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

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

• Kimberley A. Roper,
• Malcolm B. Berry and
• Steven V. Ley

Beilstein J. Org. Chem. 2013, 9, 1781–1790, doi:10.3762/bjoc.9.207

• -Wittig and Appel reactions in flow [37][38][39][40]. The immobilisation of triphenylphosphine in this manner allowed the facile production of a collection of pure compounds using flow chemistry technologies with no need for further offline purification. Following the successful application of this

• immobilising the triphenylphosphine on a solid-support [48]. A polymer-supported equivalent of triphenylphosphine has also been successfully utilised by our group and by others in batch Wittig reactions [49][50], Mitsunobu and Staudinger aza-Wittig reactions [51][52], as well as many examples concerning the

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• Saint-Aignan, France 10.3762/bjoc.9.168 Abstract A concise and regioselective preparation of 2-heteroarylmethylene decorated N-arylpyrroles is described through a metal-free Mannich/Wittig/hydroamination sequence followed by isomerization of the N-arylpyrrolidine adducts. Furthermore, the C–H

• recently described a one-pot organo-catalyzed synthesis of N-heteroarylmethylene pyrrolidines 4 [13] from readily available aldehydes 1 and imine 2 by a sequence of Mannich coupling [14][15][16][17][18][19][20][21][22][23][24], Wittig olefination with phosphonium 3, and proton-mediated hydroamination

• -heteroaromatic scaffolds is reported. Based on the isomerization of pyrrolidines prepared by a simple and efficient sequence of Mannich/Wittig olefination/hydroamination reactions, no oxidant or metallic salts were employed [31]. This study also led us to investigate the feasibility of this process with

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• dithioketal 14 (86% yield) [72][73][74]. Wittig olefination of the C-1 ketone with methoxymethylenetriphenylphosphine [75] yielded the corresponding enol methyl ether, which was hydrolyzed to the aldehyde under acidic conditions and reduced with NaBH4 to form alcohol 15 with desired diastereoselectivity at

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

• -arylbenzofurans 122a–e was prepared and studied [83]. A representative synthesis of [125I]122a, which uses a similar Wittig as in the synthesis of 121, is shown in Scheme 9A. It was found that the iodo substituent could be varied between the 5- and 6-positions, and the N,N-dimethylamino substituent could be

• 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

• access ylides [26], although phosphonium ylides for carbonyl-olefination chemistry are usually prepared by deprotonation of phosphonium salts [1][2][3][4]. In fact, phosphine trapping of lithium carbenoids followed by carbonyl olefination has been little studied since Seyferth and Wittig independently

• their utility in Wittig–Schlosser and SCOOPY-type stereoselective olefination reactions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Here we have shown a new and concise method to such valuable intermediates, directly from readily available terminal epoxides. Significantly, the

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• corresponding alcohol, which was then subjected to reaction with 2,2-dimethoxypropane (2,2-DMP) in the presence of BF3·Et2O [24] to produce N,O-acetonide 10 in 93% yield over two steps. For the preparation of the E-isomer of α,β-unsaturated ester 11, Wittig–Horner reaction employing Garner’s aldehyde has been

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• aziridination. A range of ortho-, meta- and para-substituted cinnamates were synthesised via Wittig, Heck or esterification routes (for details, see Supporting Information File 1). Each substrate was subjected to two sets of aziridination conditions, with the optimum yields reported. Electron-rich substrates

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

• -carbaldehydes 6a–h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure. Keywords: acetal; Claisen rearrangement; oxidative cleavage; ring-closure; Wittig olefination; Introduction

• method for the synthesis of 3-methylquinoline-4-carbaldehyde. It was considered that a properly substituted 2-(2-nitrophenyl)pent-4-enal [25][26][27] could be a fitting intermediate for this purpose. Such an intermediate is easily accessible through the Wittig-olefination–Claisen-rearrangement protocol

Enantioselective total synthesis of (R)-(−)-complanine

• Krystal A. D. Kamanos and
• Jonathan M. Withey

Beilstein J. Org. Chem. 2012, 8, 1695–1699, doi:10.3762/bjoc.8.192

• organocatalytic O-nitrosoaldol as the key step. A retrosynthetic analysis for complanine is depicted in Scheme 1. The synthesis was initiated by preparation of homoconjugated all-Z-diene 1 (Scheme 2). Sequential olefin preparation by using Wittig chemistry, or selective polyyne reduction represent two traditional