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

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

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• ]. Organometallic reactions on solid supports are always particularly challenging [25]. In the past, indoles were synthesized by using, for example, Fischer indole synthesis [26][27][28][29][30], Bartoli indole synthesis, Nenitzescu synthesis [31], Wittig indole synthesis [32], Madelung indole synthesis [33

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• reaction is a modification of the Wittig olefination in which a phosphoryl-stabilized carbanion reacts with an aldehyde or ketone to form an alkene and a water-soluble phosphate ester [23][24][25]. In general, this reaction preferentially gives more stable E-disubstituted alkenes, although several

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

Synthesis of 2,6-disubstituted tetrahydroazulene derivatives

• Zakir Hussain,
• Henning Hopf,
• Khurshid Ayub and
• S. Holger Eichhorn

Beilstein J. Org. Chem. 2012, 8, 693–698, doi:10.3762/bjoc.8.77

• ; ring expansion; Introduction Hydroazulene skeletons provide the basic ring systems of natural products, such as guaianolide sesquiterpenes [1][2] and the so-called furanether B series [3][4]. The stereoselective synthesis of trans-hydroazulene derivatives by a tandem Michael/intramolecular Wittig

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

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

A new phenylethyl alkyl amide from the Ambrostoma quadriimpressum Motschulsky

• Guolei Zhao,
• Chao Yang,
• Bing Li and
• Wujiong Xia

Beilstein J. Org. Chem. 2011, 7, 1342–1346, doi:10.3762/bjoc.7.158

• chain was accomplished by the selective protection of the hydroxy groups and two-time implementation of the Wittig olefination reaction. Keywords: asymmetric synthesis; beetle; fatty acid amide; isolation; Introduction The leaf beetle Ambrostoma quadriimpressum Motschulsky (Coleoptera: Chrysomelidae

• disconnected into two fragments, 2 and 3. The intermediate fragment 2 would be readily prepared from the commercially available ε-caprolactone. The crucial fragment 3 would be constructed from the intermediate 4 through Wittig olefination. The polyhydroxy compound 4 would be obtained from L-glutamic acid by

• , resulted in the deprotection of the TBDPS group. Alternatively, the alcohol 9 could be obtained by reduction with diisobutylaluminium hydride (Dibal-H) in 86% yield, which was then converted to the corresponding aldehyde 10 by oxidation with PCC. Wittig olefination of aldehyde 10 with n

Bromine–lithium exchange: An efficient tool in the modular construction of biaryl ligands

• Laurence Bonnafoux,
• Frédéric R. Leroux and
• Françoise Colobert

Beilstein J. Org. Chem. 2011, 7, 1278–1287, doi:10.3762/bjoc.7.148

• certainly one of the most fundamental synthetic transformations [39]. Although this reaction was reported by C. S. Marvel in 1927 [40], G. Wittig [41] and H. Gilman [42][43][44] were the first to apply it in organic synthesis in the late thirties. Since then, this reaction has been considered as a mature

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• corresponding zinc reagents. This makes their preparation especially important. 2.1 The preparation of heterocyclic magnesium reagents through a bromine- (or iodine-) magnesium exchange Compared to the halogen/lithium exchange, discovered in 1939 by Wittig and Gilman, the halogen/magnesium exchange is much