Regio- and stereoselective synthesis of new diaminocyclopentanols

• Evgeni A. Larin,
• Valeri S. Kochubei and
• Yuri M. Atroshchenko

Beilstein J. Org. Chem. 2014, 10, 2513–2520, doi:10.3762/bjoc.10.262

• .10.262 Abstract The optimal conditions for regio- and stereoselective epoxide ring opening of N,N-disubstituted 1,2-epoxy-3-aminocyclopentanes by different nucleophilic reagents have been developed. The substituents on the nitrogen atom in the epoxide precursor and the orientation of the oxirane ring are

• subsequent oxirane ring opening represent a viable approach for the development of new pharmaceutically relevant scaffolds. As a part of our ongoing research in the development of new aminocyclitols, we exploited cyclopentane derivatives to mimic both the 2-deoxystreptamine ring, a core component in

• starting epoxides Epoxides 3a,b (Scheme 1) were obtained by the addition of benzyl(methyl)amine or dibenzylamine to cyclopent-2-en-1-yl acetate (1) followed by epoxidation [28]. Epoxides 6a,b were synthesized from 3a,b through epoxide ring inversion using glacial acetic acid as the oxirane-cleaving agent

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• Table 1. The reaction pathway (Scheme 2) involves the quaternization of 1-substituted benzimidazoles 1 with ethyl bromoacetate (2) leading to corresponding benzimidazolium bromides 6. The attack of the bromine ion from the benzimidazolium bromide on the oxirane ring in 1,2-epoxybutane results in ring

Magnesium bis(monoperoxyphthalate) hexahydrate as mild and efficient oxidant for the synthesis of selenones

• Andrea Temperini,
• Massimo Curini,
• Ornelio Rosati and
• Lucio Minuti

Beilstein J. Org. Chem. 2014, 10, 1267–1271, doi:10.3762/bjoc.10.127

• , the corresponding oxirane 3e in 77% yield, resembling the previously reported one by oxidation with MCPBA (73% [9]). The MMPP oxidation of β-benzoylamino phenyl selenide 1f in methanol afforded exclusively the 1,3-oxazine 3f in excellent yield (84%). This result is in accordance with data reported by

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• were too low for practical upscaling. As mutasynthetic experiments with alkynyl- and propargyl(amino)benzoic acids gave best results, we decided to test the Huisgen-type cycloaddition with alkynyl derivative 23f bearing the biologically relevant ester side chain, the oxirane moiety and the carbamoyl

• pharmacophore of the maytansinoids. All other derivatives show strong to moderate antiproliferative activity, irrespective whether the lack of the N-methyl group, and or the oxirane groups or not. This is in line with the view obtained from structure–activity relationship studies that these tailoring

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

• peroxysilanes 54a,b, which upon treatment with aqueous HF gave the target dioxolanes 55a,b (Scheme 17) [250]. A similar way to 1,2-dioxolanes used an oxirane cycle for the stages of ring opening followed by 1,2-dioxolane ring closing [251]. The synthesis of spirodioxolane 59 involved the peroxysilylation of 1,3

• reactions of aryloxiranes 177a,b with oxygen in the presence of 9,10-dicyanoanthracene (DCA) and biphenyl (BiP) under irradiation produced 1,2,4-trioxolanes 178a and 178b (Scheme 46). It should be noted that the oxirane moiety is oxidized rather than the double bond in these reactions [299]. This unusual

• , desilylation, and recyclization accompanied by a ring opening of oxirane or oxetane (Scheme 62 and Scheme 63). Cobalt(II) acetylacetonate (acac) or bis-2,2,6,6-tetramethylheptane-3,5-dienoate (thd) were used as the catalyst for the peroxidation of 219. The cyclization of the intermediate peroxide 220 was

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

• are relatively comparable to a mixture of BADGE with 8, whereby the observed differences can be caused by different reactivity of the oxirane moieties or unequal solubility of the respective diepoxide with 8. By means of IR spectroscopy, ring opening polymerization of epoxides with amines can be

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• as low diastereoselectivity and product yield. To overcome this drawback of aldolases, dynamic kinetic asymmetric transformation has been carried out in which a bi-enzymatic process was performed to achieve a high yield of the product by shifting the reaction equilibrium [45]. Eupergit oxirane

• directly with the nucleophilic groups of the enzyme by forming strong covalent linkages like amino, hydroxy or mercapto functional groups. Eupergit has a high density of epoxy groups on the surface (oxirane density 300 μmol/g dry beads [47]), increasing the possibility of multipoint attachment of the

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• -aminocyclohexanecarboxylates 11–14 were prepared previously by a diastereoselective epoxidation of the corresponding 2-aminocyclohexenecarboxylates, followed by a regioselective oxirane ring opening with NaN3 [68]. Three different alkynes (phenylacetylene, diethyl acetylenedicarboxylate and ethynyl ferrocene) were employed as

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• follows two different strategies. One is based on regio- and stereoselective hydroxylation via iodooxazine formation, followed by fluorination, while the other includes stereoselective epoxidation and regioselective oxirane opening, followed by hydroxy–fluorine exchange. In the former protocol, amino

• bond oxidation with 3-chloroperbenzoic acid (MCPBA) to afford epoxy amino ester 6 cis-diastereoselectively [57] (Scheme 1). Opening of the oxirane ring in 6 with NaBH4 in EtOH at 70 °C proceeded regioselectively, providing exclusively amino ester 5 with the hydroxy function on position 4 (for analogous

• stereoisomer of 5 (Scheme 3, Figure 4). It is noteworthy that in this latter case hydroxylated amino ester 14 could not be prepared by the alternative diastereoselective epoxidation and regioselective oxirane opening strategy: according to our previous results, the opening of epoxide 15 derived from 10

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• -alkyl groups and without N-substituent in the presence of potassium carbonate as a base catalyst. When two equivalents phenacyl bromides were used in the reaction, the N-substitution reaction of isatin also finished with the formation of spiro-oxirane-oxindoles. Keywords: Darzens reaction; isatin

• ; oxindole; oxirane; spiro-epoxyoxindole; spirooxindole; Introduction The spirooxindole unit is a privileged heterocyclic motif that forms the core structure of a large family of natural alkaloids and many pharmacological agents with important bioactivity and interesting structural properties [1][2][3][4][5

• ]. The unique structures and the highly pronounced pharmacological activity displayed by the spirooxindoles have made them attractive synthetic targets [6][7][8][9]. In various heterocyclic and carbocyclic spirooxindoles, the spiro-oxirane-oxindoles are a particular class of compounds with both spiro

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• ) than path A (ca. 15 kcal mol–1 with respect to Int1). TS4, Int4 and TS5 can be considered as bicyclic structures consisting of a 3-membered oxirane and a 4-membered cyclobutane ring. The two rings are inclined to each other as indicated by the angle α measured between the midpoints of the C3–C4 and C1

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• functionalized with epoxide by reacting 2-alkynylindole with epichlorohydrin. This can then be followed by ring opening of the oxirane by azide to furnish a bis-functionalized indole intermediate having azide and alkyne groups in close proximity. Such an intermediate may then undergo annulation following an

Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance

• Torsten Dittrich,
• Nils Hanekop,
• Nacera Infed,
• Lutz Schmitt and
• Manfred Braun

Beilstein J. Org. Chem. 2012, 8, 1700–1704, doi:10.3762/bjoc.8.193

• appropriate for the removal of the N-protecting group. Again, the free amines 6b–13b were used as crude products for the reaction with the oxirane (R)-16 to give the series of new compounds. Spiroacetal 5b was commercially available. Biochemical studies The transport activity [13] of the compounds 2a–13a and

Photoreactions of cyclic sulfite esters: Evidence for diradical intermediates

• Rick C. White,
• Benny E. Arney Jr. and
• Heiko Ihmels

Beilstein J. Org. Chem. 2012, 8, 1208–1212, doi:10.3762/bjoc.8.134

• irradiation of the cyclic sulfite 8 for 3 h in acetonitrile gave phenyl acetaldehyde (3a), bibenzyl (4) and toluene (7) in Scheme 2; however, in contrast to the results of the photoreaction of the cyclic carbonate ester 1a under similar conditions, the oxirane 2a was not detected as a reaction product. The

• lack of oxirane formation may be explained by initial cleavage of the C–O bond to give the biradical BR1, whose rotation about the C–C bond to give the relaxed biradical BR1rot is significantly faster than the loss of sulfur dioxide (Scheme 3). As a consequence, the elimination of SO2 results in a

• biradical BR2 with a conformation that is unfavorable for oxirane formation, but enables efficient hydrogen migration to result in aldehyde 3a. Theoretical calculations have confirmed that acetaldehyde derivatives may be formed upon rearrangement of the 1,3-oxyethandiyl [20][21] and that a subsequent

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

• . Relative energies of alkene isomers based on RB3LYP/6-311G* calculations with MacSpartan ’06. X-Ray structure of epoxyalcohol 6. Amine building blocks for library synthesis. X-ray structure of amino alcohol 10{7}. Formation of isomerized azepinoisoindoline 3 and oxirane 5. Ring-closing metathesis of diene

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• by treatment with tetrabromomethane in the presence of triphenylphosphine gave no satisfactory results, possibly due to the formation of the corresponding oxirane and its diverse, subsequent reactions. Conclusion We achieved the efficient synthesis of enantiopure hydroxylated tetrahydro-2H-1,2

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

• Yoshihiro Nishida,
• Yuko Shingu,
• Yuan Mengfei,
• Kazuo Fukuda,
• Hirofumi Dohi,
• Sachie Matsuda and
• Kazuhiro Matsuda

Beilstein J. Org. Chem. 2012, 8, 629–639, doi:10.3762/bjoc.8.70

• compound 4a (60–70%) and bromide 5a (30–40%). In 5a, the oxirane ring was opened by nucleophilic Br− ions produced by Ph3P and CBr4. Also in the DMF-promoted reaction, a mixture of 4a (70–90%) and 5a (10–30%) was derived. In both reaction pathways, however, the glycosylation was α-selective (α:β ≥ 90:10

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• authors proposed an initial nucleophilic attack of the carbonyl oxygen on the gold(I)-activated alkyne to form a vinyl–gold intermediate XII, analogous to that previously shown in Scheme 5 (IX). Aromatization of this intermediate through C–C bond cleavage of the oxirane unit, followed by addition of the

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

• ] seem to rule out the usually proposed mechanism, that is, via the intramolecular nucleophilic addition of the oxirane oxygen on the π-metal–alkyne complex (Scheme 9, upper row). Instead, the reaction seems to proceed through a cascade initiated by an internal or external nucleophilic (the hydroxy group

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

• ), which donates oxygen to the double bond, affording the respective epoxide or oxirane and regenerating the carboxylic acid. Initial investigations illustrated the highest conversions in solvents such as hexane and toluene, with the lowest in dioxane and acetonitrile, following the lipase trend where the

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

• subsequent oxirane ring opening with the intramolecular oxygen nucleophile (an intramolecular SN2 reaction) to afford the product 2 stereospecifically [44][45]. It should be noted that the miniflow cyclization of 1a was continuously carried out to give a quantitative conversion of 2a over 2 h. Conclusion In

A biphasic oxidation of alcohols to aldehydes and ketones using a simplified packed- bed microreactor

• Andrew Bogdan and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2009, 5, No. 17, doi:10.3762/bjoc.5.17

• it enables facile removal and recycling. We recently reported the development of an effective solid support for use in packed-bed microreactors [39], AMBERZYME® Oxirane (AO, 1), a commercially available resin with pendant epoxide functionalities designed for enzyme immobilization. AO is readily

• , then heating samples from 80 to 200 °C at 17 °C/min, and holding at 200 °C for 1.94 min. The MSD temperature was held at 300 °C for 15 min. Azide modified AMBERZYME® Oxirane (AO-N3, 2) Sodium azide (5.26 g, 81 mmol, 8.1 equiv) and ammonium chloride (2.27 g, 42.4 mmol, 4.2 equiv) were dissolved in 500

• mL 90:10 v/v water in methanol. AMBERZYME® Oxirane (10.0 g, 1.0 mmol epoxide/g resin, 10.0 mmol, 1.0 equiv) was suspended in the azide solution and the reaction mixture refluxed overnight with gentle stirring. The resin was filtered using a Buchner funnel, washed with deionized H2O (2 × 50 mL), MeOH

Unexpected degradation of the bisphosphonate P-C-P bridge under mild conditions

• Petri A. Turhanen and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2008, 4, No. 7, doi:10.1186/1860-5397-4-7

• ) or phosphate buffer, pH 7.4 at 37 °C. Szajnman et. al. [25] has reported loss of two molecules of phosphite in tetraethyl oxirane-2,2-diylbis(phosphonate); however the kind of degradation which we will discuss in this paper has not been previously reported. Results and Discussion As mentioned in the

• phosphite and the oxirane ring containing derivative (route b). In route a, water or hydroxide ion attacks the carbonyl carbon and P-C bond cleavage occurs giving rise to acetic acid and dimethyl phosphite which can undergo a further reaction with water or hydroxide to give methyl phosphite. In route b, the

• attack of water on the carbon of oxirane ring yields hydrate followed by elimination of methyl phosphite and acetic acid. We believe that route a is more probable, since during the reaction with a weaker base, such as triethylamine, only the first P-C bond is cleaved and products 3 and 7 are observed. On

Part 3. Triethylborane- air: a suitable initiator for intermolecular radical additions of S-2-oxoalkyl- thionocarbonates (S-xanthates) to olefins

• Jean Boivin and
• Van Tai Nguyen

Beilstein J. Org. Chem. 2007, 3, No. 47, doi:10.1186/1860-5397-3-47

• additions of various S-alkylxanthates to vinyl epoxides and related derivatives using an excess of triethylborane (2 equiv vs xanthate) at room temperature. The mechanism is different from that reported in this note as the radical chain is maintained by the ring opening of the oxirane that produces an