Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• presence of the radical scavenger BHT no conversion was observed. (ii) The exclusion that epoxide could be an intermediate of the process. When 2-methyl-2-phenyloxirane was used in place of α-methylstyrene, poor results were obtained in terms of yield in acetophenone. (iii) The proof that the oxygen atom

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• Brad M. Loertscher Yu Zhang Steven L. Castle Department of Chemistry and Biochemistry, Brigham Young University, C100 BNSN, Provo, UT, 84602, USA 10.3762/bjoc.9.132 Abstract In the context of synthetic efforts targeting the alkaloid lyconadin A, scalemic epoxide 25 was prepared by a highly

• stereoselective sequence involving a Myers alkylation and a Shi epoxidation. Ring-opening of this epoxide with a vinylcopper complex afforded alcohol 26 instead of the expected product 27. An unusual Lewis acid promoted Payne rearrangement of an α-trityloxy epoxide is proposed to account for this outcome

• course of this work, we discovered an unusual Payne-like rearrangement process that occurred in preference to the ring-opening of a hindered epoxide. Results and Discussion Our retrosynthetic analysis of lyconadin A is shown in Scheme 1. We reasoned that 1 could be formed by an alkylation cascade

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

• 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

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• this intermediate to Jones oxidation triggered a highly efficient oxidation–epoxide opening [93][94][95][96][97][98] reaction cascade [99][100] to construct the critical D-ring of 9 (46% yield, over 3 steps). Notably, this scalable approach rendered us several hundred milligrams of compound 9, paving

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 cationic polymerization of the epoxide (r11 in Scheme 5). For the other Co_Py, a good thermal stability is found. This dual behavior of some Co_Pys, which are able to initiate both a thermal and a photochemical cationic polymerization, can be very useful to initiate the polymerization in the

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

• xanthate 51 and proceeding via adduct 52, underscores the tolerance of the process for the presence of an epoxide and, at least in this case, of a free phenol [29]. This sequence represents an attractive potential route to seco-pseudopteroxazole, 54, and to other congeners in this family. In many cases

• epoxide as an allylating agent are displayed in Scheme 27 [59]. The first corresponds to the allylation of cyclobutyl xanthate 143 with vinyl epoxide 144 to yield compound 145, while the second involves an addition–fragmentation of xanthate 146 on β-pinene to give xanthate 147, which is then subjected to

• the allylation procedure with the simplest vinyl epoxide to furnish derivative 148. It is interesting to note that the carbon–carbon bond formation takes place in ketoester xanthate 146 on the carbon bearing the least acidic hydrogens. Triethylborane, through its autoxidation, serves to initiate the

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• oxide (1) under solvent-free conditions. The epoxide ring-opening reactions were carried for 24 h at elevated temperature (32 °C) and resulted in the formation of the appropriate alcohols (±)-3a and (±)-3b in high yields (Scheme 1). In the next step, the influence of crucial parameters in enzyme

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

• Abstract A microwave-assisted three-component protocol involving N-1 alkylation of 2-alkynylindoles with epichlorohydrin, ring opening of the epoxide with sodium azide, and an intramolecular Huisgen azide–internal alkyne 1,3-dipolar cycloaddition domino sequence has been described. The efficacy of the

• 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

• product in 77% isolated yield within 1 h (Table 1, entry 6). Further stirring up to 4 h at 120 °C led to the partial conversion of 4a (by ring opening of the epoxide with NaN3) into yet another intermediate 1-azido-3-{2-[2-(4-methylphenyl)ethynyl]-1H-indol-1-yl}propan-2-ol (5a, Table 1, entry 7) in 30

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

• bisallenes, including the tetramethyl derivative 2, were epoxidized by Pasto et al. [26]. These authors showed that this hydrocarbon provides the products 35 and 36 on treatment with m-chloroperbenzoic acid (MCPBA) in dichloromethane (product ratio: 71:29). With excess dimethyldioxirane (DMDO) the epoxide 37

• 36 are identical with those given in the literature [26]. As far as the oxidation mechanism is concerned it agrees with the suggestion of Pasto (see above). When the epoxidation reagent was employed in excess (fivefold) the epoxide 37 was produced in 66% yield (with reference to 2) as a colorless oil

• resulted in the formation of 68% of 38 and a trace amount of the epoxide 39 (8%), while 24% of the substrate was recovered (GC analysis). Since the complete separation of the two products was difficult, the experiment was repeated with excess MMPP (1.5 equiv); in this case the yield of 39 was 62% and the

Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• suggests four different fragments to be assembled in the total synthesis, named unit A–D (Figure 1). Unit A is an α,β-unsaturated δ-hydroxy acid that usually also contains a benzylic epoxide or a benzylic double bond. Unit B represents a chlorinated O-methyl-D-tyrosine derivative, while unit C is a β2

• from this transformation was directly subjected to reaction with acetyl bromide to form a bromohydrin formate. This was then treated with a potassium carbonate/ethylene glycol/dimethoxyethane-emulsion to bring about cleavage of the formyl ester accompanied by epoxide formation as previously described

• concomitantly displaced the trichloroethylester at unit B to result in the macrocyclic product 30 [34]. Cleavage of the dioxolane liberated the vicinal diol, which was then subjected to the final diol-epoxide transformation to provide the cryptophycin-52 analogue 31 in a yield of 14% over the final four steps

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• fact we could only find two references describing photoreactions involving bisallenes. Thus, irradiation of the epoxide 197 in benzene-d6 (NMR experiment) yielded a plethora of photoproducts, among them two photodimers to which structure 198 was assigned by spectroscopic measurements (Scheme 47) [136

• cyclopentenones [140]. Applying the mechanism discussed in this latter context to 24, it is reasonable to propose the formation of an allene-epoxide first [141], which can exist either in a transoid, 212, or cisoid conformation, 213 (Scheme 51). Whereas the former could open up to the “stretched” zwitterion 214

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

• LTMP and PPh3 in THF at 0 °C for 24 h, gave no colour change from an initial yellow solution), becoming very intense after 3 h, although some epoxide 11 was still present after 24 h (TLC monitoring); the reduced activity of LTMP may be due to phosphine coordination [32]. At this point, following

• the presence of soluble lithium halides [33][34], the homoallylic alcohol, which would arise [35] from any reaction of β-lithiooxyphosphonium ylide and terminal epoxide, was not observed in the present studies; this suggests that the latter ylides are not capable of reacting with terminal epoxides [35

• TMP enamine) [36][37]. In the present work, neither decanal nor its corresponding TMP enamine were not detected as side-products, and we also established that the presence of LiBr (1 equiv) did not interfere in this isomerization process, giving decanal from epoxide 11 in 65% yield (67% without LiBr

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

• as racemate in the error range of the HPLC measurements. Next, several salts were explored in the ring opening of cyclohexene epoxide with aniline (Scheme 4, Table 2). A reaction in CH2Cl2 in the absence of the catalyst gave a yield of 10% after 24 h (Table 2, entry 1). The camphor based salt 16 gave

• %, respectively (Table 2, entries 6 and 7). Compared to sulfur, oxygen is a good hydrogen-bond acceptor. Hence, also imidazolinium salts with a C(2)H unit were applied in the reaction. Here, an activation of the epoxide can be also possible through hydrogen bonding next to the direct interaction with the

• –Alder reaction with ethyl crotonthioate (1) and cyclopentadiene (2). Diels–Alder reaction catalysed with imidazolinium salts. Ring opening of thiirane 12. Ring opening of epoxide 14. Synthesis of bis-imidazolium salt 17. Synthesis of amidinium salt 21. Diels–Alder reaction with 10 mol % catalyst

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• -opening protocols have been developed, synthesis of the starting NH-aziridine-2-carboxylates is multistep and low-yielding. Synthetic routes include Gabriel–Cromwell addition of ammonia to an enoate [16][17]; epoxide opening with azide, followed by ring closure [19]; and a sequence of olefin

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

• to the epoxide (R)-16, serving as the chiral building bloc in the final key step, which involves the nucleophilic attack of the secondary amino group of the precursors 2b–13b to the epoxide 16, to deliver the final products 2a–13a. The yields of the final coupling step are given in Scheme 2. The

• purification in the coupling reaction with epoxide (R)-16. The spirocyclic compounds 6c–13c were obtained by standard acid-catalyzed reaction with the corresponding diols for the formation of acetals 6c–12c and propanedithiol for 13c, starting from N-acetyl-4-piperidone. Basic hydrolysis was found to be

Polysiloxane ionic liquids as good solvents for β-cyclodextrin-polydimethylsiloxane polyrotaxane structures

• Narcisa Marangoci,
• Rodinel Ardeleanu,
• Laura Ursu,
• Constanta Ibanescu,
• Maricel Danu,
• Mariana Pinteala and
• Bogdan C. Simionescu

Beilstein J. Org. Chem. 2012, 8, 1610–1618, doi:10.3762/bjoc.8.184

• -glycidoxypropyl)polydimethylsiloxane prepolymer with Mn = 1250 until the solution became turbid (after approximately 72 h) at 65 °C, followed by the reaction of epoxide functionalities with 4-aminophenyltriphenylmethane (APhTPhM) (saturated solution in isopropyl alcohol) for 8 h at 65 °C. The slurry was then

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

• ; epoxide aminolysis; hydrozirconation; isoindolinones; metathesis; N-acyliminium ion; Introduction Isoindolinones represent a common scaffold seen in naturally occurring compounds such as magallanesine [1], lennoxamine [2] and clitocybin A [3], or drug candidates such as pagoclone [4] (Figure 1). These

• ). This result was reproduced with Zhan catalyst-1B [28][29], which gave 3 in 50% yield. The structure of alkene 3 was determined based on the X-ray analysis of epoxide 5 (Figure 2), obtained with NaHCO3-buffered meta-chloroperbenzoic acid (m-CPBA) in 57% yield [30][31]. The surprising formation of 3

• presence of the Lewis acidic additive Ti(OiPr)4 as well as the substitution pattern of the α,ω-diene precursor. With alkene 3 and the corresponding epoxide 5 in hand, a ZnI2-mediated amine alkylation protocol could be employed, which introduced a variety of nitrogen nucleophiles 8{1–13} (Scheme 4) [38][39

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

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

• from the β-face, with ring-opening of the 12α,13α-epoxide intermediate [15][44]. Quite recently, we demonstrated that the 28,13β-lactonization of 3-oxooleanolic acid 1 promoted by Bi(OTf)3·xH2O affords a 3-oxo-18α-olean-28,13β-olide product, with inversion of configuration at the C18-stereocenter, as

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

• turned out to be the most efficient for the epoxidation of the tetrahydropyridine ring, with substrate 7b epoxidised to 8b in 73% conversion. Racemic epoxide 8b was synthesised to confirm the structure of the biotransformation product and to determine the enantiomeric excess. This was found to be 18% for

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

• Ameer F. Zahoor Sarah Thies Uli Kazmaier Institute for Organic Chemistry, Saarland University, P.O. Box 151150, 66041 Saarbrücken, Germany 10.3762/bjoc.7.151 Abstract Complex amino acids with an α-acyloxycarbonyl functionality in the side chain are easily available through epoxide opening by

• % (entry 2), and similar results were obtained with a range of aryloxy-substituted derivatives 2c–2f (entries 3–7). The new stereogenic center was formed without significant selectivity. To increase the synthetic potential of this protocol we also applied the Pd-catalyzed opening of a vinyl epoxide with

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• difficult to synthesise; attempted Mitsunobu coupling failed, but we synthesised such amines by epoxide-opening. We did not achieve the formation of sec–sec linked secondary amines. The synthesis of a sec–sec amine-linked diglycoside structure by epoxide-opening was reported by Coxon [7], its formation

• being achieved in low yield (25%) under rather harsh conditions (autoclave, 140 °C), while a similar epoxide-opening reaction starting from a rather more complex substrate has been used to synthesise a pseudohexasaccharide in very low yield (12%) [8]. Kroutil et al. reported the synthesis of a number of

• , failed to give any reaction. A combination of RuCl3 and NaIO4 produced, after 4 days, a mixture of starting material and desilylated material but no oxidised product. Treatment with mCPBA failed to give an epoxide, and after a week only some decomposition of the starting material was seen. Presumably

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

• our previous studies (Scheme 1 and Scheme 5) [1][14][15][16]. Therefore, one or two equivalents of sodium methoxide were applied to 17 and the reaction resulted in the formation of 27 contrary to the expected epoxide 23 or any aromatized products (Scheme 6). In our earlier study, the X-ray packing

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

• Olivier Debleds,
• Eric Gayon,
• Emmanuel Vrancken and
• Jean-Marc Campagne

Beilstein J. Org. Chem. 2011, 7, 866–877, doi:10.3762/bjoc.7.99

• of the homopropargylic alcohol on the triple bond or a gold-catalyzed rearrangement of a transient epoxide as recently described by Blanc and Pale [74][75][76]. Synthetic developments This result prompted us to explore the synthesis of functionalized furans from various homopropargylic alcohols