Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• products (Scheme 4). Methyl benzoylformate (21) gave a mixture of pinacol and the 1,2-diol without lactone formation. The higher homologs (Table 3, entries 2–4) resulted in the corresponding lactones with ring sizes of 5 and 6, respectively, with the δ-keto ester (Table 3, entry 4) leading to the δ

• -pentyrolactone and not the corresponding seven-membered lactone. The primary product from hydroxymethylation was also isolated from the reaction of the ε-keto ester 25 [40]. Heterogeneous and dye-sensitized photocatalysis The results with the semiconductor particle TiO2 P25 under low catalyst loading conditions

• particle surfaces, CB, VB = conduction and valence band. Homogeneous sensitizer variation for the acetophenone model reaction. Substrate variation under optimized conditions. Photohydroxymethylation of keto esters: 1,2-diol and lactone formation. Heterogeneous sensitizer variation for model reaction in

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• /bjoc.10.112 Abstract The development of a reliable procedure for the synthesis of the 16-glucoside and 16-sulfate of the resorcylic acid lactone (RAL) type compound zearalenone is presented. Different protective group strategies were considered and applied to enable the preparation of glucosides and

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

• L-amicetal 4 [36]. Alternatively, we have used 2 as a substrate for a cross metathesis reaction with methyl acrylate under isomerization-free conditions to furnish enoate 5, which underwent cyclization to the lactone 6 after hydrogenation. Reduction of 6 with DIBAL-H eventually yields a protected L

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

• lactone and lactam substrates, the latter products were the only products isolated. For the six-membered lactones and lactams and for cyclopentenone the simple addition products prevailed. Keywords: cyclization; electron transfer; iridium; photochemistry; photoredox catalysis; radical reactions

• and delivered product 14 in 41% yield. Addition to cyclic α,β-unsaturated ketones Based on the results obtained with five-membered lactone 9, it was suprising to note that the related five-membered enone, 2-cyclopentenone (15), delivered mainly the direct addition product 17 instead of the tricyclic

• yield (49%) was recorded for the Ts-protected product 19b. The two protons at the ring junction show a similar coupling constant (3J = 8.1 Hz for 19a, 3J = 7.9 Hz for 19b) as the protons in the related lactone 10 suggesting a cis-annulation of the two heterocyclic rings. The instability of Boc

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• -cis-2,4,6-trimethylcyclohexanone. Subsequent Baeyer–Villiger oxidation, followed by reduction of the obtained lactone, yielded syn,syn-2,4-dimethylheptan-1,6-diol 16 (Figure 4). Protection of the primary hydroxy group gave 17 followed by a Mitsunobu sequence involving the secondary hydroxy group

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• 333.2053, calcd for [M + H]+, 333.2060). From this formula, it was suggested that 1 has seven degrees of unsaturation, of which four could be ascribed to one carbon–carbon double bond, one lactone carbonyl group, and two ketone groups, according to its 1H and 13C NMR data (Table 1); the molecule should

• , 195.9), and a lactone carbonyl group (δC 170.9). The NMR spectroscopic data indicated that 1 was a rearranged abietane. The existence of an isopropyl group was suggested by 1H,1H-COSY correlations between H-15 and protons of two methyl groups [δH 1.11 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.9 Hz, 3H)]. From

• carbonyl carbon (δC 170.9) of a δ-lactone suggested its location at C-7, while those from H2-11, H-14, and H3-20 to the quaternary carbon (δC 88.3) placed it at C-9 (Figure 2). The NOE interactions for the two methyl groups at C-4 suggested that one methyl group is located at the same side as H-5, while

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• three-component process (Scheme 3) [34]. Extension of this work to the intramolecular version is depicted in Scheme 4. The bicyclic lactone 1 was obtained stereoselectively from a diene-yne in a one-pot process with control of the relative stereochemistry of the five stereogenic centers [35]. Concerning

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

• Iguchi and co-workers [44] applied the DVCPR to the total synthesis of the marine prostanoid clavubicyclone [45]. Known aldehyde 33 (see Scheme 7) [46] was subjected to Wittig conditions to furnish an intermediate lactone, which was then opened reductively followed by selective oxidation of the allylic

• this compound was subjected to oxidative conditions both alcohols were oxidized to the corresponding aldehyde/ketone. Base-induced epoxide opening led to the formation of a double bond (C4/C5) and concomitant lactol-formation. The lactol was oxidized to the corresponding lactone under the same reaction

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

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• , 1 and 2 share with other members of this family a large portion of their chemical scaffold including the γ-lactone moiety and the ethyl-branched side chain. Even if the absolute configuration at C-4 and C-6 has been previously determined for plakilactone A (4) and notably for the corresponding 7,8

• oxygenated carbons and one acyl group. The acyl carbon signal at 175.9 ppm (C-1), along with the oxygenated carbon resonance at δC 91.9 (C-4) suggested the presence of a lactone. The olefinic methine carbon at δC 153.5 (C-3) with the quaternary carbon at δC 136.6 (C-2) completed the five-membered α,β

• -unsaturated lactone ring. The linkage of an ethyl side chain at C-2, suggested by the long range allylic coupling between protons H-3 and H2-11, was supported by the diagnostic HMBC correlations H-3/C-11 and H3-12/C-2 (Figure 2). A second isolated ethyl system was linked at C-4 on the basis of the HMBC

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

• bivalent derivatives. Installation of a leaving group on hydroxymethyl compound 4, for instance, would permit coupling with diverse N-dealkylated opiate scaffolds. Alternative attachment points would also be worth exploring, such as the C-17 lactone, which tolerates reduction and alkylation [1]. As noted

• binding pose of 1 may be similar. If so, converting the lactone to a cyclic amine may provide the desired H-bond to Asp1383.32 without the need for additional functional groups. Our results provide no evidence of negative allosteric modulation of κ-OR by low-affinity derivatives of 1, and the mutagenesis

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

• production of inhibitors of survivin promoter activity, a new drimane sesquiterpene lactone, SF002-96-1, was isolated from fermentations of an Aspergillus species. The compound inhibited survivin promoter activity in transiently transfected Colo 320 cells in a dose dependent manner with IC50 values of 3.42

• attractive target for new anticancer therapeutics [13]. In a search for new inhibitors of survivin expression from natural sources, we found that cultures of Aspergillus sp. strain IBWF002-96 produced a new drimane sesquiterpene lactone, SF002-96-1, with inhibitory activity on survivin promoter activity in

• chain (δ 173.5). The relative configuration was deduced from NOESY data. Thus, protons of a methyl group at δ 1.04 showed NOE correlations with those of one of the geminal methyl groups (δ 1.15) and one of the oxymethylene protons (δ 4.48) of the lactone ring (Figure 3). Besides, the protons of the

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• -based electrophilc activation of the C=C, with consequent nucleophilic attack by the ylidic carbon onto the internal carbon of the double bond. Finally, the intermediate lactone 92 underwent cyclopropanation, delivering SPh2 as a leaving group (Scheme 24b). 5 Addition to allylic alcohols The use of

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• to give a draft structure 8. Given the chemical shifts of the carbonyl C-2 (172.5 ppm) and of carbon C-8’ (149.2 ppm), the presence of a lactone moiety can be deduced. The resulting overall structure still lacks three oxygens, a hydrogen, and a nitrogen atom combined with one degree of unsaturation

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• this contribution, we demonstrate that this combination can be advantageously used for the synthesis of decanolides. These natural products share a ten-membered lactone structure and are normally isolated from fungi. Diverse bioactivities have been reported, such as phytotoxicity, cytotoxicity

• reagents and in particular a large excess of DMAP, in combination with higher dilution and elevated reaction temperatures. This led indeed to the formation of the desired lactone 34, which could be isolated in a moderate yield of 27% (Scheme 7). With this result in hand, we reinvestigated the cyclization

• lactone structure originally assigned to fusanolide A, as the spectroscopic data obtained for synthetic 36 differ significantly from those reported for the natural product. As we mentioned in our previous publication describing the synthesis of curvulalic acid (35) [24], all spectroscopic data obtained

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• significantly cheaper starting material D-gulono-1,4-lactone instead of expensive L-glucose. In our previous work, we discovered that two rare sugars, D-sorbose and D-psicose, were simultaneously generated when L-rhamnulose-1-phosphate aldolase (RhaD, EC 4.1.2.19) [47] catalyzed the aldol addition between DHAP

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• unstable epoxy intermediate 11 produces a six-membered lactone intermediate 12 through the breaking of a C–C bond. Subsequently, intermediate 12 tautomerizes to 13 under formation of the isocoumarin skeleton. The dihydropyrrole-fused isocoumarin intermediate 14 is formed through the intramolecular

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• modified F-ring was obtained starting again from azide 3 (see Scheme 1). Reduction of the lactone moiety to give a tetrahydrofuran was accomplished in three steps including (1) partial reduction to the lactol (DIBAl-H, THF, −78 °C to −60 °C, 95%), (2) acetylation (Ac2O, pyridine, cat. DMAP, quant.) and (3

• corresponding triflate (Tf2O, pyridine, 0 °C→50 °C, 46%) gave C-nor-D-homo-derivative 13 which, in turn, was transformed into lactone azide 14 by using Evans’ conditions (LDA, THF, −78 °C to −30 °C, 10 min; then trisylazide, THF, −78 °C, 1.5 h, 43%) [35]. From 14 two additional exo-cyclopamine derivatives

• %) and the benzenesulfonylamine (sodium naphthalenide, DME, −78 °C, 95%) gave 20-demethyl-bis-exo-cyclopamine 19 in 7% overall yield starting from 14. Starting from azido lactone 14 (see Scheme 2) a partial reduction to the lactol (DIBAl-H, THF, −78 °C to −65 °C, 88%) and the Horner–Wadsworth–Emmons

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

• reliable transformation when compared to other related rearrangement reactions. During a further telescoped procedure amine 2.83 was treated with lactone 2.84 to regenerate the corresponding lactam after mesylate formation. Finally, removal of the Boc-group with aqueous hydrochloric acid furnished

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• oxidation of allyl ether 7 may follow two alternative pathways either to the α,β-unsaturated lactone 14 or to the enone 15 (allylic oxidations at exocyclic positions are generally less favorable if radical mechanisms are operating) [35]. Due to sterical hindrance at position 5 and the strong activation for

• should thus be privileged for oxidation. As a consequence, the α,β-unsaturated lactone 17 is indeed the major product along with some unidentified more complex oxidation products. Again, oxidation in 5-position of 11 to the enone 18 was not observed. In addition, the allylic hydrogens in 9-position are

• spiroethers 7 and 11 were oxidized to the corresponding α,β-unsaturated lactone derivatives 14 and 17, whereas the close derivatives 8 and 12 containing slightly less reactive allylic C–H bonds were not converted by PSA at all. The natural product vitispirane (23) was oxidized by PSA, and three new

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• envisioned. Respective silyl-substituted diynes 16 can be traced back to phthalide (17). To differentiate between the insertion of two differently substituted silylacetylenes, the lactone 17 had to be first converted into a monoprotected diol for further transformations. Synthesis of dialkyne building blocks

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• for this system. The stereochemical outcome could be attributed to the sterically less demanding transition state 82b. The epimerization of 83 to 85 proceeded via an intermediate lactone and extended the route by seven steps. After having secured the cis-epimer 85, the diene moiety was introduced in

• of the putative tetracenomycin-like intermediate 210, the aldehyde 211 is reduced to the corresponding alcohol 212. Acetalization and introduction of the 1,2-cis-diol moiety furnishes 213. Sequential formation of the lactone and the isoindolinone generates 214. A final glycosylation step leads to

• moiety was accomplished via deprotection, palladium-catalyzed cyclization–methoxycarbonylation [166] and an acid-catalyzed lactone formation to afford 223. For the generation of the isoindolinone via a Bischler–Napieralski reaction, a chloroacetyl (CA)-protected phenol was essential to avoid competing

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• lactone pentadecanolide (exaltolide, 15) [57], a natural product that is produced industrially for use as a musk-odored perfumery fixative. Reaction of 15 with methylmagnesium bromide afforded the tertiary alcohol 16 in 98% yield (Scheme 2). Selective reduction of the tertiary alcohol of 16 was achieved

• alkene 22. Finally, oxidative cleavage (KMnO4/Bu4NBr) [54] of 22 afforded iso-C15 acid 4. The iso-C18 7 and iso-C19 8 fatty acids were synthesized through similar approaches from the related C16 lactone hexadecanolide 23 [60] (Scheme 3). Reaction of 23 with methylmagnesium bromide afforded 24

Aerobic radical multifunctionalization of alkenes using tert-butyl nitrite and water

• Daisuke Hirose and
• Tsuyoshi Taniguchi

Beilstein J. Org. Chem. 2013, 9, 1713–1717, doi:10.3762/bjoc.9.196

• the mutifunctionalized product 19 as a single isomer. The stereochemistry of 19 could be presumably assigned by considering the 1,5-hydrogen shift mechanism (entry 5) [17]. The reaction of alkene 10 bearing a methyl ester moiety gave γ-lactone 20 by intramolecular transesterification with a tertiary

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• . When 2,6-lutidine was used as the base for the reaction, a 72% isolated yield of the desired product was obtained. In this case, the use of the more nucleophilic lithium methoxide as the base led to cyclization followed by opening of the lactone ring to form methyl ester product 16b. This product did

• using less basic reaction conditions and slightly elevated temperatures. When more basic reaction conditions were used, an overoxidized product derived from the elimination of the lactone ester to form a methoxy styrene from product 20c was obtained. The elevated temperatures are known to assist the

• the cyclic benzyl radicals 21a–c are oxidized. Conclusion It was found that carboxylic acid nucleophiles can be coupled to electron-rich olefins to form lactone products in good yield without interference from competitive decarboxylation reactions. The reactions are consistent with carboxylate