Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• F1, but-3-yn-2-one reacted with a series of N-protected isatins in ethyl ether at −20 °C to afford enantioenriched spiro[furan-2,3´-indoline]-2´,4(5H)-diones with good to excellent ee's, albeit moderate yields. 2.7 [4 + 2] Annulations of allenes with activated imines Compared with phosphine-catalyzed

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• with the furan compound 52 (Table 1, entry 4). The furan derivative 52 in this reaction was probably formed through a monocyclisation, followed by β-H−-elimination and aromatisation. In the case of substrate 13 having an unprotected α-hydroxy group, the reaction provided only a mixture of unidentified

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• -substituted tryptophan was observed (Table 2, entry 6). For indoles containing 3-heterobenzyl substituents, the results were conflicting. Whereas 3-(furan-2-ylmethyl)indole (1g) did not react under the usual reaction conditions (Table 2, entry 7), bis(indol-3-yl)methane (1h) provided the desired product in an

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• and subsequent hydrogenation and reductive 6-deoxygenation [21][22]. Successful de novo approaches [14] to both enantiomers of amicetose include an Achmatowicz rearrangement–hydrogenation sequence, starting from enantiomerically pure 2-(1-hydroxyethyl)furan [23][24][25], a sequence comprising

• product 8 to a fully protected acyclic cinerulose derivative. We are aware of only one previous de novo synthesis of DL-cinerulose, which used an Achmatowicz rearrangement of 2-(1-hydroxyethyl)furan [45]. Results and Discussion The three second generation catalysts A [46], B [47][48] and C [49][50] were

• benzoylation in pyridine resulted exclusively in the formation of furan 10 (Table 2, entry 1). We reasoned that pyridine initiates an E/Z-isomerization of the enal through nucleophilic attack at the β-position, followed by lactol formation, benzoylation of the lactol and finally elimination of benzoic acid

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• reactions to the parent furan-2(5H)-one (9) and was conducted with a set of eight visible light lamps (Osram L 8W/640 cool white) [48]. A screen of potential catalysts (see Supporting Information File 2 for further details) in CH2Cl2 as the solvent (c = 0.1 M) revealed that [Ir(ppy)2(bpy)]BF4 (ppy

• the fact that oxidation of the putative intermediate B is required, which seems to occur at the expense of the substrate. If a suitable compound was found to adapt the role of an ancillary oxidant, yields could possibly be improved. PET-catalyzed addition of N,N-dimethylaniline (1) to furan-2(5H)-one

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• procedures involved the use of the Diels–Alder reaction on a furan ring to synthesize isoindoloquinoline derivatives [22][23][24][25]. Reaction of methallylmagnesium chloride with furyl aldimines produced furan-substituted N-aryl homoallylamines which reacted with maleic anhydride to undergo amide formation

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• ]. In particular, unsubstituted acylketenes, the reactivity of which towards azirines is until now unknown, cannot be generated from diazo compounds. An alternative source of acylketenes can be furan-2,3-diones, which have been used in reactions with nucleophiles and various cycloadditions [30][31][32

• ]. Aiming to broaden the scope of the reaction of acylketenes with 2H-azirines we tried to use furan-2,3-diones instead of diazo compounds as the source of ketenes. Results and Discussion Unexpectedly, with a new source of acylketenes in addition to predictable products (derivatives of 5,7-dioxa-1

• -azabicyclo[4.4.1]undeca-3,8-diene) derivatives of 4,11-dioxa-1,8-diazatricyclo[8.4.0.03,8]tetradeca-5,12-diene, a new heterocyclic system, were formed. Boiling a benzene solution of furan-2,3-dione 1a and azirine 2a (1:1) for 0.5 h gave a mixture of compounds 3a–5a, which were isolated by column

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

• Fabian Klukas,
• Alexander Grunwald,
• Franziska Menschel and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 672–679, doi:10.3762/bjoc.10.60

• -position (2d, 2g, 2o) are well tolerated. Polar substituents like alcohols (2k) can also be employed in the sequence. From the literature it is known that the naturally occurring compound 2h [16][17] and 2,5-bis(3,4,5-trimethoxyphenyl)furan (2g) are highly biological active [39]. Compound 2k is

• in a one-pot fashion, which opens a ready access to biologically active furan derivatives. In addition the investigation of the photophysical properties of these compounds reveals an intense blue luminescence in solution approaching unity for the fluorescence quantum yield Φf of distinct derivatives

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• ). Interestingly, the ketones 7a–d existed in an equilibrium with their cyclic hemiacetal tautomers as shown in Scheme 2. The predominant keto form possessed a clear singlet around 205–210 ppm for the quaternary carbonyl carbon and the furan form was indicated by two weak signals at 105–110 ppm for the hemiacetal

• 68% yield in Et3N/CH2Cl2 in a 1:1.3 ratio, while a 1:3 solvent mixture gave 11c in only 22% yield (Table 2, entries 13–15). Indeed, the furan 13h (see Table 2) resulting from nucleophilic substitution of the primary (activated) OH-function through the secondary hydroxy group of 9c formed in

• of 14a (ca. 1:1 ratio of its epimers) forms an equilibrium with its ketone tautomer in a 1.8:1 ratio. In contrast to hydroxyketones 7a–d the furan tautomer of 14a is thermodynamically more stable than the keto form. This might be rationalized by a lower steric strain in the heterocyclic form due to

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

• -protected alcohol 152. Addition of methyllithium at low temperature [133] resulted in stereoselective conjugate attachment of the required methyl group. Deprotection of the alcohol and transformation into a suitable leaving group yielded tosylate 153. Next, the furan was cleaved oxidatively, the resulting

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

• -yl)acetate (141) from the furan derivative (E)-methyl 5-hydroperoxy-5-(5-methylfuran-2-yl)pent-2-enoate (140) (Scheme 33) [264]. A simple method was developed for the synthesis of cyclopropane-containing oxodioxolanes 143a–j and is based on the hydroperoxidation of tertiary alcohols 142a–j in an

Synthesis and determination of the absolute configuration of (−)-(5R,6Z)-dendrolasin-5-acetate from the nudibranch Hypselodoris jacksoni

• I. Wayan Mudianta,
• Victoria L. Challinor,
• Anne E. Winters,
• Karen L. Cheney,
• James J. De Voss and
• Mary J. Garson

Beilstein J. Org. Chem. 2013, 9, 2925–2933, doi:10.3762/bjoc.9.329

• . Compound 1, [α]D −53 (c 0.006, CHCl3), displayed a (+)-HRESIMS ion adduct at m/z 299.1624 [M + Na]+ consistent with the molecular formula C17H24O3. The 1H NMR spectrum (CDCl3, 500 MHz) of 1 showed diagnostic signals for a furan [δH 7.33 (1H), 7.23 (1H), 6.27 (1H); δC 142.7, 140.1, 111.8] along with two

• that in 1 was shifted to δH 5.64 (brdt, J = 6.4, 9.3 Hz, 1H). The gCOSY spectrum of 1 showed cross peaks from H-5 to H-4/H-6, between the furan signals H-1/H-2 and between H-8/H-9/H-10. The H-5 proton was attached to an oxymethine carbon at δC 70.7 based on HSQC data and showed HMBC correlations to

• . The overall synthesis (Scheme 1) was adapted from Tsubuki et al. [21]. Furan-3-ylmethanol (4) was prepared in 78% yield by reduction of 2-furoic acid with LiAlH4 in dry diethyl ether, whereas geranyl bromide (5) was obtained through bromination of geraniol with carbon tetrabromide and

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• appended H-bond donors to the furan ring of 1. (Dimethylamino)methyl groups at C-15 or C-16 abolished affinity for κ-OR. Hydroxymethylation at C-16 was tolerated, but 15,16-bis-hydroxymethylation was not. Since allosteric modulators may go undetected in binding assays, we also tested these and other low

• affinity for opioid receptors [1]. In particular, most modifications of the furan ring tested to date dramatically reduce affinity for κ-OR [1], although small substituents at C-16 have little effect (Figure 1). Unexpectedly, epimerization at C-12, inverting the configuration of the furan ring, reduces

• attachment point and linker for this second moiety would also be required. Docking 1 to an early rhodopsin-based homology model of κ-OR, Kane proposed a binding pose qualitatively similar to that of the HPP moiety of JDTic, placing the furan ring near Tyr3207.43 [8][18]. Indeed, at the time we commenced our

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• R, S, R, S, and R, at C-1, C-5, C-6, C-9, and C-10, respectively. The foregoing data led to identify SF002-96-1 as (5R,5aS,9R,9aR,9bS)-9,9b-dihydroxy-6,6,9a-trimethyl-3-oxo-1,3,5,5a,6,7,8,9,9a,9b-decahydronaphtho[1,2-c]furan-5-yl hexanoate. Biological activity For the identification of active

Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• = H) and furan 11g (R1 = Ph and R2 = H) were effectively transformed to the desired carbazole 12f and benzofuran 12g in 95% yields. It can be noticed that large substituents at R1 and R2 did not affect the efficiency of the reaction. The gold(I)-catalyzed cyclization of 11h (R1 = R2 = Ph) and 11i (R1

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• reaction, including natural product related or complex small molecules (Figure 18) [37]. 3.3.3 Ni-catalyzed perfluoroalkylation of Csp2–H bonds. Two early reports by Y.-Z. Huang et al. described Ni-catalyzed perfluoroalkylation of anilines, benzene, furan, thiophene and pyrrole using ω-chloroperfluoroalkyl

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

Regioselective carbon–carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne

• Motoki Naka,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2013, 9, 2182–2188, doi:10.3762/bjoc.9.256

• , but with the latter 4JF-Hb was usually not observed. Moreover, the fact that isolation of the furan 7a in 51% yield was realized by subjection of a 70:30 mixture of inseparable 5a and 6a to the already reported Pd-catalyzed cyclization conditions [19] suggested that the major isomer should be 5a, not

• was slow. This important information allowed us to reconsider our previously proposed mechanism as shown in Scheme 5. A part of 1H NMR chart of 4 and its deuterated mixture. Proposed reaction mechanism between 1 and MeLi. Furan synthesis from a mixture of 5a and 6a. Deuteration of anionic species from

Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor

• Sylvestre Bachollet,
• Kimitada Terao,
• Shin Aida,
• Yasuhiro Nishiyama,
• Kiyomi Kakiuchi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2013, 9, 2015–2021, doi:10.3762/bjoc.9.237

• established by 1H NMR analysis. In selected cases, the products 3 and 5 were isolated by column chromatography. Octahydro-1H-cyclopenta[3,4]cyclobuta[1,2-c]furan-1-one (3) [31]: Colorless oil; 1H NMR (300 MHz, CDCl3) δ 1.43–1.92 (br. m, 6H), 2.42 (dddd, J = 7.5, 7.3, 3.6, 2.1 Hz, 1H), 2.53 (dd, J = 7.5, 2.9

Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

• Lin Yan,
• Zhiqiang Han,
• Bo Zhu,
• Caiyun Yang,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2013, 9, 1853–1857, doi:10.3762/bjoc.9.216

• with hetereoaromatic groups, such as thiophene and furan (Table 2, 2n–o). Conclusion We have developed an asymmetric allylic alkylation of MBH carbonates with α-fluoro-β-ketoesters, catalyzed by a commercially available Cinchona alkaloid. Several fluorinated adducts, with chiral quaternary carbon

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• construct the furan motif [4][5]. Among them, late transition metal-catalyzed intra- or intermolecular cyclizations of oxygenated functionalities on unsaturated carbon–carbon bonds proved to be powerful synthetic methods due to their mildness, efficiency and diversity [6][7]. In the last decade, gold

• catalysts with their carbophilic character have emerged as a new tool for furan preparation. As summarized in Scheme 1, furans could now be obtained by either gold(I) or gold(III) catalysis from various types of substrates such as allenyl ketones [8][9][10][11][12][13][14], enynes or diynes [15][16][17

• gold(III) has been reported starting from terminal alkenes, glyoxal derivatives and secondary amines [49]. In this emerging research area, we have been focusing our effort on the development of furan motifs from alkynyl epoxides [21][22][50][51] and new precursors, i.e. γ-acyloxyalkynyl ketones. The

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

• , dimethyl furan-2,4-dicarboxylate. The cryptic metabolite represents the first non-azinomycin related compound to be isolated and characterized from the soil bacterium, S. sahachiroi. The results from this study suggest that abolishing production of otherwise predominant natural products through genetic

• knockout may constitute a means to “activate” the production of novel secondary metabolites that would otherwise lay dormant within microbial genome sequences. Keywords: cryptic metabolite; dimethyl furan-2,4-dicarboxylate; genetic knockout; natural products; non-ribosomal peptide synthetase module

• inactivation led to the abolishment of azinomycin production, confirming the involvement of aziA2 in the biosynthesis of the antitumor agent [11][13] and also led to overproduction of a compound, dimethyl furan-2,4-dicarboxylate. The metabolite represents one of many cryptic pathway metabolites from the S

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

• mixture of C4 and C6 alkynylated benzofurans 9j and 9j’ was obtained (Scheme 3) [31]. Substitution on the furan ring was also possible at the C3 position (product 9h), but the use of 2-methylbenzofuran (7i) led to very a low yield in the alkynylation reaction. Finally, we wondered if the alkynylation

Interplay of ortho- with spiro-cyclisation during iminyl radical closures onto arenes and heteroarenes

• Roy T. McBurney and
• John C. Walton

Beilstein J. Org. Chem. 2013, 9, 1083–1092, doi:10.3762/bjoc.9.120

• at low temperature but again thermodynamic control takes over at higher temperatures because 14b was isolated as the main product. EPR spectra from the furan-containing precursor 3, and from the more flexible aromatic precursor 4, revealed only the corresponding ring-open iminyl radicals and neither

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• ), dried over anhydrous MgSO4, and concentrated. The crude is purified by flash chromatography. cis-9b-methyl-3,4,4a,9b-tetrahydrodibenzo[b,d]furan (14) The compound 14 is obtained by using ether 13 (314 mg, 1 mmol), NiBr2bipy (75 mg, 0.2 mmol), and manganese powder (110 mg, 2 mmol) in anhydrous DMF (5 mL