Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• functionalization through the strain-driven 1,3-dipolar cycloaddition with cyclooctyne. The original conditions of Wittig [36], the reaction of cyclooctyne with phenyl azide, and the numerous applications pioneered by Bertozzi suggest that the reaction proceeds under mild conditions [34][35][37][38][39][40

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• synthesized by Wittig reaction using different conditions (Scheme 1). A Wittig–Schlosser reaction [15] starting from a commercially available 5:1 E/Z-mixture of 1-bromobut-2-ene (17) led to preferentially (1E)-configured products. After conversion of 17 into the respective Wittig salt 18 and reaction with 2

• compound. The minor product isolated pure under these conditions was 2-((1Z,3E)-penta-1,3-dienyl)pyridine (9, streptopyridine B), indicated by the coupling constants 3J1,2 = 11.8 Hz and 3J3,4 = 15.1 Hz. To delineate the stereochemistry of the other two isomers 10 and 11, the conditions of the Wittig

• the diastereomeric mixture of Wittig salts. Conclusively, 10 must be the last possible 1Z,3Z-stereoisomer. Both compounds 10 and 11 could not be isolated in pure form, but their mass spectra and retention times were identical to those of the natural products. The mass spectrum of compound 8 indicated

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• ; polymer-supported reagent; rasta resin; triphenylphosphine oxide; Introduction One of the major drawbacks of the Wittig [1] and Mitsunobu [2][3] reactions is that they result in the formation of a stoichiometric quantity of triphenylphosphine oxide (1) as a byproduct. From an atom economy perspective

• reagents and catalysts [27][28][29][30][31][32][33], and have used easily synthesized rasta resin–Ph3P (14) in various Wittig reactions that required only filtration and solvent removal for product purification (Figure 1) [27][28][29]. Additionally, 14 was converted into phosphonium salt 15, which proved

• previously used as a bifunctional reagent in one-pot Wittig reactions [29]. Gel-phase 31P NMR spectroscopic analysis of 18 indicated that oxidation of the phosphine groups was complete, and elemental analysis was used to determine the loading level of phosphine oxide and amine groups to be 1.07 mmol/g and

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• two sucrose units. This type of dimers may be eventually used for the construction of macrocycles by (simple) connecting their C-6’ (fructose) ends. Results and Discussion Coupling of two sugar units can be performed by a number of methods. The best one in our hands was the Wittig-type methodology

•  3. First, aldehyde 7 was converted into olefin 15 by treatment with the simplest Wittig reagent: Ph3P=CH2. Subsequent osmylation of the double bond in 15 provided two stereoisomeric diols in a 1:1 ratio; the first one was identical in all respects with the diol obtained from degradation of 11. The

• C75H86NO14Si [M + NH4]+: 1252.5818; found: 1252.5819. Examples of sucrose-based macrocycles. Synthesis of higher sugar precursors by a Wittig-type methodology. CD spectra of in situ formed chiral complexes of 13 (green line), 14 (purple line) and 16 (blue line) with dimolybdenum tetraacetate recorded in DMSO

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

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• synthetic feasibility of approach b), namely the cyclopropanation of the corresponding terminal olefin derivative 18. To explore this alternative approach, we managed to prepare the ethylidene derivative 18 by using either the Wittig or the Tebbe olefination reaction [34][35][36][37]. The former reaction

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

• selective Wittig coupling. Consequently, hydrogenation of 11 yielded a mixture of all 8 possible stereoisomers of the saturated alcohol 12; for relative proportions, see Supporting Information File 1. Starting from 12 and following the sequence described for the transformation of 6 to 8, a mixture of the

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

• ]. While targeting the synthesis of 2a, the Wittig olefination of 3a with n-hexyltriphenylphosphonium bromide and t-BuOK gave olefin 4a as a diasteromeric mixture of Z and E-isomers in the ratio 9.5:0.5 as shown by 1H NMR of the crude product. The catalytic hydrogenation of alkene 4a with 10% Pd/C in

• -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

• allylation as well as an anti-selective aldol reaction. Reference compounds representing the E- and Z-configured double bond isomers as potential products of the dehydratase reaction were obtained from a common precursor aldehyde by Wittig olefination and Still–Gennari olefination. The final deprotection of

• should be accessible from aldehyde 11 through a Horner–Wadsworth–Emmons reaction and the Still–Gennari olefination as well as by a Wittig olefination with stabilised phosphoranes, respectively. The aldehyde 11 should be accessible from the known molecule 13 via 12 [15]. Synthesis of the common precursor

• . 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

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• products were obtained in excellent yields and in high diastereoselectivity when chiral imines were employed (159b, de >95%). The group of van Boom and Overkleeft reported pipecolic amides via a Staudinger–Aza-Wittig/Ugi sequence (SAWU 3CR, Scheme 51) [132]. First the Staudinger reaction between an

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

• -difluoroolefination of carbonyl compounds [17][18]. Among these methods, the latter one has been studied with several named reactions, for example Wittig, Horner–Wadsworth–Emmons, and Julia–Kocienski reactions. In the Wittig gem-difluoroolefination, the reaction is believed to proceed via an undetected

• prepare the ylide intermediate (Scheme 1, reaction 2) [22][23]. Although the difluorocarbene/phosphine procedure for Wittig olefination has been put forward by Fuqua et al. as early as 1964 [19], the formation of difluoromethylene phosphonium ylide in such a way is quite rare [24][25][26]. Established

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• Buchwald’s procedure for the catalytic asymmetric vinylation of enones [51]. However, the desired vinylated product could not be obtained under the described conditions. An alternative α-formylation/Wittig olefination sequence gave only low yields. O’Brien et al. [41] described the failure of a direct

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

• Iguchi and co-workers [44] applied the DVCPR to the total synthesis of the marine prostanoid clavubicyclone [45]. Known aldehyde 33 (see Scheme 7) [46] was subjected to Wittig conditions to furnish an intermediate lactone, which was then opened reductively followed by selective oxidation of the allylic

• the resulting carbon-centered radical with oxygen. The resulting tertiary alcohol was then protected to give acetate 41. Standard functional group interconversions led to the formation of the remaining side chain using Wittig-conditions to afford olefin 42. Another series of standard functional group

Synthesis and determination of the absolute configuration of (−)-(5R,6Z)-dendrolasin-5-acetate from the nudibranch Hypselodoris jacksoni

• I. Wayan Mudianta,
• Victoria L. Challinor,
• Anne E. Winters,
• Karen L. Cheney,
• James J. De Voss and
• Mary J. Garson

Beilstein J. Org. Chem. 2013, 9, 2925–2933, doi:10.3762/bjoc.9.329

• (+)-pallescensone. A synthetic sample ([α]D −8.7) of the new metabolite was prepared by [1,2]-Wittig rearrangement of a geranylfuryl ether followed by acetylation of purified alcohol isomers. The absolute configuration at C-5 was established as R by the analysis of MPA ester derivatives of (Z)-5-hydroxydendrolasin

• characterization of 1, in particular the configuration at C-5. The synthesis, which was completed in five steps, involved preparation of 3-furylmethanol (4) and of geranyl bromide (5), etherification, [1,2]-Wittig rearrangement of geranyl 3-furylmethyl ether (6) to produce 7a/b, and acetylation to obtain target 1

• double bond at C6/C7. The isomeric mixture of 6 was immediately subjected to [1,2]-Wittig rearrangement with t-BuLi (4 equiv) and LDA at −78 °C to afford racemic 5-hydroxydendrolasin (39% yield), again as an E/Z mixture (7a/b) for which a 3:1 ratio was determined by 1H NMR comparison with data for 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

• followed by partial reduction. This is similar to the endgame of the reported syntheses of 1 [5][9] but both of these approaches involved formation of the C9–C10 bond as the convergent step. In our approach, 1 could arise from enyne 3 and vinyl iodide 4 which could both be obtained by Wittig extension

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• ]-Wittig rearrangement, a diastereoselective epoxidation, and a microwave assisted transannular epoxide opening reaction. It is also noteworthy that the starting material 55 contains an extraneous fluorine atom which is deleted during the synthetic sequence; this approach takes advantage of the often low

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

• one-pot oxidation/Wittig procedure was implemented from 37a; treatment with the Dess–Martin periodinane [41] in the presence of the stabilised ylide afforded a 4:1 E:Z mixture of the product alkene 39a in good (74%) yield. A second purification by column chromatography isolated the E-alkene

• -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

• conjugate addition [93], and a recent synthesis of lucentamycin A was achieved using this strategy [94]. Epoxidation of A leads to a highly functional intermediate C, which has been used in the synthesis of manzacidin B [95]. Among the plethora of olefination reactions, the Wittig [96][97] and Horner

• in low yield (27%) [102]. With a different unstabilized ylide 65, the enantiopurity of the Wittig product increased to >95% ee. The erosion of enantiopurity was attributed to the ylide (Ph3P=CH2) being too basic. It is well known that phosphonium ylides form stable complexes with alkali metals during

• typical outcome with unstabilized ylides. Kim has investigated means of reversing the E/Z-selectivity to favour the E-isomer [104]. They noticed that olefination under the usual Wittig conditions provided high Z-selectivity (1:15 E/Z). When the reaction was quenched with MeOH at −78 °C, the E/Z-ratio was

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

• , Hoffman and Lossen rearrangements have been used quite often in the past and are still used for specific applications [10][11][12][13]. The Staudinger–aza-Wittig reactions have played a pivotal role in the construction of cyclic and acyclic compounds [14][15][16][17][18][19]. The replacement of phosgene

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• )phenyllithium with geranyl bromide and 1n by two Wittig reactions from 2’-(phenylethynyl)acetophenone (see Supporting Information File 1). First, the hydroxycyclization of 1m, as a pure E isomer, under the previously established conditions afforded the dihydronaphthalene derivative 7m as a single isomer (Scheme

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

• accomplished within 6 consecutive steps. Generation of the dienamine 244 with pyrrolidine in methanol at 60 °C triggered an intramolecular Diels–Alder reaction to provide the full carbon skeleton 245. The final transformations of the synthesis involved a Wittig olefination of the ketone and a

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• envisaged deoxygenation route (Scheme 2), this key transformation saved 2 steps and paved the way for a final reaction sequence that was based on our synthesis of (−)-englerin A (5) [6]. Thus, Wittig olefination of the acetyl group in 3 afforded the sensitive vinyl epoxide 10 along with some cyclized

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

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• approaches have been used: (1) two-component cross-couplings that include α-ketoester alkylation/decarboxylation [32][33], aldehyde–olefin photoaddition [34], acetylide alkylation (sp3–sp) [35][36], Wittig coupling [3][21][37][38][39], Kolbe electrosynthesis [35][40][41][42], organocadmium (sp2–sp3) [43][44