Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• ; cyclopropanations Dimethoxycarbene (6), generated in situ by thermal decomposition of 2,2-dimethoxy-2,5-dihydro-1,3,4-oxadiazole 7, reacts with E-1b yielding a mixture of the trans-configured tetramethoxycyclobutane 8 and 2,3-dihydrofuran 9 [21][22] (Scheme 3). The latter reacts further with dimethoxycarbene and

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• dihydrofuran ring. Previous studies on the stereochemistry of furanocembranoids [31][36][38][39] stated a relation between the value of the specific optical rotation, the CD Cotton effect and the configuration at C-2. Thus, a large positive specific rotation value corresponds with S configuration at C-2

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• the diols or execute a regioselective 1° or 2° mono-O-nitration was not. Eliminating the former problem Hodgson et al. [26] reported rac-17 could be generated from cheap, commercially available 2,5-dihydrofuran which, after epoxidation with meta-chloroperbenzoic acid (mCPBA), afforded epoxide 21 in a

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• spirocyclic 2,5-dihydrofuran was obtained in 98% yield when the π acid AuCl3 (5 mol %) was used. AuCl3 may coordinate one of the allene double bonds via a monodentate model. The phenol substrate did not participate in this reaction. In 2013, Ji and co-workers described the I2-catalyzed construction of pyrrolo

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• alkenylation reactions. However, the product of addition of a secondary bromo keto ester possesses an acidic α-proton. This proton can be deprotonated by diisopropylamine, and the resulting enolate cyclizes onto the newly formed benzylic halide to form the dihydrofuran (Scheme 14). This method is formally a [3

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• -transfer catalyst such as tetrabutylammonium iodide generated bicyclic compounds 341a–c. The RRM of these ether derivatives 341a–c was performed under ethylene (24) atmosphere with catalyst 5 to generate the dihydrofuran derivatives 342a–c. When compounds 340d, 340e and 340f were subjected to a metathesis

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• -limiting step. For unambiguous identification of the rate-limiting step, individual rate constants kH and kD in two parallel reactions would have to be determined [89]. Dihydrofuran (11) and pyridinium tetrafluoroborate were identified as byproducts of the dediazoniation reactions. Similarly to the

• tetrafluoroborate radical giving dihydrofuran (11) and pyridinium salt. Conclusion In conclusion, a novel dediazoniation–borylation methodology was developed based on the reaction of aryldiazonium tetrafluoroborates with pyridine and B2pin2 to give arylpinacolborates. Particular emphasis was on the synthesis of SF5

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• reacted with azetidine-2,3-diones 176 under eco-friendly reaction conditions to generate bis(allene) 177. Compound 177 was then converted into bis(dihydrofuran) 178 by using AuCl3. Macrocyclization of 178 was carried out by using a Ru(II) or Ru(III) catalyst to generate 179 as a mixture of E/Z isomers

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

• Soyoon Baek,
• Xuikui Xia,
• Byung Sun Min,
• Chanil Park and
• Sang Hee Shim

Beilstein J. Org. Chem. 2014, 10, 2955–2962, doi:10.3762/bjoc.10.313

• phenylpropanoid moiety. HMBC correlations of H-7' with C-4 allowed linkage of the oxygenated sp3 methine carbon C-7' to the oxygenated sp2 carbon C-4 through oxygen to form a dihydrofuran ring. The presence of a dihydrofuran moiety in compound 1 was also demonstrated by chemical shifts of C-4 (δ 146.9) and C-7

• different in that it did not contain a methoxy group at the C-4′ position nor an ether linkage between C-4 and C-7′ to form a dihydrofuran ring. The absolute configuration of compound 2 was determined by comparing its optical rotation with those of (R)-2,3-diphenyl-1-propanol and (S)-2,3-diphenyl-1-propanol

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• been made towards the application of BINAP-type ligands in the intermolecular asymmetric Heck reaction [15]. This reaction was pioneered by Hayashi [16], who demonstrated the arylation of dihydrofuran (1) with phenyl triflate (2a) (Scheme 1) in the presence of (R)-BINAP [16][17][18] produced isomeric

• oxidative addition of Pd(0) species 5 into the aryl triflate 2 resulting in the formation of cationic complex 6. The latter can coordinate to either of the prochiral faces of dihydrofuran (1) affording diastereomeric η2-complexes 7 and 10. Subsequent carbopalladation, followed by β-hydride elimination

• , produces species 9 and 12, respectively. It was proposed that the diastereomeric complex 12 has a higher propensity toward further hydropalladation than 9. Accordingly, the latter species releases the (S)-enantiomer of 2,5-dihydrofuran 3 (path I), while the former undergoes a series of reversible

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• six-membered rings. Five-membered dihydrofuran rings lead to the synthesis of furanomycin D [35][36], norfuranomycin E [37], and the polyoxin family F [38]. The six-membered tetrahydropyridine G synthesized via this route can be used as an intermediate in the synthesis of iminosugars, e.g., of the

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• for purification and hence was directly used for the next cyclization step (Scheme 3). After a 5-endo-cyclization of 7 employing KOt-Bu in DMSO dihydrofuran derivative 8 was obtained in 74% overall yield from 5. The strongly basic conditions as first described by Brandsma and Arens [35] used for the

• each obtained in quantitative yield showing the expected optical rotations (Scheme 8). Analogously to the reaction sequence leading to 1 and 2, the synthesis of ent-jaspine B (3) and the (2R,3S,4S)-diastereomer 4 was also achieved in similar yields employing (2R)-configured dihydrofuran 14 as starting

• . Subsequent functionalization using oxidative azidation, as shown for methoxy-substituted dihydrofuran 8, did not give the expected α-azidotetrahydrofuranones in acceptable yields, but electrophilic bromination and subsequent substitution with sodium azide turned out to be a good alternative for the synthesis

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• several microorganisms, including the E. coli, S. aureus and M. tuberculosis. (+)-Furanomycin (1a, Figure 1, X = O) was identified as a non-proteinogenic amino acid bearing a characteristic 2,5-dihydrofuran ring. The correct (αS,2R,5S)-stereochemistry was established in 1980 by the first total synthesis

• the five-membered heterocycles 9/10 are summarized in Table 2. Treatment of the α-hydroxyallene 7a with 1 mol % AuCl3 in THF [21][22][23] afforded the desired 2,5-dihydrofuran 9a with 84% yield (Table 2, entry 1). The temperature was decreased to 5 °C to avoid acetal cleavage by the Lewis-acidic gold

• epimerization of the allene, so that dihydrofuran 9b was isolated as a 4:1-mixture of diastereomers. As expected, the cycloisomerization of allenes 8 bearing an unprotected amino group is much slower [38][39] and requires rather forcing conditions. For a complete conversion of α-aminoallene 8a, 10 mol % of AuCl

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

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

• under optimum conditions. However, the other substrates, including the meso-epoxides derived from butenediol, pyrroline and dihydrofuran, gave quite disappointing enantioselectivities. Interestingly, OC-65 significantly reduced the enantioselectivities under the optimized conditions, but the chiral

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• 13 was treated with aqueous hydrochloric acid, in the hope of generating the corresponding dihydrofuran carbaldehyde 33. Instead, the diol 34 was obtained in 52% yield as a 1:1 mixture of diastereoisomers. It thus transpires that protonation and hydration of the exo-methylene double bond of 13

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• cyclization to novel bis(2,5-dihydrofuran) derivatives 102; the yields in all three steps are acceptable to good (up to 60%). A protected biallenyl diol, the derivative 104, is produced as a mixture of diastereomers in small amounts (10%) when the mesylate 103 is treated with Pd(PPh3)4 and diethyl zinc in THF

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• cocatalyst, while yields and enantioselectivities are low with strong acids, such as CF3SO3H, TsOH, or HCl, as cocatalysts [46][54][55]. Figure 8 shows that the rates of the reactions of 3a-X with 2-(trimethylsiloxy)-4,5-dihydrofuran (7b) were only slightly affected by the nature of the counterions X– (X

Conserved and species-specific oxylipin pathways in the wound-activated chemical defense of the noninvasive red alga Gracilaria chilensis and the invasive Gracilaria vermiculophylla

• Martin Rempt,
• Florian Weinberger,
• Katharina Grosser and
• Georg Pohnert

Beilstein J. Org. Chem. 2012, 8, 283–289, doi:10.3762/bjoc.8.30

• comparison of the obtained NMR and MS spectra by co-injection with authentic standards [3]. Stereochemistry of PGE2 was verified with CD spectroscopy in comparison with an authentic standard. Spectroscopic data of 5. 5-((1E,3E,5E,7Z,10Z)-hexadeca-1,3,5,7,10-pentaenyl)dihydrofuran-2(3H)-one (5) was obtained

• Fisher and van Belle [10]. 5-((1E,3,5E,7Z,10Z)-hexadeca-1,3,5,7,10-pentaenyl)dihydrofuran-2(3H)-one (5) with 1H–1H COSY (bold bonds) and relevant HMBC (arrows) correlations. Suggested pathway for the biosynthesis of 5. Supporting Information Supporting Information File 56: Spectra for metabolites 5 and

A practical microreactor for electrochemistry in flow

• Kevin Watts,
• William Gattrell and
• Thomas Wirth

Beilstein J. Org. Chem. 2011, 7, 1108–1114, doi:10.3762/bjoc.7.127

• -supported, paired electrosynthesis of 2,5-dimethoxy-2,5-dihydrofuran from furan with excellent yields and flow rates of up to 0.5 mL·min−1. A microflow system where the current flow and liquid flow are parallel was reported by Yoshida et al. [7]. Two carbon fibre electrodes were separated by a hydrophobic

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

• the gold-catalyzed cycloisomerization of α-hydroxyallenes 16 to 2,5-dihydrofurans 17 (Scheme 3) [25]. The best system was found to be AuBr3 in [BMIM][PF6]. The cycloisomerization of various alkyl- or arylsubstituted α-hydroxyallenes gave corresponding 2,5-dihydrofuran with complete axis-to-center

• gold-catalyzed synthesis of dihydrofuran-3-ones 63, in which terminal alkynes 62 were used as equivalents of α-diazo ketones to generate α-oxo gold carbenes (Scheme 12) [37]. The α-oxo gold carbenes were produced via gold-catalyzed intermolecular oxidation of 62. This provides improved synthetic

Gold-catalyzed regioselective oxidation of terminal allenes: formation of α-methanesulfonyloxy methyl ketones

• Yingdong Luo,
• Guozhu Zhang,
• Erik S. Hwang,
• Thomas A. Wilcoxon and
• Liming Zhang

Beilstein J. Org. Chem. 2011, 7, 596–600, doi:10.3762/bjoc.7.69

• toxic and potentially explosive α-diazo ketones (Scheme 1A). Synthetically useful structures such as oxetan-3-ones [22], dihydrofuran-3-ones [23], azetidin-3-ones [24] and α,β-unsaturated ketones [25] are readily accessed via these gold carbene intermediates. This led us to consider whether or not

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• cyclocondensation of alkyne diols to give substituted furans (Scheme 3, Reaction 3) [35]. Our objective, laid out in Scheme 4, was to initiate cycloisomerization with a 5-endo-dig cyclization of the homopropargyl alcohol 6, followed by 5-exo-trig cyclization onto the resulting dihydrofuran, whilst avoiding

• methanol. Path a, which corresponds roughly to our original experimental designs, involves initial gold-catalyzed 5-endo-dig cyclization to dihydrofuran 18. Once the regiochemistry is established, any number of condensation pathways would lead to spiroketal 17. For example, protonation of the enol ether

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• ethyl 3-oxopropanoate followed by saponification of the ester to yield etodolac (Scheme 31) [44]. The second described route [45][46] is similar but starts with a more readily available carbonyl surrogate; 2,3-dihydrofuran 154. The Fischer indole reaction provides a primary alcohol which is TMS

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• . When the allylic alcohol was protected with a bulky group, the catalyst reacted preferentially at the less hindered allyl ether (pathway A where R′ = H). The formation of the 4,6-bicyclic intermediate is apparently disfavored with catalyst 1a leading to largely the formation of the dihydrofuran product

• . It should be noted that when a more reactive second-generation catalyst (2) is used the selectivity for the dihydrofuran product is reduced. This selectivity was also found to be highly dependent on the size of protecting group. Significant decrease in ring-size selectivity was observed when smaller