Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• investigated, but resulted in a moderate yield of 32% only (reaction not displayed). One-pot Swern oxidation to the corresponding aldehyde and subsequent Wittig reaction with stabilized Wittig reagent 32 led to α,β-unsaturated ester 33 in 85% yield. After simultaneous reduction of the double bond and cleavage

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• position 2 underwent ca. 6% epimerization to yield 7 as a mixture of 4 stereoisomers. The synthesis of 2,6,8,12-tetramethyltrideca-2,4-diene (8) was completed by Wittig reaction using (3-methylbut-2-en-1-yl)triphenylphosphonium bromide [15]. As expected, the obtained mixture of all possible stereoisomers

• , followed by oxidation, yielded the aldehyde 10, which was chain elongated by Wittig reaction with [(2E)-1-methylbut-2-en-1-yl]triphenylphosphonium bromide [17] to afford the protected dienol 11 as a mixture of 4 racemates. This was due to partial epimerization at position 2 of the aldehyde 10 and the less

• corresponding deoxygenation steps) would produce the carbon skeleton of a 4,6,8,10-tetramethyltrideca-2,4-diene (15). Thus, from a biosynthetic point of view, the structure would be reasonable and follow established principles. To test the validity of our assumption, we transformed 13 into 15 by Wittig reaction

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

• Danny Geerdink,
• Jeffrey Buter,
• Teris A. van Beek and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2014, 10, 761–766, doi:10.3762/bjoc.10.71

• the reduction of 13 with DIBALH is a clean reaction, affording essentially pure 2 after work-up, the preparation of pure 13 was highly desirable. A stepwise olefination approach was therefore considered. Wittig reaction of aldehyde 11 with phosphorane 14 to give 15 was carried out first (Scheme 4) [27

• account for the observed 1H NMR signals. As the Wittig reaction of 11 did afford 15, although with the simultaneous formation of an inseparable side-product, we were curious to see how the analogous Horner–Wadsworth–Emmons olefination towards 15 would perform. Thus, aldehyde 11 was freshly prepared and

• intermediate, leading to a mixture of double bond isomers. The impurity previously observed as a result of the Wittig reaction was not present. In addition, the E- and Z-isomers could be separated using column chromatography affording pure E-15 in 45% yield. Reduction of 15 was achieved using DIBALH, affording

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -pentodialdo-1,4-furanose (3b) which was obtained from D-glucose in good yield as reported earlier [33]. Thus, the Wittig reaction of 3b followed by hydrogenation (10% Pd/C) gave 4-heptyl-D-threose derivative 5b (Scheme 3). Hydrolysis of 1,2-O-isopropylidene (TFA:H2O) followed by oxidative cleavage of the

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• . Synthesis of reference compounds We exploited a Wittig reaction with a suitable stabilized phosphorane for the synthesis of (E,E)-diene 6a (Scheme 4). The Wittig compound 24 was obtained in two steps from 2-bromopropionic acid following synthetic procedures described for its acetic acid analogue and the

• % yield by a Wittig reaction with stabilized phosphorane 26. The Z-isomer 10b was synthesized by Still–Gennari olefination using phosphonate 27 in 47% yield. The yield for the deprotection step was satisfying (61% for 7a and 57% for 7b) in both cases, indicating that both isomers are configurationally

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• . Conclusion: Similar to many other Wittig-type gem-difluoroolefination reactions in the presence of PPh3, the reaction of TMSCF2Cl with aldehydes and activated ketones is effective. Keywords: (chlorodifluoromethyl)trimethylsilane; difluorocarbene; gem-difluoroolefin; organo-fluorine; Wittig reaction; ylide

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• elusive cis-divinylcyclopropane (9) was characterized ten years later by Brown and coworkers [3] using a low temperature and very short-timed Wittig reaction between cis-vinylcarbaldehyde 11 and methylenetriphenylphoshorane. This review summarizes the recent synthetic applications of the

• rearrangement was followed by MOM-cleavage. Oxidation furnished an intermediate aldehyde, followed by Wacker oxidation and the Anders–Gaßner variant [106][107][108][109] of the Wittig reaction to furnish 5-epi-vibsanin E (115). Echavarren and coworkers [110] used a DVCPR to target the sesquiterpenoid

• reaction of dihydrooxepine 325 (see Scheme 38) to access vinylcyclopropane carbaldehyde 326, which was in situ converted into the corresponding imine 327 using an aza-Wittig reaction. Subsequent vinylcyclopropane carbimine–dihydroazepine rearrangement furnished cyclic 328 in excellent yield. Conclusion The

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• Abstract The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 (1) is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11

• ; resolvin D2; Sonogashira coupling; total synthesis; Wittig reaction; Introduction The resolution of inflammation is a tightly governed active process effectively mediated by a range of bioactive polyunsaturated fatty acids, peptides and proteins. In 2002, a new family of endogenously generated lipid

• using the common linchpin phosphorus ylide derived from phosphonium salt 6 [21][22] and each of the homochiral aldehydes 5 and 7 [9]. Synthesis of vinyl iodide 4 The synthesis of fragment 4 began with the production of the aldehyde 7 as shown in Scheme 2. A Wittig reaction between hemiacetal 8 [23] and

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• literature (Scheme 3); silver mediated fluorination of butenoyl bromide 15 is known [14] delivering 16 in moderate yield but via a slow and expensive reaction. Wittig reaction, following in situ reduction of ethyl fluoroacetate (17) has been reported [15], while Purrington [16] prepared 19 by direct

• -chromophoric syn-diol products. Educt elaboration was achieved via cyclic sulfate methodology, leading to the stereocomplementary anti-diols, and via acetal protection, ester reduction and one-pot oxidation/Wittig reaction, re-connecting this study to the published route to 6-deoxy-6-fluorohexoses

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• , e.g., triphenylphospine oxide. As with the Wittig reaction, the HWE reaction can also promote the epimerization of the α-proton (pKa of triethoxyphosphonoacetate in DMSO is 18.6) [109]. We have experienced this tendency especially with α-amino ketophosphonates [110], but there is also evidence that

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• halides and primary or secondary amines has been developed. The synthetic pathway combines nucleophilic substitutions and a Staudinger–aza-Wittig reaction in the presence of polymer-bound diphenylphosphine under 14 bar of CO2 pressure and has been performed in a one-pot two-step process. The protocol has

• : isocyanates; microwave-assisted reaction; one-pot reaction; tandem Staudinger–aza-Wittig reaction; urea derivatives; Introduction The industrial and commercial impact of isocyanates (R–NCO) is steadily growing. In particular, the polyurethane output has undergone yearly increases of 5% over the last decade

• volatile, solid and supported reagents. In summary, we herein report an optimized protocol for a MW-assisted Staudinger–aza-Wittig reaction with polymer-bound diphenylphosphine (PS-PPh2) in a CO2 atmosphere. The study also aimed to prepare a series of symmetric and asymmetric alkyl/aryl urea derivatives in

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

• intramolecular addition–elimination reaction. In the presence of the aldehyde 154, 153 underwent a Horner–Wittig reaction to generate 155 as a 1:2.3 mixture of E- and Z-isomers. Treatment of 155 with boron trichloride not only liberated the phenol but also isomerized the E-double bond to the Z-isomer. Finally, a

• starting materials, via a Staudinger–aza-Wittig reaction gave amine 237 as a mixture of four diastereoisomers. Conversion into 4-oxido-isoquinolinium betaine 238 could be achieved by an acid-catalyzed methanol extrusion and isomerization. Betaine 238 served as the substrate for the following 1,3-aza

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• ]. Benzofurans Replacement of the nitrogen of the benzoxazole backbone with carbon affords the benzofuran backbone of compounds 121–126 (Figure 4), which has also been successfully employed for radioimaging of Aβ plaques. The [11C]-labeled benzofuran 121 was prepared via Wittig reaction between the

• group in place of the N,N-dimethylaminopyridine group, was prepared using a Wittig reaction between the triphenylphosphonium salt of 2-hydroxy-5-methoxybenzyl alcohol (127) and 4-dimethylaminobenzoyl chloride (35), followed by O-demethylation and installation of the [18F]-labeled linker (Scheme 9C

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

• Sandeep Kumar,
• Ramendra Pratap,
• Abhinav Kumar,
• Brijesh Kumar,
• Vishnu K. Tandon and
• Vishnu Ji Ram

Beilstein J. Org. Chem. 2013, 9, 809–817, doi:10.3762/bjoc.9.92

• group as well as by Wittig reaction [23][24]. The growing importance of 3-alkenylindolin-2-ones has resulted in the design of numerous new synthetic routes. Recently, metal-catalyzed carbonylative annulation of alkynyl-arylamines has been employed for the synthesis of this class of compounds [25][26][27

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

• Krishna C. Majumdar and
• Sintu Ganai

Beilstein J. Org. Chem. 2013, 9, 503–509, doi:10.3762/bjoc.9.54

• -dioxides through an intramolecular aza-Wittig reaction. The reaction was found to be general through the synthesis of a number of benzothiadiazine 1,1-dioxides. Acid-catalyzed hydrolysis of 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxides furnished the 2-substituted benzothiadiazine-3-one 1,1-dioxides in good

• yields and high purity, which is the core moiety of RSV inhibitors. Keywords: benzothiadiazine-3-one 1,1-dioxide; 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxide; intramolecular aza-Wittig reaction; sultam; Introduction Sultams have gained popularity in the scientific community especially among synthetic

• derivatives have been reported [25][26][27][28][29][30][31][32], the development of a simpler method for the synthesis of the 1,2,4-benzothiadiazine 1,1-dioxide moiety is still desirable because of their biological significance. The aza-Wittig reaction is employed for the construction of C=N, N=N and S=N

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

• 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

Alkenes from β-lithiooxyphosphonium ylides generated by trapping α-lithiated terminal epoxides with triphenylphosphine

• David. M. Hodgson and
• Rosanne S. D. Persaud

Beilstein J. Org. Chem. 2012, 8, 1896–1900, doi:10.3762/bjoc.8.219

• with high regio- and stereocontrol (Scheme 1) [1][2][3][4][5][6][7][8][9]. These ylide intermediates can be generated by initiating a Wittig reaction between an aldehyde 1 and a phosphorane 2 at low temperature in the presence of lithium salts, which promote ring opening of the initially formed

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

• Mukund G. Kulkarni,
• Mayur P. Desai,
• Deekshaputra R. Birhade,
• Yunus B. Shaikh,
• Ajit N. Dhatrak and
• Ramesh Gannimani

Beilstein J. Org. Chem. 2012, 8, 1725–1729, doi:10.3762/bjoc.8.197

• important 3-methylquinoline-4-carbaldehydes 6a–h from o-nitrobenzaldehydes 1a–h employing a Wittig-olefination–Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a–h, which on heating under reflux in xylene

• % yield. General procedure for the Claisen rearrangement The crotyl vinyl ethers 2a–h (17 mmol) obtained from the Wittig reaction were dissolved in anhydrous xylene (35 mL) and the solution was heated under reflux for 5–7 h (TLC, ethyl acetate/petroleum ether 1:9). Then, the solvent was removed under

Cyclization of ortho-hydroxycinnamates to coumarins under mild conditions: A nucleophilic organocatalysis approach

• Florian Boeck,
• Max Blazejak,
• Markus R. Anneser and
• Lukas Hintermann

Beilstein J. Org. Chem. 2012, 8, 1630–1636, doi:10.3762/bjoc.8.186

• use of tri-n-butylphosphane (20 mol %) as a nucleophilic organocatalyst in MeOH solution allows cyclization to take place under much milder conditions (60–70 °C). Several coumarins were prepared, starting from ortho-hydroxyarylaldehydes, by Wittig reaction with Ph3P=CHCO2Me to (E)-methyl ortho

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• and 4 (Scheme 2), as reported previously [22]. Due to the instability of the corresponding amine building block bearing the indole unit, azide 27 was employed as a precursor. Staudinger/aza-Wittig reaction [43] of 27 and 20 and subsequent condensation with 6 and 21 afforded the peptidyl product 28

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• EtOH and H2O under reflux to achieve ester saponification, which was followed by decarboxylation, proceeding smoothly to give the corresponding ketone in 76% yield. The ketone was then transformed to the exocyclic alkene 15 in 61% yield by Wittig reaction with the appropriate phosphonium salt. The

Dioxane dibromide mediated bromination of substituted coumarins under solvent-free conditions

• Subrata Kumar Chaudhuri,
• Sanchita Roy and
• Sanjay Bhar

Beilstein J. Org. Chem. 2012, 8, 323–329, doi:10.3762/bjoc.8.35

• [8], Et4N+Br− in the presence of hypervalent iodine reagents [9], and NBS in tetrabutylammonium bromide under molten salt conditions [10]. There is a recent report of the preparation of 3-bromocoumarins from acyclic precursors through bromination of a Wittig reagent with NBS followed by tandem Wittig

• reaction and cyclization [11]. Many of them involve high temperature, long reaction time, toxic, exotic and costly reagents, sometimes in excess to stoichiometric requirement, and organic solvents during and after the reactions. Thus, there is always an urgency to put ardent efforts towards the development

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

• Iain Coldham,
• Adam J. M. Burrell,
• Hélène D. S. Guerrand,
• Luke Watson,
• Nathaniel G. Martin and
• Niall Oram

Beilstein J. Org. Chem. 2012, 8, 107–111, doi:10.3762/bjoc.8.11

• chemistry for the construction of the core ring system found in alkaloid natural products. Wittig reaction with aldehyde 16 should be possible to provide the core ring system found in the alkaloids meloscine and scandine [26][27][28][29][30]. However, we chose to investigate a shorter reaction sequence

• without the need for protecting groups and to carry out the Wittig reaction at an earlier stage, as shown in Scheme 6. Olefination of aldehyde 6 with the anion formed from methyltriphenylphosphonium bromide gave alkene 17, which was reduced with DIBAL-H to give aldehyde 18. Heating this aldehyde with

Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbene-methylene-3-sydnones and their synthesis

• Kristina Butković,
• Željko Marinić,
• Krešimir Molčanov,
• Biserka Kojić-Prodić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2011, 7, 1663–1670, doi:10.3762/bjoc.7.196

• -cyanotoluene (see Supporting Information File 1 for full experimental data). Bromination of o-cyanotoluene afforded 2-(bromomethyl)benzonitrile (4) [24], which was transformed to triphenylphosphonium salt 5 [25] followed by Wittig reaction with 4-methylbenzaldehyde to 2-(4-methylstyryl)benzonitrile (6a,b) [26

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

• Kimberley A. Roper,
• Heiko Lange,
• Anastasios Polyzos,
• Malcolm B. Berry,
• Ian R. Baxendale and
• Steven V. Ley

Beilstein J. Org. Chem. 2011, 7, 1648–1655, doi:10.3762/bjoc.7.194

• interest in using monolithic supports to facilitate key chemical transformations [20][21][22][23][24][25][26][27][28][29][30][31]. We recently reported on the development of a new monolithic triphenylphosphine reagent and its use in the Staudinger aza-Wittig reaction in flow [32][33]. Here we discuss the