Horner-Wadsworth-Emmons Research Articles

Diastereoselective Total Synthesis of Raputindole A

The first diastereoselective total synthesis of the bisindole alkaloid raputindole A is reported. After Au(I)-catalyzed assembly of the cyclopenta[ f]indole tricycle, it was possible to hydrogenate the indene double bond regio- and diastereoselectively through iridium catalysis, guided by a preinstalled hydroxy function. Attempted HWE reaction led to formal elimination of formaldehyde from an α-quaternary cyclopentane carbaldehyde, which was circumvented by Takai olefination. After Suzuki-Miyaura cross coupling and deprotection/oxidation, (±)-raputindole A was obtained in 13 linear steps in 18% overall yield.

Application of the Z-Selective Still–Gennari Olefination Protocol for the Synthesis of Z-α,β-Unsaturated Phosphonates

Application of the Z-selective Still–Gennari modification of Horner–Wadsworth–Emmons (HWE) reaction for the olefination of acylphosphonates is presented. A series of new Z-α,β-unsaturated phosphonates containing a carbonyl or ester moiety in the β-position were obtained in up to 94% yield and with up to 96% Z-selectivity. The standard HWE olefination of the acylphosphonates, which was performed for comparison, was either unsuccessful at all, or resulted in an inferior Z-selectivity and lower isolated yields.

Total Synthesis of Pestalotioprolide E and Structural Revision of Pestalotioprolide F.

A short and convergent strategy for the first asymmetric total synthesis of cytotoxic macrolides pestalotioprolides E and F has been developed. The key features of this synthesis include Takai olefination, Sonogashira coupling, Ni-assisted partial hydrogenation of alkyne, modified Steglich reaction to generate the ester moiety, and intramolecular Horner-Wadsworth-Emmons (HWE) olefination to complete the macrocycle. This synthetic study revised the proposed structure of pesralotioprolide F.

An Improved Synthesis of the Antibiotic Dehydrophos

Within this work an efficient procedure for the synthesis of the vinyl phosphonate tripeptide dehydrophos is described. This procedure constitutes a significant improvement over previously described strategies, since critical transformations in the synthesis of dehydrophos were carried out in only two synthetic steps, with higher yields and under smooth conditions. Thus, the dehydrophosphoalanine residue was generated by means of the Horner–Wadsworth–Emmons reaction of formaldehyde with a peptide bearing an aminomethylbis(phosphonate) moiety, whereas deprotection of the N‐terminal position of the thus‐obtained dehydrophosphonopeptide and partial hydrolysis of the dimethyl phosphonate residue took place simultaneously. In addition, we confirmed that the chiral integrity of the leucine residue was preserved throughout these transformations.

Convenient Synthesis and Physiological Activities of Flavonoids in Coreopsis lanceolata L. Petals and Their Related Compounds.

Chalcones, flavanones, and flavonols, including 8-methoxybutin isolated from Coreopsis lanceolata L. petals, were successfully synthesized with total yields of 2–59% from O-methylpyrogallols using the Horner–Wadsworth–Emmons reaction as a key reaction. Aurones, including leptosidin, were also successfully synthesized with 5–36% total yields using the Aldol condensation reaction as a key reaction. Each chalcone, flavanone, flavonol, and aurone with the 3,4-dihydroxy groups in the B-ring showed high antioxidant activity. Additionally, each of the chalcones, flavanones, flavonols, and aurones with the 2,4-dihydroxy groups in the B-ring showed an excellent whitening ability.

Synthesis and photophysical investigations of C3-triazine based star-like conjugated molecules

Here, we reported two different C3-triazine based star-like D-π-A compounds with a very good yield by Wittig-Horner reaction. Photophysical, aggregation enhanced emission and electrochemical properties were systematically studied. These compounds showed a large halochromic effect on its emission color that changes from greenish-yellow to wine red upon addition of trifluoroacetic acid. Further, the spectral changes are confirmed by 1H NMR studies.

One-Pot Synthesis of α-Substituted Acrylates

A simple and efficient synthetic method towards α-substituted acrylic esters has been developed using the Horner–Wadsworth–Emmons (HWE) reaction with HCHO after alkylation of phosphonoacetates in a one-pot reaction. This method allows the smooth introduction of various side-chains, such as natural amino acids and other biologically relevant substituents. The use of mild conditions, inexpensive reagents, short reaction times and simple work-up and purification steps provides an effective and general alternative to cumbersome multistep and low-yielding procedures described to date.

Total Synthesis and Biological Evaluation of Siladenoserinol A and its Analogues

AbstractThe total synthesis of siladenoserinol A, an inhibitor of the p53–Hdm2 interaction, has been achieved. AuCl3‐catalyzed hydroalkoxylation of an alkynoate derivative smoothly and regioselectively proceeded to afford a bicycloketal in excellent yield. A glycerophosphocholine moiety was successfully introduced through the Horner–Wadsworth–Emmons reaction using an originally developed phosphonoacetate derivative. Finally, removal of the acid‐labile protecting groups, followed by regioselective sulfamate formation of the serinol moiety afforded the desired siladenoserinol A, and benzoyl and desulfamated analogues were also successfully synthesized. Biological evaluation showed that the sulfamate is essential for biological activity, and modification of the acyl group on the bicycloketal can improve the inhibitory activity against the p53–Hdm2 interaction.

A Comparative Study of Synthetic Approaches Towards Total Synthesis of Mandelalide A, An Anti-Lung Cancer Metabolite From Lissoclinum Ascidian

The aim of this review is to provide a detailed account of the total synthetic approaches toward glycosylated Macrolide A. Mandelaide A was isolated from Lissoclinum Ascidian species found in Algoa Bay, South Africa and has been reported to exhibit potent cytotoxicity against a human lung cancer and a mouse neuroblastoma cell line. We have summarized the maneuvers in each paper by graphically detailing the synthesis, and associated reaction niceties, of only the key intermediates prepared by each research group. Fascinating structural feature of mandelalide A is a 24-membered α,β-unsaturated macrolactone, which contains a conjugated diene, a trisubstituted tetrahydrofuran (THF) segment, and a trisubstituted tetrahydropyran (THP) moiety attached to an unusual carbohydrate unit, 2-O-methyl-α-L-rhamnose. The macrolide is decorated with twelve challenging stereocenters being the part of oxygen containing heterocyclic rings. The total synthesis of mandelalide A involves a variety of renowned reactions which include Prins cyclization for the diastereoselective construction of tetrahydropyran subunit, Rychnovsky-Bartlett cyclization for the diastereoselective construction of tetrahydrofuran moiety, construction of the tetrahydropyran segment, Suzuki coupling, Horner-Wadsworth-Emmons (HWE) macrocyclization, Shiina-type macrolactonization, Sonogashira cross-coupling, Silver catalyzed cyclizations, alkyne metathesis and glycosylation to append the L-rhamnose-derived pyranoside. This review provides a critical account along with a comparison of the synthetic efforts directed to this important natural product and its analogues.

Functional Molecular System of Bis(pyrazolyl)pyridine Derivatives: Photophysics, Spectroscopy, Computation, and Ion Sensing.

A new series of conjugated donor−π–acceptor type of 2,6-bis(pyrazolyl)pyridine derivatives (compounds IK-(3–9)) have been synthesized via Horner–Wadsworth–Emmons (HWE) reaction, starting from a common phosphonate precursor and diverse donor aromatic aldehydes and characterized by routine spectral analysis including elemental analysis. Compound IK-2, one of the starting precursors, and molecule IK-3, the first member of the donor−π–acceptor series, are additionally characterized by single-crystal X-ray structure determination. Compounds IK-2 and IK-3 are crystallized in P1̅ (triclinic) and P21/c (monoclinic) space groups, respectively. The absorption maxima in the electronic spectra of the title compounds shift mainly due to intramolecular charge transfer (ICT) between different donor (dibutyl and cyclic pyrrolidine) groups and the acceptor moiety [2,6-bis(pyrazolyl) pyridine]. Solution-state emission spectral studies of all these compounds show large solvent sensitive behavior with significant amounts of Stokes shifts. The large solvent dependence of the emission indicates that the excited state is stabilized in more polar solvents due to the ICT. All chromophores exhibit solid-state fluorescence behavior except compound IK-7. The role of the position and nature of the donor functionalities in the conjugated backbone of overall donor moiety of compounds IK-(3–9), on the electronic absorption properties of the title chromophores has been demonstrated, which has further been corroborated by density functional theory (DFT) and time-dependent DFT (TDDFT) computational studies. The emission spectral results of compounds IK-3, IK-5, and IK-7 have also been supported by the DFT and TDDFT calculations. A fluorescence lifetime study on this series also shows that the excited states are stabilized in more polar solvents. Finally, one of the chromophores (chromophore IK-4) in the title series has been shown to act as a selective molecular sensor (turn-off switch) for the Cu(II) ion.

A Scalable Approach for the Synthesis of Epothilone Thiazole Fragment (C12–C21 unit) Via Wacker Oxidation

A new scalable synthesis of the common thiazole fragment (C12–C21 unit) of epothilone family of molecules (epothilone A–D) has been developed via palladium-catalyzed Wacker oxidation as a key step using (S)-2,2,3,3,9,9,10,10-octamethyl-5-vinyl-4,8-dioxa-3,9-disilaundecane, which has been prepared from commercially available chiral synthon (R)-ethyl-4-cyano-3-hydroxybutanoate. Then further chemical modifications using Horner–Wadsworth–Emmons reaction and Wittig reaction result in the common thiazole fragment (C12–C21 unit) in good yields.

Formal Synthesis of Angiopterlactone B via Enantioselective Reduction of Ketone with Daucus Carota Root

AbstractFormal synthesis of angiopterlactone B has been accomplished via. enantioselective reduction of ketone with Daucus carota, Sharpless dihydroxylation and Andos modified Horner‐Wadsworth‐Emmons (HWE) reagent to introduce Z‐olefination. Here we evolved a new path for the synthesis of (S,S)‐osmundalactone and 3–5 dihydroxy γ‐caprolactone. The initial synthetic route for both caprolactone and osmundalcactone build on biocatalytic process while in later case Sharpless dihydroxylation delivered required stereocentres. Z‐selective olefination was utilized to furnish caprolactone which was further recycled in to 1‐(5‐oxotetrahydrofuran‐2yl) ethyl 2‐phenyl acetate. Both synthetic routes found to be applicable for many synthetic reactions.

The synthesis of conjugated polymers with different length side chains and the effect on their nanoparticles

In recent years, conjugated polymers (CPs) and their nanoparticles (CPNs) were widely concerned and applied in many fields due to their outstanding advantages such as higher absorption coefficients, good photostability, low toxicity and good biocompatibility. However, most reports were focused on their applications, and rare attentions were given on the synthesis of CPs and the effect factors of CPNs’ morphology and properties. In this work, four CPs (P1, P2, P3, P4) with different length side chains were synthetized by Wittig–Horner reaction and further used to prepare CPNs by the nano-precipitation method. The CPs and CPNs were characterized and analyzed by Hydrogen Nuclear Magnetic Resonance (1H NMR), gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and transmission electron microscope (TEM). The absorbance and fluorescence emission spectra of CPs in tetrahydrofuran (THF) and CPNs solutions with different length side chains were investigated, and their quantum yields (Фs) were calculated by the reference method. The results showed that the synthetic CPs have narrow polydispersity index. Some interesting phenomenon appeared with the increased side chain length. The molecular weights will reduce except P3, and the absorbance and fluorescence emission spectra of CPs and CPNs are red-shifted. Фs are better and enlarged for CPs and CPNs, and better dispersion and uniform size were founded with longer side chains.

One-Pot Preparation of Ethyl 2(Z)-4-(Anilinoxy)pentenoate by α-Aminoxylation of Propanal Followed by Z-Selective HWE Reaction and the Study on Its Cyclization Reaction

One-Pot Preparation of Ethyl 2(Z)-4-(Anilinoxy)pentenoate by α-Aminoxylation of Propanal Followed by Z-Selective HWE Reaction and the Study on Its Cyclization Reaction

One-pot synthesis of α,α-disubstituted Aryl-1-ethanones via the Wittig-Horner reaction

GRAPHICAL ABSTRACT

Total synthesis of (+)-epiquinamide and (−)-epiepiquinamide from d-mannose

The total synthesis of (+)-epiquinamide and (−)-epiepiquinamide has been achieved starting from a 3,5-dihydroxyfuranoside synthon derived from d-mannose. The methods featured Bernet-Vasella reaction followed by Horner-Wadsworth-Emmons (HWE) reaction to provide a new chiral building block diene as the key steps. The bicyclic framework of this quinolizidine was constructed by using ring-closing metathesis, selective reduction of ester and intramolecular nucleophilic substitution-cyclization.

Fifty Years of (Benz)oxaphospholene Chemistry.

The first synthesis of benzoxaphospholenes dates back to the 1960s. Since then, the structural variety of reported (benz)oxaphospholenes has steadily increased. Organophosphorus compounds have caught the interest of synthetic chemists for a couple of decades now because of their interesting biological properties. Oxaphospholenes, in particular, could serve as carbohydrate mimetics, and benzoxaphospholenes have been reported to possess bactericidal, insecticidal, herbicidal, and fungistatical properties. Transesterification reactions and addition of phosphorus nucleophiles to carbonyl compounds were reaction types that led to the production of the first (benz)oxaphospholenes. When it was discovered that allenylphosphonates could easily be obtained from propargyl alcohols and dialkyl halophosphites, the electrophile-induced cyclization reaction of these allenylphosphonate precursors resulted in a huge boom in the amount of reports on oxaphospholene synthesis. To this day, this method is still frequently used. Ring-closing metathesis and Horner-Wadsworth-Emmons reactions have also proven their potential for the preparation of oxaphospholenes. In recent years, Pd, Rh and Au-catalysis have made their entry, generating (benz)oxaphospholenes from a wide variety of simple substrates. A couple of miscellaneous methods are summarized at the end of the Review.

Insight into the synthesis and fabrication of 5,6-alt-benzothiadiazole-based D–π–A-conjugated copolymers for bulk-heterojunction solar cell

Herein, two new 5,6-alt-benzothiadiazole-based Poly(o-arylene–vinylene) (POAV) type of D–π–A-conjugated copolymers, namely P1 and P2, have been synthesized using Horner–Wittig reaction and characterized by UV–Vis, 1H NMR, 13C NMR, and CV. With a deeper HOMO level of ≈ 5.95 eV, these two polymers have been used as donor with [6, 6]-phenyl C61-butyric acid methyl ester, PC61BM as an acceptor to fabricate solar cells with a device structure ITO/PEDOT:PSS/P1orP2-PCBM/Al or Ca:Al. Without annealing or use of additives, maximum V oc of 0.68, fill factor of 30.2%, quantum efficiency of 22%, and maximum power conversion efficiency (PCE) of 0.76% have been achieved with P2. Morphology of blended active layer, P1/P2 with PC61BM and PC71BM, has been investigated using AFM images.

Synthesis of sulfone analog of oseltamivir precursor

We describe here the synthesis of a sulfone analog of an oseltamivir precursor. The synthesis comprises cyclization of two advanced building blocks via one-pot Michael addition and Horner–Wadsworth–Emmons reaction. The first building block was synthesized by an organocatalytic Michael addition of pentyloxyacetaldehyde to a nitroalkene. The second, alkenylsulfone, building block was prepared by oxidation followed by a Mannich type reaction. The cyclization was accomplished under microwave irradiation.

Total Synthesis of Nannocystin Ax.

The total synthesis of nannocystin Ax in an overall yield of 11% with 14 steps as the longest linear sequence is reported. Nannocystin Ax is a cytotoxic 21-membered depsipeptide and was isolated from the myxobacterial genus Nannocystis sp. The synthesis uses a vinylogous Horner-Wadsworth-Emmons reaction (HWE) and a vinylogous Mukaiyama aldol reaction (VMAR) as the key steps for the construction of the polyketide fragment. The macrocycle was closed via a macrolactamization reaction using COMU.