(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

• undergo chemical transformations in their synthesis of ketoprofen bioisostere 189 (Scheme 18B) [72]. 1,3-Cuneane 186 bearing two electron-withdrawing groups was accessible by oxidation of 1,3-cuneane 185a. The 1,3-cuneane scaffold was stable to Wittig olefination and Weinreb ester formation (to 187

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• ethyl chloroformate/Et3N, followed by Wittig olefination with an ylide generated from (methoxymethyl)triphenylphosphonium chloride and LDA to give the enol ethers as E/Z mixtures. N-Phenethyl carbamates were obtained from benzaldehydes via Henry reaction with nitromethane, followed by zinc dust

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

• 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

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

• ] 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

• ) gave the C-phenyl glucoside 75 [36]. Notably, the use of oxidants other than BQ gave either the TMS enol ether or the 2,3-dihydro-6-phenyl-4H-pyran-4-one. The C-3 exocyclic methylene group was introduced by a Wittig olefination, and after the manipulation of the protecting groups, a VO(acac)2-catalyzed

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

• 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

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• alkylidene phosphoranes which in turn may undergo Wittig olefination with elimination of Ph3P=O [1][5]. Recently, a study of the tributylphosphane-catalyzed reaction of ethyl 2-butynoate and ethanol by in-situ ESIMS and NMR techniques has been published [6], and mechanistic aspects of trialkylphosphane

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

• -tryptophanol ((S)-41). The successful transformation of the aziridine alcohol (2S,1'R)-7 into ʟ-homophenylalaninol ((S)-42) depended on two crucial steps: the aziridine ring opening in the presence of phosgene to form the 4-(chloromethyl)oxazolidin-2-one (4R,1'R)-43 and Wittig olefination to add the benzyl

• sources and are known as precursors to tropane alkaloids [59]. Together with (−)-pseudohygroline (2S,2'R)-62 they were synthesized from a common intermediate (2S,1'R)-63 prepared from the aldehyde (2R,1'R)-6 by Wittig olefination [60] and a regioselective C=C bond reduction (Scheme 17) [61]. N-Methylation

• )-6 was transformed into its higher homolog (2R,1'R)-188 employing Wittig olefination, the C=C bond reduction and Swern oxidation. The required alkyl chains were introduced by Grignard reagents and mixtures of diastereoisomeric alcohols were oxidized to ketones 189a–d. Catalytic hydrogenation allowed

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

• a protected serinal (R)-23 [54]. Wittig olefination extended the alkyl chain by two carbon atoms and simultaneously installed the C=C bond which was subjected to the intramolecular epoxidation to give a >20:1 mixture of aminoepoxides with the isomer (2S,3R,4R)-117 dominating. Without isolation this

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• Christiane Schultze Bernd Schmidt Universität Potsdam, Institut fuer Chemie, Karl-Liebknecht-Straße 24–25, D-14476 Potsdam-Golm, Germany 10.3762/bjoc.14.278 Abstract 8-Allylcoumarins are conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination

• the past few years. Starting materials are allyl ethers of salicylic aldehydes or ketones 5 and the stable ylide ethyl (triphosphoranylidene)acetate (6), which upon microwave irradiation undergo a tandem Claisen rearrangement/Wittig olefination/cyclization sequence. This sequence was pioneered by the

• groups of Harwood [31][32] and Mali [33][34][35][36], and its Wittig olefination/cyclization part has been employed in the synthesis of various coumarins without alkyl substituents at position 8 [37][38][39]. In all previous reports conventional heating was used to induce the tandem sequence. In this

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• generated the cross-coupling product 22 (72%). Next, aldehyde 22 was subjected to Wittig olefination to provide the corresponding alkene 23 (69%), which on subsequent treatment with KOt-Bu in THF gave the isomerized product 24 (73%). Later, RCM of isomerized olefin 24 with the help of G-II catalyst offered

• end, aldehydes 58a,b were subjected to a Wittig olefination followed by condensation with acryloyl chloride (60) to generate the corresponding diolefinic substrates such as 61a (70%) and 61b (65%). Later, these diolefins 61a,b were subjected to RCM with the aid of G-II catalyst 2 to furnish the

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

• to Wittig olefination reaction with triphenylphosphonium salt of n-nonyl bromide 15 in presence of n-BuLi to produce the corresponding Z-olefin 28 exclusively in 83% yield. Di-desilylation of compound 28 was easily achieved with n-tetrabutylammonium fluoride to furnish the target molecule

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• -heterocyclic carbenes (NHCs, Scheme 11) [40]. The reaction was first performed on the γ,γ-difluoro-α,β-enal 52 which was synthesized via a Wittig olefination of 50. The resulting monofluoroalkene Boc-Val-ψ[(Z)-CF=CH]-Gly-OEt was obtained in good yield. Afterwards, the γ,γ-difluoro-α,β-enoylsilane 55, obtained

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• intermediate 45, which was subjected to Wittig olefination. Subsequent aza-Sakurai cyclization of intermediate 46 provided tricyclic derivative 47 as a single stereoisomer, which was then transformed into target myrioneurinol by standard operations. Addition of organometallic reagents to conjugated

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• conventional steps viz. HWE-type olefination leading to the unsaturated ester 5, saturation of the double bond in the latter to 6, reduction of the ester moiety in 6 to the alcohol 7 followed by its oxidation. The aldehyde 8 thus obtained was subjected to a Wittig olefination to obtain the desired alkene 9 in

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• ) was treated with the Wittig reagent Ph3P=CHCO2Et and the resulting unsaturated ester was then hydrogenated with Pd–C and H2 at room temperature to obtain compound 11 in 91% yield over two steps (Scheme 2). DIBAL-H (1.1 equiv, –78 °C) reduction of the ester group of 11 followed by Wittig olefination of

• of the allyl group in 16 with 9-BBN and the oxidation of the resulting organoborane with NaOH and H2O2 furnished alcohol 17 in 96% yield. A one-pot PCC oxidation–Wittig olefination (with Ph3P=CHCO2Et) of 17 provided (E)-α,β-unsaturated ester 18 in 85% yield over 2 steps. Compound 18 was then

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• to orthogonally protected amino acids 46 and 47 (Scheme 7) [58]. Installation of the C-2 stereocentre again began with Garner’s aldehyde 48 and Wittig olefination, followed by Sharpless dihydroxylation to stereoselectively afford diol 49 [59][60]. The C-2 epimer was accessed via Still–Gennari

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• carried out. Crucial steps for the strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. An oxazolidinone-containing leopolic acid A analogue was also synthesized. The antibacterial activity showed by both compounds

• reduction is in agreement with previous results and is consistent with the Cram model for a chelation controlled reduction [16][17][18]. Both OH groups of compound 9 were oxidized by PCC to obtain aldehyde 10. The long carbon chain was incorporated into 10 by Wittig olefination with n

• before, we decided to incorporate the structural features found in leopolic acid into this novel heterocyclic system. Accordingly, Wittig olefination of 14, followed by coupling with L-phenylalanine benzyl ester, and subsequent catalytic hydrogenation in EtOAc of 16 afforded the analogue of leopolic acid

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• on the possibility to extend the scope of the aforementioned one-pot procedure to the synthesis of enantiomerically pure allylic amines. It has been reported earlier the one-pot preparation of N-protected allylic amines via tandem DIBAL-H reduction–Wittig olefination of N-protected α-amino esters [17

• Discussion The experimental procedure for the tandem reduction–Wittig olefination synthesis of allylic amines reported the use of toluene as solvent for the reduction step and THF as solvent to prepare the phosphonium ylide [17]. Consequently, the Wittig olefination takes place in a 2:1 (toluene/THF) solvent

• as starting material (S)-methyl 2-(dibenzylamino)propanoate (1) [22]. In order to avoid the stereochemical drawback of the Wittig olefination (i.e., mixture of E and Z isomers), we selected the stabilized ylide ethyl 2-(triphenylphosphoranylidene)acetate, which gives the E isomer [23]. The results

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• . Reductive desulfonylation and a final Wittig olefination of the ketone then afforded racemic β-caryophyllene (22). In summary, the total synthesis of β-caryophyllene was achieved in 19 steps with an overall yield of 6.3%. Although the key intramolecular acyl transfer reaction for construction of the

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• the fruiting body of P. igniarius, is a well-known anticancer agent. To assemble the spiro-fused furanone core of phelligridin G, Wright and Cooper [55] have used a RRM process as a key step. Wittig olefination of furylbenzaldehyde derivative 265 using methyltriphenylphosphonium bromide in the

• presence of n-BuLi provided styrylfuran 270 in 72% yield. The DA reaction of styrene derivative 270 with DMAD 129 at 40 °C yielded oxabridged compound 268. Another route to 268 involves a DA reaction of 265 with DMAD at 55 °C for longer reaction time (3 days) and sequential Wittig olefination. The spiro

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• olefination In 2009, Tang and Zhou developed an annulation through tandem Michael addition/Wittig olefination, mediated by the chiral phosphine BIPHEP, for the synthesis of optically active cyclohexa-1,3-diene derivatives (Scheme 54) [97]. Although this reaction required a stoichiometric amount of chiral

• enantioselectivity. In a relatively successful example, the chiral aminophosphine G9 catalyzed the asymmetric double-Michael reaction between o-tosylamidophenyl malonate and 3-butyn-2-one to give the indoline derivative in 69% yield and up to 10% ee (Scheme 53). 2.15 Annulation through tandem Michael addition/Wittig

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• yields. Additionally, the synthesis of substrate 30 with 1,1-disubstituted C–C double bond was accomplished in 3 steps. The addition of methylmagnesium chloride to previously prepared threose 15, followed by Dess–Martin oxidation of the secondary alcohol gave methylketone 29. Subsequent Wittig

• olefination using (methylidene)triphenylphosphorane ylide and final hydrolysis of the acetonide provided the desired C5-substrate 30. The synthesis of substrates 24–28 bearing an allylic hydroxy group is pictured in Scheme 3. At first, the ester group of previously prepared intermediate E-17 was reduced using

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• accomplished through a one-pot Swern oxidation/Wittig olefination protocol followed by hydrogenation to give ketone 127. For further extension of the carbon chain and installation of the trisubstituted double bond, a modified Julia olefination with imidazole sulfone 128 was employed [100][101][102]. Thus