Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• PMB-protected 3-hydroxypropanal via Horner–Wadsworth-Emmons olefination, reduction to the allylic alcohol and Sharples epoxidation [8] (Scheme 2). Subsequent Cu-catalyzed epoxide-opening using methylmagnesium bromide [9] produced an inseparable mixture of 1,2- and 1,3-diol products, which upon

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• became accessible. Partial reduction to the lactol (DIBAl-H, THF, −78 °C to −65 °C, 88%) and Horner–Wadsworth–Emmons reaction by using previously reported dimethyl {3-[(4-methoxybenzyl)oxy]-2-oxopropyl}phosphonate [32], (Ba(OH)2, THF/H2O, 80 °C, 50%) led to 15 which, in turn, was methylenated by

• %) and the benzenesulfonylamine (sodium naphthalenide, DME, −78 °C, 95%) gave 20-demethyl-bis-exo-cyclopamine 19 in 7% overall yield starting from 14. Starting from azido lactone 14 (see Scheme 2) a partial reduction to the lactol (DIBAl-H, THF, −78 °C to −65 °C, 88%) and the Horner–Wadsworth–Emmons

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• olefination. Installation of the phosphonate and desilylation gave 76, which, after oxidation, reacted in the presence of sodium 2,2,2-trifluoroethanol (NaOTFE) in 2,2,2-trifluoroethanol (TFE) via an intramolecular Horner–Wadsworth–Emmons reaction to 77. Cytochalasin L-696,474 (78) was obtained from 77 via

• sequence. The asymmetric intramolecular Diels–Alder reaction was then catalyzed by Kristensens’ catalyst (201) to give 202. A base-promoted epimerization of the aldehyde and a Horner–Wadsworth–Emmons reaction furnished 203, the most advanced intermediate reported so far. Just recently, the group of

Continuous flow photocyclization of stilbenes – scalable synthesis of functionalized phenanthrenes and helicenes

• Quentin Lefebvre,
• Marc Jentsch and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 1883–1890, doi:10.3762/bjoc.9.221

• [27] as a powerful intermediate for the two-step synthesis of functionalisable helically chiral products. As shown in Scheme 2, Wittig or Horner–Wadsworth–Emmons reactions gave the corresponding olefins 1o–r in good yields, which were subjected to photocyclization in flow using the optimised

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• neuraminidase (NA) inhibitor, was synthesized by using a bioinspired, organocatalytic enantioselective 1,4-conjugate addition of styryl-2-pyranone with cinnamaldehyde, followed by a tandem Horner–Wadsworth–Emmons/oxa Michael addition. Keywords: bioinspired synthesis; catalysis; katsumadain A; natural product

• strategy was designed as a fallback, in which katsumadain A could be accessed from the lactol 5a and phosphonate 6 via a tandem Horner–Wadsworth–Emmons (HWE)/oxa-Michael addition reaction [16]. In turn, 5a could be derived from 3 and cinnamaldehyde (7) by an organocatalytic enantioselective 1,4-conjugate

• moieties (Ar1 and Ar2), which paves the way to access katsumadain A and its analogues for further biomedical studies. Having achieved the bicyclic core of katsumadain A in an efficient and enantioselective manner, we then moved towards its total synthesis through the proposed tandem Horner–Wadsworth–Emmons

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• the ready formation of bicyclic compound 72 [33]. The use of a phosphonate-containing alkene allows the assembly of numerous polycyclic structures by combining the radical addition of a ketone-bearing xanthate with an intramolecular Horner–Wadsworth–Emmons condensation. This strategy is highlighted in

• such reagents have been studied. The first is ketophosphonyl xanthate 101, where the intermolecular radical addition on one side of the ketone can be followed by a Horner–Wadsworth–Emmons (HWE) condensation on the other side [46]. In the transformation depicted in Scheme 21, compound 103, obtained by

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• –Emmons reaction as a key step for generating the β'-amino-α,β-enones, permits access to a range of substrates under mild conditions and in moderate to high yield. Keywords: β’-amino-α,β-unsaturated ketones; Horner–Wadsworth–Emmons reaction; stereoselective synthesis; Introduction Compounds

• did not allow the use of a wide range of functional groups and sometimes gave bad overall yields, we devised a general and simple method to easily access a variety of β’-amino-α,β-unsaturated ketones by a more convenient route using the Horner–Wadsworth–Emmons reaction [19][20] as the key step, as

• (Scheme 6, Table 1). Over the years, many examples of base-promoted Horner–Wadsworth–Emmons (HWE) reactions have been reported in the literature, and various combinations of bases and solvents (K2CO3/CH3CN[23], DBU/THF[25], NaH/THF[29], Et3N/LiCl/CH3CN[30] or Ba(OH)2/(THF/H2O)[31]) have been used. We

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• used directly in the next step without purification. Compound 4 was first treated with sodium hydride or other bases and then reacted with formaldehyde to form terminal alkene 5 through a Horner–Wadsworth–Emmons reaction [12] (two-step overall yields are 27%, 53% and 55% for 3a to 5a, 3b to 5b and 3c

• will further improve the fluorescent property of the coumarin amino acids, or add new chemical handles to the coumarin ring for some specific investigations. The Horner–Wadsworth–Emmons reaction was applied to install the terminal alkene at the 4-position. Compared with the Wittig reaction, the Horner

• –Wadsworth–Emmons reaction has a significant advantage: The resulting phosphate byproduct can be readily separated, whereas the byproduct triphenylphosphine oxide generated in the Wittig reaction is difficult to remove [17]. The effect of the base used in the Horner–Wadsworth–Emmons reaction on the reaction

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• substitution reaction of meta- and para-nitro-(pentafluorosulfanyl)benzenes and diethyl chloromethylphosphonate, undergo Horner–Wadsworth–Emmons reaction with aldehydes in the presence of potassium hydroxide in acetonitrile at ambient temperature to give (E)-2-nitro-1-alkenyl-(pentafluorosulfanyl)benzenes in

• good yields and high stereoselectivities. Follow-up transformations of the primary products provided (E)-1-alkenyl-(pentafluorosulfanyl)benzenes and 2-(2-arylethyl)-(pentafluorosulfanyl)anilines. Keywords: Horner–Wadsworth–Emmons reaction; pentafluorosulfanyl group; phosphonates; sulfurpentafluoride

• ][21][22]. Alkenyl substituted SF5-benzenes or SF5-containing stilbene derivatives are not known and would represent basic synthetic intermediates towards more elaborate structures. We envisioned a synthetic route towards these compounds through Horner–Wadsworth–Emmons (HWE) reaction of phosphonates 3

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• methyl 4,11-dimethyldodecanoate (110) from 24 by its reduction to the aldehyde 123a, Horner–Wadsworth–Emmons olefination to 124a, and catalytic hydrogenation (Scheme 3). The synthetic material was identical to the natural compound 110. A related group of compounds (Figure 3D, blue) proved to have very

• DIBAH to the aldehyde 123c, Horner–Wadsworth–Emmons olefination to 124c, and final catalytic hydrogenation afforded 112. The product exhibited the same mass spectrum and retention index (I = 1441) as the natural FAME. The slight deviations between the calculated and measured retention indices for

• , accounting for a γ-cleavage in unbranched FAMEs, suggested the presence of a methyl group in a γ-position, which leads to a γ-fragmentation with m/z = 115. A synthesis of methyl 4-methyldodecanoate (90) was performed starting from 10 (Scheme 3). Reduction to the aldehyde 123d and subsequent Horner–Wadsworth

Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• make 1a [29]. For high convergence, the analogs were dissected strategically into three complete fragments called top (8, C18–C26), middle (7, C10–C17), and bottom (6a,b, C1–C9), respectively. The top 8 and middle 7 fragments were first combined through an established Horner–Wadsworth–Emmons (HWE

• –Wadsworth–Emmons reaction sequence and an esterification. A late stage Nozaki–Hiyama–Kishi reaction was then used to form the 22-membered macrolide. The stereoselectivity of this reaction depended on the configurations of the nearby stereocenter at C6. Keywords: anticancer agents; dictyostatin

• human cancer cell lines. Two highly active analogs of dictyostatin, 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, were prepared by a new streamlined total synthesis route. Three complete carbon fragments were prepared to achieve maximum convergency. These were coupled by a Horner

A two step synthesis of a key unit B precursor of cryptophycins by asymmetric hydrogenation

• Benedikt Sammet,
• Mathilde Brax and
• Norbert Sewald

Beilstein J. Org. Chem. 2011, 7, 243–245, doi:10.3762/bjoc.7.32

• developed synthesis 3-chloro-4-methoxybenzaldehyde is reacted with rac-Boc-α-phosphonoglycine trimethyl ester (9) [13][14] to yield olefin 10 in a completely Z-selective Horner–Wadsworth–Emmons (HWE) reaction (Scheme 3). Asymmetric hydrogenation using the commercially available [(COD)Rh-(R,R)-Et-DuPhos]BF4

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• deficient pyridines in the presence of trimethylsilyl triflate, tetrabutylammonium fluoride or a montmorillonite clay. The cyclisation precursor was synthesised by using the procedure of Hayashi [48] employing a Horner–Wadsworth–Emmons olefination between nicotinaldehyde and phosphonate 10. The resulting

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• 12% yield from 9). The preparation of the amino acid 8a•HCl and the N-tosylamide 8b•HCl required the attachment of an endo-oriented acetic acid substituent at the position of the keto group in 9 (Scheme 5). Initial attempts to introduce such a side chain by Wittig or Horner-Wadsworth-Emmons reactions

An expedient synthesis of 5-n-alkylresorcinols and novel 5-n-alkylresorcinol haptens

• Kirsti Parikka and
• Kristiina Wähälä

Beilstein J. Org. Chem. 2009, 5, No. 22, doi:10.3762/bjoc.5.22

• few papers have reported Wittig reactions in water without an organic solvent, although the related Horner-Wadsworth-Emmons reactions, using ester enolate type stabilized phosphonate ylids, have often been conducted in aqueous solutions [29]. The existing cases have mostly been targeted for the

Convenient methods for preparing π-conjugated linkers as building blocks for modular chemistry

• Jiří Kulhánek,
• Filip Bureš and
• Miroslav Ludwig

Beilstein J. Org. Chem. 2009, 5, No. 11, doi:10.3762/bjoc.5.11

• easily accessible as a pure (E)-product from the pinacol ester of 4-formylphenylboronic acid and diethyl benzylphosphonate through the Horner–Wadsworth–Emmons reaction in 76% yield [36], methoxy and N,N-dimethylamino substituted (E)-4-bromostilbenes were synthesized from the corresponding benzaldehydes

• and 4-bromobenzyl(triphenyl)phosphonium bromide [37] by the Wittig reaction [37][38] in 37 and 54% yields, respectively. In contrast to the Horner–Wadsworth–Emmons reaction, this procedure afforded both (E)- and (Z)-stilbenes that were isomerized by heating with traces of iodine in toluene to afford

• the Horner–Wadsworth–Emmons reaction described above. These substituted 4-bromostilbenes could be most effectively converted to target pinacol esters 5a–c via borylation (Scheme 1, Method C) utilizing bis(pinacolato)diboron (pin2B2) [39] in a mixed solvent system DMSO/dioxane ensuring good solubility

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

Combining two-directional synthesis and tandem reactions, part 11: second generation syntheses of (±)-hippodamine and (±)-epi-hippodamine

• Annabella F. Newton,
• Martin Rejzek,
• Marie-Lyne Alcaraz and
• Robert A. Stockman

Beilstein J. Org. Chem. 2008, 4, No. 4, doi:10.1186/1860-5397-4-4

• sensitive dialdehyde 5 . Whilst we were able to purify compound 5, this resulted in a significant loss of material through degradation of the dialdehyde on the purification media, be it silica gel or neutral alumina. Thus, we found that use of the crude dialdehyde in the subsequent Horner-Wadsworth-Emmons

New modification of the Perkow reaction: halocarboxylate anions as leaving groups in 3-acyloxyquinoline- 2,4(1H,3H)-dione compounds

• Oldřich Paleta,
• Karel Pomeisl,
• Stanislav Kafka,
• Antonín Klásek and
• Vladislav Kubelka

Beilstein J. Org. Chem. 2005, 1, No. 17, doi:10.1186/1860-5397-1-17

• the corresponding 4-ethoxyquinolin-2(1H)-one. In both reactions, the fluorocarboxylate anion acts as the first observed leaving group. This observation restricts the application of the intramolecular Horner-Wadsworth-Emmons synthesis to modify quinoline-2,4(1H,3H)-diones by the annulation of

• annulation of the fluorobutenolide cycle. An analogous Horner-Wadsworth-Emmons synthesis using ethyl (diethoxyphosphoryl)-fluoroacetate prepared from ethyl fluoroiodoacetate has been reported for the preparation of the α-fluoro-α,β-unsaturated acyclic esters and lactones. [14] However, when 1-benzyl-3-butyl

• -3-(fluoroiodoacetoxy)quinoline-2,4(1H,3H)-dione (4) was reacted with triethyl phosphite an unexpected product 9 (Scheme 3) was obtained instead of the desired Horner-Wadsworth-Emmons intermediate 1-benzyl-3-butyl-3-(diethoxyphosphoryl)fluoroacetyloxy-quinoline-2,4(1H,3H)-dione. We assume the newly