Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• azodicarboxylates 2 generates the Huisgen zwitterion intermediate 8 [37][38]. Subsequent proton transfer and phosphonium migration between 8 and the MBH alcohol 1 produce an oxophosphonium intermediate 9 and a hydrazine anionic species 10 [36]. Finally, an expedient SN2' attack of species 10 on 9, probably

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• phosphites (P(OR)3), activated through oxidants such as iodine, have been reported to give the corresponding phosphates in a Michaelis–Arbuzow type reaction [83][84][85] (Scheme 5). In order to improve atom economy and side product separation, we rationalized that in the phosphonium intermediate III

• 13b was obtained in only 63% yield (entry 3). The lower yield compared to the hydroxypiperidines 11a,b and 11d (≥74%, see Table 2) might be explained by the preference of a conformation of the phosphonium intermediate III of 11a,b and 11d (Scheme 5), which is favourable for the cyclisation. This

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

• precursors for organic synthesis, but also act as bioisosteres for enzyme inhibitors. Among various methods for their preparation, the carbonyl olefination with difluoromethylene phosphonium ylide represents one of the most straightforward methods. Results: The combination of (chlorodifluoromethyl

• difluoromethylene phosphonium ylide, which can be generated in situ either by the transformation of a difluorinated phosphonium salt or by the reaction between difluorocarbene (:CF2) and a phosphine (Scheme 1) [19][20][21][22][23][24][25][26]. In 1964, Fuqua and co-workers first reported the difluoromethylenation

• of aldehydes by using ClCF2CO2Na/PPh3 [19]. In 1967, Burton and Herkes suggested that the ylide intermediate involved in the olefination process was more likely to be formed by the decarboxylation of a difluorinated phosphonium salt rather than the combination of :CF2 and a phosphine (Scheme 1

Cyclic phosphonium ionic liquids

• Sharon I. Lall-Ramnarine,
• Joshua A. Mukhlall,
• James F. Wishart,
• Robert R. Engel,
• Alicia R. Romeo,
• Masao Gohdo,
• Sharon Ramati,
• Marc Berman and
• Sophia N. Suarez

Beilstein J. Org. Chem. 2014, 10, 271–275, doi:10.3762/bjoc.10.22

• , Brooklyn College of the City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA, Fax: +1 718-951-4407, Tel +1 718-951-5000, ext. 2869 10.3762/bjoc.10.22 Abstract Ionic liquids (ILs) incorporating cyclic phosphonium cations are a novel category of materials. We report here on the

• synthesis and characterization of four new cyclic phosphonium bis(trifluoromethylsulfonyl)amide ILs with aliphatic and aromatic pendant groups. In addition to the syntheses of these novel materials, we report on a comparison of their properties with their ammonium congeners. These exemplars are slightly

• less conductive and have slightly smaller self-diffusion coefficients than their cyclic ammonium congeners. Keywords: cyclic phosphonium; ionic liquid; organophosphorus; phosphinanium; phospholanium; phosphonium; Introduction The most widely investigated and commercially available ionic liquids (ILs

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

• 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

• the ylide derived from 9 provided the alkene 10 [9] with excellent stereoselectivity. Oxidation of 10 with Dess–Martin periodinane then afforded aldehyde 7. The phosphonium salt 6 [21][22] was produced from propargyl bromide via silylation of the derived sodium salt with TIPSCl followed by reaction

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

• 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

• the dehydrohalogenation of the phosphonium salt [103]. These complexes react with carbonyl compounds differently. Addition reactions of other ylides to 1, proceeded with little or no racemization of 1. The E/Z-ratio of the reaction was 1:13 favouring the Z-adduct 66. In comparison to Beaulieu’s

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• (up to 92% ee). The 31P NMR studies of the interaction between phosphinothiourea OC-41 and HCl indicated that the initial heterolysis of HCl affords a phosphonium chloride complex which is involved in the catalytic cycle. The desymmetrization of both cyclic and acyclic aziridines proceeded smoothly to

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

• 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

• to form imines 2b,c. Hence, when imines 2b,c were exposed to aldehyde 1a in the presence of catalyst 6 (available in racemic form), the Mannich adducts 7i,j were obtained and directly reacted with phosphonium salt 3. In line with our procedure, the resulting acyclic anilines 8i,j were then exposed to

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

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• monophosphonylated quinone methide 25. The starting compound was first phosphonylated with triethyl phosphite to give the phosphonium betain 26. This compound was subsequently transformed into the corresponding 7,7-bisphosphonoquinone methide 27 by treatment with bromine. Heating of 27 under reflux in triethyl

• phosphite resulted in the trisphosphonate 18 in a yield of 40%. The phosphonium betain 28, which was expected from the reaction of 27 and triethyl phosphite was unstable and could not be isolated (Scheme 12) [35]. It should be noted that compound 18 can be easily oxidized to the corresponding stable

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

• be generated by double deprotonation of β-hydroxy primary phosphonium salts [10][11][12][13][14][15][16][17][18][19], where the latter are obtained from Ph3P and 1,2-halohydrins [10][11][12][13][14][15][16][19] or (in the presence of acid) from terminal epoxides [17][18]. In seeking a more concise

• 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

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

• conjugate addition to 1, with generation of a tributylphosphonium salt (δ = +37 ppm) of the probable zwitterionic structure 5 (Scheme 3; for the 31P NMR spectrum see the Supporting Information File 1). Similar phosphonium phenolates are known to exist either as the zwitterionic (analogue to 5) or neutral

• phosphorane structure (analogue to 5’) [43][44]. Under the conditions of the catalytic reaction, phosphonium (+37 ppm) was the only species of importance and thus represents the resting state of the catalytic reaction, which could be either 5 or 6. We did not observe a 31P NMR signal for n-Bu3P, or a signal

• the catalyst n-Bu3P present will be converted to a water-soluble phosphonium salt, which is easier to separate from the coumarin product than the neutral phosphane is. Second, the yields of coumarins were higher when the quenching procedure was used. This implies that part of the coumarin product may

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• mg, 92.5 µmol, 5.00 equiv), bromo-tris-pyrrolidino phosphonium hexafluorophosphate (PyBrOP) (43.2 mg, 92.6 µmol, 5.01 equiv) and DIEA (32.2 µL, 185 µmol, 10.0 equiv) were added. After stirring of the reaction mixture for 72 h, the solvent was removed under reduced pressure and the crude title

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• electron-deficient Lewis acid. In the case where molecular hydrogen interacts with a phosphine/borane FLP, this occurs by the formation of a phosphonium/borate ion pair (Scheme 1). For unsaturated substrates, the reaction is better described as an insertion or cycloaddition (see Scheme 2 for a

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• photonucleofuges [38][39][40][41], the stable iminium salts 3-PF6 were treated with tertiary phosphines 10 at room temperature to give the enamino-phosphonium ions 11 instantaneously (Figure 4a). Their irradiation with 7 ns laser pulses (266 nm) regenerated the iminium ions, the decay of which was monitored

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

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

• A the reaction is thought to proceed through the simple ion pair 3 formed by the reaction of one equivalent of triphenylphosphine (1) and one equivalent of carbon tetrabromide (2). This can react with the alcohol substrate to form an oxy-phosphonium 4 along with bromoform (5), which is removed under

• reduced pressure at the end of the reaction along with the solvent. The oxy-phosphonium salt 4 then reacts with the bromide counterion to produce the substituted product 6 along with the triphenylphosphine oxide byproduct (7). However, 3 is in equilibrium with the inverted ion pair 8, which can proceed

• via pathway B in which 8 reacts with a second equivalent of triphenylphosphine to form the dibromophosphorane 9 and phosphorane 10. This dibromophosphorane 9 is then able to react with an alcohol to give intermediate 4, which can proceed to the product, whereas 10 proceeds to a phosphonium salt

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• columns connected in parallel were filled with polymer-supported hydroxybenzotriazole, and during the process they worked either in loading or in elution mode. In the loading mode the columns were flushed with a solution of 49, bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBrOP) and

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• conducted in phosphonium salt-based ionic liquids (PSILs) with PdCl2(PPh3)2/CuI/DBU as the catalyst system [30]. In this case, the palladium-mediated Sonogashira coupling reaction leading to 1-halo-2-alkynylbenzene derivatives is followed by a carboxyamidation in the presence of carbon monoxide and primary

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

• -heptylidenetriphenylphosphonium bromide in the presence of n-BuLi gave adduct 11 as an (E/Z)-mixture (E/Z = 1:5) in 75% yield. Selective removal of the TBS group with pyridinium tosylate gave 12 in 98% yield [21]. With the alcohol 12 in hand, our next step was to synthesize the phosphonium salt 15 [22][23] (Scheme 4). Therefore

• , ε-caprolactone was hydrolyzed with 5% NaOH to give hydroxy acid 13 in quantitative yield, which was reacted with PBr3 in CH2Cl2 to afford compound 14 in 82% yield. Treatment of 14 with PPh3 in CH3CN gave the phosphonium salt 15 in 98% yield. The construction of the aliphatic chain was achieved

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• conditions with a phosphonium salt [23]. Piperidines III (Y = H) can undergo degradation to form dibromides I although this process is typically less efficient [12][14][15]. The piperidine ring can be reconstituted by ring-closure of I with an appropriate amine or aniline Y–NH2 [2][22]. The thianes IV are

• from diols 2a and 2b or tetrahydropyrans 3a–3d (Scheme 3). When H2SO4 was used instead of the phosphonium salt, the yield of 1b was lower (67%). The dibromides were purified on silica gel and, in addition, 1a and 1b were distilled. Preparation of diols Diols 2a and 2b, containing simple alkyl chains

• using standard conditions by reacting phosphonium salts 7a–7c and 7e with either BuLi in anhydrous THF, or NaHMDS in a 1:1 mixture of anhydrous Et2O and anhydrous CH2Cl2. Heating the corresponding alkyl halide (Br or I) with PPh3 under reflux in concentrated solutions of toluene, benzene, or

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Synthesis of indolo[3,2-b]carbazole-based new colorimetric receptor for anions: A unique color change for fluoride ions

• Ajit Kumar Mahapatra,
• Giridhari Hazra and
• Prithidipa Sahoo

Beilstein J. Org. Chem. 2010, 6, No. 12, doi:10.3762/bjoc.6.12

• ][24][25][26][27][28], there is a paucity of reports on selective naked-eye chemosensors for fluoride [29][30][31]. Nitrophenyl, nitronaphthalene urea [32][33][34], naphthalene triphenyl-phosphonium [35], benzimidazolyl pyridine [36][37] and oxidized bis(indolyl)methane [38] as signal units for

1-(4-Alkyloxybenzyl)-3-methyl-1H-imidazol-3-ium organic backbone: A versatile smectogenic moiety

• William Dobbs,
• Laurent Douce and
• Benoît Heinrich

Beilstein J. Org. Chem. 2009, 5, No. 62, doi:10.3762/bjoc.5.62

• the cations and anions the physico-chemical properties of ionic liquids can be tuned and specifically optimised for a wide range of applications [5][6][7][8][9][10][11]. Although many organic cations (e.g. phosphonium, ammonium, pyridinium, imidazolium) can be used for the design of ionic liquids

An expedient synthesis of 5-n-alkylresorcinols and novel 5-n-alkylresorcinol haptens

• Kirsti Parikka and
• Kristiina Wähälä

Beilstein J. Org. Chem. 2009, 5, No. 22, doi:10.3762/bjoc.5.22

• water solubility more generally, aryl modified phosphonium salts, carrying a –COOH group [38] or PEG attachments [39], have been developed but require extensive synthetic work. Previously, non-stabilized alkylphosphonium salts have appeared much less amenable than the benzyl analogues. A single paper

• MW catalyzed synthesis route where 3,5-dimethoxy benzaldehyde and unstabilized alkyltriphenyl phosphonium ylids react in DMSO/H2O works as well and alkylresorcinol precursors that do not have a commercially available alkanal starting material can be synthesized rapidly and efficiently by way of this