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

• olefination of 4,4'-dimethoxybenzophenone with methoxy(trimethylsilyl)methyl p-tolyl sulfide, and oxidation of the resulting 1-methoxyvinyl p-tolyl sulfide with mCPBA (Scheme 3b) [17]. The 1-chlorovinyl p-tolyl sulfoxides 2e–g were prepared through a one-pot procedure (Scheme 3c) [15]. The HWE reagent was

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

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• -ketophosphonate 89 in 86% yield (Scheme 6A) [41]. Hydrogenation of 89 followed by an intramolecular Horner–Wadsworth–Emmons olefination produced hexacyclic enone 90 in 91% yield over two steps. The conversion of enone 90 to longeracinphyllin A (10) was achieved in three steps. The syntheses of daphenylline (11

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• silyl ether-protected 2-hydroxypropanals 15a and 15b via literature procedures [10], followed by the application of the Still–Gennari Z-selective Horner–Wadsworth–Emmons olefination [11]. Koide’s group [12][13] reported that the asymmetric addition of the enyne 16 to acetaldehyde in the presence of zinc

• 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

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• olefination of a protected 1,3-dihydroxypropanone (Figure 3). However, the selective introduction of functional groups is not possible in these diols as the two hydroxy groups present similar chemical reactivity. Other approaches are available for a selective preparation of monofluoroalkenes including

• olefination or defluorination reactions or a sigmatropic rearrangement, but these approaches are limited and do not allow the synthesis of tetrasubstituted fluoroalkenes with good control of their geometry [18][19][20][21]. In order to develop a selective synthesis for tetrasubstituted fluoroalkenes we

• through an olefination reaction with benzothiazoyl sulfones (Scheme 1) [22]. With these fluoroalkylidene-oxetanes in hands, we studied the selectivity of ring-opening reactions with heteroatom nucleophiles in order to access tetrasubstituted fluoroalkenes. A control of the geometry of these reactions

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• described the combination of rhodium and photoredox catalysis for the direct C–H ortho-olefination of arylamides (Figure 7) [74]. The procedure was performed under air at 80 °C and turned out to be efficient using a low loading of a Ru-based photosensitizer. A broad range of DGs could be installed on the

• -functionalization viewpoint, thus furnishing a large panel of compounds in excellent to good yields. This C–H olefination of arenes was performed under aerobic conditions in order to reoxidize the photocatalyst (Figure 8). Interestingly, the desired products were also delivered while using a stoichiometric amount

• merging C–H activation with photoredox catalysis to allow in situ reoxidation of the metal catalyst. In 2015, a procedure combining ruthenium C–H activation of phenols derivatives bearing a pyridine moiety as DG and photoredox catalysis was disclosed (Figure 9) [75]. This ortho-olefination was performed

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

• inhibitors based on the tripeptide sequence Arg–Gly–Asp (RGD) are potential therapeutics for the treatment of idiopathic pulmonary fibrosis (IPF). Herein, we describe an expeditious three-step synthetic sequence of Horner–Wadsworth–Emmons olefination, diimide reduction, and global deprotection to synthesise

• of base (6 equiv) was required to overcome stalling of the olefination process. Reduction to compound 16 using benzenesulfonyl hydrazide (generating diimide in situ) proceeded in 80% yield and was followed by single-pot carbamate and phosphonate deprotection to afford arginine mimetic 6 in 86% yield

• purification by chromatography on silica. This, combined with the formation of phosphoramidate 13 in 94% yield, represented a marked improvement to the initial one-pot diphosphorylation (Scheme 7). Contrary to reports using 2-methylquinolines, tandem phosphorylation and olefination was not possible [15]. When

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

• of the dienic compound through a Suzuki–Miyaura coupling and Julia–Kocienski olefination, followed by a Yamaguchi lactonization, and an asymmetric epoxidation in the presence of (+)-diethyl tartrate, conveniently produced (−)-amphidinolide K (4, Scheme 7). In a remarkable work, Trost et al. [72

• 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

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• extensively developed to tune the optoelectronic properties [21]. Therefore, the development of more efficient and shorter step synthetic methods for the BODIPY derivatives, such as direct C–H functionalizations (e.g., arylation [22][23][24][25][26][27][28], annulation [29], olefination [30], styrylation [31

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• bonds. C–H olefination Weinreb amide C–H olefination: Photoredox catalysts carry the reactions forward with high regioselectivity, good functional group tolerance, and with or without an external oxidant at low temperatures. However, without photoredox catalysts, the earlier syntheses suffered from the

• dependence on external oxidants and harsh reaction conditions [83][84]. In this context, in 2014, Fabry et al. reported the use of novel dual photoredox catalytic systems made up of photoredox catalyst 11 and a rhodium catalyst to carry out the Weinreb amide C–H olefination shown in Scheme 1 [85]. By using

• 22 upon coordination with the carbonyl oxygen atom of the amide group. The complex 22 then coordinated to the acrylate product 23, which rearranged to 24, and the β-hydride elimination of 24 yielded the desired olefinated product 21. C–H olefination of phenolic ethers: Based on Ackermann and co

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

• ]. Noël and co-workers reported the C3–H olefination of indoles using Pd(OAc)2 as a catalyst and molecular oxygen as the oxidant under continuous flow conditions [29]. Jia et al. reported the synthesis of 3-alkenylindoles using Pd(OAc)2 as the catalyst and MnO2 as the oxidant under ball milling conditions

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

• selective desilylation and N-debenzylation with simultaneous N-Boc protection and served as a key intermediate for installation of a dimethylhexylene fragment in Julia–Kocienski olefination [56]. Pyrrolidine alkaloids (−)-hygrine ((S)-61) and (−)-hygroline ((2S,2'S)-62) were isolated from many natural

• 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

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

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

• keto aldehyde 18. Chemoselective dibromoolefination with ylide 19 prepared from dibromomethyltriphenylphosphonium bromide and sodium tert-butoxide [22] led to ketone 20 virtually without erosion of the relative configuration (dr = 22:1). After subjecting 20 to carbonyl olefination with unsaturated

• to 26 only proceeded with a maximum yield of 20%. Asymmetric Michael addition of aldehyde 26 to methyl vinyl ketone (15) followed immediately by treatment of the resultant unstable keto aldehyde 27 with ylide 19 delivered dibromo olefin 28 with high diastereocontrol (dr = 19:1). Olefination of ketone

• ketone 20, the one-pot conversion of ketone 28 by olefination with unsaturated ylide 21 and alkyne formation with butyllithium yielded dienediyne 8 as a 1.3:1 mixture of E and Z olefin isomers. Gratifyingly, treatment of 8 with 25 mol% of the first generation Grubbs catalyst 29 produced the desired

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• = R2 = H, instead of β-glycosyl, respectively). Results and Discussion Most syntheses of dihydrostilbenes rely on a carbonyl olefination followed by hydrogenation of the stilbene [7][8][9]. However, this route appeared not attractive, particularly as our attempts to hydrogenate highly substituted

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• cyclopropanes contrasts with the existence of few straightforward routes for their syntheses. Typical methods rely on the use of reagents containing the required cyclopropane ring, which involve multistep sequences for the installation of adequate functionalization. Thus, Wittig-type olefination with

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

• ) [53]. Starting from O-benzyl-D-serine (2S,3R)-2 was obtained in a similar way. Configurationally stable D-serinal derivative (R)-23 (prepared from D-serine [54]) which primarily exists as hemiacetal was subjected to cis-olefination with Stille's reagent at −30 °C to produce (S)-24 in good yield

• 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

• O-benzyl-L-serine. Reagents and conditions: a) (CF3CH2O)2P(O)CH2COOMe, KHMDS, 18-crown-6; b) I2, MeCN; c) Bu3SnH, AIBN, benzene, reflux; d) H2, 10% Pd/C, ethanol; e) CrO3, acetone, then CH2N2, ether; f) 3 M HCl, 80 °C. Synthesis of (2S,3R)-2 employing a one-pot cis-olefination–conjugate addition

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

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• exact definition of a reaction employed in LSF, Jiang and co-workers have described a procedure that allows the enantioselective aerobic olefination of α-amino sp3 C–H bonds, using cooperative asymmetric and organocatalysed photoredox catalysis (Scheme 29) [73]. This may not allow for direct

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• route using Wittig–Horner olefination and catalytic asymmetric hydrogenation as key steps (reactions not shown) [86][87][90][91][92]. Using 'dimeric' building blocks (S)-49, (R)-49, (S)-50, and (R)-50 (Scheme 5), automated DNA synthesis under standard conditions enabled the preparation of partially

• peptide synthesis using the monomeric 3'-amino-nucleosyl amino acids (S)-56 and (R)-56, respectively, as building blocks. The synthesis of thymidinyl amino acids 56 was again started from a corresponding 5'-aldehyde 57 using Wittig–Horner olefination and catalytic asymmetric hydrogenation as key steps

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• values (66% for 33b) are obtained. In another tandem procedure, a metal-free C(sp3)–H olefination of amidines 34 with DMSO and PIDA derivatives 20b was developed by Namitharan and co-workers [49]. A Pd(II)-catalysed Heck reaction of the formed exocyclic double bond with the emerging iodoarene yields

• amination–arylation sequence. Auto-amination and cross-coupling of PIDA derivatives 20c. Tandem C(sp3)–H olefination/C(sp2)–H arylation. Atom efficient functionalisations with benziodoxolones 36. Atom-efficient synthesis of furans 39 from benziodoxolones 36a and their further derivatisations