Metal and metal-free photocatalysts: mechanistic approach and application as photoinitiators of photopolymerization

• Jacques Lalevée,
• Sofia Telitel,
• Pu Xiao,
• Marc Lepeltier,
• Frédéric Dumur,
• Fabrice Morlet-Savary,
• Didier Gigmes and
• Jean-Pierre Fouassier

Beilstein J. Org. Chem. 2014, 10, 863–876, doi:10.3762/bjoc.10.83

• ; Scheme 11) [64]. All these described systems, producing radicals, cations or radical cations, allow efficient CP and FRPCP of cationic monomers, FRP of acrylates, simultaneous radical/cationic polymerization of epoxide/acrylate blend. The reactions can be carried out (see in [45][46][47][48][49][50][51

• ][52][53][54][55]) in formulations containing multifunctional synthetic epoxides, acrylates, monomers/oligomers or epoxide/acrylate blends (renewable raw or modified materials are usable to some extent) with lights extending from the UV to the red, using polychromatic or monochromatic light sources

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• initially-formed (E,E,E)-triene undergoes stereospecific epoxidation to a tri-epoxide and subsequent ring-opening and cyclisation to generate the polyether rings. This model has been confirmed and extended (Scheme 1) by the results of more recent work in which specific genes have been disrupted or deleted

• a transferase (MonKSX) transfers the chain to a discrete acyl carrier protein (MonACPX) [20], both of these proteins being encoded within the monensin gene cluster [16]. The flavin-dependent epoxidase MonCI then catalyses three stereospecific epoxidations to give the tri-epoxide 3, which then

• undergoes a cascade of ring opening/closing catalysed by the combined action of the unusual epoxide hydrolases MonBI and MonBII, to give the putative protein-bound intermediate dehydroxydemethylmonensin. The next steps, catalysed respectively by the cytochrome P450 hydroxylase MonD and the methyltransferase

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

• control [58]. The configuration was determined by the high coupling constant (JH4/H5 = 12.6 Hz) indicating the trans-diaxial orientation of H4 and H5. Silylation of the primary hydroxy group afforded compound 84 that was converted into the epoxide with complete stereocontrol [59]. The epoxide underwent

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

• followed by reductive epoxide opening furnished the desired alcohol 73 [72]. Alcohol-directed 1,4-reduction using LiAlH4 [73] followed by ether formation gave methyl ether 74. Reduction of the remaining ketone moiety gave the equatorial alcohol exclusively. Ortho-lithiation followed by the addition of

• ] applied the DVCPR in their total synthesis of gelsemine (146, see Scheme 20 and Scheme 21). Starting from bicycle 160 [140] epoxidation using mCPBA furnished epoxide 161 [141][142], which could be converted into vinylcyclopropanecarbaldehyde 162 upon rearrangement. Olefination using HWE-reagent 163

• , see Scheme 22) [152], isolated from the leaves of Gelsemium elegans was accomplished by Fukuyama and coworkers [153][154]. Starting from furfuryl alcohol (179) an epoxide initiated Achmatowicz reaction [155] took place to give α,β-unsaturated pyrane 180. Next in line was an enzyme catalyzed dynamic

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• disclose if the substituents of the epoxide are cis or trans-configured. The observed absolute differences for calculated versus NOE-derived distances/calculated distances (Table 2) suggested a trans-configuration for the epoxide (MAE of 4.7% vs 20.7% for cis-isomer) ring. The next step was the analysis of

• the four diastereoisomers 2a,b,e,f endowed with the epoxide moiety in a trans-configuration, by comparing the experimental vs the calculated distances (Table 3). In Table 3 only a subset of all values was used for the stereochemical structure elucidation, more specifically, the values where DFT

• consistent with anti-1,2-diol type C. Therefore the 7R,8S configuration is assigned. Notably, considering the plausible biogenetic interconversion of an epoxide and a diol, the above absolute configuration at C-7 and C-8 of plakilactone G is in full agreement with the trans-epoxide 2b. Having assigned the

N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• was reacted in a ring-opening polymerization with the primary amine α-amino-ε-caprolactam (8). 8 was synthesized by cyclization of lysine (7) (Scheme 2). Hence, an increase of the reactivity of the primary amino group towards the epoxide function compared to the amino groups in native lysine was

• monitored. The spectrum of 6 exhibits weak bands at 1253 and 895 cm−1, which can be assigned to the C–O-stretching vibration and the symmetric ring deformation vibration, respectively, of its epoxide groups. On curing at 50 °C, a broad band between 3100 and 3600 cm−1 appears which is caused by hydrogen

• bonded hydroxy stretching vibrations originating from epoxide ring opening. The epoxide bands seem to vanish after curing, which is a sign for high conversion. However, due to overlaps of broader bands in adjacent areas, no clear statement can be made in this regard (Figure S5, Supporting Information

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• diglycidyl ether to give novel oligomeric thermoresponsive epoxide–amine adducts. These oligomers exhibit a lower critical solution temperature (LCST) behavior in water. The solubility properties were influenced with randomly methylated β-cyclodextrin (RAMEB-CD) and the curing properties of the amine–epoxide

• mixtures were analyzed by oscillatory rheology and differential scanning calorimetry, whereby significant differences in setting time, viscosity, and stiffness were observed. Keywords: amino acids; curing properties; cyclodextrin; epoxide–amine oligomers; LCST; Introduction Many partially hydrophobic

• resins exhibit poor solubility in water [15][16][17]. Accordingly, epoxide–amine polymers are not yet deeply investigated in respect to LCST behavior [18][19]. At present, most available bio-based and water soluble epoxy resins are expensive and use petroleum-based curing agents [20]. Thus, in the

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

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• , anthranilate is converted to 3-aminosalicylate by a multicomponent oxygenase, AntHIJKL [33][34]. The anthraniloyl-S-AntG carboxylic acid-CoA thioester undergoes a never before seen 1,2-shift. Spiteller and colleagues suggested that AntHIJKL promotes this reaction via an epoxide intermediate similar to a

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• at C6 could not be clarified. For the epoxide moiety of curvulide A, only the relative configurations at C4 and C5 were elucidated based on H,H-coupling constants (Figure 1) [30]. So far, two syntheses of stagonolide E have been published, which both rely on asymmetric synthesis for establishing both

• transition-state model, no reaction occurred after 2 d with L-(+)-DET, and the starting material could be recovered nearly quantitatively. In contrast, the use of D-(−)-DET led to the formation of an epoxide 39b in 58% yield. A comparison of the analytical data of 39b with those reported for curvulide A

• ° in the case of the diastereomeric epoxide 39b, and this value fits well to the observed 3J(H5–H6) value (Figure 2) [65]. Conclusion In summary, we synthesized the naturally occurring ten-membered lactones stagonolide E and curvulide A, starting from the ex-chiral pool building block (R,R)-hexa-1,5

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• PMB-protected 3-hydroxypropanal via Horner–Wadsworth-Emmons olefination, reduction to the allylic alcohol and Sharples epoxidation [8] (Scheme 2). Subsequent Cu-catalyzed epoxide-opening using methylmagnesium bromide [9] produced an inseparable mixture of 1,2- and 1,3-diol products, which upon

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• in dry CH2Cl2 at –10 to –23 °C for 2 h, the desired epoxide (2R,3R)-4 was obtained in 93% yield and 88% ee. The ee was determined by HPLC analysis of its corresponding TBDPS ether. This result compares well with the ones reported in the literature: 77–95% yield and 81–95% ee [17][18][19][20][21

• ]. According to Sharpless et al. [18], 5 mol % of Ti(OiPr)4 and 7.5 mol % of DIPT were used, so at least 20% excess of tartrate ester in order to obtain the maximum enantiomeric excess. The use of freshly distilled DIPT and Ti(OiPr)4 was important to obtain consistently 88% ee. With epoxide (2R,3R)-4 at hand

• the literature [8][9]. Starting from nerol, Sharpless asymmetric epoxidation afforded the epoxide (2S,3R)-4 in a disappointing 74% ee, a result which is nevertheless in accordance with the reported values: 70–94% [25][26][27][28][29][30] (Scheme 4). Applying the same ring-opening reaction to epoxide

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• presence of sodium ethoxide delivers epoxide 1.87. The material is next subjected to hydrogenolysis using Pd/C in methanol with a 1 bar hydrogen pressure to reductively ring open the epoxide. Finally, the transformation of the alcohol to the mesylate 1.88 occurs under standard conditions. In order to

• 1.119, which is first alkylated with epichlorohydrin (1.20) [63] (Scheme 22). The resulting epoxide 1.121 can then be ring opened with methanol in the presence of a tin Lewis acid yielding alcohol 1.122, which when subjected to Jones-oxidation conditions and Raney-Ni-mediated hydrogenation furnishes in

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• clean and gives the enone 2 in good yield along with minor amounts of the corresponding allyl alcohol 3 and the epoxide 4a. This successful conversion of theaspirane (1) encouraged us to investigate the oxidation of other spirocyclic terpenoids. Many oxidized spiroethers are valuable flavor compounds or

• the literature protocol using m-chloroperbenzoic acid. The major epoxide 4a was obtained in good yield and a diastereoselectivity of 11:1. Isomerisation of epoxide 4a to allyl alcohol 22 was reported with aluminium triisopropoxide at 140 °C [46]. However, in our hands this procedure gave only complex

• detected similar oxidation products with PSA and rationalize their formation by an initial epoxidation of the endocyclic double bond to give the allyl epoxide 25, which might then be hydrolyzed to two diastereomeric alcohols 26a and 26b. The latter reaction is known for similar allyl epoxides under

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• good overall yields in a two step process. The key step involves the ring opening of the chiral epoxide with a nitrogen heterocyclic carbene (NHC) and further rearrangement to chiral N-(2,3-dihydroxypropyl)arylamides in high yields and enantioselectivity. During the reaction, no erosion in chiral

• . The phthalimido-protected chiral hydroxypropyl benzoate 5a could be synthesized by the reaction of nitrogen heterocyclic carbene, benzaldehyde and phthalimido-epoxide 4a. Phthalimido-epoxide 4a was synthesized by treating (S)-glycidol (3) with phthalimide (2) under Mitsunobu reaction conditions

• ]. When the reaction was conducted under nitrogen atmosphere, product formation was not observed. If the reaction was carried out in air, it was found that ester 5a was obtained as the only product in the presence of NHC. When a diol instead of an epoxide was used as a substrate for the oxidative

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

• reduction, acetylation and a magnesium sulfate induced rearrangement of the epoxide to the allylic alcohol. The synthesis of cytochalasin B 52 (15 steps from 73) proceeded in a similar fashion and was highlighted in detail by Hertweck [44]. The authors state that this approach is highly diversifiable and

• isopentyl pyrophosphate (IPP, 166), and orsellinic acid (168), which is derived from a fungal iterative type I polyketide pathway [142], are connected to give 169. This substrate is already poised for a polyene cyclization cascade, which only has to be triggered via activation of the epoxide. After the

• induced domino epoxide-opening/rearrangement/cyclization cascade was accomplished by the group of Katoh (Scheme 22) [144]. The synthesis commenced with the conversion of dimethyl 2,6-dihydroxyterephthalate (172) to nitrile 173 within five consecutive steps. Hydrogenation and lactam formation of 173 gave

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

• the total synthesis of the anticancer guaiane (−)-englerin A. A regio- and diastereoselective Co(II)-catalyzed hydration of the olefin and a transannular epoxide opening were used as the key reactions. Keywords: asymmetric synthesis; hydration; natural products; terpenes; transannular epoxide opening

• 3 can be utilized to generate the isopropyl group, and a regioselective transannular epoxide opening would construct the oxygen-bridged bicyclic hydroazulene framework. Alcohol 3 was traced back to the known epoxy enone 4 that already served as an intermediate for the total synthesis of 5 [6]. As

• 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

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• ). Treatment of epoxide 13, which was prepared from L-aspartic acid (12) by the known procedure [8], with 3-butenylmagnesium bromide/CuI [16] provided the corresponding secondary alcohol. Protection of the alcohol with TBSCl afforded TBS ether 14 in 91% yield in two steps. Alkene 14 was reacted with m-CPBA to

• produce epoxide 15 as a 1:1 diastereomeric mixture. Epoxide 15 was coupled with alkyne 16 [4] in the presence of n-BuLi/BF3∙OEt2 [17] to give the desired product 17 in 92% yield from 15. Hydrogenation of the alkyne moiety of 17 followed by TPAP oxidation [18] yielded ketone 18. Removal of the three TBS

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• . sahachiroi genome and is the first non-azinomycin related compound to be isolated from the S. sahachiroi strain (Figure 1). Previously isolated metabolites consisted of azinomycin intermediates lacking the 1-azabicyclo[3.1.0] ring system, including naphthoate and naphthoate epoxide derivatives [11]. The

• could be envisioned to form through nucleophilic attack of an epoxide as in the case with monensin and other similar natural products [16]. Alternatively, the biosynthesis might involve the dimerization of pyruvate [17][18][19]. Examination of a draft genome sequence of the S. sahachiroi strain has

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

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

• emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. Keywords: aziridine; desymmetrization; enantioselectivity; epoxide; organocatalysis

• enantioselective desymmetrization of a phospholene meso-epoxide by cinchona alkaloids to P,C-chirogenic 3-hydroxy-2-phospholene derivatives 93 and 94. Among the four main components of cinchona alkaloids, quinidine (OC-57) proved to be the most effective base in the enantioselective rearrangement of epoxide, and

• was 87% ee. The proposed reaction mechanism is depicted in Figure 14. The first step of the catalytic cycle is the activation of SiCl4 by chiral phosphoramide OC-62 to form a complex, which was ionized to produce a highly reactive silicon cation and a chloride ion. The epoxide was activated by the

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• , this approach was employed in the investigations of the following intramolecular radical additions to arenes. Investigation of the radical addition to substituted anilines In our preparative work, we have been mostly concerned with the catalytic synthesis of indolines via addition reactions of epoxide

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• the double oxidation of the quinolone nitrogen and the olefin epoxidation (2',3'-position) of the farnesyl chain, with the epoxide being ring-opened with 5-exo selectivity by the 4-hydroxy group of the resulting 4-hydroxyquinoline N-oxide. Taking the geranyl analogue 9 as a model compound (Scheme 2

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

• construct the C9−C10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1−C9 has been synthesized in high yield and

• demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10−C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted

• decarboxylation enables construction of the C15−C16 bond by an aldol reaction. The product of this transformation is of the correct oxidation state and potentially three steps removed from the targeted epoxide fragment. Keywords: catalysis; natural product; nickel; reductive coupling; ripostatin A; synthesis

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

• . Similar to a previously reported synthesis of (R)-3 [13], we decided to activate epoxide 5 as the m-nosyl derivative that has been shown to minimise racemisation during epoxide ring opening [15]. The synthesis of amine 6 was accomplished from commercially available 2-cyanonaphthalene (7) in four steps

• . 1H NMR analysis of the crude product showed the presence of approximately 5–10% of a structurally similar side-product that proved extremely difficult to remove by chromatography. The side product is likely the regioisomer formed by nucleophilic attack on the more sterically hindered epoxide carbon