A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• and the C8–C9 trisubstituted olefin of ripostatin A mapped onto a nickel-catalyzed coupling reaction of alkynes and epoxides developed in our laboratory (Scheme 1) [17]. In the intermolecular reaction, stereospecific cis addition across the alkyne is observed, and the stereochemistry at the epoxide is

• preserved in the transformation. Aliphatic epoxides are opened selectively (>95:5) at the terminal position. Although very high regioselectivity with respect to the alkyne is observed when R1 = Ph and R2 = Me, attempts to differentiate between aliphatic alkyne substituents lead to mixture of regioisomers

• . When a 1,3-enyne is coupled with simple epoxides, however, >95:5 regioselectivity is observed for C–C bond formation distal to the pendant alkene [18]. In conjunction with the nickel-catalyzed fragment coupling, we wished to investigate whether it would be possible to delay introduction of the

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature. Keywords: epoxides; GPCR; NPS 2143; nucleophilic aromatic substitution; pyrylium chemistry; Introduction The first G-protein-coupled receptors

• provide epoxides 16. Epoxides 16 were obtained in good yield after purification by column chromatography and subsequent recrystallization to remove residual starting material 5. Finally the target molecules rac-3 and (R)-3 were synthesised by ring-opening epoxides 16 with amine 6 in ethanol under reflux

New core-pyrene π structure organophotocatalysts usable as highly efficient photoinitiators

• Sofia Telitel,
• Frédéric Dumur,
• Thomas Faury,
• Bernadette Graff,
• Mohamad-Ali Tehfe,
• Didier Gigmes,
• Jean-Pierre Fouassier and
• Jacques Lalevée

Beilstein J. Org. Chem. 2013, 9, 877–890, doi:10.3762/bjoc.9.101

• . The large choice of Co_Pys should allow for studying the effect of the core on the MO coupling and the resulting absorption properties. The activity of these Co_Py compounds in the FRP of acrylates and the FRPCP (and eventually the cationic polymerization CP) of epoxides through a ring-opening

1-n-Butyl-3-methylimidazolium-2-carboxylate: a versatile precatalyst for the ring-opening polymerization of ε-caprolactone and rac-lactide under solvent-free conditions

• Astrid Hoppe,
• Faten Sadaka,
• Claire-Hélène Brachais,
• Gilles Boni,
• Jean-Pierre Couvercelle and
• Laurent Plasseraud

Beilstein J. Org. Chem. 2013, 9, 647–654, doi:10.3762/bjoc.9.73

• carbon dioxide transfer in the formation of ketoacetates [46][47] and carboxylation of epoxides [48]. Some of us have recently reported a green application of BMIM-2-CO2, highlighting its efficiency for the conversion of raw glycerol to glycerol carbonate by transesterification [49]. More recently, this

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• is easiest to generate. Various radical allylating agents can effect the allylation of xanthates. These include substituted allyl diphenylphosphine oxides [58], vinyl epoxides [59], and allyl trimethylsilanes [60]. In the last case it is a two-step procedure. Two examples of the use of a vinyl

• process; it also quenches the intermediate alkoxy radical, liberating concomitantly an ethyl radical to propagate the chain. Except in the cleavage of epoxides, homolytic rupture of carbon–oxygen bonds is generally a difficult process. Radicals can thus be generated next to alcohols or esters without fear

• . Construction of a trans-decalin derivative. Multiple uses of a chloroacetonyl xanthate. A convergent route to spiroketals. A modular approach to 3-arylpiperidines. A convergent route to cyclopentanols and to functional allenes. Allylation and vinylation of a xanthate and an iodide. Vinyl epoxides as allylating

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• and epoxides, hydrohalogenation (HCl, HBr addition), halogenation (Br2 and I2 addition), and [2 + 2] cycloaddition with chlorosulfonyl isocyanate. The resulting adducts were fully characterized by spectroscopic and analytical methods; they constitute interesting substrates for further organic

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• dialdehydes, epoxides, epichlorohydrin, diacyl chlorides, etc., the term cyclodextrin nanosponges were first used by DeQuan Li and Min Ma in 1998 [11] to indicate a cross-linked β-cyclodextrin with organic diisocyanates leading to an insoluble network that showed a very high inclusion constant with several

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• in 7 (n = 1) is replaced by a heteroatom, the heteroorganic bisallenes 16 result, in their simplest form as ethers (X = O), amines (X = NR), thioethers (X = S), etc. Analogously bisallenic epoxides (17, X = O) or aziridines (17, X = NR) can formally be generated from the corresponding all-carbon

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

• David. M. Hodgson Rosanne S. D. Persaud Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK 10.3762/bjoc.8.219 Abstract Terminal epoxides undergo lithium 2,2,6,6-tetramethylpiperidide-induced α-lithiation and subsequent interception

• deuterated terminal alkene, respectively, in modest yields. Keywords: alkenes; epoxides; lithiation; synthetic methods; ylide; Introduction β-Lithiooxyphosphonium ylides 4 are useful intermediates in synthesis as they react with a variety of electrophiles to provide a convergent entry to alkenes, often

• 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

Imidazolinium and amidinium salts as Lewis acid organocatalysts

• Oksana Sereda,
• Nicole Clemens,
• Tatjana Heckel and
• René Wilhelm

Beilstein J. Org. Chem. 2012, 8, 1798–1803, doi:10.3762/bjoc.8.205

• and amidinium salts as soft Lewis acid organocatalysts is described. These salts were suitable catalysts for the activation of unsaturated thioesters in a Diels–Alder reaction and in the ring opening of thiiranes and epoxides. The products were isolated in good yields. The mild catalysts did not cause

• time that these salts can interact with thiocarbonyl groups and thiiranes in order to activate these substrates. In addition, it was found that 7-membered 1,3-diazepinium cations are good catalysts for the ring opening of epoxides and that these salts are more reactive than imidazolinium salts. Diels

The preferred conformation of erythro- and threo-1,2-difluorocyclododecanes

• Yi Wang,
• Peer Kirsch,
• Tomas Lebl,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2012, 8, 1271–1278, doi:10.3762/bjoc.8.143

• -difluorocyclododecanes (5b) is shown in Scheme 1. A (1:9) mixture of cis- and trans-epoxides was treated with triethylamine trihydrofluoride [12]. This afforded diastereoisomeric fluorohydrins 7a and 7b, which could be readily separated by chromatography. Each fluorohydrin was then treated with triflic anhydride [13][14

Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases

• Christian Klein and
• Wolfgang Hüttel

Beilstein J. Org. Chem. 2011, 7, 1643–1647, doi:10.3762/bjoc.7.193

• ]. Other less common approaches include stereospecific enzyme-catalyzed hydrolyses of epoxides, stereoselective additions to ketones with hydroxynitrile lyases or carboligases, and the application of enzymes involved in terpene biosynthesis, such as dehydratases, cyclases or transferases [6][8]. An

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• coworkers were able to open meso-epoxides asymmetrically with HF equivalents and chiral chromium–salen complexes [25][26]. In the year 2000, two conceptually different applications of Banks’ electrophilic fluorinating reagent F–TEDA (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• : amino acids; chelated enolates; epoxides; Passerini reactions; Ugi reactions; Introduction Multicomponent reactions (MCR) are a very popular and powerful tool in modern organic synthesis [1][2][3][4]. Besides a wide range of heterocycle syntheses [5] and catalytic cross coupling reactions [6], the

• epoxides, followed by oxidation of the hydroxy amino acid formed. While aryl-substituted epoxides react preferentially at the benzylic position giving rise to the terminal primary alcohols [25], the corresponding alkyl-substituted epoxides provide secondary alcohols 1 by nucleophilic attack of the enolate

• conclusion, we showed that the ring opening of epoxides, either directly or Pd-catalyzed, with chelated enolates combined with Passerini reactions is a suitable tool for the synthesis of highly functionalized α-hydroxy and α-amino acid derivatives. These new compounds are interesting building blocks for

Selectivity in C-alkylation of dianions of protected 6-methyluridine

• Ngoc Hoa Nguyen,
• Christophe Len,
• Anne-Sophie Castanet and
• Jacques Mortier

Beilstein J. Org. Chem. 2011, 7, 1228–1233, doi:10.3762/bjoc.7.143

• carbonyl compounds and epoxides either exclusively or predominantly at the γ-position [41][42][43]. Previous work also showed that cyclic enaminoketones, esters and nitriles were converted into their enolate with n-BuLi and alkylated with a variety of alkylating agents, affording the product of an

Functionalization of anthracene: A selective route to brominated 1,4-anthraquinones

• Kiymet Berkil Akar,
• Osman Cakmak,
• Orhan Büyükgüngör and
• Ertan Sahin

Beilstein J. Org. Chem. 2011, 7, 1036–1045, doi:10.3762/bjoc.7.118

• stereochemistry. For example, although both hydroxy compounds obtained from hexabromides 2 and 3 [1] afforded epoxides 4 and 5 upon treatment with sodium methoxide (Scheme 1, Scheme 5), dihydroxy compound 17 produced olefinic compound 27, whose oxidation gave diketone 28. We also observed different reactivities

• towards the base for the hydroxy and the methoxy compounds. For example, the methoxy compounds aromatize to give 10 and 11, but the diols convert either to the epoxides by cyclization (Scheme 1 and Scheme 5) or to the alkene by elimination of 1 mol HBr (Scheme 6). In addition, however, the base-induced

• mechanism for the formation of methoxyanthracenes 10 and 11. The formation mechanism for dihydroxy 17. Base-promoted reaction of the dihydroxides and formation of the epoxides. Synthesis of compounds 27 and 28. Supporting Information Supporting information features copies of 1H NMR and 13C NMR spectra for

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• epoxides as nucleophiles In general, dihydrofuran analogs can be constructed from alkynes by palladium-catalyzed intramolecular hydroalkoxylation reactions. However, the more common way to synthesize dihydrofurans is the gold catalyzed cyclization of vinyl allenols [17]. For instance, hydroxyallenic esters

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• and trapping of the carbocation by the sulfonamide. Subsequent intramolecular hydroamination gave the pyrrolidine products. 1.3 Oxiranes As an oxophilic Lewis acid, gold can activate epoxides towards the attack of nucleophiles. A good example is the AuCl3 catalyzed ring opening of aryl alkyl epoxide

• 24 to give 3-chromanol 25, which was reported by He and co-workers in 2004 (Scheme 8) [25]. The same year, Hashmi and co-workers described the first example of a gold-catalyzed conversion of alkynyl epoxides 26 into furans 27 [26][27]. Mechanistic studies performed later by Pale and co-workers [28

• activation of the alkyne in 48, addition of the azide moiety followed by a loss of dinitrogen affords a gold-stabilized cationic intermediate 49. A subsequent 1,2-H shift gave, after tautomerization, the 1H-pyrrole 50. Epoxides can also be used as nucleophiles for the preparation of heterocarbocycles via

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• chemistry. This mini-review focuses on the most recent achievements on gold-catalyzed oxygen transfer reactions of tethered alkynones, diynes or alkynyl epoxides to cyclic enones. The corresponding mechanisms for the transformations are also discussed. Keywords: alkyne–carbonyl metathesis; cyclic enones

• product was isolated, which provided strong support for the proposed mechanism. Gold-catalyzed formation of cyclic enones from alkynyl epoxides Hashmi and co-workers synthesized a number of 2-alkynyl aryl epoxides 21 intended to be used as substrates for a gold-catalyzed rearrangement to naphthols

• compiles recently reported gold-catalyzed oxygen transfer reactions used to build cyclic enones from tethered alkynyl ketones, 1,6-diynes or 2-alkynyl aryl epoxides. Most of these reactions take place under mild conditions and the corresponding products were isolated in good yields. The mechanisms for

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• : Excellent leaving groups and electron withdrawing, non-aromatic and small substituents at the reactive centre all favour invertive substitution. Under basic conditions, epoxides also undergo invertive reactions, even at quaternary centres. Sulfur-based nucleophiles have been employed in nucleophilic ring

• opening of epoxides in hindered systems [18][19][20][21][22][23], with most examples of the latter occurring at quaternary carbon atoms which are part of ring systems [18][19][20][21][22], and in particular in steroids [18][19][20]. For example, the thiol-containing androgen 19 is prepared in 71% yield by

Carbasugar analogues of galactofuranosides: α-O-linked derivatives

• Jens Frigell and
• Ian Cumpstey

Beilstein J. Org. Chem. 2010, 6, 1127–1131, doi:10.3762/bjoc.6.129

• electron-withdrawing group, the C3 benzyl ether. Ogawa has extensively used epoxide-opening reactions as a coupling method to access N- and O-linked pseudodisaccharides based on carbapyranoses [10]. The epoxides were opened by amines in uncatalysed reactions, or by alcohols under Lewis acidic, but more

• , which must rearrange to give the diequatorial product. As the skew-boat is a higher energy conformation, this situation is disfavoured from a stereoelectronic point of view. Carbapyranose 1,2-epoxides with the β-manno configuration 2 (Figure 1) were opened efficiently with attack at C1 (sterically and

• major factor in explaining the generally low reactivity of carbohydrates (at non-anomeric positions) in SN2 reactions. Carbapyranose 1,2-epoxides with α-gluco 3 and α-galacto configurations did not give such good results. With amine nucleophiles, attack was often unregioselective [15]: attack at C1

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• prepared by a 100% atom economical reaction between epoxides and CO2 (Scheme 2) [65]. The green credentials of propylene carbonate are enhanced by the commercialization of a low temperature synthesis of propylene oxide from propene and hydrogen peroxide [66][67][68][69][70], by the development of a greener

• synthesis of hydrogen peroxide [71], and by the combination of these processes into a one-pot synthesis of propylene oxide from propene, hydrogen and oxygen [72][73]. In addition, it has been shown that in the presence of an appropriate catalyst, the reaction between epoxides and carbon dioxide can be

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• ) and suggests that 5 equiv of the base may not always be needed to effect efficient rearrangement. Asymmetric access to an aziridinylphosphonate was also explored to demonstrate further the utility of the above methodology. As terminal epoxides are readily available as single enantiomers [37], terminal

Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines

• Susan Kelleher,
• Pierre-Yves Quesne and
• Paul Evans

Beilstein J. Org. Chem. 2009, 5, No. 69, doi:10.3762/bjoc.5.69

• [16][17]. Unfortunately, however, under a variety of conditions it proved impossible to elaborate these species. For example, reductive ring-opening using triethylsilane, conditions previously reported for N-sulfonylamino-α,β-epoxides [18][19], led only to recovery of starting material and not the

Three step synthesis of single diastereoisomers of the vicinal trifluoro motif

• Vincent A. Brunet,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2009, 5, No. 61, doi:10.3762/bjoc.5.61

• manner. Conversion of the free hydroxyl group to fluorine would generate α-fluoro-epoxides B. Epoxide ring opening with an HF source could then provide difluoroalcohols C. Insertion of the third fluorine would reasonably be achieved by fluorination of the free hydroxyl group of C to generate D. Such a

• reactions following Sharpless’ methodology [16]. The anti-epoxy alcohols were easily generated, however it proved more difficult to prepare the syn-epoxides cleanly. Treatment with titanium isopropoxide (Ti(OiPr)4) and D-diisopropyl tartrate (D-DIPT) favoured formation of the anti-α,β-epoxy alcohols. In the

• and relative stereochemistry of the crystalline threo-isomer (2R,3S,4S)-7a was confirmed by X-ray structure analysis as shown in Figure 2. With a strategy to access both stereoisomeric series of the allylic alcohol epoxides A in place, the fluorination reactions were then explored. The fluorination of