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

• cores for these compounds in high yields (63–83% over 3 steps) with no need for chromatography. Key to this transformation is the phosphoramidate protecting group, which is stable to metalation steps. Keywords: arginine; Horner–Wadsworth–Emmons; integrin; phosphoramidate; tetrahydronaphthyridine

• 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

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

• peptidyl nucleosides with primarily antifungal properties. The stereoselective synthesis of (+)-polyoxamic acid ((2S,3S,4S)-144) was successfully carried out starting with Horner–Wadsworth–Emmons olefination of the aziridine aldehyde (2R,1'R)-6 which provided a 98:2 mixture of trans- and cis-acrylates 69b

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• –Wadsworth–Emmons (H.W.E.) reaction of n-hexanal with phosphonoester 19 [15] afforded an E/Z mixture of olefinic diesters, purification of which by silica gel column chromatography afforded a fraction of the desired E diester 20 (60%), a second fraction comprised of a 5:1 E/Z mixture and a third fraction of

• effort to reduce the complexity of the NMR spectra observed for the diastereomeric onchidal–pyrrole adducts, a range of simpler achiral n-pentyl 11–14 and cyclohexylmethyl 15–18 side-chained model compounds, as either the dialdehyde or masked dialdehyde variants, were prepared (Figure 2). Horner

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• of the four desired stereogenic centers. By extending compound 5 via a Horner–Wadsworth–Emmons (HWE) reaction [15] and subsequent stereoselective introduction of the corresponding nitrogen functionality, a route to four different 2-amino sugar stereoisomers has been elaborated. Results and Discussion

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• –Wadsworth–Emmons reaction with triethyl 2-phosphonopropionate (19) yielded ethyl (E)-2,4-dimethylhex-2-enoate (20) as a separable mixture of E and Z stereoisomers (E/Z = 10:1). The purified E diastereomer was reduced with DIBAl-H to the corresponding alcohol 21. A PCC oxidation and addition of

• (Figure 2A) that was similar to a data base spectrum of manicone ((E)-4,6-dimethyloct-4-en-3-one, 10), but no retention index for this compound was available from the literature. For unambiguous structural verification compound 10 was synthesised starting from 2-methylbutanal (18, Scheme 3). A Horner

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• and co-workers and incorporated an intramolecular Horner–Wadsworth–Emmons reaction as a crucial step [10]. Due to their diverse biological activities, a variety of synthetic pathways to 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones has been developed over the past two decades [10][11][12][13][14

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

• interested in the Horner–Wadsworth–Emmons (HWE) olefination to develop the synthesis of α-fluoro-α,β-unsaturated ester 3, which can be used as a precursor for the synthesis of monofluoroalkene-based dipeptide isosteres [23]. Cbz-Gly-ψ[(Z)-CF=CH]-Gly 5 was obtained in seven steps (Scheme 1). First, triethyl 2

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

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• trifluoroacetate at −80 °C, a Horner–Wadsworth–Emmons reagent [17] activated by LiBr and Et3N [18][19][20] was introduced to this solution at room temperature, leading to the formation of (E)-6 after the NaBH4 reduction of the resultant products (see Supporting Information File 1 for the detailed procedure). As

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• alcohol 49 in 76% over 2 steps [83]. Before TBS protection the Weinreb amide was generated and then conversed into the phosphonate 50 as a precursor for a Horner–Wadsworth–Emmons reaction. The olefination led to unsaturated ketone 52 in 79% yield. For the final fragment synthesis the ketone was reduced

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• same length, but of more extended conjugation we made use of the Horner–Wadsworth–Emmons (HWE) reaction. Phosphonate 4 was reacted with the respective aldehyde 1. In a facile three-step one-pot process the emerging α,β-unsaturated ester 5 was immediately converted to the alcohol 6 in 87% yield in the

• . Conclusion In conclusion, we have developed a robust approach to three oligoene-shaped fluorescent fatty acids whose fluorescence efficiency is markedly boosted by an unpolar benzo[c][1,2,5]thiadiazole (BTD) moiety as terminal headgroup. Wittig reactions in combination with Horner–Wadsworth–Emmons reactions

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• -decalins and trans-hydrindanes (Scheme 1) [22][23][24][25]. It relies on the use of sugar-derived allyltin (such as 5) followed by ZnCl2-induced fragmentation into dienoaldehyde 6, subsequent Horner–Wadsworth–Emmons olefination, and intramolecular Diels–Alder reaction. In this paper, we explore the

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• avoided exposure to strong bases or reducing agents, a limitation that significantly guided the choice of reagents and conditions for the subsequent steps. Dess–Martin periodinane oxidation of alcohol 6 followed by Horner–Wadsworth–Emmons olefination with triethyl 2-phosphonopropionate (9) furnished the

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• dephosphorylated by treatment with lithium aluminum hydride to give isoindolin-1-ones 61 (Scheme 15). Also the Kabachnik–Fields reaction of formylbenzoic acid (55), dimethyl phosphonate and amines 62 or 66 followed by subsequent Horner–Wadsworth–Emmons reaction of the resulting cycloadducts 63 and 67 with

• -oxopropyl)phosphonate (225) in a one-pot, two-step three-component method for the synthesis of phosphonylpyrazoles has been presented by Kumar et al. The phosphonate 225 acted both as a 1,3-dipole precursor and as a Horner–Wadsworth–Emmons (HWE) reagent. Therefore, the reaction of phosphonate 225 with

• isoindolin-1-one-3-phosphonates. A microwave-assisted Kabachnik–Fields reaction toward isoindolin-1-ones. The synthesis of 3-arylmethyleneisoindolin-1-ones through a Horner–Wadsworth–Emmons reaction of Kabachnik–Fields reaction products. An efficient one-pot method for the synthesis of ethyl (2-alkyl- and 2

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• 7TJ, UK 10.3762/bjoc.12.103 Abstract Here we report the chemoselective synthesis of several important, climate relevant isoprene nitrates using silver nitrate to mediate a ’halide for nitrate’ substitution. Employing readily available starting materials, reagents and Horner–Wadsworth–Emmons chemistry

• . Its application was restricted by its propensity to generate difficult to separate structure and stereoisomeric mixtures of allylic bromides and alcohols, e.g., (E)-45–rac-48. We contemplated using Wittig or Horner–Wadsworth–Emmons (HWE) chemistry to construct (E)-alkyl 3-methyl-4-chlorobut-2-enoates

• ester via a Horner–Wadsworth–Emmons reaction caught our attention [47]. Changing tack and in a slightly modified procedure to that originally reported by Fujiwara et al. triethyl phosphonoacetate was deprotonated (NaH) and the resulting stabilised ylide (not shown) reacted by slow addition of

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

• subsequent in situ addition of organophosphorus reagents yielded the corresponding allylic amines without the need to isolate the intermediate aldehyde. This circumvents the problem of instability of the aldehydes. The method tolerates well both Wittig and Horner–Wadsworth–Emmons organophosphorus reagents. A

• Wittig and Horner–Wadsworth–Emmons (HWE) organophosphorus reagents (Table 2). When considering phosphonium ylides (Table 2, entries 1 and 2), better Z-(dia)stereoselectivity was observed when compared to the previous one-pot method. The olefination with the semistable ylide obtained by the addition of KN

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• signals corresponding to two protons of the epoxide at δ 4.18 and 3.54 [44]. Since the yield of 32 was low, we considered a Horner–Wadsworth–Emmons reaction of aldehyde 31 with triethyl phosphonoacetate as an alternative. Unfortunately, it was not successful, probably due to the interference of the

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• ,β,γ,δ-unsaturated thioesters produced from a Horner–Wadsworth–Emmons reagent were submitted to a 1,6-ACA catalyzed by the L8/CuBr·SMe2 system, followed by a reconjugation reaction in the presence of DBU to selectively afford 37 (ratio between 1,6 and 1,4-ACA products ranged from 85/15 to 99/1) in

Cross-metathesis reaction of α- and β-vinyl C-glycosides with alkenes

• Ivan Šnajdr,
• Kamil Parkan,
• Filip Hessler and
• Martin Kotora

Beilstein J. Org. Chem. 2015, 11, 1392–1397, doi:10.3762/bjoc.11.150

• vinyl β-C-deoxyribofuranoside was based on transformation of 6-O-tert-butyldiphenylsilyl-3,5-dideoxy-5-iodo-L-lyxo-hexofuranose [14]. A reaction sequence relying on Horner–Wadsworth–Emmons/ring closure–halogenation/Ramberg–Bäcklund/Wittig reaction gave rise to the equimolar mixture of styryl α- and β-C

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• ; oxaphospholanes; phosphinates; phosphine oxides; Introduction Organophosphorus compounds containing phosphorus to carbon bond(s) are widely used in organic transformations. Textbook examples are the Wittig and the Horner–Wadsworth–Emmons reactions. Moreover, the vast majority of ligands used in organometallic

New tris- and pentakis-fused donors containing extended tetrathiafulvalenes: New positive electrode materials for rechargeable batteries

• Shintaro Iwamoto,
• Yuu Inatomi,
• Daisuke Ogi,
• Satoshi Shibayama,
• Yukiko Murakami,
• Minami Kato,
• Kazuyuki Takahashi,
• Kazuyoshi Tanaka,
• Nobuhiko Hojo and
• Yohji Misaki

Beilstein J. Org. Chem. 2015, 11, 1136–1147, doi:10.3762/bjoc.11.128

• undesired byproducts. The homo-coupling reaction using 11 might give 12 in a good yield, however, toxic and expensive mercury(II) acetate has to be used for the synthesis of 11. Thus, the cross-coupling reaction is useful for saving 11. The Horner–Wadsworth–Emmons reaction of 12 with 2 equiv of aldehydes

A hybrid electron donor comprising cyclopentadithiophene and dithiafulvenyl for dye-sensitized solar cells

• Gleb Sorohhov,
• Chenyi Yi,
• Michael Grätzel,
• Silvio Decurtins and
• Shi-Xia Liu

Beilstein J. Org. Chem. 2015, 11, 1052–1059, doi:10.3762/bjoc.11.118

• Discussion Synthesis Under Knoevenagel condensation reaction conditions, the corresponding aldehydes 4 and 7 can readily react with cyanoacetic acid leading to the target sensitizers 1 and 2, as depicted in Scheme 1. For the synthesis of the aldehyde precursor 4, the Horner–Wadsworth–Emmons (HWE) reaction

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• methylenedioxyphenyl groups in ketone 8 would be added by sequential addition of aryllithiates to both the carbonyl and aldehyde groups, derived from the terminal alkene, of a homoallylic carboxylic acid derivative 9. Our route to ketone 8 began from salicylaldehyde (10) which underwent a Horner–Wadsworth–Emmons

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

• groups of the previously prepared diol 33, followed by OsO4 dihydroxylation of the C–C double bond provided the corresponding diol in good yield. The resulting vicinal diol was then cleaved by sodium periodate to the corresponding aldehyde, which was immediately subjected to a Horner–Wadsworth–Emmons

• –Wadsworth–Emmons olefination of aldehyde 15 furnished the corresponding separable mixture of Z and E alkenes 16 and 17. In the case of utilising stabilised phosphorane ylides, the Wittig reaction provided only Z alkenes 18 and 19. Following acidic hydrolysis provided α-O-benzyl substrates 20–23 in good

• preparation of substrates 20–23 having a symmetrically disubstituted C–C double bond is depicted in Scheme 2. The synthesis started from known threose 15 [31] followed by a common synthetic sequence comprising the olefination reaction and the hydrolysis of the acetonide protecting group. Thus, Horner

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

• ‘typical’ Wittig and Horner–Wadsworth–Emmons reagents were screened. In addition, cyclic phosphonamides were utilized as olefination reagents (Table 1). Employing phosphonamides 24e and 77 in the olefination of 72 favored the formation of the desired E-isomer of 73a, however the mixture of isomers was