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

• ) [26]. Asymmetric induction can be achieved in [2 + 2] cycloadditions through the use of a chiral auxilliary. The [2 + 2] reaction shown in Scheme 3 employed a chiral ester function to direct the facial selectivity of the addition of the enone to cyclopentene. Diastereoselectivity was found to be

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• -containing esters could be the aromatic nature of the squaramide functional group in catalyst IX, allowing additional π–π-interactions. The properties of the enone double bond of the substrate depend on the nature of the substituents in the phenyl ring. Therefore, the electronic effect of the para

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• benchmarking. As a rough indication of activity, we started out by investigating quinine (1) and supported catalyst 10a–d in the Michael addition of 3-methoxythiophenol and cyclohex-2-enone (Table 1) [17]. Although the performance of quinine in this reaction is poor with regards to selectivity (providing only

• supported thiourea catalyst 12 in the Michael addition of thiophenol and cyclohex-2-enone [17], a transformation known to be very efficiently catalysed by the free thiourea catalyst 3 (Table 3) [19][20]. The immobilized catalyst 12 proved highly active (the uncatalysed reaction is very slow), rapidly giving

• CH2Cl2 (70 mL) for 12 h, and the purified beads were left to dry at room temperature for 24 h (62% yield). Catalyst loadings were determined by CHN analysis. General procedure for asymmetric Michael addition of 3-methoxythiophenol to cyclohex-2-enone: 3-Methoxythiophenol (0.30 mL, 3.10 mmol), and

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• mutants and mutasynthetic approaches. We suggest that the formation of these derivatives is based on elimination at C-7/C-8 followed by reduction(s) of the intermediate enone. In bioactivity tests, only ansamitocin derivatives bearing an ester side chain at C-3 showed strong antiproliferative activity

• ). Indeed, the expected deoxygenated product 13b could be detected, but was also accompanied by the formation of alcohol 9b. Compound 9b may either have resulted from Michael addition of water to the suspected intermediate enone 17 (see later in Scheme 5) or from hydrolytic cleavage of the carbinolamide 12

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• central problem we wished to address was the preparation of the 3-alkyl-2-pyridone moiety of 36 by an unusual [3 + 3] construction developed in our laboratory [80]. This chemistry (Scheme 7) promotes the condensation of a cyanoacetamide 37, with an enone or enal 38, in the presence of t-BuOK in DMSO

Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• , we turned to the initial fragment couplings as summarized in Scheme 4. Fragments 7 and 8 were first combined by a proven sequence starting with an HWE reaction mediated by Ba(OH)2 [42] to provide enone 22 in good yield (80%). This enone was then treated with Stryker’s reagent [43] to selectively

Cyclization of 5-hexynoic acid to 3-alkoxy-2-cyclohexenones

• Anne T. Hylden,
• Eric J. Uzelac,
• Zeljko Ostojic,
• Ting-Ting Wu,
• Keely L. Sacry,
• Krista L. Sacry,
• Lin Xi and
• T. Nicholas Jones

Beilstein J. Org. Chem. 2011, 7, 1323–1326, doi:10.3762/bjoc.7.155

• can be found in Supporting Information File 1. Additional evidence for the participation of chloride ion in this reaction was given by the isolation of the known 3-chloro-2-cyclohexenone (4) [11] from reactions that involved sterically hindered alcohols such as tert-butanol (Table 2). Enone 4 was

One-pot Diels–Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework

• Boubacar Sow,
• Gabriel Bellavance,
• Francis Barabé and
• Louis Barriault

Beilstein J. Org. Chem. 2011, 7, 1007–1013, doi:10.3762/bjoc.7.114

• ][22]. Results and Discussion The synthesis began by a C-alkylation of enone 8 [23] using LDA and MeI to give the corresponding ketone in 90% yield (Scheme 2). A second alkylation to add the propargyl chain was carried out using LDA and propargyl bromide to afford 9 in 62% yield as an inseparable

• steps from enone 8. However, one might recognize that the low chemical yields encountered in some steps undermine the efficacy of the Au(I)-catalyzed cyclization approach. In order to solve this issue, we assumed that bicyclo[3.3.1]nonenone scaffolds can be directly obtained through an intermolecular

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

• , such that a consecutive cyclopropyl ring expansion affords the bicyclic [3.2.0]heptane skeleton 68 in excellent yield and selectivity [53]. Treatment of 68 with a protic acid in water should activate the enone system triggering the nucleophilic attack of water to give hydroxy ketones 69. The synthetic

• pivalate quantitatively. In situ hydrolysis and subsequent equilibration with NaOMe/MeOH yielded thermodynamically favored ketone 97 in 68% yield and >90% ee. Since this bicyclic enone has been recently elaborated to frondosins A and B [60][61] this approach represents a streamlined formal enantioselective

A racemic formal total synthesis of clavukerin A using gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes as the key strategy

• Jae Youp Cheong and
• Young Ho Rhee

Beilstein J. Org. Chem. 2011, 7, 740–743, doi:10.3762/bjoc.7.84

• developed by us [15]. This reaction provides cycloheptane frameworks in a unique manner and illustrates the utility of the gold-catalyzed reactions [16][17][18][19][20][21][22][23]. From a retrosynthetic point of view, we envisioned two different approaches to the key enone intermediate 1 [3] to clavukerin

• A, starting from the cycloheptenone 4 (Scheme 1). In the first approach, enone 1 could be prepared by the sequential cyclization and the chemo- and stereoselective hydrogenation from cycloheptenone 4 (path A). Alternatively, enone 1 could be accessed by the hydrogenation of 4 and the subsequent

• in the formal synthesis of clavukerin A was explored. We first investigated the cyclization–hydrogenation strategy (path A in Scheme 4). Deprotection of 4 and the aldol condensation of the resulting diketone under basic conditions proceeded smoothly to give the enone 2 in good yield. However

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• conjugated enone substructure has attracted the interest of synthetic chemists for decades. Among numerous methodologies, aldol condensations and Wittig-type reactions have been widely utilized [9][10][11][12][13][14][15][16][17][18]. Recently, it was found that conjugated enones could be generated from the

• investigated in this reaction, and the corresponding enone products 2 were isolated in good yields. They employed the alkyne–carbonyl metathesis in the preparation of fused ring systems and obtained two six-membered bicyclic products. However, if the original ring was five- or eight-membered, the reaction

• intermediate, which then generates an oxetenium intermediate. After several electron transfer steps, the cyclic enone product is formed. A similar [2 + 2] pathway has also been invoked for the Brønsted acid- or Lewis acid-mediated intramolecular and intermolecular alkyne–aldehyde metatheses. If terminal

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• of the enantiomers of hindered enone 46 by addition, oxidation and elimination of a sulfenic acid under basic conditions (Scheme 18) [45]. Xiao and co-workers developed an organocatalytic process for the addition of thiols to nitroalkenes [46]. Using thiourea organocatalyst 48, conjugate addition of

• of enone 46. Organocatalytic conjugate addition to nitroalkenes 49. Preparation of β-amino acid 54. Sulfur migration within oxazolidine-2-thiones 56. Preparation of thiols 62 by self-regeneration of stereocentres. Synthesis of (5R)-thiolactomycin. Preparation of tertiary thiols and thioethers via α

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• dianthryls. Photocycloaddition of enone with benzene. Intramolecular photocycloaddition affording multicyclic compounds via [4 + 2]. Photocycloaddition described by Sakamoto et al. Proposed mechanism by Sakamoto et al. Photocycloaddition described by Jones et al. Proposed mechanism for the formation of

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• . This suggests charge–charge repulsive effects in this system. When camphor (44) is reacted with HF-SbF5, three products are isolated (Scheme 10) [22]. A mechanism is proposed for conversion of ketone 45 to enone 47. Initially, the carboxonium ion 45a is formed by protonation of the carbonyl oxygen. A

• formation of a tertiary-carbenium ion 45c which ultimately leads to the stable enone structure 47. When 2-cyclohexen-1-one (47) is reacted with HF-SbF5, a ring contraction occurs to give 3-methyl-2-cyclopenten-1-one (50, Scheme 11) [23]. This conversion involves diprotonation of 48 to give a

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• been proposed that an intermediate in the synthesis of [5]peristylane may be a viable precursor to the still unknown D3h [43.56]nonahedrane, (13). As shown in Scheme 12, the diene-dione 63 can be readily converted to the double enone 64 which undergoes [2 + 2] photocyclization to yield the pentacyclic

Synthesis of 2a,8b-Dihydrocyclobuta[a]naphthalene-3,4-diones

• Kerstin Schmidt and
• Paul Margaretha

Beilstein J. Org. Chem. 2010, 6, No. 76, doi:10.3762/bjoc.6.76

• -diones, i.e. (formal) 1,2-naphthoquinone + alkyne [2 + 2] cycloadducts. Results Irradiation of 1 in the presence of alkynes affords the – known [3] – pentacyclic dimers and variable amounts (0–33%) of enone + alkyne cycloadducts as indicated by 1H NMR spectroscopy. The yields of mixed cycloadducts with

• (relatively) low yield of mixed cycloadduct formation from excited 1 and alkynes seems disappointing. Nevertheless, one should bear in mind that a) dimer formation on irradiation of phenyl-conjugated enones, e.g., 3-phenylcyclohex-2-enone, is not suppressed even in neat alkenes as solvent [6], as these

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

End game strategies towards the total synthesis of vibsanin E, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

• Brett D. Schwartz,
• Craig M. Williams and
• Paul V. Bernhardt

Beilstein J. Org. Chem. 2008, 4, No. 34, doi:10.3762/bjoc.4.34

• , however, to procure this transformation (i.e. 16), that is reaction of isoprene and oxygenated derivatives, with enone 12 completely failed. Davies [16][17], however, demonstrated that a photochemical assisted thermal [4+2] cycloaddition does proceed but with incorrect relative stereochemistry and limited

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• , treatment of substrate 94 with TBSCl in the presence of imidazole and a catalytic amount of DMAP provided 99. The Nagata reagent [49] readily transformed 99 into 100, presumably by 1,4-addition of cyanide ion and ensuing elimination of methanol. Unexpectedly, enone 100 was immune to the one-pot enol

Part 1. Reduction of S-alkyl- thionocarbonates and related compounds in the presence of trialkylboranes/air

• Jean Boivin and
• Van Tai Nguyen

Beilstein J. Org. Chem. 2007, 3, No. 45, doi:10.1186/1860-5397-3-45

• . Alternatively, radical C might fragment to conjugated enone E and stabilised TolSO2• radical. Neither compounds D nor enones E were ever isolated in the present work. Similarly, these compounds were not seen in a precedent work in which a "fast" hydrogen atom donor (hypophosphorus acid) or a "slow" hydrogen

Allylsilanes in the synthesis of three to seven membered rings: the silylcuprate strategy

• Asunción Barbero,
• Francisco J. Pulido and
• M. Carmen Sañudo

Beilstein J. Org. Chem. 2007, 3, No. 16, doi:10.1186/1860-5397-3-16

• result from the addition of the two organometallic species present in the solution (silylcuprate and R1Li). When R1Li is an alkenyllithium this reaction opens new alternatives for preparation of 7-membered rings by intramolecular Michael addition of the allylsilane group to the enone (Scheme 10

• structures ranging from three to seven membered rings, through processes which imply addition of the intermediate silylcuprate to an electrophile (enone, epoxide, nitrile, imine, etc) followed by Lewis-acid catalysed intramolecular cyclization, where the electrophile used determines the type of process and

One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

• Dipak Prajapati,
• Partha P. Baruah,
• Baikuntha J. Gogoi and
• Jagir S. Sandhu

Beilstein J. Org. Chem. 2006, 2, No. 5, doi:10.1186/1860-5397-2-5

• with the addition of enone 2a to a clear solution. After completion and usual work-up, the product 3a was obtained in 85% yield. The reaction did not indicate the formation of any six-membered ring product pyrimido [4,5-c]pyridazine 5 as expected via [4+2] cycloadditions, which would have occurred

• synthetic scope this reaction, we reacted 1,3-dimethyl-6-hydrazinouracil 1 with an α-ketoalkyne (3-hexyn-2-one) in refluxing ethanol, the reaction proceeded somewhat differently from that with an enone (Scheme 2), as the intermediate could undergo a 5-exo-trig cyclisation in preference to 7-exo-trig. Here

A convenient synthesis of γ-functionalized cyclopentenones

• Nour Lahmar,
• Taïcir Ben Ayed,
• Moncef Bellassoued and
• Hassen Amri

Beilstein J. Org. Chem. 2005, 1, No. 11, doi:10.1186/1860-5397-1-11

• chromatography on silica gel (EtOAc/hexane). 4-Benzyl-3-methylcyclopent-2-enone (4d) Purified by column chromatography (hexane/AcOEt, 8/2). 1H NMR (300 MHz, CDCl3) δ 2.09 (s, 3H), 2.26–2.59 (m, 2H), 2.71 (m, 1H), 3.21 (m, 2H), 5.92 (s, 1H), 7.17–7.28 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 19.4, 37.0, 39.0, 48.0

Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: Exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives

• Andrew Kennedy,
• Adam Nelson and
• Alexis Perry

Beilstein J. Org. Chem. 2005, 1, No. 2, doi:10.1186/1860-5397-1-2

• (Scheme 2).[24][25][26][27][28][29][30][31][32] Two-directional[33] oxidative ring expansion of 1,3-difuryl 1,3-amino alcohol derivatives 4 would yield a densely functionalised bis-enone which would be ripe for further functionalisation. The term "two-directional synthesis" is usually used to describe the