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

• transformations. Keywords: β-lactams; conjugated bisallenes; cyclopentenones; epoxidation; halogen addition; hydrohalogenation; ionic additions; metalation; Introduction Whereas the use of hexa-1,2,4,5-tetraene (1) and its derivatives in pericyclic reactions is well documented [2][3][4][5][6], relatively little

• hydrocarbon 30. Oxidation of conjugated bisallenes The oxidation of allenes has already been studied previously. In seminal papers Crandall and his students described the epoxidation of differently substituted monoallenes and showed that methylene oxiranes are the initial oxidation products. These, however

• , which is in equilibrium with its conformational isomer 32. Ring-opening of these strained intermediates then provides the “stretched” and the “closed” zwitterions 33 and 34, respectively. Whereas the open form 33 is intercepted by the anion derived from the epoxidation reagent, m-chlorobenzoic acid

Synthesis of a library of tricyclic azepinoisoindolinones

• Bettina Miller,
• Shuli Mao,
• Kara M. George Rosenker,
• Joshua G. Pierce and
• Peter Wipf

Beilstein J. Org. Chem. 2012, 8, 1091–1097, doi:10.3762/bjoc.8.120

• synthesis was achieved by a subsequent alkene epoxidation and zinc-mediated aminolysis reaction. The resulting library products provided selective hits among a large number of high-throughput screens reported in PubChem, thus illustrating the utility of the novel scaffold. Keywords: chemical diversity

• process, we conducted a ring-closing metathesis in the absence of Ti(OiPr)4 (Scheme 2). The resulting product was different from 3, based on a TLC analysis, but proved to be quite labile during workup. Therefore, it was immediately subjected to m-CPBA epoxidation conditions to give a modest yield of the

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• , overnight), whereas in the case of enyne 11b, under the same reaction conditions, only the triple bond was reduced to furnish enol ether 14e selectively. In three cases we further functionalized the 1-alkylated glycals by an epoxidation/epoxide-opening sequence [30][31][32][33]. Dimethyldioxirane (DMDO) was

• used as a neutral epoxidation reagent leading to a facial-selective epoxide formation [34][35][36]. The so-obtained highly reactive acetal epoxide was either attacked by a superhydride, such as LiBHEt3 [31], or by a Lewis acidic hydrogen transfer agent, such as DIBAL-H [32][33]. In the former case, an

• SN2-type reaction takes place leading to the α-gluco-configured C-glycoside 15a in a moderate yield of 30% (Table 4). The aluminium centre coordinates the epoxide oxygen allowing the hydride to attack from the same side, leading to β-configured alkyl-C-glycosides. The epoxidation/ring-opening sequence

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• epoxidation, aziridination and olefination reactions [12][13] are common reaction channels. The intramolecular formation of sulfonium ylides from α-diazocarbonyl compounds tethered with alkylthio or arylthio groups has been studied by the research groups of Davies [14], Moody [15], and West [16]. From α-diazo

Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives

• Jorge A. R. Salvador,
• Vânia M. Moreira,
• Rui M. A. Pinto,
• Ana S. Leal and
• José A. Paixão

Beilstein J. Org. Chem. 2012, 8, 164–169, doi:10.3762/bjoc.8.17

• , respectively, required higher amounts of the reagent and longer reaction times (Table 1, entries 4 and 5). The formation of the oleanolic δ-hydroxy-γ-lactones 2, 4, 6, 8 and 10, may be explained by epoxidation of the parent Δ12-oleanane compound, followed by nucleophilic attack of the 28-carboxyl group at C13

Valence isomerization of cyclohepta-1,3,5-triene and its heteroelement analogues

• Helen Jansen,
• J. Chris Slootweg and
• Koop Lammertsma

Beilstein J. Org. Chem. 2011, 7, 1713–1721, doi:10.3762/bjoc.7.201

• et al. using a double dehydrohalogenation of 1,2-dibromo-4,5-epoxycyclohexane [38][53], but is also accessible by epoxidation of Dewar benzene followed by photolytic or thermal ring expansion [54]. The molecular structure of the 2-tert-butoxycarbonyl oxepine showed a boat configuration with bow (α

Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope

• Aélig Robin,
• Valentin Köhler,
• Alison Jones,
• Afruja Ali,
• Paul P. Kelly,
• Elaine O'Reilly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173

• ; P450 monooxygenase; substrate engineering; Introduction P450 monooxygenases are a ubiquitous family of enzymes found in a wide variety of organisms in all domains of life. These enzymes catalyse oxidation reactions such as hydroxylation, epoxidation, N- and O-dealkylation and heteroatom oxidation

• were hydroxylated by all three P450cam-RhFRed mutants, with the double mutant Y96F/V247A showing >99% conversion after 24 h (only one hydroxylated product was detected in the extracts). Epoxidation of tetrahydropyridine 7a to compound 8a with P450cam(Y96A)-RhFRed was shown to occur with low conversion

• (12%) with carboxybenzyl as a protecting group. In order to optimise the epoxidation reaction further, the N-protection group was used as another variable in the screening and a variety of N-protecting groups were installed to generate a set of tetrahydropyridine derivatives 7. An increase in

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

• continuous epoxidation of 1,7-octadiene (70) to (R)-7-epoxyoctene (72) by a strain of Pseudomonas oleovorans growing on heptane (71) (Scheme 23) [51]. In a continuous operation, with regard to the aqueous phase, substrates for both growth and biotransformation were supplied in the gas phase from a reservoir

• -acetylneuraminic acid (17) in a continuously operated enzyme membrane reactor. E1: Epimerase; E2: Aldolase [27]. Chemo-enzymatic epoxidation of 1-methylcyclohexene (18) in a packed-bed reactor (PBR) containing Novozym 435 (E) [28]. Continuous production of (R)-1-phenylethyl propionate (24) by dynamic kinetic

• ]. Continuous epoxidation of 1,7-octadiene (70) to (R)-7-epoxyoctene (72) by a strain of Pseudomonas oleovorans in a closed-gas-loop bioreactor (CCGLB). R: Reductase; Fe: Rubredoxin [51]. Oxidation of styrene (73) to (S)-styrene oxide (74) in a continuously operated biofilm tube reactor containing cells of

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• or stereoselective epoxidation followed by regioselective epoxide opening) produced the racemic iminocyclitols (18–20) in good overall yields (Scheme 3). In addition, Blechert showed that this method was more adaptable as it could also yield enantiopure 18–20, provided that racemization was avoided

• 1-deoxygalactonojirimycin (64) and 1-deoxyidonojirimycin (93), transformation of 86 proceeded via syn (step c) and anti (step h) epoxidation of the internal double bond in 86, respectively, and subsequent hydrolysis. Quite recently, an interesting synthesis of three 1-deoxynojirimycin-related

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• ]. Rearrangement of the resulting allylic bromide to the more stable regioisomer at this stage occurs readily and debromination can be achieved on treatment with tributyltin hydride. Penkett has shown that 3-chloroperbenzoic acid (m-CPBA) can take the role of an electrophile in the epoxidation of the double bond

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• "building". Towards this goal, 67 was first converted into the cyclopentadiene derivative 68, whose carbon skeleton was subsequently extended, and then bent into a convex shape by an epoxidation reaction (formation of 69). After the still saturated C2-bridge had been reduced to an etheno bridge, the

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• substitution for improved activity and selectivity. Pyrrolidine 35 (Figure 9) is a highly selective catalyst for the epoxidation of α,β-unsaturated aldehydes (e.g. 36) [33]. In the first step of the reaction, aldehyde 36 and pyrrolidine 35 react together to form the iminium ion 37. This has a LUMO-lowering

• . The proposed bioactive conformation is shown in Newman projections. Capsaicin (33) and fluorinated analogues (R)-34 and (S)-34. Asymmetric epoxidation reaction catalysed by pyrrolidine 35. Inset: the geometry of the activated iminium ion intermediate 37 is stabilised by a gauche F–C–C–N+ alignment

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• determined by NOE measurements. Further oxidation with PCC gave the aldehyde rac-15, albeit in low 13% overall yield from rac-9. As an alternative, the epoxidation of rac-13 with MCPBA was investigated, which delivered the spirocyclic exo-configured epoxide rac-16 in 46% overall yield from rac-9 as the sole

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

• ). Functionalisation of the N-sulfonyl enamines 5a and 5b was subsequently studied with the ultimate aim of introducing substituents, in a stereoselective fashion, to the masked pyrrolidine ring. Thus, epoxidation of 5a and 5b (Scheme 3) using m-CPBA proceeded smoothly for both substrates and as hoped, occurred under

• -hydrogenation and double reduction sequence as a means of accessing cis-disubstituted pyrrolidine 3. The synthesis of 5a and 5b by an intramolecular Heck cyclisation reaction. Diastereoselective epoxidation of 5a and 5b. cis-Selective dibromination of 5a (NOE indicated by arrows). Dibromination studies of 5b

Can we measure catalyst efficiency in asymmetric chemical reactions? A theoretical approach

• Shaimaa El-Fayyoumy,
• Matthew H. Todd and
• Christopher J. Richards

Beilstein J. Org. Chem. 2009, 5, No. 67, doi:10.3762/bjoc.5.67

• material, or a reaction for which there currently exist few alternatives. The Sharpless Asymmetric Epoxidation, for example, suffers from a low ACE. From an academic viewpoint, this transformation is nevertheless important because of the breakthrough nature of this relatively low cost reaction. It has few

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

• metathesis reaction and the products were obtained in good yields predominantly as the (E)-isomer. It was not possible to separate the minor (Z)-isomer at this stage, however isomer separation was more readily achieved after the subsequent epoxidation step. Thus (S)-4 and (S)-5 were subjected to epoxidation

• absolute configuration (Figure 1). Generation of the syn-α,β-epoxy alcohols Aa was more challenging. This stereoisomer will ultimately deliver the all-syn Da trifluoro motif (Scheme 1). Epoxidation of (S)-5 with L-DIPT showed poor stereoselectivity and under optimised conditions the resultant α,β-epoxy

• -alcohols 7a and 7b were obtained in a 3:1 ratio. Epoxidation reactions with m-CPBA and Ti(OiPr)4 gave diastereomeric ratios of between 2:1 and 3:1, thus L-DIPT showed only a modest improvement in the stereoselectivity. These diastereoisomers were not easily separated by chromatography, however the absolute

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

The development and evaluation of a continuous flow process for the lipase- mediated oxidation of alkenes

• Charlotte Wiles,
• Marcus J. Hammond and
• Paul Watts

Beilstein J. Org. Chem. 2009, 5, No. 27, doi:10.3762/bjoc.5.27

• on the lipase-mediated oxidation of 1-methylcyclohexene, with the optimised reaction conditions subsequently employed for the epoxidation of an array of aromatic and aliphatic alkenes in 97.6 to 99.5% yield and quantitative purity. Keywords: Candida antarctica lipase B; continuous flow; epoxidation

• , coatings and paints [1][2], with some epoxides even exhibiting biological activity [3][4]. As such, over the years, convenient and efficient techniques have been sought for their preparation. Within the research laboratory, epoxidation of alkenes is achieved using organic peroxides and metal catalysts [5

• situ generated peracids derived from formic acid or acetic acid (1)/hydrogen peroxide (2). As H2O2 (2) is itself not sufficiently electrophilic to epoxidise a non-conjugated double bond directly, its use in the formation of a peracid has afforded a route to the epoxidation of alkenes in the presence of

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• of asymmetric transfer hydrogenation in flow have also been reported [51][52]. Supported catalysis has been extended to reactions involving the use of continuous flow membrane reactors [19][20][21][22]. For example, the asymmetric epoxidation of a chromene derivative 49, catalyzed by homogeneous

• ). Continuous-flow asymmetric cyclopropanation. Continuous asymmetric hydrogenation of dimethyl itaconate in scCO2. Continuous asymmetric transfer hydrogenation of acetophenone. Asymmetric epoxidation using a continuous flow membrane reactor. Enzymatic cyanohydrin formation in a microreactor. Resolution of (R/S

Oxidative cyclization of alkenols with Oxone using a miniflow reactor

• Yoichi M. A. Yamada,
• Kaoru Torii and
• Yasuhiro Uozumi

Beilstein J. Org. Chem. 2009, 5, No. 18, doi:10.3762/bjoc.5.18

• time to afford the erythro-product 2e in 70% conversion (entry 5). These stereochemical observations indicate that the cyclization involves a stereospecific reaction pathway. The reaction pathway of the present oxidative cyclization should proceed via the epoxidation of the alkene 1 with Oxone and

A short stereoselective synthesis of (+)-(6R,2′S)-cryptocaryalactone via ring- closing metathesis

• Palakodety Radha Krishna,
• Krishnarao Lopinti and
• K. L. N. Reddy

Beilstein J. Org. Chem. 2009, 5, No. 14, doi:10.3762/bjoc.5.14

• : Carreira asymmetric alkynylation; Cryptocarya bourdilloni GAMB (Lauraceae); ring-closing metathesis; Sharpless asymmetric epoxidation; Introduction Natural products play an important role in the development of drugs and mankind has always taken advantage of nature as pharmacy: approximately 40% of the

• alcohol that was obtained from a regioselective ring-opening reaction of 2,3-epoxy alcohol 8. The known 2,3-epoxy alcohol 8 was synthesized from the corresponding dienyl alcohol by the well-established Sharpless asymmetric epoxidation conditions in >94% ee as described in literature [38][39]. Compound 8

• wherein a chiral 2,3-epoxy alcohol was the starting material and Sharpless asymmetric epoxidation and Carreira asymmetric alkynylation were used as key steps for generating unambiguous assigned stereocenters. More importantly, the Grubbs’ ring-closing metathesis protocol was applied to construct the final

N-acylation of ethanolamine using lipase: a chemoselective catalyst

• Mazaahir Kidwai,
• Roona Poddar and
• Poonam Mothsra

Beilstein J. Org. Chem. 2009, 5, No. 10, doi:10.3762/bjoc.5.10

• (triacyl glycerol hydrolases EC 3.1.1.3) catalyze hydrolysis, esterification, transesterification, thioesterification, amidation, epoxidation etc. [5][6][7][8][9][10]. The use of immobilized lipases is on the rise, as these work well with non-aqueous media [11]. Apart from the convenient handling, these

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals

• Mohan Mahesh,
• John A. Murphy,
• Franck LeStrat and
• Hans Peter Wessel

Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1

• approximately equal yield. In entry (iii) of that table, these yields were estimated from a calibrated NMR determination; following this, the mixture was subjected to epoxidation with mCPBA, leading to isolation of 20b and the epoxide 20c (not shown in Scheme 3) derived from 20a. From this series of experiments

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• materials (e.g. amino acids, sugars, tartaric acid, etc.) or on asymmetric reactions {e.g. Sharpless asymmetric epoxidation (AE), Sharpless asymmetric dihydroxylation (AD), diastereoselective Williamson etherification, etc.}. Semi-synthesis of natural ACGs as well as derivatised ACGs (e.g. amines, esters

• absolute configuration of natural-8 at C-8 to R (Scheme 3). In their synthesis, asymmetric epoxidation of 19 directed by L-(+)-diisopropyl tartrate gave epoxy alcohol 20; the THF ring of 21 was then constructed under CSA catalyzed one-pot transformation. After deprotection of the isopropylidene acetal of

• building block 45 by means of the Sharpless AD reaction and cyclization catalyzed by Co(modp)2 (the Mukaiyama epoxidation method) under mild reaction conditions. The connection of the THF unit 46 with the γ-lactone segment 47 was carried out by means of a Wittig reaction. The target compound 42 had

End game strategies towards the total synthesis of vibsanin E, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

• Brett D. Schwartz,
• Craig M. Williams and
• Paul V. Bernhardt

Beilstein J. Org. Chem. 2008, 4, No. 34, doi:10.3762/bjoc.4.34

• procedure based on the epoxidation of silyl enol ethers. Ketone 23 was smoothly converted into the TBS enol ether 27 (85% yield) with TBS triflate, which was then treated with dimethyldioxirane (DMDO). When work up was restricted to a simple 1 M hydrochloric acid wash (i.e. separatory funnel) only the