lowering the number of synthetic steps and increasing the overall yield [2]. Furthermore, no problematic byproducts are formed, and good

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• unsuccessful to be prepared by the Schlosser modification of the Wittig olefination (Scheme 26) [33]. A similar isomerization method was also used by Holmes in the synthesis of (−)-gloeosporone. Under irradiation conditions, diphenyl disulfide helped to convert the Z-alkene 76 to the E-alkene 77 (Scheme 27) [34

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

• were synthesized through Wittig reactions and subjected to photochemical cyclization, in terms of obtaining the new annulated structures. As part of this study, the aldol reaction of the starting 2-substituted carbaldehyde with acetone was also performed, which produced the thieno-fused benzobicyclo

• [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

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• (III)–P(V) redox cycle, such as in catalytic Wittig-, aza-Wittig-, Staudinger-, Appel- and other reactions [16][17][18][19][20][21]. The ring strain of the four- and five-membered derivatives makes them highly susceptible to deoxygenation, thus they are ideal organocatalysts in P(III)–P(V) redox

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• to build the desired 1,3-dienic units. The advantageous association of this approach with name reactions like Grignard, Wittig, Diels–Alder, Suzuki–Miyaura, Heck cross-coupling, etc. is illustrated. Examples unveil the generality of such tandem reactions in providing not only the intricate structures

• ][39][40][41][42][43]. In ingeniously elaborated procedures, olefin metathesis has been frequently employed as such or associated with name reactions like Grignard, Wittig, Diels–Alder, Suzuki–Miyaura, Heck, etc., resulting in the assembly of diverse intricate building blocks of the targeted structures

• dienyne precursors in three steps, from (S)- and (R)-citronellal, through a diastereoselective Michael addition, chemoselective dibromoolefination, and a one-pot Wittig olefination/alkyne-bond formation. The enantiopure dienynes were then converted into the enantiomeric hydroazulenes in 53% and 55% yield

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

• the pheromone structures was attached giving compound 20 in 74% yield. Next, removal of the protecting group from the secondary alcohol followed by a Swern oxidation gave aldehyde 21 which was subjected to Wittig reactions with either of the two different alkyl derivatives and catalytic hydrogenation

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 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• following three categories: (i) by Wittig or Doebner reaction of indoles bearing a 3-aldehyde group; (ii) by 1,4- or 1,2-addition of α,β-enones or carbonyl compounds, followed by oxidation or elimination, respectively; (iii) by Pd-catalysed oxidative coupling of indoles with activated alkenes. Several

• groups have used Wittig reactions for the synthesis of 3-alkenylindoles [13][14][15]. Another variant that uses the Doebner condensation was reported by Singh and co-worker, who condensed indole-3-carbaldehyde with phenylacetic acid in the presence of pyridine as the solvent/base and piperidine as the