Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• coupling reaction. Thus, the olefination reaction of aldehyde 15 with phosphonate 23, followed by the reduction of the obtained ester 24 using DIBAL led to the alcohol 25. The latter was submitted to the reaction with carboxylic acid 26 under Mitsunobu conditions [30], giving the corresponding ester 27 in

• ] between halide 37 and phenol 38 leading to the formation of diaryl ether 39, which was subjected to a regioselective iodination reaction to give compound 40. Conversion of the nitrile in compound 40 into the corresponding aldehyde 41 followed by Z-selective Still–Gennari olefination gave the cis α,β

• proved to be important for the selectivity of the reaction, where significant cleavage of the benzyl group resulted when ethanol was the solvent of choice. Subsequent ester hydrolysis gave compound 112 (Scheme 22) [55]. In parallel, a Still–Gennari olefination using aldehyde 52 lead to the cis-alkene 113

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• opening of the epoxide (15%). From 41 having the correct tetracyclic skeleton, a transient protection followed by Petasis olefination, deprotection, selenide-mediated α,β-dehydrogenation and Mukaiyama oxidation afforded an advanced intermediate 42 bearing most of the target’s functionalities. A sequence

• compound 60 was employed to form an α,β-epoxyketone intermediate which underwent SmI2 reduction at −78 °C, giving access to the desired syn diastereomer with good selectivity (dr = 8.5:1). The free alcohol was then protected with an ethoxymethyl ether (EOM). Finally, Peterson olefination, stereoselective

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• (Brønsted acidity/basicity, hydrogen-bonding units, and counter-anions toward metals) [48][49]. In 2019, Shi, Lin, and co-workers achieved an enantioselective synthesis of axially chiral quinoline-derived biaryl atropisomers via Pd-catalyzed C–H olefination of 8-phenylquinoline (11) using a novel chiral

• spirophosphoric acid (CPA 4). A wide range of quinoline-derived biaryls 13 with various substituents was synthesized in good to excellent yields (up to 99%) with excellent enantioselectivities (up to 98% ee) (Scheme 5). A working model for the origin of enantioselectivity in C–H olefination was provided by

• density functional theory calculations [46]. Recently, Shi, Lin and co-workers reported the atroposelective synthesis of axially chiral biaryls by Pd(II)-catalyzed free amine-directed atroposelective C–H olefination using chiral spirophosphoric acid CPA 5 as an efficient ligand and Ag2CO3 as the oxidant

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

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• functionalized pyridine and pyrrole derivatives from easily available 1,3-enynes. Therefore, the significant challenges will focus on the following aspects in the future: i) development of more functionalizations of pyridines and pyrroles (such as fluorination, trifluoromethylthiolation, olefination

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

• through Horner–Wardsworth–Emmons olefination of the known precursors 111 and 112, which are prepared from ᴅ-mannitol and ʟ-lactic acid methyl ester, respectively. The synthesis commenced with the reaction between aldehyde 111 and phosphonate ester 112 using Ba(OH)2·8H2O to provide the unsaturated ketone

• ) asymmetric dihydroxylation and epoxidation; 3) asymmetric hydrogenation; 4) Horner–Wadsworth–Emmons olefination; and 5) cyclopropanation, which are summarized in Table 4, including the overall yields and the number of steps required. This work is expected to provide useful information for researchers to

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• widespread applications being aldol or Mannich-type addition reactions with carbonyl compounds and imines, respectively [4], and Galat olefination reactions of aldehydes [5][6][7]. Nevertheless, these developments have been mostly described with unsubstituted MAHOs, and the use of mono-substituted MAHOs

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